Coronavirus (COVID-19) Resources
In Chronological Order

The COVID-19 pandemic is a major health crisis straining the healthcare system and affecting us all. The IARS is committed to supporting our members who are addressing this illness on the front lines in any way we can.

IARS has assembled a content base with the latest peer-reviewed articles on COVID-19 from leading medical journals, sorted by topic and chronologically. In the COVID-19 Resource Newsletter healthcare professionals on the frontlines are given access to global peer experiences and education from publications hand-selected and reviewed by the IARS COVID-19 Scientific Advisory Board. All of these articles are openly available without login.

 

Click on a timeframe below to see articles posted on that date. To search by keyword, select Ctrl + F on a PC and Command + F on a Mac. Then, enter keyword and Enter.

Updated Frequently:

Retractions:

January 19, 2021:

  • Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19). 1/12/2021. van Kampen JJA. Nat Commun.
    The CDC currently uses a minimum disease duration of 10 days in their symptom-based strategy as the statistically estimated likelihood of recovering replication-competent virus approaches zero after ten days of symptoms. In a study of 129 hospitalized patients, duration and key determinants of infectious SARS-CoV-2 shedding in patients with severe and critical COVID-19 was assessed. Median time for infectious virus shedding was 8 days post symptom onset; ≤5% probability for isolating infectious SARS-CoV-2 when duration of symptoms was ≥ 15.2 days. Median viral load was significantly higher in culture + samples than culture – samples. Probability of isolating infectious virus was < 5% when neutralizing antibody titer was 1:80 or higher. Detection of subgenomic RNAs outlasted detection of infectious virus. Based on their findings, a longer disease duration could be considered for severely-ill patients.
  • Lung ultrasound score predicts outcomes in COVID-19 patients admitted to the emergency department. 1/11/2021. de Alencar JCG. Ann Intensive Care.
    Lung ultrasound (LUS) was performed in the emergency department (ED) on 180 patients who were PCR positive for COVID-19. The protocol involved the examination of 12 lung regions, was performed at bedside by experienced ED physicians, and typically required five minutes. LUS scores correlated with findings from chest CT (when performed) and predicted the estimated extent of parenchymal involvement, death, endotracheal intubation, and ICU admission. The authors feel LUS is more sensitive than CXR, requires less resource and infection risk than CT, and could be used as an effective evaluation tool, particularly in resource-constrained settings.
  • Persistent Post-COVID-19 Inflammatory Interstitial Lung Disease: An Observational Study of Corticosteroid Treatment. 1/12/2021. Myall KJ. Ann Am Thorac Soc.
    This is a well-written narrative following 837 Covid-19 patients seen between February and May 2020 in metropolitan London, UK hospitals. Four weeks after discharge, 39% had not returned to baseline and underwent further study. Thirty patients with persistent respiratory symptoms and interstitial lung disease received prednisolone 0.5mg/kg with rapid weaning over a 3-week period which improved diffusion capacity by 31.6% and FVC by 9.6% and resulted in symptomatic and radiological improvement. This preliminary data requires further study into the natural history and potential treatment for patients with persistent inflammatory interstitial lung disease following SARS-CoV2 infection.
  • Stability of SARS-CoV-2 on critical personal protective equipment. 1/13/2021. Kasloff SB. Nature Scientific Reports.
    Persistence of viable virus was measured on eight PPE materials. Viable SARS-CoV-2 persisted for 21 days on plastic, 14 days on stainless steel, 7 days on nitrile gloves and 4 days on chemical resistant gloves, though at significantly reduced levels compared to the initial inoculum. Viable SARS-CoV-2 was nearly undetectable, however, could still be recovered from N-95 and N-100 materials for up to 21 days. On 100% cotton, the virus underwent rapid degradation and was not viable within 24 hours. These findings underline the importance of appropriate handling of contaminated PPE and a potential advantage of cotton.
    SAB Comment: Many of the results in this study differ from other often-quoted reports. This is not surprising as experimental conditions including contaminating load, medium, ambient temperature and humidity have a large influence on the time viruses remain viable and vary among studies.
  • Ventilator-associated pneumonia in critically ill patients with COVID-19. 1/12/2021. Maes M. Crit Care.
    This retrospective observational study from the UK studied ventilator-associated pneumonia (VAP) in mechanically ventilated COVID-19 (n=81) and non-COVID-19 (n=144) patients at a single hospital. All patients were studied between March and August 2020, and VAP was defined by the European Center for Disease Control using clinical and microbiological criteria. COVID-19 was associated with an increased risk of VAP (28 per 1,000 ventilator days) compared with non-COVID-19 patients (13 per 1,000 ventilator days). Although the distribution of organisms causing VAP was similar between the two groups, aspergillosis was only found in COVID-19 patients (n=3, none on steroids).

January 15, 2021:

  • COVID-19, Personal Protective Equipment, and Human Performance. 1/6/21. Ruskin KJ. Anesthesiology.
    This article addresses the issue of the varieties of PPE worn by healthcare workers. The authors discuss how various varieties of PPE may cause increased work of breathing, reduced field of vision, communication mishaps, thermoregulation derangements, limitations of physical dexterity and mental, physical, and psychological fatigue and stress which lead to decreased human performance. These effects are not individual weaknesses. Here the authors suggest some helpful remedies to address the physiologic and psychologic challenges imposed by non-standardized PPE. There is a need for a new, standardized, integrated design for PPE to improve the safety of patients and healthcare workers.
  • Early corticosteroids are associated with lower mortality in critically ill patients with COVID-19: a cohort study. 1/5/21. Monedero P. Crit Care.
    This is a prospective, multicenter, observational, cohort study in 882 critically ill adult patients with COVID-19 admitted to 36 critical care units in Spain. Beginning in early March to the end of June 2020, patients receiving corticosteroids within 48 hours of ICU admission had a lower mortality compared to those receiving steroids later (30 vs. 40% – HR 0.71) or not at all. Patients treated early did better overall with shorter ICU stays, fewer ventilator days and a lower incidence of organ dysfunction. Higher dosages were found to be more effective. Corticosteroid administration occurred on average 12 days after symptom onset. The authors recommend corticosteroids as early as day 7 provided inflammatory markers are elevated.
  • Facial Pressure Injuries from Prone Positioning in the COVID-19 Era. 1/3/21. Shearer SC. Laryngoscope.
    This study highlights the high frequency (48%) of facial pressure injuries associated with intubated COVID-19 patients placed in the prone position at a single US institution. Most of these patients were continuously in the prone position. Of 143 intubated ICU patients proned for an average of 123 hours, cheek and ear injuries accounted for the majority of damage, with the likelihood of injury increasing as proning times increased. A particular problem seemed to be pressure caused by commercial endotracheal tube fasteners. Suggestions for reducing these injuries are made. The study did not address injuries to the eye or elsewhere on the body.
  • Prone Positioning in Moderate to Severe Acute Respiratory Distress Syndrome Due to COVID-19: A Cohort Study and Analysis of Physiology. 12/31/2020. Shelhamer MC. J Intensive Care Med.
    This retrospective cohort study from an overwhelmed hospital in the Bronx supports prone positioning as an intervention to increase survival and improve physiologic parameters in patients on mechanical ventilation with moderate to severe ARDS due to COVID-19. Of 261 patients who qualified for prone positioning by specific criteria, 62 received proning from a specially developed team for at least 16 hours per day, and outcomes were compared to those not proned (n=199). The proned group had 40% less mortality, with a mortality benefit (number needed to treat) of 8.

January 13, 2021:

  • 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. 1/8/21. Huang C. Lancet.
    175-199 days after symptom onset, 1733 of 2469 discharged Wuhan COVID-19 patients (median age 57) completed questionnaires to evaluate symptoms and quality of life along with physical examinations, a 6-min walking test, and blood tests. Reduced 6-min walk, fatigue, pulmonary abnormalities, and anxiety or depression were prevalent. 73% of men and 81% of women reported at least one symptom (76% overall). Most common were fatigue or muscle weakness (63%), sleep difficulties (26%), and anxiety or depression (23%). Symptoms were positively correlated with previous COVID-19 illness severity.
    SAB Comment: Many with mobility or neurologic issues were excluded, therefore accurate percentages may be higher.
  • Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults. 1/6/21. Libster R. N Engl J Med.
    This article describes an Argentine randomized, double-blind, placebo-controlled trial of convalescent plasma (CP) with IgG titers >1:1000 against SARS-CoV-2 within 72 hours following the onset of mild COVID-19. CP reduced disease progression in adult patients older than 75 years or 65-74 years old with co-morbidities. Severe respiratory disease developed in 13/80 patients (16%) who received 250 ml of CP and 25/80 (31%) who received 250 ml normal saline (relative risk, 0.52). Benefit was more frequent following units with higher IgG titers, indicating a dose-dependent effect. Deaths were 2/80 in the CP group vs. 4/80 in the placebo group.
  • Impact of cardiovascular disease and risk factors on fatal outcomes in patients with COVID-19 according to age: a systematic review and meta-analysis. 12/18/20. Bae S. Heart.
    This is a retrospective meta-analysis to investigate the impact of cardiovascular disease (CVD) and associated risk factors (hypertension, diabetes) on age-related mortality in COVID-19 patients. Fifty-one studies, including 48,171 patients were included, along with PRISMA diagrams and tables. Unsurprisingly, CVD, hypertension and diabetes increased mortality across all groups. However, when present in younger ages, the odds ratio of mortality compared with same age patients without the risk factors was disproportionately higher than the same age ratio in the elderly. While young patients had lower prevalence rates of cardiovascular comorbidities than elderly patients, relative risk of fatal outcome in young patients with hypertension, diabetes and CVD was higher than in elderly patients.
  • SARS-CoV-2 Transmission From People Without COVID-19 Symptoms. 1/7/21. Johansson MA. JAMA Netw Open.
    A decision analytical model was used including multiple scenarios for the infectious period and the proportion of transmission from individuals who never have COVID-19 symptoms. Baseline assumptions were taken from meta-analyses and included an incubation period of a median of 5 days. In the various analyses peak infectiousness was varied between 3 and 7 days. Under a broad range of values for each of these assumptions, at least 50% of new SARS-CoV-2 infections were estimated to have originated from exposure to individuals who were asymptomatic at the time of transmission (combining those who never develop symptoms with those who are pre-symptomatic).
    SAB Comment: This highlights the importance of mask-wearing and social distancing even as vaccines are rolled out.

January 11, 2021:

  • Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers. 12/28/20. Lumley SF. N Engl J Med.
    This is an original article from 4 Oxford University Hospitals that followed its employees for SARS-CoV-2 infection. Testing was performed every 2 weeks or if symptomatic. 10% of 12,541 staff tested positive from March through November 2020. Polymerase chain reaction assays of both anti-spike IgG and anti-nucleocapsid IgG demonstrated that healthcare workers who tested positive suffered mild disease and were afforded immunity for the length of the study, 31 weeks.
  • Promising Therapy for Heart Failure in Patients with Severe COVID-19: Calming the Cytokine Storm. 1/6/2021. Peng X. Cardiovasc Drugs Ther.
    This detailed and well referenced review covers key mechanistic links between Covid-19 cytokine-storm, subsequent myocardial injury and progression to heart failure (HF). Heightened release of cytokines may result in myocardial damage through direct injury, general inflammation, thrombosis, hypoxemia and downregulation of ACE2 on cardiomyocytes and vascular endothelium. Key inflammatory cytokines include TNFa and IL-1b; both produce accumulation of interstitial collagen fibers and IL-6 which can induce cardiomyocyte hypertrophy and diastolic dysfunction. HF therapies may include cytokine inhibitors, corticosteroids, type-I and -III interferons, but their timing needs investigation. Current guidance suggests maintaining or starting ACEIs and ARBs; benefits may outweigh risks.
  • SARS-CoV-2 Variant – United Kingdom of Great Britain and Northern Ireland. 12/21/20. WHO.
    UK scientists sequenced a SARS-CoV-2 variant (VUI 202012/01) now representing >50% of isolates in South East England. The variant shows 14 mutations resulting in amino acid changes and three deletions. Significant mutations in the receptor binding domain are N501Y and P681H. A deletion at position 69/70 affects the Spike (S)-gene. The variant increases transmissibility between 40-70%, adding 0.4 to R0 bringing it to 1.5-1.7. Investigations are ongoing to determine if this variant will change symptom severity, antibody responses or vaccine efficacy. Most PCRs target multiple sequences and therefore the impact of the variant on diagnostics is not anticipated to be significant.
    SAB Comment: In order to understand the epidemiology of any variant, widespread and frequent genetic sequencing of viral testing samples is needed. Currently, the US lags far behind the UK in this regard, sequencing ~1% of samples vs. >10% in the UK. Therefore, relatively little is known about the spread of the “UK variant” in the US.

January 8, 2021:

January 6, 2021:

  • Corticosteroid use in COVID-19 patients: a systematic review and meta-analysis on clinical outcomes. 12/15/20. van Paassen J. Crit Care.
    This well-conducted systematic review and meta-analysis to evaluate safety and effectiveness of corticosteroids in COVID-19 included 44 studies and 20,197 patients collected between December 1, 2019 and October 1, 2020. Primary outcomes were short-term mortality and viral clearance (based on RT-PCR in respiratory specimens). Secondary outcomes were need for mechanical ventilation, other oxygen therapy, length of hospital stay and secondary infections. Non-peer reviewed and pre-published manuscripts were excluded from analysis. Findings from observational studies and RCTs confirm beneficial effect of corticosteroids on short-term mortality and reduction in mechanical ventilation. A possible signal of delayed viral clearance and an increase in secondary infections was noted. Optimal timing, dose and duration of corticosteroids, in relation to safety, remain subjects for further investigation.
  • Corticosteroids for Patients With Coronavirus Disease 2019 (COVID-19) With Different Disease Severity: A Meta-Analysis of Randomized Clinical Trials. 12/10/20. Pasin L. J Cardiothorac Vasc Anesth.
    In this meta-analysis of 5 studies involving treatment with steroids of 7,692 COVID patients, the authors note that the effect of corticosteroids therapy on survival with COVID patient varies with different respiratory support. The use of corticosteroids may be detrimental to patients who do not require oxygen support (NNH/number needed to harm=29) and increases mortality. Its effectiveness for mechanically ventilated patients was (NNT/number needed to treat=19). The majority of COVID-19 patients not requiring oxygen/mechanical ventilation will have a better survival benefit without steroids.
  • COVID-19 Convalescent Plasma Treatment of Moderate and Severe Cases of SARS-CoV-2 Infection: A Multicenter Interventional Study. 12/7/20. Alsharidah S. Int J Infect Dis.
    SAB Comment: This is a non-randomized observational study from Kuwait. Research is needed to determine patient groups that benefit.
    One hundred and thirty-five patients with moderate-severe COVID-19 disease who received 2 units of convalescent plasma (CP) within 3 days of hospital admission had an earlier and higher rate of clinical improvement compared with 233 control patients. Moderate disease was found in 86.5% of CP group (n=89) who had a time to clinical improvement of 7 days versus 68% of controls with time to clinical improvement of 8 days (p=0·006). Severe disease was found in 61% of CP group (n=46) with time to clinical improvement of 7 days vs. 35% of controls with time to clinical improvement of 15.5 days (p=0·003). Overall 30-day mortality was 18% CP group vs. 39% controls. Moderate disease patients had a significantly lower mortality following CP (11% vs. 30%, p= 0.001).
  • Factors Associated With Severe SARS-CoV-2 Infection. 12/16/20. Ouldali N. Pediatrics.
    This 60-hospital French national study used an established meningitis surveillance network to study demographics of COVID-19 pediatric patients. Data collection was from February 15-June 1, with 397 children and included an estimated 38.5% of the total cases in France. The primary outcome was the proportion of patients with disease progression, and secondary outcomes were defined by age groups. The median age was 16 months. Three percent of children (4/135) <90 days old developed severe disease. MIS-C increased with age. There was severe disease overall in 11% (23/306). Of the 6 mortalities only one was entirely due to COVID-19. Findings suggested that the rate of severe forms was the lowest in very young children and was the highest for children ≥ 10 years.
  • Masking the 6 Minutes-Walking-Test in the COVID-19 Era. 12/14/20. Salles-Rojas A. Ann Am Thorac Soc.
    A small study of 77 COVID-19 pneumonia survivors who each performed the 6-Minute Walking Test twice, once with a surgical or an N-95 mask and once without a mask. No differences were observed between wearing or not wearing a mask in the meters walked, SpO2, HR, dyspnea or fatigue.
  • Variation in US Hospital Mortality Rates for Patients Admitted With COVID-19 During the First 6 Months of the Pandemic. 12/22/20. Asch DA. JAMA Intern Med.
    This cohort study from a US-managed health company evaluated outcomes for 38,517 adults with COVID-19 admitted to 955 US hospitals during two time periods (January to April and May to June). The primary outcome was the hospitals’ risk-standardized event rate (RSER) of 30-day in-hospital mortality or referral to hospice, adjusted for patient-level characteristics. RSERs declined from 16.6% to 9.3%. Individual hospitals did better when the prevalence of COVID-19 in their surrounding communities was lower. The article speculates on possible causes for this improvement, including fewer overwhelmed hospitals, improved knowledge and medical care, and possibly smaller infective inoculums as mask-wearing became more common.

January 4, 2021:

  • Genetic mechanisms of critical illness in Covid-19. 12/11/20. Pairo-Castineira E. Nature.
    Oriented towards research, this genome-wide association study (GWAS) examined 2,244 critical COVID-19 patients in 208 UK ICUs to uncover gene variants that are severity markers and potential treatment targets. GWAS findings implicated antiviral restriction enzyme activators (OAS1/OAS2/OAS3), high tyrosine kinase-2 (TYK2), dipeptidyl peptidase- 9 (DPP9) and low interferon receptor gene IFNAR2. Mendelian randomization techniques implicated as “causal” low IFNAR2 and high TYK2 expression. Lung tissue transcriptome-wide association implicated high monocyte/macrophage chemotactic receptor CCR2. These gene alterations implicating early anti-viral defense (IFNAR2, OAS) and late inflammation (DPP9, TYK2, CCR2) can be evaluated in clinical trials using licensed drugs (interferons, JAK inhibitors, CCR2 inhibitors, etc.).

December 18, 2020:

  • Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. 12/11/20. Kalil AC. N Engl J Med.
    This article provides the encouraging outcome of a randomized trial enrolling 1033 patients in 8 countries, led by the team that conducted ACTT-1, the remdesivir randomized control trial. The oral anti-inflammatory drug baricitinib, a selective inhibitor of Janus kinase (JAK) 1 and 2, in combination with remdesivir, proved safe and superior to remdesivir alone for the treatment of hospitalized patients with COVID-19. While the primary outcome, time to recovery, improved by one day only, patients with impending respiratory failure benefitted most with progression to death or invasive ventilation being 31% lower in the combination group. The discussion includes a detailed review of the drugs’ potential dual action as an anti-inflammatory and antiviral and makes a pertinent comparison with dexamethasone and the RECOVERY trial.
    The incidence of side effects of JAK inhibitors (immunosuppression, secondary infections, and thrombosis) were not significantly higher when baricitinib was added.
  • Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations. 12/8/20. Diorio C. Blood Adv.
    This study, designed for researchers, examined 50 COVID-19 pediatric hospitalized patients for soluble C5b9 and thrombotic microangiopathy. C5b9 were found to correlate with the severity of disease and serum creatinine. Thrombotic microangiopathy was found in 17 of the 19 patients examined. These data help characterize COVID-19 disease in the pediatric population and help form the building blocks for further study.
  • On the whereabouts of SARS-CoV-2 in the human body: A systematic review. 10/30/20. Trypsteen W. PLOS Pathogens.
    This article is a well-presented review of available literature through June 2020. The strength of this paper resides in its focus on viral presence and evidence of replication and infectivity in different organ systems. It acknowledges the fact that the presence of an ACE2 receptor does not control viral cell entry per se. It concludes that while we have a good understanding of the presence and replication mechanisms in the respiratory system, a full understanding of the underlying mechanism of organ toxicity – direct viral, micro-vascular or inflammatory – in other systems (heart, kidney, CNS) remains inconclusive.

December 16, 2020:

December 14, 2020:

  • Association between statin use and outcomes in patients with coronavirus disease 2019 (COVID-19): a nationwide cohort study. 12/5/20. Butt JH. BMJ Open.
    This study utilized the Danish public health record system to disprove claims of a June 2020 published observational study from China which found a relative risk reduction in mortality of 42% among COVID-19 inpatients receiving statins.
    In a tightly controlled cohort study, recent statin exposure did not influence all-cause mortality of severe SARS-CoV-2 infection. Theories of a cardio-protective, anti-inflammatory or immune-response modulating mechanism could not be substantiated.
  • Cardiac complications in patients hospitalised with COVID-19. 11/23/20. Linschoten M. Eur Heart J Acute Cardiovasc Care.
    This article shows results from a 3011 patient multi-national/institutional study designed to determine the role of cardiovascular (CV) disease in COVID-19 patients admitted to the hospital enrolled between April and June. Eleven and a half percent (349) of the patients had CV complications with AF 4.7% (142) being the most common. Eight hundred thirty-seven patients required ICU/high dependency unit, of which 87% required mechanical ventilation; overall mortality was 19.8%. Patients with pre-existing cardiac disease (ischemia, heart failure) were more likely to develop complications. Pulmonary embolism was reported in 6.6% of patients overall but was found in 18.9% of those who were admitted to the ICU. These results suggest that elevated troponin levels in absence of electro- or echocardiography abnormalities should be interpreted cautiously and may more likely be related to demand ischemia. The authors conclude that incidence of cardiac complications during hospital admission is low, despite frequent patient histories of pre-existing cardiovascular disease.
    SAB Comment: This article highlights difficulty in diagnosing primary cardiac complications from biomarkers alone. While not diagnostic, elevated troponin levels have been associated with increased mortality in COVID-19 patients as well as in other ARDS-associated conditions (e.g. septic shock, post-traumatic injury).
  • Right ventricular dysfunction in critically ill COVID-19 ARDS. 11/26/20. Bleakley C. Int J Cardiol.
    Interesting observational study/retrospective analysis of RV echocardiographic data collected on 90 patients requiring invasive ventilation revealed that RV dysfunction was under-diagnosed with long axis views of the RV. Analysis noted radial measurement of RV dysfunction correlated with elevations in hs-Tn1 and NT pro-BNP, indicators of myocardial injury possibly related to high afterload. The authors suggest a new phenotype of RV dysfunction in COVID-19 not seen in other ARDS diagnoses. Of note, 42% of patients were receiving vino-venous ECMO. The authors suggest that findings that indicate hyperdynamic results on longitudinal views may represent a response to radial dysfunction. Excellent descriptions and tables are included.

December 11, 2020:

  • Association of inhaled and systemic corticosteroid use with Coronavirus Disease 2019 (COVID-19) test positivity in patients with chronic pulmonary diseases. 12/4/20. Liao SY. Respir Med.
    This study of 928 patients tested at National Jewish Health respiratory hospital for COVID-19 found 113 (12%) were positive. Retrospective analysis showed that using inhaled corticosteroids was not associated with a change in the likelihood of testing positive for COVID-19. Being treated with systemic corticosteroids was actually associated with a slight decrease in the likelihood of testing positive for COVID-19, especially in patients with chronic pulmonary disease or airway diseases (asthma or COPD).
  • Characteristics of Adults aged 18-49 Years without Underlying Conditions Hospitalized with Laboratory-Confirmed COVID-19 in the United States, COVID-NET – March-August 2020. 12/3/20. Owusu D. Clin Infect Dis.
    This article describes a Center for Disease Control-funded, cross-country study of non-pregnant adults younger than 50 years old providing the causes of hospital admissions due to COVID-19. While fever was a common presenting symptom, the illness primarily affected the pulmonary system. 22% were admitted to ICU although death occurred in <1%. 74% of patients were male and authors discuss the possibility of genetics linked to ACE2 receptor as a cause of infection severity.
    Of note, 42% of patients were Hispanic/Latino; treatment was not controlled; obesity and the use of steroids were not reported; 20% of patients were healthy prior to infection; 12% received remdesivir.
  • Controversies in airway management of COVID-19 patients: updated information and international expert consensus recommendations. 12/1/20. Wei H. Br J Anaesth.
    This editorial by a panel of international experts summarizes the COVID-19 airway management literature on the effectiveness of personal protective equipment (PPE), transmission of the virus during high flow nasal oxygen therapy (HFNO), and the debate over early vs. late intubation. Tables nicely summarize the examined literature. Their consensus includes:
    • The higher the PPE level, the better the protection.
    • There is no convincing evidence that HFNO increases the risk of COVID-19 cross-infection to healthcare workers.
    • Timing of intubation will depend upon individual pathophysiology, the trajectory of the illness, and the response to trials of noninvasive airway management.
    • More study is needed.
  • COVID-19 Associated Thrombosis and Coagulopathy: Review of the Pathophysiology and Implications for Antithrombotic Management. 11/24/20. Ortega-Paz L. J Am Heart Assoc.
    This is a comprehensive, well-written, albeit lengthy, review of COVID-19 pathophysiology and therapies. Cardiovascular, thrombotic, and coagulopathic manifestations are emphasized along with the importance of individual risk assessment for venous thromboembolism (VTE). Multiple validated VTE risk assessment tools are enumerated. A theory of imbalanced ACE/ACEII receptors as a risk factor for SARS-CoV-2 infection is discussed. Useful summary figures and tables include knowledge gaps and ongoing areas of research.
  • Pulmonary embolism in COVID-19 patients: Prevalence, predictors and clinical outcome. 12/3/20. Scudiero F. Thromb Res.
    This retrospective database study from 7 Italian hospitals looked over the echocardiogram results of 224 patients with COVID-19 of whom 14% had PE confirmed by CTA. The purpose was to identify which echocardiographic findings best predict pulmonary embolism. PE patients were hospitalized a longer time after symptom onset, showed higher D-dimer level and a higher prevalence of myocardial injury. At multivariable analysis, tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary arterial pressure were the only parameters independently associated with PE. Mortality rates (50% vs 27%; p = 0.010) and cardiogenic shock (37% vs 14%; p = 0.001) were significantly higher in PE patients.
  • The ADAMTS13-von Willebrand factor axis in COVID-19 patients. 11/23/20. Mancini I. J Thromb Haemost.
    This study examines the VWF antigen to ADAMTS13 activity ratio in 50 COVID-19 hospitalized patients and demonstrates that this ratio was strongly associated with COVID-19 severity. Three groups of patients were studied, namely those receiving nasal oxygen, CPAP treatment, or intubation with ventilatory support. The authors suggest that these data represent potential new markers of disease severity and further support the concept of micro thrombogenesis in patients with severe COVID-19.
    SAB Comment: This is new scientific information to help understand pathophysiology of micro thrombosis but routine ADAMTS13 testing isn’t recommended.
  • Tobacco use as a well-recognized cause of severe COVID-19 manifestations. 11/30/20. Gupta AK. Respir Med.
    Though we have reviewed articles, some saying that COVID-19 is worse in smokers and others that it is not, the authors reviewed 23 articles that met their criteria. The authors noted that pre-existing comorbidities in tobacco users such as cardiovascular diseases, diabetes, respiratory diseases, and hypertension are found to further aggravate the disease manifestations. More generally, smoking is a potential risk factor for, not only contracting the viral infection, but also making the treatment of such COVID-19 patients more challenging.

December 7, 2020:

  • Early Percutaneous Tracheostomy in Coronavirus Disease 2019: Association With Hospital Mortality and Factors Associated With Removal of Tracheostomy Tube at ICU Discharge. A Cohort Study on 121 Patients. 11/17/20. Rosano A. Critical Care Medicine.
    This single-center Italian study reviewed outcomes of 121 COVID-19 patients treated with early percutaneous tracheostomy between 4 and 12 days (median 6) following ICU admission. Includes detailed discussion of rationale, inclusion criteria, methods, decannulation strategies and rehabilitation. Outcomes include procedural safety and efficacy for providers and patients, ability to decannulate survivors in ICU and trend to improved survival. Also discussed are improved/earlier weaning, and easier management and discharge from ICU. A useful comparison with other relevant studies is provided.
  • Early Percutaneous Tracheostomy During the Pandemic “As Good as It Gets”. 11/19/20. Auzinger G. Critical Care Medicine.
    This related editorial discusses percutaneous tracheostomy risk/benefit related to COVID-19 as well as other ICU conditions including ARDS and MERS. Strengths of the related article, the largest single-center study of percutaneous tracheostomy for COVID-19 disease, include a pragmatic approach relating to timing and choice of percutaneous vs. surgical approach based on well-described protocols for management and decannulation extant prior to the pandemic. This editorial compares the study’s strengths to others in literature and notes that while early tracheostomy may be considered a risk to the procedural team, the incidence of subsequent +COVID tests in participants was lower than in other ICU staff. This editorial amplifies Rosano’s manuscript and understanding regarding timing and potential benefits of early tracheostomy in COVID-19 patients.
  • Loneliness, Mental Health, and Substance Use among US Young Adults during COVID-19. 10/28/20. Horigian VE. J Psychoactive Drugs.
    Frequently discussed in mass media, this paper presents the psychologic issues associated with the COVID-19 pandemic. In addition, intensivists and anesthesiologists should be aware of possible alcohol and drug use intended by the patient to relieve depression associated with this illness and its treatment.
  • No evidence for increased transmissibility from recurrent mutations in SARS-CoV-2. 11/25/20. van Dorp L. Nat Commun.
    SARS-CoV-2 is not becoming more transmissible or virulent. In jumping from animal to human, SARS-CoV-2 might evolve or adapt toward higher transmissibility. This study examined whether viral changes have emerged repeatedly and independently (homoplasies) and if repeated mutations in human lineages made the virus more transmissible. Using a 99-country dataset of 46,723 SARS-CoV-2 genomes compared to the reference Wuhan-Hu-1, investigators did not identify a single recurrent mutation convincingly associated with increased viral transmission. So far, as an endemic human pathogen, recurrent mutations appear to be evolutionary neutral, single lineage and primarily induced via RNA editing, rather than being signatures of adaptive pressure and a new separate phenotype.
  • Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. 11/30/20. Meinhardt J. Nature Neurosci.
    Viral penetrance of the CNS is likely through diverse routes. These investigators demonstrate in 33 autopsies morphological changes associated with SARS-CoV-2 neurotropism, such as thromboembolic ischemic infarction of the CNS and the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. By exploiting the proximity of olfactory mucosal, endothelial and nervous tissue, including olfactory and sensory nerve endings, virus can cross into the olfactory CNS. Subsequently, SARS-CoV-2 appears to penetrate other areas of the CNS, including the primary respiratory and cardiovascular control centers in the medulla oblongata.
  • Repurposed Antiviral Drugs for Covid-19 – Interim WHO Solidarity Trial Results. 12/2/20. WHO Solidarity Trial Consortium. N Engl J Med.
    Beginning in March 2020, the WHO Solidarity trials enrolled 11,330 patients in 405 hospitals in 30 countries representing all six WHO regions and randomly assigned them to receive either remdesivir, lopinavir, hydroxychloroquine or interferon beta-1a regimens or to receive hospital-specific standard care. None of these drugs achieved the desired goal of a reduction in 28-day mortality. Except for remdesivir, all trials have since been discontinued.
    SAB Comment: Despite a negative outcome, this work is encouraging as it shows WHO’s capability to direct a rigorous global study protocol and a complex data collection and report it in a timely manner.
  • Tissue-specific Immunopathology in Fatal COVID-19. 11/20/20. Dorward DA. Am J Respir Crit Care Med.
    In eleven post-mortems these authors investigated whether inflammation is primarily a direct reaction to SARS-CoV-2 or an independent organ-specific immunopathologic reaction. Using multiplex PCR and in situ viral spike protein detection, SARS-CoV-2 organotropism was mapped. Multiple virus-independent aberrant immune responses mostly in lungs and reticuloendothelial system were found. These viral-independent immunopathologic features included monocyte/myeloid-rich pulmonary artery vasculitis, pulmonary parenchymal expansion of monocytes/macrophage-lineages and in the reticuloendothelial system, iron-laden macrophages and plasma cell responses. They concluded that a disconnect between viral presence and inflammation implicates immunopathology as a primary mechanism of organ injury in severe COVID-19.

December 4, 2020:

  • A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia. 11/24/20. Simonovich VA. N Engl J Med.
    Convalescent plasma with a median titer of 1:3200 of total SARS-CoV-2 antibodies was administered a median of 8 days after the onset of symptoms to 228 hospitalized patients with severe COVID-19 pneumonia. Placebo was administered to 105 patients. Other therapy was not standardized. After 30 days there was no significant difference in outcome. Adverse effects of plasma transfusion could not be evaluated. This also suggests that passive immune therapy with monoclonal antibodies may not be beneficial to such a population.
    SAB Comment: Other studies indicate that antibodies administered early after onset of symptoms to patients with mild disease are beneficial.
  • Assessment of 135,794 Pediatric Patients Tested for Severe Acute Respiratory Syndrome Coronavirus 2 Across the United States. 11/23/20. Bailey LC. JAMA Pediatr.
    This is an epidemiologic, retrospective study of 135,794 patients younger than 25 years old tested for SARS-CoV-2 during the first 9 months of 2020 — 3% of the nation’s 2.5 million children — in a country-wide study of a consortium of children’s hospitals admissions. An overall low positive COVID-19 rate of 4% was found. Black, Hispanic and Asian youth were underrepresented yet produced higher positive results. Of the 5374 children testing positive, only 359 were hospitalized and 8 died. Six of the deaths had complex preexisting comorbidities.
    Preexisting respiratory and cardiac morbidity was not a significant issue in those hospitalized. Endocrine, metabolic and malignancy-associated illnesses were linked to hospitalizations from COVID-19. Obesity was not defined.
  • Association Between ABO and Rh Blood Groups and SARS-CoV-2 Infection or Severe COVID-19 Illness: A Population-Based Cohort Study. 11/24/20. Ray JG. Ann Intern Med.
    This population-based study of adults and children who had previous ABO blood group assessed, and who subsequently had SARS-CoV-2 testing found that O (adjusted odds ration 0.89) and Rh− (adjusted odds ration 0.80) blood groups may be associated with a slightly lower risk for SARS-CoV-2 infection and severe COVID-19 illness. Data came from 225,556 persons with a + PCR test for SARS-CoV-2 between 15 January and 30 June 2020 of 2,659,328 who had ABO/Rh measured during 2007-2019 in Ontario, Canada, a province with universal health care.
  • Dosing of thromboprophylaxis and mortality in critically ill COVID-19 patients. 11/23/20. Jonmarker S. Crit Care.
    This is a retrospective analysis for 2 ICUs in Stockholm. In March, patients received low-dose LMWH and in April, all got medium- or high-doses. The baseline characteristics for these 152 COVID-19 patients were similar. For patients who received high-dose prophylaxis, 28-day mortality was lower (13.5%) compared to those who received medium dose (25.0%) or low-dose (38.8%), p = 0.02. Hazard ratio was 0.33 among those who received high-dose prophylaxis. There were fewer thromboembolic events in the high- (2.7%) vs medium- (18.8%) and low-dose thromboprophylaxis (17.9%) groups, p = 0.04. Bleeding rates were similar.
  • Incidence of venous thromboembolism and bleeding among hospitalized patients with COVID-19: a systematic review and meta-analysis. 11/17/20. Jiménez D. Chest.
    This is a systematic review with meta-analysis of the world’s incidence of DVT, PE and bleeding with COVID-19. The paper offers a snapshot but also analyzes the data and points to the way forward. Forty-eight studies were selected with 18,093 patients with VTE in 17% (2/3 with DVT) and any bleeding event in 7.8%. The authors point out that this varies with whether VTE was detected by duplex screening or clinical diagnosis, percentage of ICU patients and the degree of anticoagulation. The authors point out the lack of optimal strategies and the need for controlled trials.
  • SARS-CoV-2 analysis on environmental surfaces collected in an intensive care unit: keeping Ernest Shackleton’s spirit. 11/23/20. Escudero D. Intensive Care Med Exp.
    This study analyzed environmental contamination by SARS-CoV-2 of surfaces in a Spanish intensive care unit dedicated exclusively to the care of patients with COVID-19 and equipped with negative pressure of – 10Pa and an air change rate of 20 cycles per hour. None of 102 surface samples collected at different times of day over 2 weeks were positive by RT-PCR nor did any of the 237 ICU workers become infected by the virus. The ICU was cleaned with detergent and sodium hypochlorite twice daily. Authors discuss the contrast with studies sampling surfaces in other institutions.
  • SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis. 11/19/20. Cevik M. Lancet.
    This meta-analysis of 79 COVID-19 articles characterized viral load kinetics and dynamics, duration of viral RNA shedding, and viable virus shedding. Despite evidence of prolonged SARS-CoV-2 RNA shedding (mean 17 days) in respiratory samples, viable virus shedding appears to be short-lived (9 days maximum). Therefore, RNA detection cannot be used to infer infectiousness. High titers of SARS-CoV-2 RNA are detected from symptom onset to day 5 of illness, which probably explains the efficient spread of SARS-CoV-2 compared with SARS-CoV and MERS-CoV. These findings emphasize the importance of early case finding and prompt isolation.

December 2, 2020:

  • Aerosol Retention Characteristics of Barrier Devices. 10/30/20. Fidler RL. Anesthesiology.
    Investigators studied 6 barriers designed to protect health care professionals from potentially infectious aerosolized particles during airway interventions. Particle counters and mass spectrometry were used to evaluate particle spread following experimental aerosol generation and simulated cough. Performance varied widely, with closed devices performing best. Some increased exposure to the operator compared with no device. Addition of smoke evacuation techniques (e.g. suction) was also evaluated. All barriers should be used in conjunction with appropriate PPE.
    An accompanying editorial discusses the importance of bioaerosol science to mitigate disease transmission in health care settings. Current experimental aerosol models remain imperfect surrogates for airborne viral disease transmission. Collaboration with bioaerosol scientists is lauded.
  • Comprehensive health assessment three months after recovery from acute COVID-19. 11/21/20. van den Borst B. Clin Infect Dis.
    This is a well-performed and conducted study on 124 mild (not admitted), moderate and severe (ICU survivors) COVID-19-positive patients at 3-month follow-up. The comprehensive (anthropometric, psycho-social, exercise tolerance, frailty, social coping, PTSD, etc.) study indicates that significant abnormalities persisted in majority of patients irrespective of initial illness severity. Improvement in lung radiography was present in severe cases, but pulmonary function remained mildly depressed including decreasing pulse oximetry on 6-minute walk test. The conclusion is that COVID-19, as previously noted, presents long-term health care challenges including physical, psychological, neurologic and quality of life which could lead to significant future personal and societal health care burden.
  • Decline in SARS-CoV-2 Antibodies After Mild Infection Among Frontline Health Care Personnel in a Multistate Hospital Network – 12 States, April-August 2020. 11/27/20. Self WH. MMWR Morb Mortal Wkly Rep.
    In this MMWR/CDC regarding 156 (median age 38, 94% female) frontline health care personnel who had a positive COVID-19 antibodies test result, 94% experienced a decline at repeat testing 60 days later and 28% sero-reverted to below the threshold of positivity. Health care workers with robust antibody responses were more likely to have a slower antibody decay. Whether the slimmer response of the antibody increases risk for reinfection remains unanswered. These results suggest that serology testing at a single point in time is likely to underestimate infection and a negative serologic test result might not reliably exclude prior infection.
  • Efficacy and Safety of Favipiravir, an Oral RNA-Dependent RNA Polymerase Inhibitor, in Mild-to-Moderate COVID-19: A Randomized, Comparative, Open-Label, Multicenter, Phase 3 Clinical Trial. 11/19/2020. Udwadia ZF. Int J Infect Dis.
    Favipiravir is under investigation by the WHO and in use in Japan and Russia. It appears to accelerate viral shedding and has been used successfully for Influenza and Ebola.
    Among 300 patients enrolled between May 15 and July 3, a significance in the difference in time to cessation of oral shedding, the primary endpoint, could not be achieved but the overall effect of the drug appeared favorable.
  • Estimated SARS-CoV-2 Seroprevalence in the US as of September 2020. 11/24/20. Bajema KL. JAMA Intern Med.
    Residuals of 177,919 serum samples collected for non-COVID-19 tests by two US national commercial clinical labs were retested for antibodies to SARS-CoV-2. Four sets of samples from every state were tested from periods in late July to late September 2020. Seroprevalence varied from 23% for New York State to less than 1% for several states and was less than 10% for the vast majority of states. Nowhere was seroprevalence close to the 60% to 80% estimated to be necessary to achieve herd immunity. An excellent figure summarizes the results for each period in all 50 states.
  • Veno-venous extracorporeal membrane oxygenation allocation in the COVID-19 pandemic. 11/21/20. Murugappan KR. J Crit Care.
    This is a well-researched and referenced discussion regarding appropriate allocation and utilization of VV-ECMO based on institutional practice. It includes ethical, practical and decision-maker considerations as well as preemptive end-of-life care discussions in severe cases. It introduces the concept of a “bridge to nowhere,” i.e., when the decision to prolong life mechanically has no future alternative/resolution. The article discusses the importance of clear communication between the health care team and patient/family consortium. It highlights the importance of clear understanding of ethical and practical implications of initiation and utilization of a scarce resource.

November 30, 2020:

  • Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study. 10/29/20. COVID-ICU Group on behalf of the REVA Network and the COVID-ICU Investigators. Intensive Care Med.
    In this multi-center (149 ICUs) European cohort study, the results of 4244 COVID-positive patients admitted 02/25-05/04 with ICU and 90-day follow-up were reported; ARDS severity, ventilator management and outcome at 90 days. Detailed demographic information, ventilator management, laboratory findings, ICU LOS, additional interventions and 90 day outcome reported. Overall mortality was 31% with a decrease in overall mortality noted during study; mortality was higher in older, immunocompromised, obese, diabetic patients and those with increasing ARDS severity. Higher mortality was noted in patients with shorter time between first symptoms and ICU admission.
  • Delirium in Older Patients With COVID-19 Presenting to the Emergency Department. 11/19/20. Kennedy M. JAMA Netw Open.
    Delirium at presentation occurred in 28% of patients older than 65 years presenting to 7 US Emergency Departments. In this retrospective chart review, a total of 817 patients (mean age 78) with COVID-19 were analyzed and 16% presented with delirium as a primary symptom. Associated conditions and multivariant risk factors were identified, and impaired consciousness was listed as the predominant symptom occurring in 54% of patients with a delirium diagnosis. Delirium as a leading symptom is frequently underreported but associated with adverse outcomes and hence an important marker for poor patient outcomes (ICU stay, intubation and hospital death).
  • Immunomodulation as Treatment for Severe COVID-19: a systematic review of current modalities and future directions. 11/20/2020. Meyerowitz EA. Clin Infect Dis.
    This current review of COVID-19 therapeutics stresses approaches to immune dysregulation and its evolving role in severe disease. Distinct early innate responses (first 5-7 days) and later adaptive immune responses must be recognized and treated accordingly. Antiviral treatment alone may be insufficient. To date, only dexamethasone shows a mortality benefit in randomized control trials when used later in the course. Late infectious and other steroid complications may be underreported. Various immunomodulatory strategies including early use of Janus kinase (JAK) inhibitors to rebalance the JAK-STAT pathways and Type I interferons are discussed. Promising early data are summarized for emerging therapies.
  • SARS-CoV-2 has displaced other seasonal respiratory viruses: results from a prospective cohort study. 11/15/20. Poole S. J Infect.
    This is a study performed in a county in South East England on the English Channel coast of viral PCR results of tests done from March through May on patients with respiratory symptoms in the emergency department or acute care ward in most of years from 2015 through 2020. Before 2020, a non-SARS-CoV-2 virus was detected in 54% patients (202/371) compared to only 4.1% (20/485) in 2020. SARS-CoV-2 was associated with asthma or COPD exacerbations in a smaller proportion of infected patients compared to other viruses (1.0% vs 37%).

November 23, 2020:

  • SAB Comment: These two studies used data from the same database.
  • COVID-19-associated Non-Occlusive Fibrin Microthrombi in the Heart. 11/16/20. Bois MC. Circulation.
    This study represents new data in autopsy results from patients with COVID-19 (n=15), influenza A/B (n=6), and non-virally mediated deaths (n=6). There were 12 COVID-19 cases with non-occlusive microthrombi and 2 cases each in the other groups. Focal myocarditis was seen in 4 active COVID-19 patients limited in extent. Direct invasion of the virus into myocardial cells was not seen. The authors conclude that the high incidence of microthrombi in the cardiac vascular system is a potential reason to use anticoagulants in these patients. A higher risk of complications including death may be seen in patients with cardiac disease, particularly those with amyloidosis.
  • Diaphragm Pathology in Critically Ill Patients With COVID-19 and Postmortem Findings From 3 Medical Centers. 11/16/20. Zhonghua S. JAMA Internal Med.
    This research letter describes evaluation of autopsy specimens of diaphragm muscle obtained from 26 consecutive deceased COVID-19 patients, 24 of whom had been on mechanical ventilation for a mean of 12 days. Specimens from 8 deceased non-COVID-19 patients mechanically ventilated for a similar amount of time were used as a control group. ACE-2 receptors were present on diaphragm myofiber membranes in all patients. Viral RNA was found in the myofibers of 4 of the 26 COVID-19 patients. Significantly more fibrosis was present in the diaphragms of the deceased COVID-19 patients than in the diaphragms of the control patients predicting more diaphragmatic weakness in the COVID-19 patients.
  • Immune suppression in the early stage of COVID-19 disease. 11/18/20. Tian W. Nat Commun.
    Using elegant quantitative advanced mass spectrometry proteomics and integrated data analysis with hierarchical clustering and functional correlational network strategies, these authors analyzed urine samples from COVID-19 (n=14), non-COVID-19 pneumonia cases (n=13) and healthy donors (n=10). A total of 5991 proteins were identified; 1986 proteins were significantly changed in the COVID-19 vs the other groups. More than 10 pathways significantly changed and 10x were more down-regulated than up-regulated. Showing heatmaps and protein interaction diagrams, the molecular signatures suggested a two-stage pathogenesis: immunosuppression and tight junction/cell-cell adhesion impairments early on and an activated immune response in late stages of severe COVID-19 pneumonia.
  • SAB Comment: Interferon (IFN) gets its name because it “interferes” with viral replication. Suspecting that interferon is inadequately produced and/or its actions blocked, two important Science papers (below) examined possible mechanisms. Zhang et al, reports finding loss of function gene variants in 3.5% of severe COVID-19 patients that control induction and amplification of Type I IFNs. The effects of these lifelong inborn variants, not found in mild disease or healthy controls, are only exposed with development of severe viral pneumonia. In the other paper, Bastard, et al, found (presumed preexisting) high-titer IgG neutralizing autoantibodies against Type I IFNs-alpha and -omega only in severe COVID-19. The autoantibodies occur in at least 2.6% of women and 12.5% of men. The defects identified by Zhang, et al, if discovered early on, could be treated with Type I IFNs, and by Bastard et al, treated with Type I IFN-beta in particular, as autoantibodies against IFN-beta are rare.
    • Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. 10/23/20. Zhang Q. Science.
      These authors examined 659 severe COVID-19 patients for mutations in genes involved in the regulation of type I and III interferon (IFN) immunity. Following exome or genome sequencing examining rare variants at 13 candidate loci they found genetic defects in 3.5% of severe patients at eight of the 13 candidate loci involved in the TLR3- (double stranded RNA-responsive) and Interferon-regulatory factor-7 (IRF7)-dependent induction and amplification of type I IFNs. These variants resulted in enrichment of loss of function variants not found in mild COVID-19 patients or healthy individuals. Early type I IFN administration may benefit patients with these inborn variants.
    • Autoantibodies against type I IFNs in patients with life-threatening COVID-19. 10/23/20. Bastard P. Science.
      In COVID-19 pneumonia, at least 101/987 patients had low or undetectable serum IFN-α and high-titer neutralizing IgG autoantibodies (auto-Abs) against interferon-omega (IFN-ω) (13 patients), against the 13 types of IFN-α2 (n=36), or against both (n=52). In vitro, auto-Abs blocked IFNs inhibition of SARS-CoV-2. Auto-Abs were not present in asymptomatic or mild SARS-CoV-2 infection (n=663) and in only 4/1227 healthy individuals; 95/101 with auto-Abs were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity (seen in Zhang) accounts for life-threatening COVID-19 in at least 2.6% of women and 12.5% of men who could be treated with IFN-beta.
  • Influence of room ventilation settings on aerosol clearance and distribution. 11/16/20. Sperna Weiland NH. Br J Anaesth.
    This study from the Netherlands used actual hospital rooms and ventilation systems to measure the clearance of aerosols after a simulated aerosol generating procedure. Higher air exchange rates were much more effective than manipulating the pressure gradient (i.e. negative or positive pressure rooms). A freestanding air purification unit also markedly improved aerosol removal. In positive pressure rooms, small amounts of aerosol were detected in adjacent hallways. This information could be useful when deciding on the best location for aerosol-generating procedures in SARS-CoV-2 infected patients.
  • Preexisting and de novo humoral immunity to SARS-CoV-2 in humans. 11/6/20. Ng K. Science.
    Using diverse assays for antibodies recognizing SARS-CoV-2 proteins, these investigators examined preexisting humoral immunity to the novel and older coronaviruses in humans. Using flow cytometry, predominately IgG class cross-reacting antibodies particularly targeting the S2 subunit of the spike glycoprotein were detectable in the SARS-CoV-2-uninfected, especially children and adolescents. SARS-CoV-2 infection induced higher titers of SARS-CoV-2 S-reactive IgG antibodies, targeting both proteolytically-cleaved S1 (attachment) and S2 (entry) subunits, along with contemporaneous IgM and IgA. Notably, SARS-CoV-2-uninfected donor sera exhibited specific neutralizing activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes. Cross-reacting immunological memory may be critical to understand susceptibility to SARS-CoV-2 infection.
  • Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial. 11/15/20. Monk PD. Lancet Respir Med.
    A small company-sponsored pilot study comparing the clinical course of 48 patients treated for 14 days with a daily dose of nebulized interferon beta-1a to the clinical course of 50 placebo-treated patients as assessed by 9-point WHO Ordinal Scale for Clinical Improvement [OSCI]. Patients receiving the medication had greater odds of improvement on the OSCI scale (odds ratio 2.32) and a higher percentage of recovered patients (58% vs 35%) at the end of the observation period (day 28). The medication was well tolerated compared with placebo. Larger studies are planned. These results contrast with the absence of effect noted in a prior trial of interferon beta-1a given subcutaneously.

November 18, 2020:

  • Acute Cardiovascular Manifestations in 286 Children with Multisystem Inflammatory Syndrome Associated with COVID-19 Infection in Europe. 11/9/20. Valverde I. Circulation.
    A European multi-institutional study of 287 children admitted with COVID-19 demonstrated a high incidence of cardiac involvement. Most children admitted suffered GI symptoms, rash and conjunctival changes in addition to cardiac involvement. Forty percent presented with cardiac shock. Markers of cardiac involvement were present on admission including D-dimers. Treatment was not controlled. 286 were eventually discharged. Twenty-five percent had a diagnosis of coronary artery dilation by echocardiography, requiring follow-up.
  • Comparison of Clinical Features and Outcomes in Critically Ill Patients Hospitalized with COVID-19 versus Influenza. 11/13/20. Cobb NL. Ann Am Thorac Soc.
    This is a retrospective cohort analysis “case matching” 74 seasonal influenza with 65 COVID-19 patients from 01/01/19 to 04/15/20. Diagnoses were confirmed by RT-PCR and ICU courses studied. COVID-19 patients had different demographics, longer prodrome, increased numbers of presenting symptoms and co-morbidities, higher incidence of ARDS, longer duration of mechanical ventilation and higher mortality. Includes an interesting discussion with tables.
  • Review of Cardiac Involvement in Multisystem Inflammatory Syndrome in Children. 11/9/20. Alsaied T. Circulation.
    Though the prevalence of multisystem inflammatory syndrome in children is unknown, there have been more than 300 cases now reported in the literature. It is more common in the US in Black and Hispanic children; typically occurs a few weeks after acute infection and the putative etiology is a dysregulated inflammatory response to SARS-CoV-2 infection. Persistent fever and gastrointestinal symptoms are the most common symptoms. Cardiac manifestations are common and include ventricular dysfunction, coronary artery dilation and aneurysms, arrhythmia and conduction abnormalities, vasodilatory or cardiogenic shock requiring fluid resuscitation, inotropic support, and in the most severe cases mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Most patients recover within days to a couple of weeks and mortality is rare. Long-term cardiovascular complications are not yet known.
  • Ventilation management and clinical outcomes in invasively ventilated patients with COVID-19 (PRoVENT-COVID): a national, multicentre, observational cohort study. 11/10/2020. Botta M. Lancet Respir Med.
    This multicenter, retrospective, epidemiological study from the Netherlands examines 553 COVID-19 positive VE patients from 18 ICUs regarding the ventilatory variables (modes, TV, PEEP, *P, CTL) and its outcomes in 28 days in a comparative way.
    • The variations of ventilatory parameters were not different between ICUs,
    • COVID-19 ARDS allows for better use of lung-protective ventilation than does ARDS due to other causes,
    • All patients had low compliance,
    • No conclusion for Best PEEP,
    • Majority prefer to treat the refractory hypoxia by prone positioning,
    • An enormous burden on ICUs/hospital systems,
    • High tidal volume and low respiratory system compliance on the first day of ventilation were associated with a higher risk of 28-day mortality.

    The study supports low TV, Ppl< 30, low driving pressure, prone position in ICU.

November 16, 2020:

  • Analgesia and sedation in patients with ARDS. 11/10/2020. Chanques G. Intensive Care Med.
    A “state of the art“ narrative review by an international panel of experts written to support clinicians in their management of ARDS patients. Proper ventilator settings, followed by analgesia, then sedation, then neuromuscular blockers form the heart of suggested approaches to analgesia and sedation. Separate sections address ARDS and COVID-ARDS, and several flow diagrams suggest various treatments. An “ABCDEF-R” approach is suggested.
  • Association between red blood cell distribution width and mortality of COVID-19 patients. 11/7/2020. Lorente L. Anaesth Crit Care Pain Med.
    Red blood cell distribution width (RDW), a parameter of RBC form and size variability, is associated with increased mortality in a number of disease states. This prospective observational study from 8 Canary Islands ICUs analyzed data from 118 survivors and 25 deaths with COVID-19. RDW performed comparably to APACHE II and SOFA scores in predicting mortality and is easier to measure. Levels were higher on admission to ICU and when >13% predicted mortality. RBC transfusion, hemoglobin disorders, and myelodysplastic syndromes increase RDW values.
  • Current and evolving standards of care for patients with ARDS. 11/6/20. Menk M. Intensive Care Med.
    Written by an international group of experts, this narrative review is a succinct and up-to-date review of caring for ARDS and COVID-ARDS patients, and is very useful for a frontline worker wanting a broad overview. It briefly explains the studies that establish the current standards and discusses therapies of promising interest (evolving standards). Nicely summarized in a table and discussed in the text are: ventilatory management (tidal volume, PEEP, driving pressure, mechanical power, etc.), ventilation adjuncts (proning, neuromuscular blockade, ECMO, etc.) and pharmacotherapy (steroids, fluid therapy, etc.).
  • Frequency of venous thromboembolism in 6513 patients with COVID-19: a retrospective study. 11/2/20. Hill JB. Blood Adv.
    This single health-system venous thromboembolism (VTE) study described the use of standard heparin or LMWH prophylaxis in most of the 6513 COVID-19 patients. Dose was increased if BMI >40 and decreased if creatinine clearance < 30. Ninety-day VTE rate was 2.2% (n=86) when receiving prophylaxis vs. 11% without. Eighty-four of 86 VTE patients had received prophylaxis. PADUA Score was high in 89%. Including arterial thrombosis in 7 patients, the overall incidence of VTE was 3.1% and 7.2% if mechanically ventilated. Fifty percent inpatient VTEs met the definition of prophylaxis failure. Only three of 2075 hospitalized patients (0.14%) without VTE surviving to discharge had VTE after discharge. The authors conclude these data support a traditional approach to VTE prophylaxis both during and following hospitalization.
    SAB Comment: We note a surprisingly low rate of VTE in this large, retrospective study, equally divided between DVT and PE. It did not include thrombosis in the microcirculation or ECMO circuit. Most were failures or breakthroughs on VTE prophylaxis. One may question the use of so few risk factors for modification of standard dosing and the conclusion that the data support a traditional approach.
  • Neutrophil extracellular traps and thrombosis in COVID-19. 11/5/20. Zuo Y. J Thromb Thrombolysis.
    Forty-four patients with COVID-19 had blood collected for neutrophil extracellular traps (NETs) and neutrophil activation. Eleven of these patients developed thrombosis despite at least prophylactic heparin. Thrombosis in COVID-19 was associated with higher levels of circulating NETs and calprotectin (neutrophil activation). These data further add to the characterization of COVID-19 and the stepwise understanding of how to combat the epidemic.
  • Prone position in ARDS patients: why, when, how and for whom. 11/10/20. Guérin C. Intensive Care Med.
    This is a thorough and excellent review of the use of prone position in ARDS including a detailed explanation of its effects on pulmonary physiology, gas exchange and hemodynamics. The significant benefits in mortality are discussed. As noted in many studies, the improvement in mortality does not correlate with the degree of oxygenation improvement but appears more likely to be related to a decrease in ventilator-induced lung injury. Specific recommendations and cautions for practical application are provided. The use of prone positioning in spontaneously breathing, non-intubated patients is commonly used with COVID-19, and studies are planned to verify if this strategy can reduce the rate of intubation and improve survival.

November 11, 2020:

  • Birth and Infant Outcomes Following Laboratory-Confirmed SARS-CoV-2 Infection in Pregnancy – SET-NET, 16 Jurisdictions, March 29-October 14, 2020. 11/5/20. Woodworth KR. MMWR Morb Mortal Wkly Rep.
    The authors of this article about pregnant women with SARS-CoV-2 state, “Among 3,912 infants with known gestational age born to SARS-CoV-2 infected women, 12.9% were preterm (<37 weeks), higher than a national estimate of 10.2%. Among 610 (21.3%) infants with testing results, 2.6% had positive SARS-CoV-2 results, primarily those born to women with infection at delivery.” Half of positive infants were preterm. Median maternal age was 28.9 years. Forty-six percent were Hispanic/Latina. One or more underlying medical condition was reported for 45.1%. Pre-pregnancy obesity was the most common (35.1%). Eight-four point four percent had infection identified in the third trimester. None had neonatal IgM, placental tissue or amniotic fluid testing; thus, routes of transmission could not be assessed.
  • Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes. 10/16/20. Leisman. Lancet.
    The hypothesis that a “cytokine storm” occurring later in severe COVID-19 disease may be causative for the excess inflammatory response noted in terminal disease has provoked studies of anti-cytokine therapies, specifically interleukin-6 antagonists. This systematic review and meta analysis of studies published between November 1, 2019 and April 14, 2020, including interleukin-6 levels in the results, compared cytokine levels in four disease categories associated with elevated levels: sepsis (5,320); cytokine release syndrome (72); ARDS unrelated to COVID-19 (2,767); and COVID-19 (1,245). While COVID-19 levels were raised, the mean interleukin-6 levels in all three other conditions were statistically higher than noted in COVID (e.g. 27 times higher in sepsis and 12 times higher in non-COVID ARDS while over 1,000 times in CRS). The authors question the impact of a “cytokine storm” in COVID-19 organ dysfunction. Other arguments offered a detailed, well-presented discussion.
  • Cytokine Levels in Critically Ill Patients With COVID-19 and Other Conditions. 9/3/20. Kox. JAMA.
    This retrospective, single-center study admitted 204 patients between 2010 and 2020 with sampling recorded plasma concentrations of proinflammatory cytokines TNF, IL-6 and IL-8 and determined (2020) in consecutively ventilated COVID-19 patients (49) with ARDS. Previously recorded levels in patients with bacterial septic shock with ARDS (51), septic shock without ARDS (15), out-of-hospital cardiac arrest (30), and multiple traumas (62) were compared with those from the COVID-19 population. COVID-19 patients had higher BMI, co-morbidities and cardiac dysfunction; however, cytokine levels were lower than in other diseases mentioned questioning the importance of a “cytokine storm” as a primary therapeutic target in COVID-19 disease.

November 9, 2020:

  • Benchmarking Critical Care Well-Being: Before and After the Coronavirus Disease 2019 Pandemic. 11/2/2020. Gomez S. Crit Care Explor.
    This is the result from the survey with comparison of 2 periods, 16 ICUs of 4 Hospitals to understand burnout and fulfillment among critical care healthcare (N= 482) its impact on well-being. Authors state that a rise of burnout is expanding to all across the team including APPs & Pharm D. & increased during the pandemic. These results reveal that burnout is a threat to the future of critical care team, notes that clinicians with less years of work experience were more likely to suffer adversely from burnout possibly from work load/ schedules. Professional fulfillment varied across the professional/ time/ hospital… To mitigate the burnout the Critical Care Societies Collaborative developed a “Call to Action” in 2016 & recommends that measures of well-being should be benchmarked and compared across ICUs and medical centers. Also consider offering resilience training, professional coaching, mindfulness training all across the team.
  • Combining lung ultrasound and Wells score for diagnosing pulmonary embolism in critically ill COVID-19 patients. 11/4/20. Zotzmann V. J Thromb Thrombolysis.
    This article presents the results of a retrospective evaluation of 20 ICU COVID-19 patients who had all undergone CT pulmonary angiography and lung ultrasound for suspected pulmonary emboli in a tertiary referral ARDS/ECMO center. The study showed that subpleural consolidations ≥ 1cm detected in lung ultrasound were found frequently in COVID-19 ARDS patients with pulmonary embolism. By combining a Wells score ≥ 2 and a lung ultrasound showing subpleural consolidations, PE could be predicted with a sensitivity of 100% and a specificity of 80% in these 20 patients, 12 of whom were found to have pulmonary emboli by CT pulmonary angiography.
  • COVID-19 seropositivity and asymptomatic rates in healthcare workers are associated with job function and masking. 11/5/20. Sims MD. Clin Infect Dis.
    This prospective cross-sectional cohort study evaluated seropositivity among 40k employees of a Detroit healthcare system who were both frontline workers and support staff, including administrators. About half of the employees participated and 8.8% were seropositive, 44% of those were asymptomatic. Those wearing N95 masks had a significantly lower seropositivity rate (10.2%) compared to surgical masks (13.1%) or no masks (17.5%).
  • COVID-19: what the clinician should know about post-mortem findings. 11/3/20. Jonigk D. Intensive Care Med.
    This succinct and easily read editorial summarizes multisystem pathologic findings in COVID-19. Clinical presentation does not always correlate with organ involvement at autopsy. The figure illustrates alterations frequently identified in each organ system at autopsy.
  • Decision-making around admission to intensive care in the UK pre-COVID-19: a multicentre ethnographic study. 11/3/2020. Griffiths F. Anaesthesia.
    As triage of ICU beds during COVID-19 becomes a topic of concern, this multicenter ethnographic study conducted between June 2015 and May 2016 in six UK NHS hospitals attempts to explore the decision-making process applied to ICU admissions through observations, interviews and retrospective analysis outside the pandemic. Fifty-five decision events were observed and analyzed and 44 physicians, varying in training and specialty, were interviewed. Results are reported in multiple vignettes and the heuristic nature of the decision-making process is reviewed. Suggestions for improving transparency, consistency and equity of decision‐making around ICU admission are offered.
  • Hematologic predictors of mortality in hospitalized patients with COVID-19: a comparative study. 10/30/20. Mousavi SA. Hematology.
    This study looks over 225 COVID-19 patients in the hospital and focuses on the admission blood test as it relates to mortality. Hematologic predictors of a fatal outcome included elevated neutrophil to lymphocyte ratio and platelet lymphocyte ratio, lower than normal Hb (<12 gram/ dl) and platelet (<150,000 ), elevated D-dimer prolonged prothrombin time and elevated inflammatory indicators, higher than normal erythrocyte sedimentation rate (>15 mm/h) and C-reactive protein( > 6 mg/L).
  • Lack of antibodies to SARS-CoV-2 in a large cohort of previously infected persons. 11/4/20. Petersen LR. Clin Infect Dis.
    In this study, sera from 2,547 known PCR+ healthcare workers and first responders were tested at least 2 weeks after symptom onset for IgG against spike protein. Sero-negativity was found in 6.3%, or 1 in 16 persons. The proportion lacking antibodies increased only slightly from 14 to 90 days post-symptom onset (p=0.06), pointing to reassurance of low sero-reversion. Sero-negativity was 0% in 79 previously hospitalized, but increased to 11.0% among 308 persons with asymptomatic infections and 31.9% on immunosuppressive medications. Black race (2.7%), severe obesity (3.9%) and those with more symptoms were less likely to be seronegative.
  • SARS-CoV-2 Infections Among Children in the Biospecimens from Respiratory Virus-Exposed Kids (BRAVE Kids) Study. 11/3/20. Hurst JH. Clin Infect Dis.
    A BRAVE Kids study demonstrates the issues beyond the science of COVID-19 spread and infection. The sociologic impact of ethnicity (Hispanic), family life, and the role of children as a potential viral reservoir are presented. The nasopharyngeal viral loads suggest that symptom-free children might be a source for disease spread in their homes and families.

November 4, 2020:

  • Characterization of Myocardial Injury in Patients With COVID-19. 10/30/20. Giustino G. J Am Coll Cardiol.
    This retrospective, international, multicenter cohort study (7 hospitals in NYC and Milan) reviewed 305 patients with documented RT-PCR COVID-19 diagnosis with myocardial injury diagnosed at admission or during hospitalization. Inclusion criteria included elevated cardiac troponins, EKG abnormalities and full TTE examination. Findings indicated that severity of cardiac disease indicated by serial increases in troponins associated with graded TTE abnormalities (none, moderate, severe) was a useful prognostic indicator of outcome. Of 305 patients, myocardial injury was documented by elevated troponins in 190 (62.3%). When compared with patients with no myocardial injury, increasing severity of myocardial injury was associated with increased mortality with discrimination noted between “no” and minor TTE abnormalities versus significant abnormalities and increased inflammatory biomarkers and troponins. Effects of co-morbidities and BMI were noted as additional risk factors for myocardial damage and TTE abnormalities.
  • Cardiac Injury in COVID-19-Echoing Prognostication. 10/30/20. Lavie CJ. J Am Coll Cardiol.
    This editorial is best summarized in the following direct quote underlining the importance of the Giustino et al manuscript. “The current recommendations of the American College of Cardiology (ACC) endorse the measurement of cTn levels when a diagnosis of acute myocardial infarction is being considered in patients with SARS-CoV-2 infection. This indication seems somehow inadequate according to the information collected by Giustino et al. (above), (12), whereby there is now evidence that Tn-positive COVID-19 patients may benefit from routine TTE, which would allow practitioners to garner useful prognostic information and to establish specific therapeutic options in patients with cardiac injury.” An excellent discussion and table are included in the editorial.
  • Characteristics of cardiac injury in critically ill patients with COVID-19. 10/24/20. Doyen D. Chest.
    This prospective study of 43 consecutive COVID-19 positive patients admitted to two French ICUs was designed to characterize incidence and time course of cardiac injury by serial measurements of cardiac biomarkers (troponin), EKGs and echocardiographic investigations. Extensive cardiac involvement documented with 49% demonstrating injury on ICU admission and 70% experiencing injury within the 14-day observation window. New atrial dysrhythmias, and RV and LV systolic as well as diastolic dysfunction noted with greater RV systolic dysfunction associated with increased disease severity. Conclusion: Cardiac injury is common in COVID-19, occurs early in disease, and patients with injury exhibit more RV than LV systolic dysfunction.

November 2, 2020:

  • SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. 10/28/20. Chen P. N Engl J Med.
    This BLAZE-1 phase 2 interim safety analysis involved 452 mild or moderate COVID-19 outpatients within three days of diagnosis. In a study funded by Eli Lilly, patients received a single infusion of spike-protein-RBD neutralizing antibody LY-CoV555 in one of three doses (700, 2800 or 7000 mg) or placebo. Change from baseline viral load by quantitative RT-PCR at day 11 was the primary outcome and decreased in all groups. Only the middle, 2800 mg dose significantly diminished load more than placebo at day 11. All doses reduced symptoms on days 2-6, and hospitalizations (1.6% vs. 6.3%), particularly in high-risk cohorts. Although 70% had high-risk co-morbidities, no deaths occurred.

October 30, 2020:

  • Aspirin Use is Associated with Decreased Mechanical Ventilation, ICU Admission, and In-Hospital Mortality in Hospitalized Patients with COVID-19. 10/23/20. Chow JH. Anesth Analg.
    This multi-center cohort study of 412 COVID-19 patients explored the theory that aspirin’s anti-platelet and anti-inflammatory properties might be beneficial in lowering the risk of serious outcomes. Ninety-four patients who had taken aspirin within 7 days of admission were compared with 314 patients who had not. Aspirin use was independently associated with decreased hazard ratio (HR) of mechanical ventilation (HR 0.56), ICU admission (HR 0.57), and in-hospital mortality (HR 0.53). There were no differences in major bleeding (p=0.69) or overt thrombosis (p=0.82) between aspirin users and non-aspirin users and confounding variables were carefully controlled. Potential mechanisms are discussed including aspirin’s ability to lower interleukin-6, C-reactive protein, and macrophage stimulation. Randomized controlled trials are necessary to confirm these results.
  • Awake prone positioning for COVID-19 hypoxemic respiratory failure: A rapid review. 10/23/20. Weatherald J. J Crit Care.
    Using a “rapid review” technique, these authors from Calgary synthesize 35 studies (none randomized) evaluating the effect of awake proning in 414 COVID-19 patients with respiratory failure. All but one study showed improvement in oxygenation while prone, but generally not sustained when returned to the supine position. 29% of patients went on to require intubation. The authors conclude that “many questions remain unanswered when considering the use of awake prone positioning.”
  • Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomized controlled trial (PLACID Trial). 10/22/20. Argwal A. BMJ.
    A randomized, controlled trial of convalescent plasma (CP) in 227 treated and 224 control hospitalized patients with moderate COVID-19 from 39 hospitals in India. Patients who received 200 ml of CP x 2 had less dyspnea and fatigue and a 24% higher rate of negative PCR on day 7 (P<0.05). No difference in the levels of inflammatory markers such as ferritin, C-reactive protein, D-dimer, or LDH was observed. However, there was no difference in progression to severe disease or mortality at 28 days between groups, including a subgroup of patients who received plasma with neutralizing antibody titers >1:80.
  • Convalescent plasma is ineffective for covid-19. Lessons from the Placid Trial. 10/22/20. Pathak EB. BMJ.
    In light of the prevalence of micro-thrombosis and the large number of thrombotic complications in COVID-19 patients, authors of this accompanying editorial highlight the pro-thrombotic properties of plasma and recommend that future blinded convalescent plasma (CP) trials exclude plasma without detectable neutralizing antibodies or treatment of control groups with other plasma. They point out that coagulation-related events in previous CP trials were not rigorously screened for their potential relationship to the treatment.
  • COVID-19 Gastrointestinal Manifestations Are Independent Predictors of PICU Admission in Hospitalized Pediatric Patients. 10/26/20. Gonzalez Jimenez D. Pediatr Infect Dis J.
    This multicenter Spanish brief report describes 91 patients with an average age of 10. GI symptoms were the initial cause for reporting ill in 10% of children. 40% were found to have elevated LFTs. Children overall were less ill than adults; however, all 11 severely ill children suffered GI symptoms.
    SAB comment: Although pediatric cases are uncommon compared to adults with multi-system illness, GI symptoms might be overlooked in children and are significant in the progress of the disease.
  • Improving Survival of Critical Care Patients With Coronavirus Disease 2019 in England: A National Cohort Study, March to June 2020. 10/26/20. Dennis JM. Crit Care Med.
    This retrospective, observational study of COVID-19 inpatients reviewed mortality by week of admission. High dependency unit (n = 15,367) survival went from 71.6% in March/April to 92.7% in May/June while ICU (n = 5,715) went from 58% to 80.4% in the same time period. The authors attributed this to the introduction of effective treatments as part of the RECOVERY trial, improved physician understanding of the disease process, and a falling critical care burden rather than to any changes in age, sex, ethnicity or major comorbidity burden in the patient population.
  • Venous Thromboembolism in COVID-19. 10/25/20. Schulman S. Thromb Haemost.
    This is an excellent review regarding the mechanisms and pathogenesis of the disease biomarkers and their clinical usefulness. Risk assessment models are discussed as well as the type and strength of prophylaxis based on available evidence. Recommendations or position statements from 10 sources are discussed along with treatment recommendations according to current guidelines. Thrombosis prophylaxis with low molecular weight heparin is recommended for most hospitalized patients along with a recommendation against escalating anticoagulant doses. Therapeutic anticoagulation is advised only in response to a very high suspicion or in the presence of documented venous thromboembolism. An excellent algorithm regarding VTE treatment is presented.

October 28, 2020:

  • Aspergillosis Complicating Severe Coronavirus Disease. 10/21/20. Marr KA. Emerg Infect Dis.
    Mounting evidence suggests that severe respiratory virus infections, especially influenza and coronavirus 2 infections, can be complicated by Aspergillus airway overgrowth with pulmonary infection characterized by mixed airway inflammation and bronchial invasion. This article reviews these issues succinctly and adds data on 20 COVID-19 patients to the growing world literature. The authors note that the syndromes of pulmonary aspergillosis complicating severe viral infections are distinct from classic invasive aspergillosis. They state that combined with severe viral infection, aspergillosis in COVID-19 pneumonia comprises a constellation of airway-invasive and angio-invasive disease and see an urgent need for strategies to improve diagnosis, prevention, and therapy.
    SAB comment: An article previously highlighted in the Newsletter clarifies some of the important issues specific to diagnosing and treating pulmonary aspergillosis in COVID-19 patients.
  • Characteristics Associated With Racial/Ethnic Disparities in COVID-19 Outcomes in an Academic Health Care System. 10/21/20. Gu T. JAMA Netw Open.
    In this cohort study of 5698 University of Michigan Health System patients tested for or diagnosed with COVID-19, preexisting type 2 diabetes or kidney diseases and living in high–population density areas were associated with higher risk for COVID-19 hospitalization. Adjusting for covariates, non-Hispanic Black patients were 1.72-fold more likely to be hospitalized than non-Hispanic White patients, though the reasons for hospitalization were not defined. However, no significant race differences were observed in intensive care unit admission and mortality.
  • Reusability of filtering facepiece respirators after decontamination through drying and germicidal UV irradiation. 10/22/2020. Vernez D. BMJ Glob Health.
    A “drying cycle” (30 min, 70°C) plus 60 mJ/cm2 of UV-C irradiation (UVGI) effectively decontaminated 2 Staphylococcus aureus’ bacteriophages on 2 models of FFP2 disposable respirators (the European standard most similar to N95) with preserved functional characteristics after 10 cycles. (n=12) Testing included cultures, scanning electron microscopy, Fourier-transform infrared spectroscopy, 10–300 nm NaCl aerosol particle penetration, and visual inspection. 4 respirators treated with the heat alone showed complete decontamination of the phages however UVGI adds protection. H2O2 production during UVGI was observed. Respirators worn for 1 work shift showed slightly increased particle penetration. No fit testing reported.
  • What have we learned ventilating COVID 19 patients? 10/12/20. Trahtemberg U. Intensive Care Med.
    These leaders in ARDS research provide a crisp review of ventilatory management of COVID-19-induced ARDS (CARDS), based on the underlying pathophysiology and contend that the similarities in the spectrum of CARDS versus that of non-COVID ARDS outweigh the differences. They find a paucity of data exists to justify early intubation. They favor lung protective ventilation for all patients, and they argue for prone positioning for patients with moderate-to-severe ARDS (PaO2/FiO2 ratio < 150 mmHg). In summary they write, “ventilatory management of patients with COVID-19 ARDS should be similar to that for other causes of ARDS, tailored to the specific patient.”

October 26, 2020:

  • Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. 10/21/20. Stone JH. N Engl J Med.
    This is a prospective, randomized, placebo-controlled study where treated patients received a single dose of 8mg/kg of tocilizumab (161 of 243 enrolled patients). The results showed that tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with COVID-19.
  • Physiological and quantitative CT-scan characterization of COVID-19 and typical ARDS: a matched cohort study. 10/21/20. Chiumello D. Intensive Care Med.
    This detailed Italian physiologic study compared 32 COVID-19 ARDS (CARDS) patients with two other matched historical groups of typical ARDS patients; one matched with the CARDS patients by SpO2/FiO2, and one matched by respiratory compliance. As noted previously by this group (but not some studies by other groups), they found CARDS patients to have higher compliance than the group of non-COVID ARDS patients who were matched for SpO2/FiO2. They also found the CARDS patients had lower SpO2/FiO2 than non-COVID ARDS patients who were matched for compliance. Increasing PEEP from 5 to 15 improved oxygenation in CARDS patients but did not improve respiratory mechanics or CO2 clearance as usually seen in ARDS. These authors continue to recommend low PEEP and low driving pressure in early CARDS.
  • Prediction models for covid-19 outcomes. 10/21/2020. Sperrin M. BMJ.
    A risk prediction algorithm to estimate hospital admission (n=10,776) and mortality (n=4,384) from covid-19 was created and validated using a UK dataset derived from 6.08 million 19-100 year old patients and validated with data from an additional 2.17 million. Study period was Jan 24-April 30 for the initial cohort and May 1-June 30, 2020 for the validation cohort. The model, including age, ethnicity, deprivation, BMI, and a range of comorbidities, predicted ¾ of deaths with excellent discrimination (Harrell’s C statistics >0.9). People in the top 20% of predicted risk of death accounted for 94% of deaths.
  • Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality from coronavirus 19 in adults: national derivation and validation cohort study. 10/21/2020. Clift AK. BMJ.
    Editorial discussing the potential utility of prediction models referencing article 1528 and a second BMJ report published in September on the 4C mortality score (calculated at hospital admission to predict in-hospital mortality for patients with confirmed or likely covid-19). Models have serious shortcomings and require constant updating however may also inform public health policies, vaccine allocation, and provide decision support for treatment.
  • Sensible Medicine—Balancing Intervention and Inaction during the COVID-19 Pandemic. 10/15/20. Seymour CW. JAMA.
    This article, which contains a discussion relevant for all practitioners engaged in clinical care cautions against abandoning clinical experience and consultation for early adoption of unproven and potentially harmful therapies. The authors urge that practitioners use sensible medicine, a blend between doing nothing and going all in. Their argument is well illustrated and supports the current therapeutic state in which good clinical care in well-managed ICUs following established protocols appears to be effective management strategy. No therapeutic agent has demonstrated significant mortality benefit with the exception of dexamethasone administered appropriately. The discussion supports the decision to steer a middle course with elegance and logic and is refreshing, timely and relevant.
  • Targeting complement cascade: an alternative strategy for COVID-19. 10/19/20. Ram Kumar Pandian S. 3 Biotech.
    The authors present well-referenced experimental support that complement cascade inhibition will counteract COVID-19 inflammation. Complement dysregulation can lead to cytokine storm and ARDS pathology. Activation and deposits of complement components are seen in animal models and at autopsy of COVID-19 patients. Pre-clinical and clinical studies using current and pipeline agents show pathway inhibition aids ARDS recovery. Viral infections including COVID activate complement via the lectin pathway via mannose-binding lectin associated serine protease 2 (MASP2). Complement inhibitors including monoclonal antibodies, proteins, peptides and small molecules exhibit promise blocking the complement components and their downstream effects in various pathological conditions including SARS-CoV.
  • Time to Reassess Tocilizumab’s Role in COVID-19 Pneumonia. 10/20/20. Parr JB. JAMA Intern Med.
    The author’s conclusions in this excellent editorial are informed by three studies (two are randomized prospective) reported in this issue of JAMA Internal Medicine and by two additional randomized prospective studies. Although observational studies by the STOP-COVID investigators and others report mortality benefit and other positive outcomes, findings from the randomized prospective trials described herein (total of 542 patients treated) do not support routine tocilizumab use in COVID-19. A well-constructed summary table of the five studies is provided.

October 23, 2020:

October 21, 2020:

  • Famotidine Use Is Not Associated With 30-day Mortality: A Coarsened Exact Match Study in 7158 Hospitalized COVID-19 Patients from a Large Healthcare System. 10/15/20. Yeramaneni S. Gastroenterology.
    This large retrospective study from HCA Healthcare repudiates 2 smaller studies from Columbia and Hartford which reported a two-fold reduction in risk of death or intubation for COVID-19 inpatients. One thousand one hundred twenty-seven patients (15.7%) received famotidine and 6031 (84.3%) did not. Applying multivariable logistic regression within a carefully matched cohort showed no association between in-hospital famotidine use and 30-day mortality after adjustment for WHO severity, smoking status, and listed medications.
    SAB Comment: Due to famotidine’s ability to inhibit a protease essential for SARS-CoV-2 virus replication in vitro, it is under intense study in many centers. A clinical trial administering high-dose IV treatment (120 mg IV q8h) is currently under way at Columbia.
  • The duration of infectiousness of individuals infected with SARS-CoV-2. 10/13/20. Walsh KA. J Infect.
    The potential duration of patient infectiousness, as derived from virus culture and contact tracing studies, for those individuals in whom SARS-CoV-2 RNA is detected is summarized. Thirteen various quality studies and 2 large contact tracing studies were included. The data suggests that COVID-19 patients with mild-to-moderate illness are highly unlikely to be infectious beyond 10 days from symptom onset. Evidence from a limited number of studies indicates that patients with severe-to-critical illness, and/or those who are immunocompromised, may be infectious for a prolonged period, possibly for 20 days or more. Research is needed to confirm these findings and to provide information on the duration of infectiousness in subgroups such as children, and asymptomatic and immunosuppressed patients.
  • Transmission Dynamics by Age Group in COVID-19 Hotspot Counties – United States, April-September 2020. 10/15/20. Oster AM. MMWR Morb Mortal Wkly Rep.
    CDC analyzed temporal trends in percent test positivity by age group in COVID-19 hotspot counties before and after their identification as hotspots. Among 767 U.S. hotspot counties identified during June and July 2020 (24% of counties, 63% of population) early increases in the percent positivity among persons 24 years old and younger were followed by several weeks of increasing percent positivity in persons 25 years old and older, particularly those in the South and West. Addressing transmission among young adults is an urgent public health priority.

October 19, 2020:

  • A score combining early detection of cytokines accurately predicts COVID-19 severity and intensive care unit transfer. 10/2/2020. Nagant C. Int J Infect Dis.
    These investigators prospectively examined (n=63) levels of twelve serum cytokines following admission (days 0-3) to seek combinations that could discriminate progression to severe (PaO2 <93% or PaO2/FiO2≤300 mmHg) vs non-severe disease and predict ICU transfer (ventilator/ICU monitoring). Combinatorial (multiplication of levels of IL-6, IL-10, IL-8) score had the highest sensitivity and specificity to predict severe disease (n=44) at a cutoff value of 2068 pg/mL vs non-severe disease (n=19). Levels of IL-6 x IL-10 (cut-off value of 178 pg/mL) predicted ICU transfer (n=35) vs non-critically ill (n=28). Use of this score could improve patient triage and therapeutic strategies within clinical trials.
  • Acute Respiratory Distress Syndrome: Contemporary Management and Novel Approaches during COVID-19. 10/5/20. Williams GW. Anesthesiology.
    This is a succinct, well-written review of best practice treatment strategies for non-COVID-19 ARDS with research-based updates on appropriate strategies for COVID-19 associated-ARDS treatments. Figures and brief descriptions are provided on the research supporting low tidal volumes, PEEP levels, prone positioning, PaO2 targets, steroid treatment, fluid management, ECMO and early neuromuscular blockade.
  • Aerosolisation during tracheal intubation and extubation in an operating theatre setting. 10/12/20. Dhillon RS. Anaesthesia.
    This study reports measurements and size characterization of aerosols generated and spread throughout a standard positive pressure operating room (with 26 room volume air exchanges per hour) during intubation and extubation of 3 study patients. Face-mask ventilation, tracheal tube insertion and cuff inflation generated small particles 30–300 times above background noise that remained suspended in airflows and spread from the patient’s facial region throughout the confines of the operating room. The authors believe that these findings support careful use of PPE throughout standard ventilation operating rooms.
  • Blood purification therapy with a hemodiafilter featuring enhanced adsorptive properties for cytokine removal in patients presenting COVID-19: a pilot study. 10/12/2020. Villa G. Crit Care.
    Italian preliminarily prospective observational study of 37 patients receiving immunomodulatin or support of renal function using Baxter’s oXiris heparin-coated extracorporeal hemodiafilter Feb-April 2020. Compared to the expected (65%!) mortality rates, as calculated by APACHE IV, the mean observed rates were 8.3% lower after treatment. Reduction in serum IL-6 concentrations correlated with improved organ function, measured as decreased SOFA score. The best improvement in mortality rate was observed in patients receiving early treatment during in ICU. Anticoagulation regimens were inconsistent. 7 treatments (19%) resulted in clotting.
  • Convalescent plasma for patients with severe COVID-19: a matched cohort study. 10/10/20. Rogers R. Clin Infect Dis.
    This small study from 3 hospitals compared 64 recipients of 1-2 units of CP (median 7 days after symptom onset) with 177 matched controls. Neither in-hospital mortality (~15%) nor overall rate of hospital discharge differed significantly, although the rate of hospital discharge among patients older than 65 years who received convalescent plasma (CP) was significantly higher (RR 1.86, 95% CI 1.03 – 3.36). There was a greater than expected frequency of transfusion reactions in the CP group (2.8% per unit transfused). Authors suggest adequately powered randomized studies should target patients older than 65 years when assessing CP treatment efficacy.
  • COVID-19 Transmission in US Child Care Programs. 10/1/20. Gilliam WS. Pediatrics.
    This is an analysis of a survey completed in late May 2020 by 57,335 childcare providers from all 50 states that were asked about their exposure, their transmission mitigation efforts and whether or not they had ever tested positive for having COVID-19. While 427 (0.7%) of the respondents had tested positive, there was no association found between exposure to childcare and contracting COVID-19. The authors note that results may depend upon the mitigation efforts taken (outlined in the article) and on the relatively low prevalence rates across the United States at the time of the study. Transmission home to parents or siblings was not evaluated.
  • Evidence of a wide gap between COVID-19 in humans and animal models: a systematic review. 10/7/2020. Ehaideb SN. Crit Care.
    In this comprehensive literature review, replication-competent animal models were assessed for recapitulating full-spectrum human COVID-19, as well as prophylaxis, therapies, or vaccines. Animals included nonhuman primates (n = 13), mice (n = 7), ferrets (n = 4), hamsters (n = 4), and cats (n = 1). All animals supported high viral replication in the respiratory tract with mild clinical manifestations, lung pathology, IgG antibodies and full recovery. Older animals had more severe illness. None developed respiratory failure, multiple organ dysfunction or death. Transient systemic inflammation was observed occasionally in nonhuman primates, hamsters, and mice. No animals unveiled cytokine storms or coagulopathy supporting a wide gap between human and animal disease.
  • Longitudinal Profile of Laboratory Parameters and Their Application in the Prediction for Fatal Outcome Among Patients Infected With SARS-CoV-2: A Retrospective Cohort Study. 10/13/2020. Zeng HL. Clin Infect Dis.
    In this retrospective study of 642 patients with COVID-19, 55 laboratory values profiled along the entire disease course. Three distinct clinical stages were identified: a. acute stage 1-9 days after symptoms, slightly deviated indicators of liver damage, renal damage, and impaired immunity; b. the second stage, 10–15 days after disease onset, with corresponding ICU admission, and c. a third or convalescence stage with clinical symptoms beginning to resolve and laboratory measurements gradually reverting to normal, compared to thrombocytopenia and decreases in monocytes, exclusively observed in fatal cases; LDH, PCT, lymphocyte count, and IL-6 t were highly important prognostic markers.
  • The Effect of Temperature on Persistence of SARS-CoV-2 on Common Surfaces. 10/7/20. Riddel S. Virology.
    In this study, SARS-CoV-2 viability was measured on polymer and paper bank notes, stainless steel, glass, vinyl and cotton cloth at 20, 30, and 40°C. High titer virus was applied, and samples stored in the dark at 50% relative humidity. Half-lives were a few days on all surfaces at 20°C and reduced to a few hours at 40°C. Hard surfaces support viable virus longer than absorbent ones. Some remained detectable for 28 days on nonabsorbent surfaces at ambient temperature. Fomite transmission may be more important than previously thought. Concerns regarding bank notes, touchscreens and mobile phones are of particular importance.
  • The Impact of High-Flow Nasal Cannula Use on Patient Mortality and the Availability of Mechanical Ventilators in COVID-19. 10/13/2020. Gershengorn HB. Ann Am Thorac Soc.
    This sophisticated simulation looked at scenarios of COVID-19 surges in the US as a whole, with variable strategies for using high flow nasal oxygen (HFNO) and invasive mechanical ventilation (IMV). The strategy that resulted in the fewest deaths and greatest ventilator availability was using HFNO initially, coupled with early IMV when ventilator supply was sufficient.
  • The impact of protocol-based high-intensity pharmacological thromboprophylaxis on thrombotic events in critically ill COVID-19 patients. 10/12/20. Atallah B. Anaesthesia.
    This study was conducted to discover if high-intensity thromboprophylaxis would lead to fewer thrombotic events in COVID-19 positive patients. These patients were selected for high-intensity thromboprophylaxis when the D-dimer level was > 2ug/ml, and for therapeutic anticoagulation when the level was >3ug/ml. High-intensity thromboprophylaxis (enoxaparin 40 milligrams bid), but not therapeutic anticoagulation was associated with fewer thromboembolic events. Low D-dimer levels were independently associated with fewer venous thromboembolism events. Bleeding events in the high intensity thromboprophylaxis group were 2.7% compared to 16.5% using therapeutic anticoagulation. The authors conclude that high intensity thromboprophylaxis may reduce the incidence of thrombotic events without a significant increase in bleeding.
  • Treatments Considered for COVID-19. 10/15/20. The Medical Letter.
    This latest edition of The Medical Letter’s “Treatments Considered for COVID-19” was released on October 15, 2020 and included comprehensive (over 100 pages) up-to-date tables of drug, vaccine and other treatment classes. The columns include “Drug and Dosage,” “Efficacy,” “Adverse Effects/Interactions” and “Comments,” all with thorough referencing.
    Updates added to this edition include:
    • remdesivir – new guidelines from NIH and IDSA,
    • convalescent plasma – new guidelines from IDSA,
    • monoclonal antibodies, mesenchymal stem cell therapy, corticosteroids – new guidelines from NIH and IDSA,
    • IL-6 Inhibitors – new guidelines from IDSA; JAK inhibitors – data from NIH’s ACTT-2 trial on baricitinib, and
    • antimalarials – results from the RECOVERY trial, PPIs, vaccines and SSRIs.

October 14, 2020:

  • A quantitative evaluation of aerosol generation during tracheal intubation and extubation. 10/6/20. Brown J. Anaesthesia.
    This is a pertinent report on measurement of 0.3-10 nm aerosolized particles using real-time, high-resolution environmental monitoring in ultraclean ORs with laminar flow ventilation and 500–650 air changes / hour. Tracheal intubation sequences including face-mask ventilation produced very low particle quantities (average concentration, 1.4 particles/L, n = 14, p < 0·0001 vs. cough). Tracheal extubation, particularly when the patient coughed, produced a detectable aerosol (21 particles/L, n = 10), 15-fold greater than intubation (p = 0.0004) but 35-fold less than a volitional cough (p < 0.0001). The study does not support the designation of elective tracheal intubation as an aerosol-generating procedure.
  • Duration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infectivity: When Is It Safe to Discontinue Isolation? 10/8/20. Rhee C. Clin Infect Dis.
    In the review, SARS-CoV-2 is most contagious right before and immediately after symptom onset, and contagiousness rapidly decreases to near-zero about 10 days from symptom onset in mild-moderately ill patients and 15 days in critically ill and immunocompromised patients. The longest duration of viral viability reported is 20 days from symptom onset. Persistently positive SARS-CoV-2 RNA PCR does not indicate replication-competent virus and is not associated with contagiousness. Chain reaction assays that alternate between positive and negative results in recovered patients from COVID-19 most likely reflect sampling variability. The infection confers at least short-term immunity in most cases, but duration of immunity is unclear and several cases of re-infection have now been confirmed.
  • In-hospital cardiac arrest in critically ill patients with covid-19: multicenter cohort study. 9/30/20. Hayek S. BMJ.
    This article discusses a multicenter (68 sites) US study which followed 5019 admitted COVID-19 patients, 701 (14%) of whom had in-hospital cardiac arrest. The influence of patient demographics, co-morbidities and critical care facilities on outcome are also described. Patients younger than 45 years were more likely to receive CPR with 21.2% (11/52) surviving to hospital discharge with normal or mild neurocognitive deficit compared to 2.9% in patients 80 years or older. The article confirms generally poor results of CPR in COVID-19 but provides interesting discrimination between age, ICU size and co-morbidities. It raises key questions regarding triage and informed assent discussions.
  • Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. 10/5/20. RECOVERY Collaborative Group. Lancet.
    This article reports results of a prospective, controlled, open-label adaptive platform trial designed to test effectiveness of lopinavir-ritonavir (1616) against usual care (3424) in patients admitted to hospital with COVID-19 between March 19 and June 29. Lopinavir-ritonavir treatment was not associated with any primary endpoint benefit, including 28-day mortality, hospital length of stay, risk of progressing to mechanical ventilation or death. The results do not support use of lopinavir-ritonavir to treat COVID-19 patients.
  • Antiviral monotherapy for hospitalised patients with COVID-19 is not enough. 10/5/20. Cao B. Lancet.
    Commentary on accompanying article findings from the RECOVERY trial that lopinavir-ritonavir addition to usual care in managing COVID-19 patients admitted to hospital conveyed no outcome benefit for the primary endpoints of death at 28 days, hospital length of stay or progression to mechanical ventilation. The authors suggest that despite negative trial results, future research in this area should continue and that evaluation and efficacy of antiviral and immunomodulator combination therapy be continued.

October 12, 2020:

  • Clinical criteria for COVID-19-associated hyperinflammatory syndrome: a cohort study. 9/29/20. Webb BJ. Lancet Rheumatol.
    Defining the scourge of COVID-19 hyperinflammatory syndrome. 9/29/20. Cron RQ. Lancet Rheumatol.
    These authors are first to propose specific criteria for COVID-19-associated hyperinflammatory (cytokine storm) syndrome (cHIS). They validated the cHIS scale using retrospective data from 299 COVID-19 inpatients from their 22-hospital system. The six-criterion additive scale: fever, macrophage activation (hyperferritinemia), hematological dysfunction (neutrophil to lymphocyte ≥10:1 ratio), hepatic injury (lactate dehydrogenase or aspartate aminotransferase), coagulopathy (D-dimer), and cytokinemia (C-reactive protein, interleukin-6, or triglycerides). Meeting ≥2 criteria was associated with increased mortality and mechanical ventilation risk. External validation is needed. The cHIS scale may better target populations for trials and immunomodulation and diminish heterogeneity of treatment effect analyses of trials with undifferentiated patients.
  • Compassionate Use of Remdesivir in Pregnant Women with Severe Covid-19. 10/8/20. Burwick RM. Clin Infect Dis.
    This is a multicenter review of the outcomes for 67 pregnant and 19 immediate post-partum patients with moderate to severe COVID-19 treated with remdesivir. Outcomes were generally good, but there was no comparison to a control group. Remdesivir was well tolerated, with a low incidence of serious adverse events (16%). Most adverse events were related to pregnancy and underlying disease; most laboratory abnormalities were Grades 1 or 2. There was one maternal death attributed to COVID-19 and no neonatal deaths.
  • Remdesivir for Adults With COVID-19: A Living Systematic Review for an American College of Physicians Practice Points. 10/5/20. Wilt TJ. Ann Intern Med.
    Of the 89 pertinent articles that these authors reviewed, only 4 fit their strict criteria and were chosen for this review. They concluded that from the best evidence available so far, remdesivir probably improves recovery, reduces serious adverse events and may reduce mortality and time to clinical improvement in hospitalized adults with COVID-19. For patients not on a ventilator, a 5-day course may provide similar benefits to, and fewer harmful effects, than a 10-day course. The review is titled “Living” because these authors, from the VA system, plan to update their literature search every 2 months through December 2021.
  • Remdesivir for the Treatment of Covid-19 — Final Report. 10/8/20. Beigel JH. N Engl J Med.
    This article is a follow-up to the initial “preliminary report” that was published May 22, 2020 and was included as 47% of the patients in the review above. This “final report” of the ACTT-1 study provides later outcomes and analysis of the same 1062 patients in the “preliminary” report, randomized between February 21 and April 19 to receive 10 days of remdesivir or placebo. Similar to the analysis in the first report, those who received remdesivir had a median recovery time of 10 days compared with 15 days among those who received placebo. Kaplan–Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and estimates of mortality by day 29 (new in this report) were 11.4% with remdesivir and 15.2% with placebo.
  • Susceptibility of tree shrew to SARS-CoV-2 infection. 9/29/2020. Zhao Y. Sci Rep.
    SARS-Co-V-2 research has been hampered by poor susceptibility of animal models to SARS‑CoV‑2 infection, particularly the mouse. These investigators examined if a domesticated tree shrew, a species genetically close to primates and used in hepatitis, influenza and other research may be useful. SARS-CoV-2-infected tree shrews showed no clinical signs except mild fevers. Histologically, low levels of virus shedding and replication in tissues were observed. Mild pulmonary abnormalities were the main changes observed. The tree shrew may not be suitable for COVID‑19 research. However, tree shrew may be a potential asymptomatic intermediate host of SARS‑CoV‑2 besides bats and pangolins.
  • Updated guidance on the management of COVID-19: from an American Thoracic Society/European Respiratory Society coordinated International Task Force (29 July 2020). 10/6/20. Bai C. Eur Respir Rev.
    In this article, the Task Force (American Thoracic Society/European Respiratory Society coordinated International Task Force 29 July 2020) make consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but not with hydroxychloroquine except in the context of a clinical trial. COVID-19 patients with a venous thromboembolic event can be treated with therapeutic anticoagulant therapy for 3 months. Routine screening of patients for depression, anxiety and post-traumatic stress disorder was also suggested by the task force.

October 9, 2020:

  • Psychological Impact of COVID-19 on ICU Caregivers. 9/29/20. Caillet A. Anaesth Crit Care Pain Med.
    In this survey conducted among 208 ICU staff of a French teaching hospital, the incidence of anxiety and depression was 48% and 16% respectively, and PTSD was present in 27%. Use of the “Hospital Anxiety and Depression Scale” (HADS) and “Impact of Event Scale – Revised” (IES-R) revealed lack of critical care training as an important independent risk factor for anxiety syndrome and PTSD. COVID-19 unit assignment was responsible for anxiety syndrome and a prior history of burnout were risk factors for PTSD. The authors suggest intensified training and awareness of individuals’ history to address some of these issues.
  • Surgical mask on top of high-flow nasal cannula improves oxygenation in critically ill COVID-19 patients with hypoxemic respiratory failure. 9/29/20. Montiel V. Ann Intensive Care.
    This study (n= 21) points out that placing a surgical mask on a patient’s face along with high-flow nasal cannula (heated / humidified/ 60 L/m device), had a statistically significant improvement of oxygenation (PaO₂:FiO₂, saturation, PaO₂) in COVID-19 hypoxemic respiratory failure. They noted an insignificant change in PaCO₂. This suggests the usefulness of a small change of a modality which can be rendered safely outside the ICUs in an overwhelming surge. Authors advocate that this step precede non-invasive ventilation to improve oxygenation.
  • Survival of SARS-CoV-2 and influenza virus on the human skin: Importance of hand hygiene in COVID-19. 10/3/20. Hirose R. Clin Infect Dis.
    In this in vitro cadaveric skin model, and insert surfaces, these investigators noted that COVID viruses survive statistically significantly longer (8x) when compared with influenza virus. The authors found the virus can be completely inactivated within 15 seconds of exposure to 80% (w/w) ethanol. Thus, appropriate hand hygiene using ethanol-based disinfectants leads to rapid viral inactivation and may reduce the risk of contact infections. It should be noted that these studies were carried out at room temperature, which may allow longer viral viability compared with normal in vivo skin temperature.
  • Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial (HESACOVID). 9/20/2020. Lemos ACB. Thromb Res.
    This paper randomized 20 COVID-19 patients requiring mechanical ventilation. Ten patients were assigned to either therapeutic enoxaparin (enoxaparin) or to prophylactic anticoagulation (SQ heparin). There was an increase in the PaO2/FiO2 ratio in the therapeutic group, p=0.0004 which was not seen in the prophylactic group, p=0.487. Patients in the therapeutic group had a rate of successful liberation from mechanical ventilation (hazard ratio: 4.0, p=0.031) and more ventilator-free days (15 days versus 0 days, p = 0.028). There was no difference in mortality.  While the dataset is small, it does show promise and is an introduction for larger upcoming trials.

October 7, 2020:

October 5, 2020:

  • Convalescent Plasma for the Treatment of COVID-19: Perspectives of the National Institutes of Health COVID-19 Treatment Guidelines Panel. 9/25/20. Pau AK. Ann Intern Med.
    Data are currently insufficient for the NIH to recommend for or against convalescent plasma (CP) for COVID-19. Enrollment in adequately powered US RCTs is slow.

    FDA analysis (4330 patients):

    • 7-day mortality following high-titer vs. low-titer plasma
      • No difference overall.
      • Intubated patients (~1/3) – No difference.
      • Non-intubated patients: 11% high-titer vs. 14% low-titer.
    • Non-intubated patients <80 years treated w/in 72 hrs. of diagnosis, 6.3% high-titer vs. 11.3% low-titer (P = 0.0008).

    Analysis of 3082 patients / 35,322 who received plasma by 4 July 2020 via Mayo Clinic’s parallel Expanded Access Program, developed to provide broader access to CP yet NOT designed to generate definitive safety or efficacy data as no untreated control group.

    • 30-day mortality 29.1% in low-titer group vs. 24.7% in the high-titer group (not statistically significant).
    • Suggestion that high-titer plasma beneficial when administered within 72 hours of Dx.
  • COVACTA trial raises questions about tocilizumab’s benefit in COVID-19. 9/9/20. Furlow B. Lancet Rheumatol.
    IL-6 has both pro-inflammatory (e.g. “cytokine storm”) and anti-inflammatory effects. Retrospective studies suggested that the IL-6 antagonist tocilizumab reduced mortality. On July 29, 2020, Hoffmann-La Roche announced results of COVACTA, a Phase 3 tocilizumab randomized controlled trial in severe COVID-19 pneumonia. Tocilizumab failed to meet the primary endpoint of improved clinical status or mortality. However, treated patients spent a week less in the hospital. The full results await publication. Proper timing of administration assessing clinical signs of hyperinflammation may prove crucial. The results of the much larger tocilizumab RECOVERY trial are pending.
  • Detection of SARS-CoV-2 with SHERLOCK One-Pot Testing. 9/16/2020. Joung J. N Engl J Med.
    Both CRISPR (clustered regularly interspaced short palindromic repeats)- based diagnostic tests and SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) can detect viruses, but are not practical for Point of Care testing. The newly described “STOPCovid.v2” (SHERLOCK Testing in One Pot version-2) uses a novel magnetic bead RNA extraction with loop-mediated isothermal amplification and CRISPR-mediated detection, all in 15-45 minutes using minimal equipment and available reagents. Nasal swab testing showed a sensitivity of 93.1% and a specificity of 98.5%. STOPCovid.v2 false negative samples had RT-qPCR Ct values greater than 37. STOPCovid.v2 detected a viral load 1/30th detected by RT-qPCR.
  • High Frequency of SARS-CoV-2 RNAemia and Association With Severe Disease. 9/23/20. Hogan CA. Clin Infect Dis.
    Paired nasopharyngeal and plasma samples from 85 COVID-19 patients, median age 55, revealed plasma RNAemia in 28/85 (32.9%), including 22/28 (78.6%) who required hospitalization, and older age (63 vs. 50 years; P = .04). In models adjusted for age, RNAemia was more frequent in individuals who developed severe disease including ICU admission (32.1% vs 14.0%; P = .04), invasive mechanical ventilation (21.4% vs. 3.5%; P = .02), and all 4 deaths. Plasma RNA persisted for a maximum of 10 days. Authors suggest potential utility as a prognostic indicator.
  • High Potency of a Bivalent Human VH Domain in SARS-CoV-2 Animal Models. 9/4/2020. Li W. Cell.
    Using a phage-generated library, these investigators found spike glycoprotein (S) -receptor binding domain-avid high-affinity VH binder ab8. Bivalent VH, VH-Fc ab8, bound with high avidity to S and to patient-derived S-mutants. VH-Fc ab8 was markedly effective as a prophylactic and a therapeutic, interfering in ACE-2 binding in a mouse-adapted SARS-CoV-2 and in a hamster model. The potency was enhanced by its relatively small size vs. a complete antibody (80 vs. 150 kDa). S-specificity was shown; VH-Fc ab8 did not aggregate and did not bind to 5,300 human membrane-associated proteins. These data provide a strong rationale for its therapeutic evaluation.
  • Reduced Monocytic Human Leukocyte Antigen-DR Expression Indicates Immunosuppression in Critically Ill COVID-19 Patients. 9/14/20. Spinetti T. Anesth Analg.
    Major histocompatibility complex (MHC) Class II molecules present processed extracellular proteins and are only expressed on the surface of “professional” antigen presenting cells such as dendritic cell and macrophages/monocytes. As such, there are clear implications for SARS-CoV-2. This small monocentric prospective study examined CD14+ monocytic HLA-DR (mHLA-DR) expression in 9 ICU vs. 7 non-ICU hospitalized COVID-19 patients. The investigators found on flow cytometry significant downregulation of surface expression of this marker indicating immunosuppression. The decrease found on ICU admission persisted on days 3 and 5. The authors suggest that immune monitoring in the ICU could indicate who might benefit from immunological intervention (e.g. GM-CSF, IFNγ).

October 2, 2020:

September 30, 2020:

  • New Studies on COVID-19 Epidemiology
    The following four articles examine risk factors for developing COVID-19, for having severe disease and for death. Common findings include an increased risk of infection and hospitalization in Blacks but no increase in mortality. It should be noted that the mentioned hospitalization rates may depend on socio-economic factors and may not be a clear indicator of severity of disease.
    • Patterns of COVID-19 testing and mortality by race and ethnicity among United States veterans: A nationwide cohort study. 9/22/20. Rentsch CT. PLoS Med.
      This article presents a nationwide VA data set study (~6 million patients, February 8 to July 22) comparing positive COVID-19 test results with 30-day mortality. Healthcare disparities were explored by evaluating “associations between race/ethnicity and receipt of COVID-19 testing, a positive test result, and 30-day mortality, with multivariable adjustment for demographic and clinical characteristics including comorbid conditions, health behaviors, medication history, site of care, and urban versus rural residence.” The study confirms prior reports indicating that “Black and Hispanic individuals experience excess burden of SARS-CoV-2 infection” but not increased mortality and notes that these disparities “are not entirely explained by underlying medical conditions or where they live or receive care.” The article contains interesting distinctions and reinforces the importance of designing “strategies to contain and prevent further outbreaks in racial and ethnic minority communities.”
    • Risk Factors for Hospitalization, Mechanical Ventilation, or Death Among 10 131 US Veterans With SARS-CoV-2 Infection. 9/23/20. Ioannou GN. JAMA Netw Open.
      This large study showed no increase in mortality associated with Black or Hispanic race, obesity, COPD, hypertension or smoking (contrary to what has been found in smaller, prior studies). It did find the expected association of increased severity and mortality with older age (>50) and multiple comorbidities.
    • Association of Race and Ethnicity With Comorbidities and Survival Among Patients With COVID-19 at an Urban Medical Center in New York. 9/25/20. Kabarriti R. JAMA Netw Open.
      Among 5902 patients with positive COVID-19 diagnosis treated at a single academic center in urban New York, non-Hispanic Black and Hispanic patients had a higher proportion of more than 2 medical comorbidities and were more likely to require inpatient hospitalization, but had outcomes including mortality that were at least as good as, and maybe even marginally superior to, their non-Hispanic White counterparts when controlling for age, sex, and comorbid conditions at presentation.
    • Racial Disparities in Incidence and Outcomes Among Patients With COVID-19. 9/25/20. Muñoz-Price LS. JAMA Netw Open.
      This article investigates the goal-described patterns and outcomes of COVID-19 by race, controlling for age, sex, socioeconomic status, and comorbid conditions among 2595 urban patients. COVID-19 positivity was associated with Black race. Among patients with COVID-19, both race and poverty were associated with higher risk of hospitalization, but only poverty was associated with higher risk of intensive care unit admission. The findings also imply that adverse outcomes and greater population mortality associated with Blacks early in the course of the US pandemic were primarily attributable to greater incidence of COVID-19 among African American residents rather than worse survival once hospitalized.
  • Cardiopulmonary exercise and the risk of aerosol generation while wearing a surgical mask. 9/11/20. Helgeson SA. Chest.
    The authors quantified the number of various-sized airborne particles 6 feet from exercising normal volunteers wearing type II procedural surgical masks. They found there was a minimal increase of particle number at low and moderate exercise but a doubling of the ambient baseline of small respirable particles (0.3–0.5 micrometer) with very hard exercise. Larger droplet sized particles were not significantly increased during any stage of exercise. These results may be applicable to gyms and health clubs if all participants wear surgical masks.
  • Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis. 9/22/20. Buitrago-Garcia D. PLoS Med.

    Ninety-four reviewed studies identified from 25 March through 10 June 2020:

    • ~20% remain asymptomatic when infected with SARS-CoV-2 (79 studies); 31% in screened populations (7 studies).
    • Compared with symptomatic contacts, relative risk of transmission from asymptomatic contacts = 0.35 (95% CI 0.10–1.27); from presymptomatic contacts = 0.63 (95% CI 0.18–2.26).
    • “Easing of restrictions will only be possible with wide access to testing, contact tracing, and rapid isolation of infected individuals.” Prevention measures (enhanced hand hygiene, masks, social distancing) and quarantine of close contacts are essential to prevent onward transmission during asymptomatic or presymptomatic periods.
  • SARS-CoV-2-Associated Deaths Among Persons Aged <21 Years – United States, February 12-July 31, 2020. 9/18/20. Bixler D. MMWR Morb Mortal Wkly Rep.
    This CDC Morbidity and Mortality Weekly Report describing deaths in <21 year old population. Most patients are Hispanic or Black, and 45% had 2 or more associated illnesses. Most of the deaths occurred in 18-20 year olds. Of curiosity, only 8% exhibited the inflammatory illness possibly due to the large number that died out-of-hospital or in the ER. Most significant is that although 391,814 cases were reported in the age group, only 121 deaths occurred, a fatality rate of 0.08%.

September 25, 2020:

  • Association of Daily Wear of Eyeglasses With Susceptibility to Coronavirus Disease 2019 Infection. 9/16/20. Zeng W. JAMA Ophthalmol.
    While the public has not received guidance to wear eye protection to decrease the risk of COVID-19, Zeng raised the question of whether ordinary eyeglasses may help prevent infection, as in their observational study of 276 COVID-19 inpatients of which only 5.8% wore glasses vs. 31.5% in a reference population. This editorial highlights the study’s weaknesses, including that the “local population” data were from another region of China and another time period altogether. Although the data are unlikely to be by chance alone, an inference of cause requires additional study.
  • Glucocorticoid therapy does not delay viral clearance in COVID-19 patients. 9/22/2020. Ji J. Crit Care.
    This is a (LtE) retrospective observational study regarding glucocorticoids and Covid viral clearance. Out of 684 patients noted 29.5% had viral RNA clearance within 14 days after illness onset and 30.7% cases had viral RNA clearance between 14 and 28 days, and 39.8% cases had viral RNA clearance over 28 days. There were no differences on the age, gender, and underlying diseases between different groups. The degree of decrease in CD4 T cell and B cell counts on admission was related with the prolonged viral RNA clearance. The results show that GC therapy shortened hospital stay days but had no effect on the virus clearance time. This is true for the severe and critical patients as well. The GC treatment had no effect on the peripheral lymphocyte counts, including CD4 T cells, CD8 T cells, NK cells, and B cells.
  • COVID-19 concerns aggregate around platelets. 9/10/20. Battinelli EM. Blood.
    This is a well-written, useful editorial which describes the essence of the following two papers, including its limitations and future steps.
  • Platelet gene expression and function in patients with COVID-19. 9/10/20. Manne B. Blood.
    Using platelet RNA sequencing, this group profiles gene expression in the platelets of COVID-19 patients (n= 41) and finds altered gene expression profiles in pathways associated with ubiquitination, antigen presentation, and mitochondrial dysfunction. Patients with COVID-19 have higher levels of platelet activation at rest and increased interactions with neutrophils, monocytes, and T cells compared with healthy donors. Platelet functionality studies demonstrate hyperactivity, as evidenced by increased aggregation, spreading on fibrinogen and collagen through upregulation of the MAPK pathway, and increased thromboxane generation. These new data help extend prior data into the basic science of the hypercoagulable state of COVID-19.
  • Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19. 9/10/20. Hottz E. Blood.
    This group demonstrates that COVID-19 is associated with increased platelet activation. They show that the platelets of critically ill COVID-19 patients exhibit increased platelet aggregation and platelet-monocyte aggregation. Further, these changes correlate with a worse outcome. Changes in platelet activation were associated with increased platelet expression of P-selectin and CD63. Platelets from patients with severe COVID-19 infection induce monocyte-derived tissue factor (TF) expression that is diminished by pretreating COVID-19 patient platelets with an anti–P-selectin neutralizing antibody or the clinically approved anti-αIIb/β3 monoclonal antibody, abciximab. These data are new and add to the understanding of the role that platelets play in the hypercoagulable state of COVID-19.
  • Probative Value of the D-Dimer Assay for Diagnosis of Deep Venous Thrombosis in the Coronavirus Disease 2019 Syndrome. 9/15/20. Gibson CJ. Crit Care Med.
    The authors tested the utility of the D-dimer assay for the diagnosis of deep vein thrombosis. Despite the excellent correlation between the D-dimer and the presence of DVT, the positive predictive value was 21.8%. DVT is only one aspect of the thrombotic problems in these patients. Many do not recommend leg duplex scanning using the sole criteria of D-dimer. One interesting aspect of this study was that all ICU patients received therapeutic anticoagulation. That may have been reflected in the low incidence of DVT discovered in these patients. Unfortunately, there are no data presented regarding the incidence of bleeding in these patients.
  • Stroke Risk, phenotypes, and death in COVID-19: Systematic review and newly reported cases. 9/15/20. Fridman S. Neurology.
    This is a complex study of stroke characteristics in COVID-19 patients by an international team of neurologists who pooled results from 10 studies with their own case series for a total of 160 patients. Their goal is to estimate overall incidence of stroke (1.8%) and mortality (34.4%), determine risk factors, particularly in patients under age 50, and identify clinical phenotypes and associated mortality separating all strokes from ischemic etiology. Large vessel occlusion contributed to a high percentage of strokes in younger patients and occurred before the onset of COVID-19 symptoms in 49% of those cases, while pulmonary involvement correlated with strokes in older patients and poor outcomes.

September 23, 2020:

September 21, 2020:

  • Elevated D-dimers and lack of anticoagulation predict PE in severe COVID-19 patients. 9/9/20. Mouhat B. Eur Respir J.
    This article reviews 162 patients who had computed tomography pulmonary angiography (CTAP) with clinical pulmonary deterioration taken from 349 patients with COVID-19 in a French hospital. Twenty-seven percent had pulmonary embolism (PE). Review of their data with multivariate analysis demonstrates lack of anticoagulation and D-dimer > 2590 ng/ml to be predictive of PE. A D-dimer level >2590 ng/mL−1 was associated with a 17-fold increase (!), and lack of anticoagulation with a 4-fold increase in the risk of PE. Linearity was verified for D-dimers in the study population (test of linearity <0.001). This paper adds more details to the literature and helps guide the clinician.
  • Favorable outcomes of COVID-19 in recipients of hematopoietic cell transplantation. 9/8/20. Shah GL. J Clin Invest.
    From Sloan Kettering, a retrospective study of 77 COVID-19 PCR+ recipients of allogeneic and autologous hematopoietic cell transplant and chimeric antigen receptor T cell therapy (44% admitted). Of the 77 cellular therapy recipients, the results were: Allo = 35, Auto = 37, CAR-T = 5. The median time from cellular therapy was 782 days. Overall survival at 30 days was 78%. Clinical variables significantly associated with more severe disease (greater than non-rebreathing mask oxygen) or death were number of comorbidities, infiltrates and neutropenia. Worsening graft-versus-host-disease was not identified. The authors observed rapid recovery in lymphocyte populations across lymphocyte subsets which are critical to anti-viral responses and immune reconstitution.
  • Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study. 6/25/20. Varatharaj A. Lancet Psychiatry.
    Report on a nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19 in the UK combined with a call for similar initiative to collect data on short- and long-term neurological and psychiatric sequelae of COVID-19 worldwide. The authors used a secure rapid-response case report notification portal that was made available to all pertinent professional organizations and obtained valuable and timely data to be reviewed by clinicians, researchers and funders.
  • Racial/Ethnic Variation in Nasal Gene Expression of Transmembrane Serine Protease 2 (TMPRSS2). 9/10/20. Bunyavanich S. JAMA.
    Nasal epithelium contains a protease (transmembrane serine protease 2 – TMPRSS2) which facilitates SARS-CoV-2 virus entry into the body. In a racially diverse cohort participating in an asthma study between 2015 – 2018, Black individuals exhibited a significantly higher expression of TMPRSS2 in nasal epithelium compared with other self-identified races/ethnicities. This finding may shed further light on the observed higher burden of COVID-19 among Black individuals. Protease inhibitors, like camostat mesylate, are undergoing clinical trials to test their utility for COVID-19 treatment via TMPRSS2 inhibition.
  • The coronavirus is mutating – does it matter? 9/8/20. Callaway E. Nature.
    In an article from Nature, mutations in the SARS-CoV-2 are reviewed. Mutations in RNA viruses such as SARS-CoV-2 containing “proofreading” enzymes occur slowly. One distinct mutation in the spike protein gene occurs at the 614th amino-acid position: the aspartate (D, in biochemical shorthand) is replaced by glycine (G) in the virus’s 29,903-letter RNA code. The “D614G mutation” became the dominant SARS-CoV-2 lineage in Europe and the US. Despite early alarm, it does not enhance spread or affect antibody defense. More than 12,000 mutations in SARS-CoV-2 are catalogued. The author speculates that worrisome mutations could arise especially if antibody therapies producing selection pressure are not used wisely.

September 16, 2020:

September 14, 2020:

September 9, 2020:

September 4, 2020:

September 2, 2020:

  • Anakinra in COVID-19: important considerations for clinical trials. 5/21/20. King A. Lancet Rheumatol.
    This comment is of interest for clinicians and researchers working with the Interleukin IL-1α and IL-1β inhibitory agent anakinra in COVID-19 patients with evidence of hyperinflammation. The authors review and critique 10 ongoing trials with anakinra and suggest using worsening lymphopenia as a marker of disease progression and severity and increasing C-reactive protein as evidence of worsening inflammation. They also favor subcutaneous administration due to the drug’s short half-life and implore the trial gate keepers to ensure collection of core outcome measures, like ferritin levels for current and future trials.
  • Respiratory physiology of COVID-19-induced respiratory failure compared to ARDS of other etiologies. 8/28/20. Grieco DL. Crit Care.
    This article provides a detailed comparison of the respiratory mechanics of 30 COVID-19 ARDS patients measured within 24 hours of initial intubation with 30 non-COVID matching ARDS patients based on PaO2/FiO2, FiO2, PEEP, and tidal volume. The average compliance and ventilatory ratio were slightly higher in COVID-19 patients. Inter-individual variability of compliance was similar in both groups. In COVID-19 patients, PaO2/FiO2 was linearly correlated with respiratory system compliance. High PEEP improved PaO2/FiO2 in both cohorts, but more remarkably in COVID-19 patients. Recruitability was not different between cohorts. The authors conclude that overall the respiratory mechanics were similar in the two groups but were marked by prominent intra-group variability in both.
  • Viral dynamics and immune correlates of COVID-19 disease severity. 8/28/20. Young BE. Clin Infect Dis.
    One hundred COVID-19 patients from Singapore underwent prospective study of infectivity and immune response on days 1, 3, 7,14, 21 and 28 after enrollment. No positive viral cultures were found in respiratory samples (n=21) obtained more than 14 days after symptom onset and all positive viral cultures occurred in patients with PCR cycle threshold values <30. Disease severity was associated with earlier seroconversion, higher peak IgM and IgG levels, and higher levels of inflammatory markers, but not duration of viral shedding by PCR. Results have implications for duration of isolation/quarantine and from whom to potentially obtain convalescent plasma.

August 31, 2020:

August 26, 2020:

August 25, 2020:

August 19, 2020:

  • A physiological approach to understand the role of respiratory effort in the progression of lung injury in SARS-CoV-2 infection. 8/10/20. Cruces P. Crit Care.
    A thorough, well-written review of the physiology of patient-induced lung injury and of ventilator-induced lung injury adding information from the authors’ detailed CT scan profiles of lung injury in animal models. The article concludes with a balanced discussion of when to support Covid-19 pneumonia patients with non-invasive measures such as high flow nasal cannula versus when to intubate and support with mechanical ventilation. While no new approaches are provided, their recommendations support a complete evaluation of the patient’s condition and show clear consideration for the consequences of patient-induced lung injury.
  • Association Between Anxiety and New Organ Failure, Independently of Critical Illness Severity and Respiratory Status: A Prospective Multicentric Cohort Study. 7/30/20. Mazeraud A. Crit Care Med.
    Interesting, multi-center prospective study evaluating patient’s admission anxiety level on new organ system failure within seven days following ICU admission. While not directly related to COVID-19 (or any specific admission diagnosis), patients identified with moderate to severe anxiety (State anxiety-assessed using state component of State-Trait Anxiety Inventory State) associated with disease severity (Simplified Acute Physiology Score II and Sequential Organ Failure Assessment) associated with increased risk for further deterioration when compared to lower stress comparators. Interesting with obvious implications for current pandemic given long prodrome with variable symptomatology and outcome increasing general anxiety in population with some estimates indicating a recent reported 25% incidence of suicidal ideation in younger age groups.
  • Convalescent plasma for COVID-19. 8/8/20. Mucha SR. Cleve Clin J Med.
    While convalescent plasma has yet to be proven effective, it has generated great interest as a possible COVID-19 therapy and clinical trials are underway. For those interested in a well-written review of the questions and potential risks that must be taken into consideration, this report is a worthwhile read. Potential downsides include TACO, TRALI, antibody dependent enhancement of infection and attenuated immune response. Current limitations include obstacles to effective testing of donor neutralizing antibody levels. This topic is at the center of the current controversy surrounding a potential FDA emergency use authorization for convalescent plasma, (now on hold).
  • Delirium and encephalopathy in severe COVID-19: a cohort analysis of ICU patients. 8/8/20. Helms J. Crit Care.
    Following up on the concept that neurotropism of the SARS-CoV-2 virus has been confirmed, French investigators focused on the neurological status of 140 consecutive patients with COVID-19 linked ARDS (mean age 62, 71% male) to determine the incidence of delirium and abnormal neurological exams. 84% developed delirium and of those, 69% presented with agitation and 63% had long-tract signs. Of 28 patients who underwent lumbar puncture and MRI, 65% had perfusion abnormalities and 61% had signs of a disturbed blood brain barrier, 64% showed inflammatory signs in CSF and one was PCR positive for SARS-CoV-2 in CSF. Delirium associated with ARDS and COVID-19 is a distinct entity caused by the corona virus which prolongs and complicates recovery, both short term and possibly in the long term as well.
  • Extracorporeal membrane oxygenation for refractory COVID-19 acute respiratory distress syndrome. 7/31/20. Le Breton C. J Crit Care.
    A brief single center report stating that 11 of 13 patients treated with ECMO were successfully weaned from ECMO (medium treatment of 13 days) and eventually from mechanical ventilation (median treatment 29 days). The authors support ECMO use in carefully selected cases.
  • Infection Prevention Precautions for Routine Anesthesia Care During the SARS-CoV-2 Pandemic. 8/3/20. Bowdle A. Anesth & Analg.
    Authors promote precautions that are practical, affordable, and efficient to adjust routine anesthesia care to the current and near-future environment. Consideration for asymptomatic and pre-symptomatic SARS-CoV-2 infection, and the potential for false-negative tests inform recommendations to reduce the risk of transmission via anesthesia care behaviors. Universal N95 or higher respiratory protection is proposed for anesthesia providers with consideration given to whether the entire surgical team should use equivalent respiratory protection. Tables provide a useful summary of PPE, hand hygiene and other recommendations.
  • Late Onset Infectious Complications and Safety of Tocilizumab in the Management of COVID-19. 8/14/20. Pettit NN. J Med Virol.
    Tocilizumab while previously showing some positive results in treating COVID-19, in this controlled study demonstrated higher complication rates, especially infectious, and death.
  • Prominent coagulation disorder is closely related to inflammatory response and could be as a prognostic indicator for ICU patients with COVID-19. 8/8/20. Liu Y. J Thromb Thrombolysis.
    Interesting discussion highlighting interrelationship between inflammatory and coagulation systems; suggests coagulation abnormalities (PT, D-Dimer, FDP and AT III) can predict deterioration and mortality; also notes the neutrophil/lymphocyte ratio is a potential inflammatory marker in disease. Recognizes importance of prophylactic thromboprophylaxis and accurate timing of systemic anticoagulation.
  • Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients. 8/12/20. Remmelink M. Crit Care.
    The authors found in this study of 17 patients, a great heterogeneity of COVID-19-associated organ injury and the remarkable absence of any specific viral lesions, even when RT-PCR identified the presence of the virus in many organs. Pulmonary findings revealed early-stage diffuse alveolar damage 15/17; microthrombi in small lung arteries in 11 patients and no evidence of myocarditis, hepatitis, or encephalitis. Onset of symptoms and death ranged from 2 to 40 days.

August 17, 2020:

August 14, 2020:

  • Cerebrovascular Complications of COVID-19. 8/8/20. Katz JM. Stroke.
    Retrospective case review focusing on imaging confirmed stroke incidence among COVID-19 inpatients treated in a largely metropolitan health care system. 86 stroke patients were identified and compared to 499 stroke patients admitted a year earlier. COVID-19 patients were significantly more likely to have a stroke while hospitalized (48% vs 5%). Additional important findings among the COVID-19 group includes a predominance of ischemic stroke and a high frequency (67%) of non-focal neurologic presentations and a higher incidence among racial minorities.
    In-hospital stroke among COVID-19 patients is a strong independent risk factor and deserves a high grade of suspicion when patients develop neurologic symptoms.
  • Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2: A Systematic Review. 8/4/20. Abrams JY. J Pediatr.
    This article is a comprehensive description of multisystem inflammatory syndrome in children (MIS-C) authored by Centers for Disease Control scientists.
  • SARS-CoV-2 viral load in the upper respiratory tract of children and adults with early acute COVID-19. 8/6/20. Baggio S. Clin Infect Dis.
    Click here to take this CME activity.

    This prospective cohort study from Switzerland compared the viral load in patients of all ages during the first 5 days of COVID-19 symptoms. Viral loads as measured by cycle thresholds of RT-PCR testing were similar across all age groups (0-82 years old). This study of viral load in symptomatic patients helps clarify confusing results from other studies and may be especially pertinent as schools try to reopen.

  • The COVID-19 Vaccine Race: Challenges and Opportunities in Vaccine Formulation. 8/5/20. Wang J. AAPS PharmSciTech.
    This article is an in-depth review of vaccine development and delivery strategies, particularly as they apply to SARS-CoV-2. The proper choice of the type of vaccine, carrier or vector, adjuvant, excipients (other ingredients), dosage form, and route of administration can directly impact not only the immune responses and efficacy against COVID-19, but also the logistics of manufacturing, storing, distributing the vaccine and mass vaccination. The 13 vaccines under development (as of May 29, 2020) are nicely compared. The tables and graphics are excellent.

August 12, 2020:

August 10, 2020:

August 7, 2020:

  • Post-discharge venous thromboembolism following hospital admission with COVID-19. 8/3/20. Roberts LN. Blood.
    These authors identified 1,877 patients with COVID-19 discharged from the hospital, and noted that there were nine episodes of Hospital Associated Venous Thromboembolism (HA-VTE) diagnosed within 42 days compared with 2019 hospital discharge data. The authors calculated an odds ratio of 1.6 compared to historically “similar” groups of patients. They concluded that hospitalization of patients with COVID-19 does not appear to increase the risk of post-discharge HA-VTE compared to hospitalization with other acute medical illnesses. Their data suggests empiric post-discharge thromboprophylaxis is not necessary, thereby supporting the ACCP recommendations to not offer post-discharge thromboprophylaxis.
  • Reopening Primary Schools during the Pandemic. 7/29/20. Levinson M. N Engl J Med.
    This is a narrative summary and commentary on the literature and debate around reopening primary schools in the US, written by educators and medical epidemiologists. Primary schools in many other countries have re-opened successfully for in-person classes, but that success hinged on low community transmission rates, and extensive testing and surveillance. The authors believe that there is time in the US to achieve successful reopening in some areas if resources and effort are increased. The argument is made that primary schools are essential services, and “whether (or how) to reopen primary schools is not just a scientific and technocratic question. It is also an emotional and moral one.”
  • Reprocessing filtering facepiece respirators in primary care using medical autoclave: prospective, bench-to-bedside, single-centre study. 8/4/20. Harskamp RE. BMJ Open.
    Dutch investigators studied standard autoclave machines for decontamination of FFP2 and FFP3 respirators. They found that one model of FFP2 (the closest European Standard to US N95 respirators) tolerated up to 3 decontamination cycles at 121°C x 17 min. without significant change in filtration, resistance, or fit. Others, including the tested FFP3 model (higher filtration), did not. Referenced published studies support efficacy of this temperature to kill SARS-CoV-2. This study corroborates great variation between mask models observed in other studies and the critical importance of careful fit testing with each donning when considering decontamination and reuse of filtering facepiece respirators.
  • SARS-CoV-2 Infection and COVID-19 During Pregnancy: A Multidisciplinary Review. 5/30/2020. Narang K. Mayo Clin Proc.
    A long summary: 15 pages. There’s obviously different physiology concerning gestation and pregnancy. Earlier reports suggest higher rates of preeclampsia and other pregnancy-related complications. Angiotensin-converting enzyme 2 receptor is upregulated in normal pregnancy. So, with higher ACE2 expression, pregnant women may be at elevated risk for complications from SARS-CoV-2 infection. Upon binding to ACE2, SARS-CoV-2 causes its downregulation, thus lowering angiotensin-(1-7) levels, which can mimic/worsen the vasoconstriction, inflammation, and pro-coagulopathic effects that occur in preeclampsia. Indeed, early reports suggest that, among other adverse outcomes, preeclampsia may be more common in pregnant women with COVID-19.
  • To Toci or Not to Toci for COVID-19: Is That Still the Question? 7/31/20. Cheng GS. Clin Infect Dis.
    This is a very well written editorial describing the emergence of inflammatory inhibitors, such as tocilizumab, as potential treatment choices for COVID-19, and how the recent University of Michigan study adds credence to that choice.

August 5, 2020:

  • COVID-19 Lung Injury and High-Altitude Pulmonary Edema. A False Equation with Dangerous Implications. 8/1/20. Luks AM. Ann Am Thorac Soc.
    This is a well written opinion piece responding to the claim (now seen frequently on social media) that the pathophysiology of COVID pneumonia and high-altitude pulmonary edema (HAPE) are similar and may respond to similar therapies. The striking differences between the pathophysiologies of the two diseases are well described as are the expected responses of each to standard therapies for HAPE. The significant risk for adverse effects treating COVID pneumonia as HAPE are elucidated.
  • EDITORIAL: COVID-19: a complex multisystem disorder. 6/30/20. Roberts CM. Br J Anaesth.
    COVID-19 has extensive effects on virtually all the organs. The virus binds to angiotensin converting enzyme 2 (ACE2) receptors present in vascular endothelial cells, lungs, heart, brain, kidneys, intestines, liver, pharynx, and other tissue. It can directly injure these organs. In addition, systemic disorders caused by the virus lead to organ malfunction. It can cause cytokine storm which can culminate in death. It causes inflammation, endotheliitis, vasoconstriction, hypercoagulability, and edema. Lymphocytopenia, elevated D-dimer, elevated fibrin degradation products (FDPs), and disseminated intravascular coagulation (DIC) are observed. Deep vein thrombosis (DVT), venous thromboembolism, pulmonary embolism (PE), systemic and pulmonary arterial thrombosis and embolism, and ischemic stroke are reported. In the heart, it can cause acute coronary syndrome, congestive heart failure, myocarditis, and arrhythmias. Kidney injury is usually secondary to systemic abnormalities. Stroke occurs even in young patients. Delirium and seizures are common. Anosmia and impaired sense of taste are reported. Psychological problems are common among patients as well as providers. Stool may contain virus. Lactate dehydrogenase may be elevated. Various skin manifestations including patchy erythematous rash are reported. Injury to an organ may become apparent long after the acute infection has subsided. Different organs may be affected at different times. Chronic injury may occur. Rehabilitation can be long and difficult.
  • Outcomes in COVID-19 Positive Neonates and Possibility of Viral Vertical Transmission: A Narrative Review. 8/1/20. Sheth S. Am J Perinatol.
    Click here to take this CME activity.

    This is an international review, mostly from China, of transmission from COVID-19 infected pregnant women to newborns. Of the 39 published reports, it includes only 326 COVID-19 positive women. Despite the small numbers, newborns were infrequently infected with COVID-19 at birth. Of the 23 COVID-19-positive neonates reported, no deaths resulted.

  • Prevalence and Impact of Myocardial Injury in Patients Hospitalized With COVID-19 Infection. 8/4/20. Lala A. JACC.
    This is a retrospective analysis of troponin-I levels taken within 24 hours of admission from 2,736 patients admitted to Mount Sinai Health System hospitals between February 27 and April 12. Thirty-six percent of patients showed elevated levels (normal <0.03 ng/ml). After correction for co-morbidities and clinical severity, small elevations were associated with increased morbidity and mortality. Elevations greater than three times normal (>0.09ng/ml) were associated with significantly higher risk. Troponin may be a useful indicator of cardiac involvement and may aid disease stratification.
  • EDITORIAL: Myocardial Injury in COVID-19 Patients: The Beginning or the End? 8/1/20. Uriel N. J Am Coll Cardiol.
    This editorial accompanies the article by Lala et al entitled, “Prevalence and Impact of Myocardial Injury in Patients Hospitalized with COVID-19 Infection,” and suggests pathophysiological pathways of cardiac involvement and underscores the importance of troponin-I elevations as markers of disease severity and outcome. The editorial reinforces the importance of cardiac involvement in COVID-19 disease and suggests troponin elevations could be a useful adjunct in disease stratification.

August 3, 2020:

  • Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases. 7/27/20. Lindner D. JAMA Cardiol.
    Despite reports of fulminant myocarditis in patients with SARS-CoV-2 infection, this study of cardiac tissue from 39 consecutive autopsies of patients who died from confirmed disease demonstrates the presence of the virus in cardiac tissue but does not suggest an inflammatory reaction consistent with clinical myocarditis. The authors suggest further studies and clinical correlations are necessary to determine long-term consequences of SARS-CoV-2-specific myocardial infections.
  • Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). 7/27/20. Puntmann VO. JAMA Cardiol.
    This is a report of 100 cardiac magnetic resonance (CMR) imaging studies on recovered COVID-19 patients compared with 50 healthy age- and sex-matched controls and 50 risk-factor matched, non-COVID-19 patients. Seventy-eight percent of recovered patients had CMR abnormalities, while 60% had findings consistent with ongoing myocardial inflammation independent of preexisting conditions, disease severity and course of acute illness and recovery. Ongoing investigation is needed to determine course and long-term cardiac morbidity of COVID-19.
  • EDITORIAL: Coronavirus Disease 2019 (COVID-19) and the Heart-Is Heart Failure the Next Chapter? 7/27/20. Yancy CW. JAMA Cardiol.
    This editorial raises the question of prevalence of cardiac involvement in COVID-19 disease and its impact on mortality and long-term morbidity. It discusses two relevant manuscripts and raises awareness of an important disease manifestation, the long-term implications of which are unknown and require investigation.
  • Characteristics and Strength of Evidence of COVID-19 Studies Registered on ClinicalTrials.gov. 7/27/20. Pundi K. JAMA Intern Med.
    As an indication of how difficult it is to obtain quality data, this evaluation of 1,551 clinical studies of COVID-19 patients listed on ClinicalTrials.gov up to May 19, 2020 found that only 29.1% were designed in a way that the results could possibly change clinical practice (i.e., be classified as Level 2 evidence by the Oxford Centre for Evidence-Based Medicine level of evidence framework). In the 664 randomized clinical studies included, only 14% included mortality as a primary or composite outcome (arguably the most important research question). The authors state that, “Even before results are known, most studies likely will not yield meaningful scientific evidence at a time when rapid generation of high-quality knowledge is critical.”
  • Emerging pharmacological therapies for ARDS: COVID‑19 and beyond. 7/11/2020. Horie S. Intensive Care Med.
    Members of the Regenerative Medicine Institute of the National University of Ireland authored this exhaustive overview of the current state of promising emerging pharmacological therapies of ARDS in patients with and without COVID-19. The review focuses on ongoing clinical and preclinical trials and uses well-designed tables and diagrams to enhance a complex array of pathophysiological mechanism and therapeutic interventions ranging from immune response modulation, to epithelial and endothelial integrity repair, anticoagulation and COVID-19 specific antiviral and anti-inflammatory therapies.
    A valuable source, aimed at the research community, the authors express hope for identification of subtypes of ARDS and application to allow better targeting of specific therapeutic interventions in the future.
  • NIH Launches Platform to Serve as Depository for COVID-19 Medical Data. 7/29/20. Rubin R. JAMA.
    Though not a research article, the news report, based on an NIH news release, summarizes an NIH effort to store and study medical record data from people across the country who have been diagnosed with coronavirus disease 2019. Certainly, research articles will be published in the future that will be based on this effort. For more information for institutions on how to contribute data, visit https://ncats.nih.gov/n3c/about/program-faq.

July 31, 2020:

  • Age-Related Differences in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Levels in Patients With Mild to Moderate Coronavirus Disease 2019 (COVID-19). 7/30/20. Heald-Sargent T. JAMA Pediatrics.
    Although published only as a letter, the article contains timely data regarding the potential infectivity of children lacking significant symptoms. Nasal viral load as measured by nasopharyngeal swab PCR demonstrated higher levels in young children when compared to adults. At issue is that the study was performed in a pediatric center yet describes adult testing without elaborating how those samples were obtained. Timely article with the start of school approaching.
  • COVID-19 and thrombotic or thromboembolic disease: Implications for prevention, antithrombotic therapy, and follow-up. 6/16/20. Bikdeli B. J Am Coll Cardiol.
    This article is an excellent clinically relevant review of thrombotic complications of COVID-19. Systemic and pulmonary venous and arterial thrombosis and thromboembolism are common in COVID-19. Thrombi are observed in virtually every organ. This is caused by inflammation, platelet activation, hypercoagulability, endothelial dysfunction, constriction of blood vessels, stasis, hypoxia, muscle immobilization, and disseminated intravascular coagulation (DIC).
    Fever and inflammation cause hypercoagulability and impair fibrinolysis. Cytokine interleukin-6 (IL-6) levels correlate with hypercoagulability and disease severity.
    Elevated antiphospholipid antibodies are associated with thrombosis. The liver increases production of procoagulant substances. Prothrombin time and activated partial thromboplastin time are moderately prolonged. Moderate thrombocytopenia is observed. C-reactive protein is elevated. Cytokine storm and excessive systemic inflammation are associated with lymphocytopenia, elevated D-dimer, elevated fibrin degradation products (FDP), and DIC. D-dimer levels and DIC are prognostic.
    Guidelines recommend thromboprophylaxis. Prophylaxis with low-molecular weight or regular heparin, fondaparinux, or a direct oral anticoagulant such as apixaban or rivaroxaban should be considered. Heparins bind tightly to COVID-19 spike proteins impeding the entry of the virus into cells. Heparins also downregulate IL-6 and reduce immune activation. A non-randomized study suggests that among patients requiring mechanical ventilation, systemic anticoagulation may be associated with reduced mortality without increasing major bleeding. However, systemic anticoagulation has not proven to be beneficial in ARDS due to other etiologies. After hospital discharge prolonged prophylaxis may be beneficial.
  • COVID-19 pandemic and the skin: what should dermatologists know? 3/24/20. Darlenski R. Clin Dermatol.
    Skin manifestations of COVID-19 are like those of other viruses and chronic inflammatory diseases like acne, eczema, psoriasis, and rosacea. Vascular problems associated with skin manifestations can be neurogenic, microthrombotic, or immune complex-mediated.
    Of the patients with skin manifestations, a majority have patchy erythematous rash. Some have widespread urticaria or hives. A few also have chickenpox-like fluid-filled vesicles or blisters. They can have measles-like rashes. The most affected area is the trunk. Itching is mild or absent. Some patients have skin eruptions at symptom onset, and others after hospitalization. Lesions usually heal in a few days. Skin manifestations do not correlate with the severity of COVID-19.
    Patients may develop livedo reticularis. It is a purplish net-like discoloration of the skin, often a result of blood clotting abnormalities. Lacy, dusky rashes, including dead skin cells are observed on the arms, legs, and buttocks. They are associated with hypercoagulability. Petechiae are present. Nonpruritic blanching livedoid vascular eruption, possibly due to vaso-occlusion may be present. They appear as mottled, netlike red or pink patches. Also present are chilblains, which are purplish, slightly firm and often tender. COVID toes and fingers have frostbite-like areas with red or purple rash or hive-like eruption.
  • Distinct clinical and immunological features of SARS-COV-2-induced multisystem inflammatory syndrome in children. 7/23/2020. Lee PY. J Clin Invest.
    The authors retrospectively studied 28 confirmed cases of multisystem inflammatory syndrome in children at Boston Children’s Hospital from March to June 2020. Pediatric Multisystem Inflammatory Syndrome that includes classic features of Kawasaki disease, heterogeneous manifestations of systemic inflammation and shock. These children may exhibit heart failure, shock and coronary artery abnormalities, with a disproportionate representation among Blacks and Hispanics. Preexisting risk factors include obesity, asthma and heart disease. Acute respiratory distress syndrome was not a feature, but instead preponderance of cardiac complications including ventricular dysfunction and coronary abnormalities. The degree of inflammation as measured by CRP and procalcitonin is much greater in these children compared to those patients with COVID-19 pneumonia. Rapid diagnosis, multidisciplinary management and suppression of systemic inflammation was associated with a favorable outcome.
  • Genomewide association study of severe Covid-19 with respiratory failure. 6/17/20. Ellinghaus D. N Engl J Med.
    Genetic differences may in part explain the difference in response of different persons to SARS-CoV-2. They compared hospitalized patients with respiratory failure with controls. They studied 835 patients and 1255 controls from Italy and 775 patients and 950 controls from Spain.
    They found 3p21.31 gene cluster is a genetic susceptibility locus. Patients with blood group A were found to be at a higher risk of infection (odds ratio, 1.45) and develop more severe symptoms. Patients with blood type O were found to be at a lower risk of infection (odds ratio, 0.65). Although the results are statistically significant, the effect size is small. Results on the association with blood group has been reviewed by the SAB in several articles previously.
  • Prevalence of Gastrointestinal Symptoms and Fecal Viral Shedding in Patients With Coronavirus Disease 2019: A Systematic Review and Meta-analysis. 6/11/20. Parasa S. JAMA.
    Gastrointestinal (GI) symptoms of COVID-19 include loss of appetite, nausea, vomiting, diarrhea, and abdominal discomfort. These symptoms might start before or occur with or without other symptoms such as fever, myalgias, and cough. Lower gastrointestinal tract is rich in ACE2 receptors.
    About 40% of the patients’ stool tests positive for SARS-CoV-2 RNA. This is primarily due to RNA fragments of the virus. One study showed live virus on electron microscopy in a small percentage of patients. These patients’ stools are infectious. Patients who have virus in the stool take longer to clear it. Although a small percentage of patients have GI symptoms, up to one-half shed virus in the stool. Virus protein shell is also found in gastric, duodenal, and rectal cells.
    More than one-half of COVID-19 hospitalized patients have elevated lactate dehydrogenase and other liver enzymes indicating injury to the liver or bile ducts. This is likely to be due to an overactive immune system or due to drugs causing liver damage.
  • Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. 5/15/20. Grifoni A. Cell.
    To be effective, a COVID-19 vaccine has to elicit strong T cell immunity. Vaccines stimulate B cells to make antibodies against the virus. Helper T cells promote this. Those antibodies join with the virus, preventing it from entering a host cell and mark the virus for destruction. Once the virus infiltrates the host cell, antibodies are not effective. However, cytotoxic T cells can destroy infected host cells.
    T cell immunity does not prevent re-infection but reduces the severity of symptoms. Among patients recovered from COVID-19, CD4+ T cells were observed in all and CD8+ T cells were observed in about 70%. CD4+ responses to spike antigen correlated with IgG and IgA antibody titers. Each of M, spike, and N antigens accounted for 11%–27% of the total CD4+ response. The remaining responses were against other SARS-CoV-2 antigens. This suggests that vaccines that target multiple antigens may be more effective than the ones targeting only the spike antigen.
    T cell immunity is observed in persons infected and in about one-half of persons uninfected with SARS-CoV-2. The latter may have been previously infected with a virus such as one of the four human coronaviruses that cause colds. Thus, there is cross reactivity with other corona viruses. This may be a reason for variability in severity of clinical illness after infection.
    Many of the vaccine candidates lead to production of the spike protein and antibodies against it. If the vaccine does not produce the spike protein with correct confirmation, the generated antibodies may be binding but not neutralizing antibodies. This can promote viral replication or form complexes that trigger more inflammation. Memory B and T cells that recognize the virus can provide protective immunity for years although the antibody titers may decline within months. Efforts are being made to genetically modify certain immune cells to target the virus.

July 29, 2020:

  • Characterization of experimental and clinical bioaerosol generation during potential aerosol-generating procedures. 7/15/20. Doggett N. Chest.
    This prospective study from Toronto quantified aerosol production pre and post two presumed aerosol generating procedures (AGPs); intubations in pigs (n=16) and elective bronchoscopies in human adults (n=39). Though overall, there was a significant reduction in larger particle aerosols during the procedures, and no significant increase in small particle aerosolization during the procedures, some bronchoscopies did produce significantly increased small particle aerosols. The authors conclude that the variability of aerosol generation reinforces the need for PPE during AGPs, and that more research is needed, especially in the more uncontrolled environments typical of a COVID-19 surge.
  • Considering the potential for an increase in chronic pain after the COVID-19 pandemic. 7/24/20. Clauw DJ. Pain.
    An International panel reviews the underlying factors likely to lead to or exacerbate chronic pain in individuals during a pandemic whether or not an infection actually takes place. Addressing both chronic pain management professionals and acute care providers, this synopsis reminds us of post-SARS syndrome and urges us to prepare for post-COVID-symptomatology which includes chronic debilitating illnesses, like chronic fatigue, irritable bowel syndrome and interstitial cystitis and other conditions marked by a chronic pain experience. Registries, awareness and multidisciplinary teams will be required to deal with this likely scenario.
  • Remdesivir for Severe COVID-19 versus a Cohort Receiving Standard of Care. 7/25/20. Olender SA. Clin Infect Dis.
    Pharma-sponsored proof of benefit of remdesivir in patients with severe COVID-19 is demonstrated by comparing patients’ clinical status on day 14 during two parallel studies. One is an international, 16-site retrospective cohort study of clinical outcomes in 800+ patients receiving standard-of-care treatment for severe COVID-19 infection; the other is an international, 45-center, phase 3, randomized, open-label trial comparing two courses of remdesivir in 312 patients. Remdesivir was associated with significantly greater recovery (74 vs 59%) and 62% reduced odds of death versus standard-of-care treatment. 
  • Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System. 7/20/20. Bilaloglu S. JAMA.
    This research letter reports retrospective data analysis from 3,334 consecutive hospitalized COVID-19 patients from four NYC hospitals. “Most” received low-dose thromboprophylaxis. Sixteen percent experienced thrombotic events defined as DVT, PE, MI, or CVA (no screening). ICU patients: 13.6% venous, 18.6% arterial. Ward points: 3.6% VTE, and 8.4% arterial. Mortality with event was 43% vs. 21% without. Age, male sex, Hispanic ethnicity, CAD, prior MI, and higher D-dimer at hospital presentation were associated with a thrombotic event, but not BMI or current smoking Hx.

July 27, 2020:

  • A proposal for staging COVID-19 coagulopathy. 7/21/20. Thachil J. Res Pract Thromb Haemost.
    Authors from three continents propose a framework within which to stage COVID-19 associated hemostatic abnormalities, and potentially guide treatment. A theory that infected lung epithelium acts as the epicenter of coagulation with early stages that are difficult to diagnose is described, along with a 3-stage disease model. Currently there are no reliable markers to guide treatment; however patterns and questions for researchers are outlined. A table outlines 11 current international clinical trials on approaches to coagulopathy and are listed on clinicaltrials.gov.
  • Design for Implementation of a System-Level ICU Pandemic Surge Staffing Plan. 7/23/20. Thakur N. Crit Care Explor.
    Authors provide a comprehensive description of the design, dissemination, and implementation of an algorithm for multidisciplinary critical care staffing during surge demand, as implemented by a 40-hospital multi-state healthcare system. Staff is tiered according to skills and experience with team leadership roles for the most appropriate. On-site and telemedicine supervision are employed to optimally leverage oversight and scaling of patient loads. The plan provides for doubling of 750 ICU beds out of a total 5,500 beds. Consistent terminology and role-definition facilitate redeployment and allocation of human resources to meet changing local needs across diverse hospitals.
  • Inflammation Profiling of Critically Ill Coronavirus Disease 2019 Patients. 7/23/2020. Fraser DD. Crit Care Explor.
    Report of a study comparing inflammatory profiling using multiple immunoassays between COVID-19 positive and negative ICU patients and a matched series of normal controls identifying a unique combination of six analytes distinguishing COVID-19 disease. Reported analytes were: tumor necrosis factor; granzyme B; heat shock protein 70; interleukin-18; interferon-gamma-inducible protein 10; and elastase 2.
    Discussion notes COVID-19 patients demonstrate findings consistent with systemic inflammation including increased circulating cytokine levels and lymphopenia potentially characterizing the “purported” cytokine storm frequently mentioned.
    Authors conclude: “In summary, we report sustained elevations in a unique combination of inflammatory analytes in COVID-19+ ICU patients. Our exploratory data are consistent with the slow, or absent improvement in COVID-19+ patients despite state-of-the-art ICU care, and could aid future hypothesis-driven research using larger ICU cohorts.”
  • Pulmonary embolism in hospitalised patients with COVID-19. 7/10/20. Whyte MB. Thromb Res.
    A single center retrospective review of the results of 214 computer tomography pulmonary angiography studies performed on hospitalized Covid-19 patients with suspected pulmonary emboli. 31% of studies were positive for pulmonary emboli which represents 5.4% of all patients admitted during the study’s time interval. Elevated Wells score greater or equal to 4 did not predict results. Median D-dimer was 8000 ng/ml for patients with a positive study versus 2060 ng/ml for patients with a negative study, but low D-dimer had limited utility excluding patients with pulmonary emboli.
  • Pulmonary immune responses against SARS-CoV-2 infection: harmful or not? 7/19/20. Guillon A. Intensive Care Med.
    A brief, well written review of the literature on COVID-19 immune responses claiming that the critical processes occur primarily in the lung and that the immune injury phase of the disease is not well described as a generalized “cytokine storm.” A T-cell subpopulation called innate T-cells appears to be diminished and have impaired function in peripheral blood but is found in increased numbers and activation in the airways of these patients.
  • Review of Viral Testing (Polymerase Chain Reaction) and Antibody/Serology Testing for Severe Acute Respiratory Syndrome-Coronavirus-2 for the Intensivist. 7/23/20. Motley MP. Crit Care Explor.
    A nice review of nucleic acid amplification technology (PCR) and serological assays to diagnose, treat, and limit the spread of SARS-Cov-2 and it includes a discussion of the strengths and limitations of individual assays.
  • Strategies to Optimize ICU Liberation (A to F) Bundle Performance in Critically Ill Adults With Coronavirus Disease 2019. 7/23/20. Devlin JW. Crit Care Explor.
    Click here to take this CME activity.

    Multi-institutional panel reviews option to modify and apply the ICU Liberation Bundle to COVID-19 scenarios in the ICU. They strongly recommend applying the Bundle to effectively deal with pain, agitation and delirium wherever possible and offer a number of valuable suggestions, among those dealing with lack of resources, like PPE and utilizing non-critical care trained clinicians. 

July 24, 2020:

  • Blood type and outcomes in patients with COVID-19. 7/12/2020. Latz C. Ann Hematol.
    Retrospective study of 1289 SARS-CoV-2 + patients /7648 tested patients w/ known ABO blood type. No blood group had an increased or decreased risk of severe disease, inflammatory markers, intubation, or death.  Type A had the expected risk of +PCR, type A, type O had a lower risk and types B and AB and Rh+ patients had a higher risk.  These results contrast w/ previous reports, however data are not fully comparable.
  • COVID-19 and the kidney: what we think we know so far and what we don’t. 7/22/20. Farouk SS. J Nephrol.
    Review by the SAB
    These authors are troubled by existing data related to true incidence, etiopathology, and its management with Covid-19. A heterogeneous report, with respect to population size, location, severity of illness, and definitions of acute kidney injury (AKI), show a wide range of rates of AKI occurrence in patients, from 1-46% and an equally wide percentage range of patients who were treated with kidney replacement therapy (KRT) (10-35%). Most patients with KRT were in the ICU (data was from the UK, Ireland, Italy, China, and the USA) and it has overwhelmed the nephrology services the world over. Potential explanations for these differences include the prevalence of co-morbid conditions and heterogeneity along racial and ethnic lines, local institutional policies about KRT timing, the use of extracorporeal KRT beyond classical “nephrological” indications. Using AKI as defined by “the 2019 Kidney Diseases: Improving Global Outcomes Consensus Conference” may standardize the whole process (a work in progress?). Mode of injury is also noted to be multifactorial. Though the link between AKI and poor outcomes is clear, prevalence and outcomes of COVID-19 in patients with chronic kidney disease and end-stage kidney disease has not yet been reported. In patients on immunosuppression like those with kidney transplants or glomerular disease, COVID-19 has presented a management dilemma.
  • Nutrition of the COVID-19 patient in the intensive care unit (ICU): a practical guidance. 7/19/20. Thibault R. Crit Care.
    Review by the SAB
    By Dr. Heinrich Wurm, on behalf of the SAB
    French authors propose a flow chart and identify ten key issues for optimizing the nutrition management of COVID-19 patients in the ICU. Prominent among those is a preference for enteral nutrition whenever possible, attention to avoid the refeeding syndrome and awareness of the propofol infusion syndrome. Existing guidelines like GLIM* are valuable and their application encouraged. The use and limitations of indirect calorimetry during Covid-19 is discussed.
    * Global Leadership Initiative on Malnutrition
  • Personalized Ventilation to Multiple Patients Using a Single Ventilator: Description and Proof of Concept. 7/17/20. Han JS. Crit Care Explor.
    A proof of concept: the authors used components readily available in their hospital to assemble two “bag-in-a-box” breathing circuits. This shared ventilator function is proposed as a “last ditch” ventilatory assist device and not as a preferred ventilation mode. In a time of crisis where resources are limited, they introduced a system of multiple secondary breathing circuits driven by a ventilator in preference to that of simply splitting the breathing circuits. The authors hope, though, that this will not be needed. But these were all test conditions, not actually used on a patient.
  • Prospective study in 355 patients with suspected COVID-19 infection. Value of cough, subjective hyposmia, and hypogeusia. 7/21/20. Martin-Sanz E. Laryngoscope.
    Click here to take this CME activity.

    Review by the SAB
    By Dr. Lance Lichtor, on behalf of the SAB
    Of 355 patients who were healthcare personnel, there was a significant association between positive PCR and subjective hyposmia. If cough was added, the odds of having a positive RT-PCR increased significantly. The measurement of fever as the only method for screening of COVID-19 infection resulted in a poor association. 

  • The role of chest radiography in confirming Covid-19 pneumonia. 7/18/2020. Cleverley J. BMJ.
    An introductory summary of chest X-ray findings in COVID-19 pneumonia for the non-radiologist. Characteristic findings are illustrated however none is diagnostic. Studies show that X-ray imaging may initially appear normal or lag behind disease progression. Chest CT has been shown to be more sensitive however its initial use varies among countries. Includes no mention of chest ultrasound.
  • The Structural and Social Determinants of the Racial/Ethnic Disparities in the U.S. COVID-19 Pandemic: What’s Our Role? 7/17/20. Thakur N. Am J Respir Crit Care Med.
    A call to arms for critical care and pulmonary specialists: black, Latinx, and Native Americans test positive for and die from coronavirus at higher proportion than other racial and ethnic groups. Their mortality rates far exceed the proportion of the population that these groups represent. Historically disadvantaged communities have reduced capacity to adopt preventive measures. Minority communities with low socioeconomic status (SES) and/or limited English proficiency receive less public communication during crisis and pandemics; access to testing and care is greatly limited in low-SES and minority communities. This article advocates for under-represented minority patients, who are becoming critically ill and dying at disproportionate rates.

July 22, 2020:

  • Association Between Universal Masking in a Health Care System and SARS-CoV-2 Positivity Among Health Care Workers. 7/14/20. Wang X. JAMA.
    This research letter from the Mass General Brigham healthcare system reports an association between the requirement for universal masking for their healthcare workers and a reduction in their percent positive COVID-19 PCR test results during a period of time when the disease continued to increase in the general population. The decrease in healthcare worker infections could have been confounded by other interventions inside and outside of the health care system, such as restrictions on elective procedures, social distancing measures, and increased masking in public spaces. However, the authors contend these results support universal masking as part of a multi-pronged infection reduction strategy in healthcare settings.
  • Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report. 7/17/20. The RECOVERY Collaborative Group. N Engl J Med.
    Click here to take this CME activity.

    Review by the SAB
    These authors (Nuffield /Oxford) provide preliminary results (recruitment ended on June 8) of the controlled, open-label-randomized evaluation of COVID-19 Therapy (RECOVERY) trial of dexamethasone in patients hospitalized with COVID-19. The primary outcome was mortality within 28 days after randomization.
    In patients hospitalized with COVID-19, the use of dexamethasone (6mg either IV or PO up to 10 days) resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support (may harm). In a 2:1 randomization, 2,104 patients received dexamethasone and 4,321 received the usual care. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82). There was a trend showing the greatest absolute and proportional benefit among patients who were receiving invasive mechanical ventilation (11.5 by chi square test for trend). Patients in the dexamethasone group had a shorter duration of hospitalization than those in the usual care group (median, 12 days vs. 13 days) and a greater probability of discharge alive within 28 days (rate ratio, 1.10; 95%). It is likely that the beneficial effect of glucocorticoids in severe viral respiratory infections is dependent on a selection of the right dose, at the right time, in the right patient. Viral replication peaks in the second week of illness in SARS, while viral shedding in SARS-CoV-2 appears to be higher early in the illness and declines, thereafter when dexamethasone is most effective. At that stage, the disease may be dominated by immunopathological elements, with active viral replication playing a secondary role. 

  • Excess Deaths From COVID-19 and Other Causes, March-April 2020. 7/1/20. Woolf, SH. JAMA.
    The initial symptomatology, prodromal infective potential, anticipated course/severity, value of PPE and myriad additional variables were unknown when COVID-19 began its international journey. Early optimism in terms of containing and controlling the virus rapidly deteriorated as disease progression was recognized, the ability of asymptomatic carriers were known to be highly infectious and the initially unexpected benefit of universal face mask adoption created uncertainly about not only the viral spread but also the safety and reliability of the health system. Death is usually categorized accurately and reliable “death rate” statistics have been accumulated; the authors use seasonally adjusted U.S. death rates from December 29, 2013 to February 29, 2020 and compare historical to actual death rates reported between March 1, 2020 and April 2020 and include a secondary analysis in the five states most severely affected by the virus during the collection period. Careful data analysis was used to determine all-cause mortality and how COVID-19 influenced the total. The results attribute 65% of excess deaths to COVID-19-related causes and suggest that the total number is likely higher. Analysis was able to distinguish significant increases in other diseases during the period.
    Also included is an insightful discussion underscoring importance of accurate determination of COVID-19’s true impact on not only death but also on hidden morbidity (including COVID-19 delayed treatment and/or resource constraints) which is still being elaborated.
  • EDITORIAL: Mortality and Morbidity: The Measure of a Pandemic. 7/1/20. Zylke JW. JAMA.
    This editorial accompanying “Excess Deaths” further elaborates on the importance of, and difficulties associated with, estimating impact of COVID-19 on health systems and society. Peripheral effects are included and discussed. Together, the articles underscore the importance of classification and clarification in estimating disease impact, prevalence and spread in vulnerable populations and on society at large.
  • Hospitalization and Mortality among Black Patients and White Patients with Covid-19. 6/25/20. Price-Haywood EG. N Engl J Med.
    Review by the SAB
    By Heinrich Wurm, on behalf of the SAB
    This retrospective cohort study takes a critical look at incidence, mortality and concomitant risk factors among black and white non-Hispanic members of the Ochsner integrated delivery health system.
    Black patients far exceeded white non-Hispanics in getting infected (70 vs. 30% of enrolled patients were PCR positive), requiring hospital admission (77%) and dying (71%). But black race was not independently associated with a higher mortality (HR death vs. white race 0.89; 95 CI, 0.68-1.17) when adjustments for differences in socio-demographic and clinical characteristics were made.
    Blacks had a greater prevalence of underlying disease (obesity, diabetes, hypertension, chronic kidney disease), presented with higher levels of inflammatory markers, elevated creatinine and were more likely to live in low-income areas and receive public insurance. Greater occupational exposure in service industries and higher incidence of morbid obesity and chronic kidney disease were also discussed.
  • Impact of delays on effectiveness of contact tracing strategies for COVID-19: a modelling study. 7/16/20. Kretzschmar ME. Lancet Public Health.
    Review by the SAB
    By Dr. Lance Lichtor, on behalf of the SAB
    The authors used a mathematical model that describes the different steps of a symptomatic contact tracing strategy for COVID-19. They found reducing the testing delay (i.e., shortening the time between symptom onset and a positive test result, assuming immediate isolation) is the most important factor for improving contact tracing effectiveness. Reducing the tracing delay (i.e., shortening the time to trace contacts, assuming immediate testing and isolation if found positive) might further enhance contact tracing effectiveness, though this additional effect rapidly declines with increasing testing delay.
  • Neurobiology of COVID-19. 6/30/20. Fotuhi H. J Alzheimer’s Dis.
    Review by the SAB
    By Heinrich Wurm, on behalf of the SAB
    This review by a panel of U.S. experts goes beyond analyzing neurological manifestations of COVID-19 and provides us with plausible and well-illustrated pathophysiological theories and a 3-stage evolution of a condition termed Neuro-COVID. A synopsis of worrisome post-COVID-19 neurological sequelae, ranging from poor memory and slow processing speed to lasting depression, Parkinson’s, multiple sclerosis and Alzheimer’s, concludes this remarkable publication and points us towards a future of COVID-related sequelae.
  • Outcomes from intensive care in patients with COVID‐19: a systematic review and meta‐analysis of observational studies. 6/30/20. Armstrong B. Anaesthesia.
    Fascinating meta-analysis of 10,150 adult patients in 24 studies (enrollment was December 16, 2019 until May 28, 2020) from 11 countries with ICNARC (UK) database (national, rapidly updated registry) accounted for most cases in the study (results were unchanged when removed) with ICU death as primary endpoint. Mortality trended down from ~50% to 41.6% over time with confirmed by meta regression analysis by publication date indicating decreasing mortality. Discussion includes possibility of increasing sophistication of care outside ICU and despite likely increasing severity of ICU patients, therapeutic sophistication improvement was likely responsible for better outcome.
    Excellent analysis with interesting discussion and conclusions emphasizing need for better national data reporting in real time to better follow disease progression and resource utilization.
  • Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. 7/6/20. Pollan M. Lancet.
    Review by the SAB
    By Dr. Robert Coffey, on behalf of the SAB
    This article reports the results of antibody testing of 61,000 individuals across Spain, from April 27 to May 11, showing an overall national seropositive rate of only 5% (the majority of new diagnoses in Spain’s severe epidemic were made by May 1). Regions that experienced a more intense epidemic such as Madrid did have a seropositive rate of greater than 10%. Approximately one-third of the seropositive subjects reported having had no symptoms suggestive of COVID-19 infection. While specific locales such as Bergamo, Italy and some neighborhoods in Queens, NY may have seropositive rates high enough to confer local herd immunity, this does not seem to be occurring at a national level after severe epidemic episodes.
  • Race, Postoperative Complications, and Death in Apparently Healthy Children. 7/1/20. Nafiu OO. Pediatrics.
    In a retrospective article of over 170,000 healthy children with care provided by anesthesiologists, African American children suffered more postsurgical complications, especially bleeding and death.
  • Redefining cardiac biomarkers in predicting mortality of inpatients with COVID-19. 7/17/2020. Qin JJ. Hypertension.
    Detailed, retrospective analysis of available cardiac biomarkers of 3219 patients admitted to 9 hospitals in Hubei province between December 31st, 2019 and March 4th, 2020. Entry criteria included patients from 18 to 75 years old with documented COVID-19 on admission (RT-PCR and/or Chest CT) and high sensitivity cardiac troponin (hs-cTnI) or CKMB on admission with primary endpoint 28-day mortality. Statistical processing includes additional biomarker profiles, primary and secondary cardiac effects and analysis suggesting that in COVID-19 need to redefine reference range for Upper Limit of Normal to understand impact of cardiac effects.
    The authors conclude “the abnormal cardiac biomarker pattern in COVID-19 patients was significantly associated with increased mortality risk, and the newly established COVID-19 prognostic cutoff values of hs-cTnI, CK-MB, (NT-pro)BNP, CK, and MYO were found to be much lower (~50%) than reference upper normal limits for the general population.” Valuable information that needs to be confirmed in different populations.

July 21, 2020:

July 20, 2020:

  • CPR in the COVID-19 Era – An Ethical Framework. 7/9/20. Kramer DB. N Engl J Med.
    Review by the SAB
    By David Clement, on behalf of the SAB
    This opinion paper provides important reading on the ethics of how the surge of patients with COVID-19 complicate standard CPR practices. An ethical framework of three crisis standards is proposed: acknowledge resource limitations, forgo CPR in certain circumstances, and impose selective constraints on CPR to ensure the safety of healthcare personnel. Hospitals need to develop such explicit crisis standards for CPR to help clinicians and the public understand when strict adherence to established resuscitation protocols may no longer be appropriate.
  • Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. 7/15/20. Mathew D. Science.
    Review by the SAB
    By Dr. Uday Jain, on behalf of the SAB
    Previously uncharted role of lymphocytes in COVID-19 is discussed. A wide variability in immune response was observed among hospitalized COVID-19 patients. Responses were barely detectable in about one-fifth of the patients. This was associated with pathology due to the virus and reduced survival. Remaining patients had CD8 and/or CD4 T lymphocyte and plasmablast responses that were heterogeneous among the patients and were divided into immunotypes. In many patients who became seriously ill with Covid-19, helper and killer cells do not work well cooperatively. An overabundance of helper cells is proinflammatory. An overabundance of killer T cells is not ideal but consistent with survival.
  • Individualizing Risk Prediction for Positive COVID-19 Testing: Results from 11,672 Patients. 6/20/20. Jehi L. Chest.
    Review by the SAB
    By Dr. Lance Lichtor, on behalf of the SAB
    The authors of this article developed an online risk calculator that can identify individualized risk of a positive COVID-19 test. All patients from Cleveland Clinic in Ohio and Florida were tested, not just those who had the disease. Findings included: lower risk for Asians vs whites; lower risk for those who had pneumococcal polysaccharide vaccine and flu vaccine; higher risk with poor socioeconomic status; and reduced risk of testing positive in patients who were on melatonin, carvedilol, and paroxetine.
  • Protecting healthcare workers from SARS-CoV-2 infection: practical indications. 4/3/20. Ferioli M. Eur Respir Rev.
    Review by the SAB
    By Dr. Jay Przybylo, on behalf of the SAB
    A “how to” based on oxygen therapy and dispersed exhaled breath. The importance of the article concerns exhaled breaths dispersion which depends on the mode of oxygen therapy. The remainder of the article is not scientifically based.
  • SARS-CoV-2 infection protects against rechallenge in rhesus macaques. 5/20/20. Chandrashekar A. Science.
    Review by the SAB
    By Dr. Uday Jain, on behalf of the SAB
    Nine adult rhesus macaques infected with SARS-CoV-2 developed humoral and cellular immune responses leading to protective immunity. On re-challenge by SARS-CoV-2, there was a major attenuation of viral load in nasal mucosa and bronchoalveolar lavage in all of them. As the virus was still detectable, the protection was not sterilizing and the macaques could infect others. These results in primates suggest that patients who have COVID-19 may develop immunity to it. This is also essential for the development of a vaccine and determination of herd immunity.
  • The Impact of Coronavirus Disease 2019 Pandemic on U.S. and Canadian PICUs. 7/8/20. Sachdeva R. Pediatr Crit Care Med.
    Review by the SAB
    By Dr. Philip Lumb, on behalf of the SAB
    This report is from a large pediatric ICU registry (Virtual Pediatric Systems, Los Angeles, CA), with data from over 200 hospital units and >1.5 million patient admissions. In order to determine the manner in which COVID-19 was affecting PICU’s, VPS expanded data collection related to COVID-19 to all Canadian and US PICU’s regardless of prior VPS membership to provide a near real-time dashboard including admissions, patient demographics and comorbidities, therapeutic interventions, deaths and length of stay. Data collection, from March 4 to May 20, represented 3,228 bed capacity comprising most US and Canadian resources from major teaching institutions to smaller hospitals with multifunctional PICU’s. At the peak of the admissions in late April, ~40% of admissions >18yo and ~12% >30yo indicating unusual age disparity than normally seen and providing insight into future PICU adjustments. Detailed description of analysis and future research directions are provided, demonstrating the value of high reliability registry with capability to provide rapid resource allocation and patient demographic, therapeutic and outcome information.
  • Therapeutic Plasma Exchange: A potential Management Strategy for Critically Ill COVID-19 Patients. 7/16/20. Tabibi S. J Intensive Care Med.
    Review by the SAB
    By Dr. Lydia Cassorla, on behalf of the SAB
    This report briefly discusses various approaches currently being investigated to treat SARS-CoV-2 with a focus on potential benefits of therapeutic plasma exchange (TPE). TPE may alleviate the need for polypharmacy to combat various cytokines along with their associated side effects and necessary adjustments for comorbidities. TPE has been used to treat H1N1-associated ARDS, myasthenia gravis, Kawasaki disease, early septic shock, and various multi-organ dysfunction syndrome phenotypes including thrombocytopenia purpura. Reports of its use to treat severe COVID-19 are reviewed. TPE appears generally safe. Concerns involve blood supply, availability, and potentially cost. A proposed set of criteria that overlap with those for convalescent plasma and Spectra Optia Apheresis System is outlined, including early ARDS, severe disease, and life-threatening disease. Clinical trials are underway.

July 17, 2020:

  • ABO Phenotype and Death in Critically Ill Patients with COVID-19. 7/1/20. Leaf RK. Br J Haematol.
    Review by the SAB
    By Lydia Cassorla, on behalf of the SAB
    In this Letter to the Editor, ABO blood type data from adults admitted to ICUs over 38 days in the 67-center Study of the Treatment and Outcomes in critically ill Patients from COVID-19 (STOP-COVID) study were analyzed. Patients were followed until hospital discharge, death, or May 8, 2020 – a date that included a minimum of 28 days follow-up for those still hospitalized. 2033/3239 (62.8%) had ABO data available. 799/2033 (39.3%) died within 28 days. Death rates were similar across ABO phenotypes in all race/ethnicity categories, as well as Rh status. Among White patients, the observed distribution of ABO phenotypes differed from expected, primarily due to blood type A being over-represented (45.1% observed vs. 39.8% expected) and blood type O being under-represented (37.8% observed versus 45.2% expected). Among Black and Hispanic patients the observed and expected distributions of ABO phenotypes were similar.
  • An mRNA Vaccine against SARS-CoV-2 – Preliminary Report. 7/14/20. Jackson LA. N Engl J Med.
    EDITORIAL: The Covid-19 Vaccine-Development Multiverse. 7/14/20. Heaton PM. Cardiovasc Res.
    Review by the SAB
    By Dr. David Clement, on behalf of the SAB
    This paper and the associated editorial report the Phase 1 trial of a SARS-CoV-2 vaccine developed by the National Institute of Allergy and Infectious Disease and the private company, Moderna. In a dose escalation, 2 injection trial in 45 adults using a spike RNA viral antigen, the vaccine induced anti-SARS-CoV-2 immune responses in all participants, similar to the immune responses of recovered COVID-19 patients. Adverse events were common, but none were serious.
    The accompanying editorial gives an overview of traditional vaccine development, how the current efforts have accelerated this usual process, and describes hurdles yet to be overcome.
  • COVID-19 Disease Severity Risk Factors for Pediatric Patients in Italy. 7/16/20. Bellino S. Pediatrics.
    Click here to take this CME activity.

    Review by the SAB
    By Dr. Jay Pryzbylo, on behalf of the SAB
    This large pediatric study demonstrates that infection by COVID-19 increases with age (severe illness in the youngest) is uncommon in the pediatric age group with only 1.8% of total infections over all ages. The study reported only 4 deaths, all in children with complex underlying medical issues.

  • Covid-19: What do we know about “long covid”? 7/14/20. Mahase E. BMJ.
    Review by the SAB
    By Dr. Barry Perlman, on behalf of the SAB
    This non-peer reviewed article discusses “Long COVID,” a term used for lasting effects after recovering from COVID-19 infection or symptoms that persist longer than expected.
    Ongoing health problems may include “breathing difficulties, enduring tiredness, reduced muscle function, impaired ability to perform vital everyday tasks, and mental health problems such as post-traumatic stress disorder, anxiety, and depression.”
    HNS England will be launching an online portal for those with long-term effects of COVID-19 to communicate with nurses, physiotherapists, and mental health specialists.
    A Facebook “long Covid Support group” has >7000 members, and the hashtag “longcovid” enables personal experiences to be shared on social media.
    Research on the long-term effects of COVID-19 infection is needed. The Post-hospitalization COVID-19 Study plans to follow 10,000 UK patients for a year, but it will not include milder cases that didn’t require hospital care.
  • Neurological manifestations of COVID-19: a systematic review. 7/15/20. Nepal G. Crit Care.
    Review by the SAB
    By Dr. Heinrich Wurm, on behalf of the SAB
    This well-organized review of the world literature up to May 20, 2020 analyses 37 articles, many of them case reports. The authors critically review each neurological symptom or disease entity currently known to exist with the intent to provide practitioners with an overview of a host of manifestations ranging from mild headaches to taste and smell disorders to strokes, hemorrhage and central and peripheral nervous system inflammatory reactions like encephalo-myelits and Guillain-Barré syndrome.
  • Palliative care for patients with severe covid-19. 7/14/20. Ting R. BMJ.
    Review by the SAB
    By Dr. Lance Lichtor, on behalf of the SAB
    We usually think about a cure, but not everyone can be saved. This is a good article about managing patients with distressing symptoms, explaining the importance of having a strategy to manage patient deterioration and death, and stressing the importance of communication with the family with the sensitivity of noting that their loved one may soon die.
  • Relationship between ABO blood group distribution and clinical characteristics in patients with COVID-19. 6/21/20. Wu Y. Clin Chim Acta.
    Review by the SAB
    By Lydia Cassorla, on behalf of the SAB
    Retrospective case controlled study of Wuhan patients admitted to a single Chinese hospital 1/20/20 – 3/5/20. 187 study patients were admitted with COVID-19 while 1991 control patients were COVID negative individuals admitted during the same time period. The proportion of patients with type A blood in the COVID-19 group was significantly higher than that in the control group (36.90% vs. 27.47%, P = 0.006), while the proportion of patients with type O blood in the COVID-19 group was significantly lower than that in the control group (21.92% vs. 30.19%, P = 0.018). Blood group A patients had a higher risk of COVID-19 than non-A blood group patients. (OR = 1.544, 95% CI = 1.122–2.104, P = 0.006). Blood group O patients had a lower risk of COVID-19 than non-O blood group patients (OR = 0.649, 95% CI = 0.457–0.927, P = 0.018).

July 15, 2020:

  • Clinical Implications of SARS-CoV-2 Infection in the Viable Preterm Period. 7/3/20. Gulersen M. Am J Perinatol.
    Review by the SAB
    The authors in this article conducted a retrospective, logistic regression analysis for preterm birth (PTB) from boroughs in New York of patients diagnosed with COVID-19 infection with pregnancy between 23 and 37 weeks of gestation during March and April of 2020. PTB was noted to be in two groups: 23 to 33 weeks (n = 7/36) and the other one was 34+ (n = 18/29) with p= 0.0001. Most women with COVID-19 infection in the early preterm period recovered and were discharged home. The majority of PTB were indicated and not due to spontaneous preterm labor. Delivery during the current admission was noted as statistically significant for the group of patients with 34+ weeks. No correlation was noted with severity of the COVID-19 disease grade or treatment regimes (antibiotics and antimalarial) but no interleukins or steroids were given to the late group. Gestational age at diagnosis of COVID-19 infection had an odds ratio of 2.9.
  • Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis. 7/11/20. Lecronier M. Crit Care.
    Review by the SAB
    By Dr. Lance Lichtor, on behalf of the SAB
    In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to patients who received standard of care only on the proportion of patients who needed treatment escalation at day 28.
  • Differential Ventilation Using Flow Control Valves as a Potential Bridge to Full Ventilatory Support during the COVID-19 Crisis: From Bench to Bedside. 7/2/20. Levin MA. Anesthesiology.
    Review by the SAB
    By Dr. Lance Lichtor, on behalf of the SAB
    Proof of concept: single ventilator with split circuit. The author could increase one patient’s minute ventilation without affecting the other patient. Effective use for a crisis situation. The authors used custom-designed and manufactured flow control valves.
  • Factors affecting stability and infectivity of SARS-CoV-2. 7/6/20. Chan KH. J Hosp Infect.
    Review by the SAB
    Authors from a Chinese laboratory report the results of several (virus strain line, temperature, tissue infectivity dose, humidity, pH, etc.) experiments for the COVID-19 virus and its survival under different environmental situations. COVID-19 was able to retain viability for 3-5 days in dried form or 7 days in solution at room temperature, could be detected under a wide range of pH (2-13) conditions for several days and also 1-2 days in stool at room temperature but lost 5 logs infectivity. Common fixatives, nucleic acid extraction methods, and heat inactivation were found to significantly reduce viral infectivity. That will likely ensure hospital and laboratory safety during the COVID-19 pandemic but transmission related to food handlers and workers in meat and poultry processing facilities is possible. The presence of the virus on high-risk hospital surfaces should lead to concern about cleaning on other surfaces. It is estimated that 18% of infections are asymptomatic. With its propensity to cause milder infections, COVID-19 spreads more efficiently in communities in the absence of rigorous social distancing and environmental cleaning measures.
  • Is clinical effectiveness in the eye of the beholder during the COVID-19 pandemic? 7/9/20. Sandoval JL. BMJ Evid Based Med.
    Review by the SAB
    By Dr. Philip Lumb, on behalf of the SAB
    Editorial noting the importance of maintaining clinical practice based on sound scientific evidence despite the current data overload from multiple poorly controlled or prematurely reported studies. Notes the importance of scientific balance in the media influenced public response to frequently incomplete, unsubstantiated, or erroneous data.
  • Risk factors for myocardial injury and death in patients with COVID-19: insights from a cohort study with chest computed tomography. 7/8/20. Ferrante G. Cardiovasc Res.
    Review by the SAB
    By Dr. Philip Lumb, on behalf of the SAB
    Interesting study reporting admission CT Scan results on 332 consecutive patients with documented COVID-19 disease. Of these, 123 had myocardial injury defined as high-sensitivity troponin I above 20 ng/ml. Included patients had a median follow up of 12 days with 20.5% (68) deaths. Co-morbidities and course are well described; however, CT findings are consistent with lung involvement in COVID-19.
    The study concludes that “myocardial injury, as assessed by cardiac troponins, occurs in approximately one third of COVID-19 cases and is associated with an adjusted two-fold mortality increase. An increased PA diameter, as assessed on chest CT, is an independent predictor of both myocardial injury and death.”
  • Tocilizumab for treatment of mechanically ventilated patients with COVID-19. 7/11/20. Somers EC. Clin Infect Dis.
    Click here to take this CME activity.

    Review by the SAB
    By Dr. David Clement, on behalf of the SAB
    An observational, controlled study of 154 adult, ventilated COVID-19 patients, half of whom received tocilizumab. Tocilizumab-treated patients had a 45% reduction in hazard of death, improved status on some secondary outcomes, and twice as many superinfections. Extensive tables, figures and statistical analysis provide insight.  A randomized study is needed to confirm these findings. 

July 14, 2020:

  • Prevention of thrombotic risk in hospitalized patients with COVID-19 and hemostasis monitoring. 6/19/20. Susen S. Crit Care.
    Review by the SAB
    By Dr. Lydia Cassorla, on behalf of the SAB
    Authors of this practical review article from a multinational European working group recommend a strategy to categorize thrombotic risk level and to increase anticoagulation above standard prophylactic doses for hospitalized COVID-19 patients with additional risk factors including obesity (BMI>30), respiratory failure, findings of major inflammation (D-dimer>3mcg/ml. or fibrinogen >8 g/L) or evidence of consumptive coagulopathy. They propose baseline testing repeated q48 hrs. and include a color-coded chart to quickly determine the risk category for individual patients. Not discussed: management of consumptive coagulopathy, thrombolysis, antiplatelet therapy, and arterial thrombosis. Their management strategy is based upon previously published international data.

July 13, 2020:

  • Characteristics and serological patterns of COVID-19 convalescent plasma donors: optimal donors and timing of donation. 7/6/20. Li L. Transfusion.
    Review by the SAB
    By Dr. Barry Perlman, on behalf of the SAB
    Study from Wuhan, China of 49 blood donors who recovered from mild-moderate COVID-19 to determine optimum convalescent plasma donor strategy.
    Nucleocapsid (N) and Spike protein receptor-binding domain (S-RBD) antibodies were measured by ELISA assay. S-RBD ELISA results were correlated with a SARS-CoV-2 viral neutralization assay, as the authors state that recent studies suggest that S-RBD antibodies may provide immunity.
    N specific IgM declined 3 weeks after infection and reached low levels after 6 weeks. S-RBD and N specific Ig G increased after 4 weeks from symptom onset.
    Those who donated > 28 days from symptom onset, and whose fever > 38.5°C or lasted longer than 3 days, had higher levels of S-RBD IgG.
    Further studies with larger sample size, plasma from asymptomatic donors, and clinical validation are needed.
  • COVID-19 Clinical Trials: Unravelling a Methodological Gordian Knot. 7/7/20. Mathioudakis AG. J Thromb Thrombolysis.
    Review by the SAB
    By Dr. Lance Lichtor, on behalf of the SAB
    During a pandemic, in part because of the limit in a patient population that might shrink in the coming months, clinical trials might need to enroll a patient for more than 1 trial. In addition, because of the need to get information out quickly, interim data meta-analyses (or network meta-analyses) powered to evaluate key outcomes, may be useful. At least, strategies and methodologies need to be developed to allow the best use of data collected.
  • Extracorporeal Membrane Oxygenation During the Coronavirus 2019 Pandemic. 6/26/20. Mikkelsen ME. Crit Care Med.
    Review by the SAB
    By Dr. Jay Przybylo, on behalf of the SAB
    An editorial addressing the use of ECMO in COVID-19 elaborating on an article describing ECMO for critically ill patients and demonstrating that survival was minimally better than conventional treatment of mechanical ventilation.
  • How to Quantify and Interpret Treatment Effects in Comparative Clinical Studies of COVID-19. 7/7/20. McCaw ZR. Ann Intern Med.
    Review by the SAB
    By Dr. Jay Pryzbylo, on behalf of the SAB
    Concise but in depth explanation using the example of two previously published articles to demonstrate that the statistical techniques used do not necessarily accurately describe the outcomes achieved. At issue is that negative outcomes (e.g., deaths) are not adequately accounted for in positive outcome statistical evaluation (days to recovery). The authors advance a method to do so that alters the outcomes of the studies.
  • IS SURGICAL TRACHEOSTOMY BETTER THAN PERCUTANEOUS TRACHEOSTOMY IN COVID-19 POSITIVE PATIENTS? 7/2/20. Bassi M. Anesth Analg.
    Review by the SAB
    By Dr. Barry Perlman, on behalf of the SAB
    Discussion of risks and benefits of percutaneous tracheostomy versus surgical tracheostomy, with strategies for safely performing percutaneous tracheostomies in COVID-19 settings. However, they recommend that a surgical tracheostomy is the first choice in the case of goiter, obesity, pneumomediastinum, difficult anatomy, coagulopathy, hemodynamic or respiratory instability.
  • Managing Anxiety in Anesthesiology and Intensive Care Providers during the Covid-19 Pandemic: An Analysis of the Psychosocial Response of a Front-Line Department. 7/8/20. Fleisher LA. NEJM Catalyst.
    Click here to take the CME activity.

    Review by the SAB
    A survey about “anxiety / stress induced crisis of health care provider – HCP” conducted by Dr. Lee Fleisher of 242 MDs and CRNAs in the anesthesia and critical care medicine departments at University of Pennsylvania comes up with the best guidelines to follow for healthcare workers’ emotional well being during this pandemic.
    Recommends:

    1. Covid-19 Task Force
    2. Development of a protocol
    3. Simulation training
    4. PPE training for all – addressing comfort level.
    5. Communication through a town hall meeting regarding the root of anxiety, identification of symptoms (insomnia, appetite, living situation).
    6. Complementing weakness and strength of traits, culture, gender, experience, psychology, age-related burnout while addressing shared expertise of healthcare workers in the field.

    Leadership should render the necessary training, psychological support, and clinical support, with acknowledgement of value of their work, to improve emotional health. The author stresses the role of meditation, maintaining routine including sleep, exercise, friends, and psychological assistance, and training.

  • Thromboelastography Profiles of Critically Ill Patients With Coronavirus Disease 2019. 6/26/20. Yuriditsky E. Crit Care Med.
    Review by the SAB
    By Dr. Philip Lumb, on behalf of the SAB
    Interesting retrospective study of 64 critically ill COVID-19 patients with available/reported thromboelastograph studies within 72 hours of ICU admission; 50% showed hypercoagulable profile defined as a Clotting Index (CI) >3. It is noted that D-Dimer > 2,000 ng/ml associated with median CI 3.4 while D-Dimer <2,000 ng/ml median CI 2.1. Discussion indicates TEG profiles consistent with fibrinogen and platelet effect and authors suggest further studies evaluating platelet aggregation profiles. While value of TEG evaluation in COVID-19 patients has not been confirmed, nonetheless further investigation is warranted as results consistent with clinical severity markers, D-Dimer elevations and requirements for appropriate and timely anticoagulation.
  • Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19. 6/29/20. Arshad S. Int J Infect Dis.
    Review by the SAB
    By Dr. Barry Perlman, on behalf of the SAB
    Multi-center retrospective observational study of 2,541 consecutive RT-PCR confirmed COVID-19 admissions from March 10 to May 2 in Detroit to determine impact of hydroxychloroquine +- azithromycin on inpatient mortality.
    Standard, uniform treatment guidelines established by a system-wide interdisciplinary COVID-19 task force also included corticosteroids and tocilizumab, which were used in 68% and 4.5% respectively.
    In hospital mortality:
    • Overall 18%
    • No hydroxychloroquine or azithromycin 26%
    • Azithromycin alone 22%
    • Hydroxychloroquine + azithromycin 20%
    • Hydroxychloroquine alone 13.5%
    • Mortality predictors were age > 65, CKD, decreased O2 sat on admit, ventilator use, and in contrast to previous studies, white race.

    Propensity matched regression analysis showed a mortality hazard ratio of .49 for patients who received hydroxychloroquine.
    Of note, no deaths due to major cardiac arrhythmias, such as torsades, were seen with hydroxychloroquine treatment.
    The authors suggest that early medication treatment (91% within 48 hours of admission), standardized dosing, and inpatient telemetry with electrolyte protocols may have accounted for the positive results seen with hydroxychloroquine.

July 10, 2020:

  • Critical Care Transesophageal Echocardiography in Patients during the COVID-19 Pandemic. July 1. Teran F. J Am Soc Echocardiogr.
    This is a consensus statement from North American experts in TEE for emergency and critical care patients. There is a subset of intubated COVID-19 patients who may benefit from goal-directed TEE to gain information of immediate utility in determining clinical management. They emphasize pre-planning and individual assessment of who is likely to benefit when other POCUS is insufficient.
  • EDITORIAL: SARS-CoV-2 viral load and antibody responses: the case for convalescent plasma therapy. 7/8/20. Casadevall A. J Clin Invest.
    Review by the SAB
    By Dr. David Clement, on behalf of the SAB
    Using a study on the kinetics of viral load and antibody response as an introduction, this article summarizes what is known about convalescent plasma therapy for COVID-19. The case is made for using sera from patients who recovered from severe COVID-19 disease (because of higher antibody titers), certainly giving therapeutic sera earlier (less than 10 days from symptom onset), and possibly giving therapeutic sera to patients with severe disease later in the course of their disease.
  • Improved Clinical Symptoms and Mortality on Severe/Critical COVID-19 Patients Utilizing Convalescent Plasma Transfusion. 6/23/20. Xia X. Blood.
    Review by the SAB
    By Dr. Lydia Cassorla, on behalf of the SAB
    This article may be of interest to those looking to learn from the Chinese experience with convalescent plasma (CP). 138/1568 COVID-19 patients from this retrospective single-center Chinese cohort study received CP. Death (2.1% vs. 4.1%) and requirement for ICU care (2.4% vs. 5.1%) in the CP group were close to half of that in the untreated patients. Patients with higher initial lymphocyte counts and those who received CP treatment within 7 wks. from onset of clinical disease were more likely to respond.
  • Incidence of pulmonary embolism in non-critically ill COVID-19 patients. Predicting factors for a challenging diagnosis. 6/29/20. Mestre-Gómez B. J Thromb Thrombolysis.
    Review by the SAB
    By Dr. Barry Perlman, on behalf of the SAB
    Retrospective review of EMR data of 452 consecutive patients admitted to the general ward with COVID-19 (based on WHO clinical criteria and/or RT-PCR) in Madrid to determine the incidence of PE in non-critically ill COVID-19 patients and identify predictive factors.
    • 91 of these patients had CT pulmonary angiography (CTPA) to rule out PE, with 29 (32%) positive for acute PE.
    • Incidence of PE was 6.4% — 29/452 patients.
    • Of note, 79% were receiving prophylactic LMWH at the time PE was diagnosed
    • PE was not associated with a significantly increased risk of ICU admission or mortality
    • Multivariate analysis showed lack of history of dyslipidemia and elevated D-dimer were independent predictors of PE.
    • D-Dimer peak median was 2x higher in PE patients. Cut off predictor was > 5000 ug/dl.
    • Patients with history of dyslipidemia had a 9x lower risk of PE. It is not known if this is due to statin use prior to admission. Hospital statin administration was not significantly different among the two groups.

    While the study concludes that an elevated D-Dimer > 5000 ul/dl and lack of dyslipidemia history are independent predictors of COVID-19 related PE risk, it is limited by small sample size, retrospective nature, and lack of DVT studies.

  • Rate of venous thromboembolism in a prospective all-comers cohort with COVID-19. 7/2/20. Rieder M. J Thromb Thrombolysis.
    Review by the SAB
    By Dr. Lydia Cassorla, on behalf of the SAB
    This German prospective single-center study analyzed 190 ED patients with suspected COVID-19 March-April 2020. 49 SARS-CoV-2 positive (25.8%). 141 SARS-CoV-2-negative patients served as a control group. After 30-day follow-up, VTE was diagnosed in 3 SARS-CoV-2-positive patients (6.1%, including 2 ICU patients) vs. 5 SARS-CoV-2-negative (3.5%), however the difference was not statistically significant (p = 0.427). 30-day mortality was similar (6.1% vs. 5%, p = 0.720). COVID-19 disease severity correlated with the maximum D-dimer level during follow-up, but not D-dimer at admission.
    Dyspnea was more common in the SARS-CoV2 negative group (41.7% vs. 52.4%, p = 0.002), whereas cough (58.3% vs. 37.6%, p < 0.0001) and fever (75% vs. 48.2%, p < 0.0001) were more frequent in COVID-19 patients. The rate of hospital admission was higher in the SARS-CoV-2 positive group (81.6% vs. 66.7%, p = 0.068) D-Dimers at admission did not differ between both groups (1.1 ± 1.4 mg/l vs. 0.8 ± 1.7 mg/l, p = 0.3).
  • Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion. 6/22/20. Verweij PE. Intensive Care Med.
    Review by the SAB
    Although the number of COVID-19-associated aspergillosis (CAPA) cases that have been reported is a small number, in two series, similarities and differences with Influenza with Invasive Aspergillosis (IAP) and COVID-19 are pointed out. Here a group of authors (EU, USA and Taiwan) are seeking to change the definition of IAP (inclusive of clinical and radiological signs). They make a point that an under-estimation of IAP requires a need for vigilance for IAP in the ICU, an early diagnosis, holding steroids, judicious use of antiviral to avoid a fatal outcome due to an IAP patient in comparison to Influenza with IAP.
    For CAPA:
    • 85% host factors are -ve but Lymphopenia/monocyte hyperimmune response is present
    • IPA tracheobronchitis is not known
    • The entry point ACE 2 – anti-fungal immunomodulation by antifungal not likely?
    • Serum GM + ve – need a study in COVID-19 to understand the implication.
    • No specificity of secondary infection organism types.

July 8, 2020:

July 6, 2020:

  • Compassionate Use of Tocilizumab for Treatment of SARS-CoV-2 Pneumonia. 6/23/20. Jordan SC. Clin Infect Dis.
    Review by the SAB
    By Dr. Heinrich Wurm, on behalf of the SAB
    Single center review by a multidisciplinary team from Cedars-Sinai following 27, mostly intubated, patients with confirmed SARS-CoV-2 pneumonia who received a single dose of 400 mg tocilizumab intravenously under a compassionate use protocol. Decreasing vasopressor support and oxygen requirements as well as lower C-reactive protein levels and temperature were observed in a majority of subjects monitored to assess anti-inflammatory effectiveness and clinical improvement.
    Tocilizumab proved beneficial in reducing inflammation and improving clinical outcome including mortality. Final proof of the drug’s efficacy awaits a placebo-controlled trial, now underway.
  • Drug-Induced Liver Injury and COVID-19 Infection: The Rules Remain the Same. 6/8/20. Olry A. Drug Saf.
    Review by the SAB
    By Dr. Philip Lumb, on behalf of the SAB
    Editorial noting that patients have been discontinued/withdrawn from studies because of suspected drug-induced liver damage that does not meet international guidelines for association. A summary of currently used drugs in COVID-19 and possible interactions that may cause liver damage is listed. However, the authors state that since many drugs used in therapeutic interventions may be related to liver damage, it is important to discuss acute liver injury on internationally defined biologic criteria “on the Upper Limit of Normal of serum alanine aminotransferase activity (ALT), serum alkaline phosphatase activity (ALP) and serum concentration of total bilirubin,” which are provided in the editorial as well as a severity grading score to include in association. Internationally recognized criteria for DILI should be satisfied to confirm the diagnosis prior to premature removal of patients from potentially important clinical trials.
  • Extracorporeal Membrane Oxygenation for Critically Ill Patients with COVID-19 Related Acute Respiratory Distress Syndrome: Worth the Effort? 6/16/20. Falcoz PE. Am J Respir Crit Care Med.
    Review by the SAB
    By Dr. David Clement, on behalf of the SAB
    A prospective, single-center study from France following 17 COVID-19 patients who met defined criteria and were placed on ECMO. The endpoints at 60 days were death (6 patients, 35%), discharge from hospital (9 patients, 41%), inpatients off the ventilator (3 patients, 17%) and still ventilated (1 patient, 6%). Nearly half of the patients had major bleeding or thrombotic complications. The authors conclude that “Considering the high frequency of severe adverse events, ECMO should probably remain a rescue therapy and therefore be undertaken only in ECMO-expert centers with adequate resources.”
  • Inhalational volatile-based sedation for COVID-19 pneumonia and ARDS. 6/25/20. Jerath A. Intensive Care Med.
    Click here to take this CME activity.

    Review by the SAB
    By Dr. Heinrich Wurm, on behalf of the SAB
    In light of a growing shortage of sedatives and intravenous anesthetics, this narrative review from Toronto highlights the benefits and technical details of volatile anesthetics for sedation in the critical care unit during the COVID-19 pandemic. 
    Spearheaded in Europe – volatile anesthetics using in-line vaporizers may provide added benefits, like bronchodilatation and an anti-inflammatory effect, but safe use requires trained teams familiar with volatile anesthetics administration in the ICU. The authors provide a comprehensive and realistic review of available options and alternatives.

July 1, 2020:

  • COVID and Coagulation: Bleeding and Thrombotic Manifestations of SARS-CoV2 Infection. 6/3/20. Al-Samkari H. Blood.
    Review by the SAB
    This is a retrospective observational study of data from 400 COVID-19 in-patients with D-dimer on admission to 5 affiliated Boston area hospitals between March 1 – April 5, 2020 with a data cutoff of April 8, 2020. All received prophylactic anticoagulation except one who was fully anticoagulated. Incidence of thrombosis and bleeding was similar to that reported in non-COVID-19 patients with equivalent illness severity. (9.5% had thrombosis and 4.8% hemorrhage w/ higher fractions in the critically ill.) There were no deaths from thrombosis and 1 from intracerebral hemorrhage. D-dimer on admission was predictive of thrombosis, bleeding, illness severity and death. The authors recommend that clinicians await the results of randomized clinical trials before increasing thromboprophylaxis dosages for COVID-19 patients, including the critically ill.
  • Prevention, diagnosis and treatment of venous thromboembolism in patients with COVID-19: CHEST Guideline and Expert Panel Report. 5/26/20. Moores LK. Chest.
    Click here to take this CME activity.

    Review by the SAB
    By Dr. Jay Przybylo, on behalf of the SAB
    The vast majority of data over the years support combination antiplatelet and anticoagulant prophylaxis. In summary, this is a very important document that will be used by the medical authorities, the legal profession, hospitals, and societies to be a reference for clinical behavior.

  • The association of lung ultrasound images with COVID-19 infection in an emergency room cohort. 6/11/20. Bar S. Anaesthesia.
    Review by the SAB
    For emergency room patients with suspected COVID-19 disease, the delay in RT-PCR testing results can cause unnecessary isolation of patients and a strain on hospital resources. This prospective study of 100 ER patients from France found that a POCUS protocol (BLUE) in conjunction with the quick SOFA score accurately predicted RT-PCR positive patients and worse outcomes.

June 29, 2020:

  • Occurrence and Timing of Subsequent SARS-CoV-2 RT-PCR Positivity Among Initially Negative Patients. 6/7/20. Long DR. Clin Infect Dis.
    Review by the SAB
    By Dr. Barry Perlman, on behalf of the SAB
    Detailed, retrospective electronic medical record data analysis showing that a small percentage of symptomatic patients who initially test negative for SARS-CoV-2 may have a positive result on repeat testing.
    A combined 21,000 patients underwent nasopharyngeal swab testing at Stanford and University of Washington. Testing was performed for either clinical reasons (symptoms with pertinent risk factors or clinical judgement) or universal asymptomatic preoperative screening.
    • 91% of the patients initially tested negative.
    • 96% of those who initially tested negative did not have a repeat test within 7 days and did not require subsequent care.
    • Of the remaining 626 patients who were initially negative and underwent repeat testing within 7 days for persistent or worsening symptoms, 14 of 338 (4.1%) UW and 8 of 288 (2.6%) Stanford patients were positive on repeat testing.
    • Subgroup analysis excluding UW asymptomatic preop patients yielded similar results.

    Overall occurrence of testing discordance for patients who had persistent or worsening symptoms was 3.5%, suggesting that the initial test was false negative.
    Nasopharyngeal swab RT-PCR testing sensitivity or specificity cannot be determined from this analysis due to:

    • lack of a gold standard confirmatory test to determine whether initial or subsequent results were false positive or false negative.
    • not all patients with an initial negative result were retested
    • incomplete clinical information regarding patients who had a negative result but did not undergo retesting.
    • possibility of newly acquired infection during the 7-day interval.
    • lack of complementary serology or RT-PCR testing of samples from other sites.

    However, it does support retesting of patients with a negative RT-PCR test who have persistent symptoms, although the optimal method of retesting needs to be determined.

  • Risks to healthcare workers following tracheal intubation of patients with COVID-19: a prospective international multicentre cohort study. 6/9/20. El-Boghdadly K. Anaesthesia.
    Click here to take this CME activity.

    Review by the SAB
    By Dr. Heinrich Wurm, on behalf of the SAB
    The “intubateCOVID project” is an ongoing prospective multicenter cohort study using a web-based, self-reporting registry for providers involved in endotracheal intubations. Over 1700 providers in 500 hospitals and 17 countries are registered and as of June 2 performed over 5000 intubations. Of the 184 providers (10.7%) that became infected, only two required hospitalization. Multiple procedural and epidemiological aspects were tracked and statistically evaluated. There was an unexplained higher incidence among women and considerable variation among countries. The authors list a number of serious limitations of this study, among those infection from other sources, self-reporting bias and asymptomatic seroconversion. As the study is ongoing, we will report updates as they become available.

  • The Laboratory Diagnosis of COVID-19 – Frequently Asked Questions. 6/8/20. Fang FC. Clin Infect Dis.
    Review by the SAB
    By Dr. Lydia Cassorla, on behalf of the SAB
    This review from the clinical laboratories of the University of Washington breaks down information about testing for COVID-19 in a useful question-and-answer format. Subjects include PCR, serology, point-of-care testing, correlation with clinical disease, and biomarkers.
  • Ventilator Sharing During an Acute Shortage Caused by the COVID-19 Pandemic. June 9. Beitler JR. Am J Respir Crit Care Med.
    Detailed report discussing a 2 patient on one ventilator sharing strategy, with results and lessons learned from 3 pairs of patients with COVID-19 ARDS at NY-Presbyterian/Columbia University Irving Medical Center who shared ventilators for 2 days without adverse events.
    • Pre-specified criteria shown in Table 1 were used to identify compatible patient pairs.
    • Minimizing between-patient driving pressure differences was prioritized.
    • Deep sedation and neuromuscular blockade were maintained.
    • Ventilators were set to pressure-control.
    • After determining average identical ventilator settings while on separate machines, patients were transitioned to a shared ventilator with the same settings.
    • An unused rescue ventilator was available.
    • Single patient ventilators are needed for weaning and individualized support.
    • ICU ventilators are superior to anesthesia machines for sharing.
    • Multiple antimicrobial filters and matching by pathogen decreases risk of sharing infection.
    • Frequent changing of CO2 absorbent and heat moisture exchange filters was needed.

    Since the safety and utility of sharing > 48 hours is not known, the authors suggest that ventilator sharing is most reasonable as a stopgap to allow relocating of ventilators or patients to meet demand.

  • Wearing an N95 Respiratory Mask: An Unintended Exercise Benefit? 6/1/20. Davis BA. Anesthesiology.
    Review by the SAB
    By Dr. Lydia Cassorla, on behalf of the SAB
    The authors of this letter to the editor discuss the physiologic effects of N95 FFR use.  They review data from previous studies, particularly one by Sinkule in 2013 that measured the potential physiologic effects of using an N95 respirator with and without a surgical mask in front of it.  The data were generated using an automatic breathing and metabolic simulator.  Effects are largely due to increased work of breathing due to the resistance of the respirator, and increased dead space ventilation.  Vvaries with mask design (folded models have more VD than molded models) and tidal volume (lower tidal volumes increase % VD).  At 2 METs energy expenditure (~walking quietly) average inspired O2 is estimated to be 16.1-17.5% and CO2 is estimated to be 2.5-3.5%.  With increased efforts and associated ventilation, minute ventilation increases, along with the work of breathing. However, effects of dead space decrease.  Consequently, N95 users may experience multiple symptoms, even with minimal activity. Associated work of breathing and more marked thoracic pressure swings also generate cardiopulmonary training, a potential benefit.

June 15, 2020:

  • Ventilator Sharing During an Acute Shortage Caused by the COVID-19 Pandemic. June 9. Beitler JR. Am J Respir Crit Care Med.
    Detailed report discussing a 2 patient on one ventilator sharing strategy, with results and lessons learned from 3 pairs of patients with COVID-19 ARDS at NY-Presbyterian/Columbia University Irving Medical Center who shared ventilators for 2 days without adverse events.
    • Pre-specified criteria shown in Table 1 were used to identify compatible patient pairs.
    • Minimizing between-patient driving pressure differences was prioritized.
    • Deep sedation and neuromuscular blockade were maintained.
    • Ventilators were set to pressure-control.
    • After determining average identical ventilator settings while on separate machines, patients were transitioned to a shared ventilator with the same settings.
    • An unused rescue ventilator was available.
    • Single patient ventilators are needed for weaning and individualized support.
    • ICU ventilators are superior to anesthesia machines for sharing.
    • Multiple antimicrobial filters and matching by pathogen decreases risk of sharing infection.
    • Frequent changing of CO2 absorbent and heat moisture exchange filters was needed.

    Since the safety and utility of sharing > 48 hours is not known, the authors suggest that ventilator sharing is most reasonable as a stopgap to allow relocating of ventilators or patients to meet demand.

June 9, 2020:

  • Effectiveness of N95 Respirator Decontamination and Reuse against SARS-CoV-2 Virus
    June 3. Fischer RJ. Emerging Infectious Diseases.
    Opinion from SAB Member: Dr. Lydia Cassorla
    Using SARS-CoV-2, this study sponsored by the US government builds on the knowledge needed to evaluate the efficacy of decontamination methods that are being used around the world to extend the life of N95 masks due to shortages of new masks. N95 fabric discs and some whole masks were studied following treatments with ethanol, vaporized hydrogen peroxide (VHP), UV-C irradiation (UVGI), and dry heat. Data was modeled and extrapolated to calculate expected 3-log (threshold considered decontamination) and 6-log (threshold considered sterilization) reductions in viral load. For 3-log reduction, dry heat at 70°C took 46.3 min and UVGI took a dose of 2J/cm2, delivered to one side only. SARS-CoV-2 virus was undetectable after the initial treatment time for VHP, so no modeling was done. Mask fit and filtration performance was tested on 6 whole N95 masks per method for 3 cycles using a quantitative fit test that results in a fit score. Mask fit and filter function (tested in 6 masks/method after wearing for 2 hours) was good following 3 cycles of VHP and UVGI, but began to decline following the 3rd cycle of heat (note: their conditions were drier than some recommend). While ethanol sterilized well, it caused mask function failure and is not recommended. Control data with no treatment showed a median viral half-life of 78.5 min at 21-23°C with 40% relative humidity and a calculated 3-log reduction in 13 hrs. Despite limitations, this work adds important data regarding SARS-CoV-2 viability on N95 fabric along with measures of N95 fit and function under control and after test conditions. VHP provided the best combination of effectiveness and speed with good retention of fit and filtration function for 3 cycles (all that was tested) but requires proprietary equipment (note, some companies providing VHP equipment have received Emergency Use Authorizations from the FDA during the pandemic). UVGI and heat require care to take the time required to achieve the desired reduction in viral load and ensure procedures are followed to prevent cross-contamination, as they are not necessarily sterilizing techniques. Readers will also find data regarding stainless steel surfaces (not discussed in this summary). The CDC continues to provide some guidance regarding this issue on its website, where the publication is currently posted in pre-print form.

June 8, 2020:

  • Association of noninvasive oxygenation strategies with all-cause mortality in adults with acute hypoxemic respiratory failure: a systematic review and meta-analysis. June 4. Ferreyro BL. JAMA.
    A meta-analysis studies respiratory failure oxygenation techniques in use at multiple facilities and adds a systematic review. The paper defines participants with respiratory failure and the studies produced, but complicates the results by analyzing “records” and in a table indicates 99% of these were excluded from analysis. Statistics beyond the comprehension of this clinician conclude that face mask noninvasive ventilation was associated with lower to equal mortality as compared to endotracheal intubation. Helmet ventilation is not discussed in results but added to tables.
  • Alternatives to Invasive Ventilation in the COVID-19 Pandemic. June 4. Patel BK. JAMA.
    Editorial that states the complexity of oxygenation failure and its treatment as raised in Ferreyro article requires prospective study controlling for the cause of failure and the technique for re-establishing ideal oxygenation.
  • Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study. June 4. Gao C. Eur Heart J.
    This is a large retrospective observational cohort study regarding a history of hypertension in 2877 consecutive patients admitted to a Covid-19 hospital in Wuhan. No HTN: n=2027. HTN n=850. “A total of 34/850 (4.0%) patients died in the hypertension cohort and 22/2027 (1.1%) died in the no hypertension cohort (crude HR 3.75, 95% CI 2.19–6.41, P < 0.001; Figure 1A). After adjustment for confounders, hypertension was still associated with a two-fold increase in the risk of mortality as compared with no hypertension (adjusted HR 2.12, 95% CI 1.17–3.82, P = 0.013; Table 2). The time from symptom onset to discharge was comparable between the two cohorts; however, patients with hypertension had the propensity to develop more severe/critical COVID-19 disease (P for trend < 0.001) and were more likely to receive invasive mechanical ventilation (P < 0.001).”
    The SBP on admission was 10mmHg higher (136 vs. 126) in the HTN cohort, and DBP 80 vs. 83.5. Among the HTN group, there was no difference in admission BP between those on Rx. vs. those w/o Rx, and no difference between RAAS Rx and other anti-HTN Rx. 90 (64.3%) of the HTN by history patients that were untreated on admission received anti-HTN Rx after admission, none with RAAS inhibitors. 95% of patients on anti HTN Rx were continued, largely on the drugs they were on. (There appears to be an error in the percent calculations of RAAS inhibitor patients in their flow chart).
    Results of a meta-analysis including 3 additional Chinese studies with a combined total of 808 patients are also included in their discussion.
    “The main findings of this analysis can be summarized as follows: (i) after adjustment for confounders and compared with the non-hypertensive patients, the hypertensive patients continued to demonstrate a two-fold relative increase in the risk of COVID-19 mortality; (ii) the patients with a history of hypertension but without antihypertensive treatment were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments; and (iii) the relative rates of mortality, the severity of COVID-19, and percentages of ventilation were not statistically different between the patients treated with RAAS inhibitors and non-RAAS inhibitors. However, in the meta-analysis, RAAS inhibitors tend to be associated with a lower risk of mortality.”
    As described above, these data showed that untreated hypertensive patients are at the highest risk. There are remaining questions: (i) which kind of medication should be given to those patients (CCBs or RAAS inhibitors); (ii) could such medications mitigate the risk of these patients; and (iii) will the use of RAAS inhibitors affect the risk of infection when equally exposed to the virus?
    Limitations: Retrospective, observational study. “While 2877 patients enrolled, only 183 patients with RAAS inhibitors and 527 patients with non-RAAS inhibitors were compared. (Statistically underpowered), our findings should be interpreted cautiously.” Short-term outcome study.
  • Characteristic of COVID-19 infection in pediatric patients: early findings from two Italian Pediatric Research Networks. June 3. Parri N. Eur J Pediatr.
    We published a summary from China. Also, Docmatter had another summary from the MMWR which was a summary from the US. Is another similar one needed? They did reference that article: clinical presentation was only available in 9%. Yet their findings were similar to others: COVID-19 in children is mostly a mild disease.
  • Renin-angiotensin system inhibitors in the COVID-19 pandemic: consequences of antihypertensive drugs. June 4. Ruilope LM. Eur Heart J.
    An editorial concurring with the conclusions of the large retrospective by C. Gao et al. on the association of HBP and HBP Rx on mortality in Covid-19 patients. The author points out that after pooling previously published data in a study-level meta-analysis, patients taking RAAS blockers were actually shown to have decreased mortality rates, and suggests a need to investigate RAAS blockers as possible specific treatment for COVID-19 patients.

June 5, 2020:

  • Impact of anticoagulation prior to COVID-19 infection: a propensity score-matched cohort study
    May 27. Tremblay D. Blood.
    Opinion from SAB Member: Dr. Joseph Anthony Caprini, Dr. Anil Hingorani
    JC: This is a very clever analysis looking at patients who did or did not have therapeutic anticoagulation prior to developing the viral infection as a result of their underlying condition. The same analysis was done in patients on antiplatelet therapy. The results showed no benefit of either anticoagulation or antiplatelet therapy in changing all-cause mortality, mechanical ventilation, and hospital admission. They comment that the results of this study do not rule out the possibility that among some groups of patients suffering from the virus therapeutic anticoagulation following diagnosis may be important and beneficial. They further comment that their findings agree with the current recommendations of the American Society of Hematology that state that the benefit of therapeutic anticoagulation in patients with COVID-19 is unknown.
    AH: These data are from Mount Sinai. The authors use retrospective propensity matching for anticoagulation usage before COVID-19 diagnosis. No benefit of any single anticoagulation type was noted. The article suggests we may need multiple types of treatment. This paper is novel and raises good questions.
  • Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study
    May 29. CovidSurg Collaborative. The Lancet.
    Opinion from SAB Member: Dr. Anil Hingorani, Dr. Joseph Anthony Caprini
    AH: 30-day results of an international cohort study assessing postoperative outcomes in 1128 adults with COVID-19 who were undergoing a broad range of surgeries. SARS-CoV-2 infection was diagnosed postoperatively in more than two-thirds of the patients (806 [71·5%]). The primary outcome was overall postoperative mortality at 30 days, and the rate was high at 23·8% (268 of 1128 patients). Pulmonary complications occurred in 577 (51·2%) patients and 30-day mortality in these patients was 38·0% (219 of 577).
    JC: This represents a very important study demonstrating a high incidence of relatively severe complications including death postoperatively. There are obvious flaws in this study as expressed by both the authors and in the subsequent editorial. Nevertheless, these data emphasize the importance of improved preventative measures including the vaccine as well as a multimodal therapeutic approach involving drugs representing hematologic immunologic and inflammatory pathways.
  • Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis
    June 1. Chu DK. The Lancet.
    Opinion from SAB Member: Dr. Barry Perlman
    Meta-analysis published in Lancet and featured in the NYT 6/2/20 reporting that physical distancing > 1 m and use of face mask and eye protection decrease transmission of virus. However, a variety of issues limit the strength of their conclusions.
    2 m distance was more effective than 1 m. As compared with no mask use, N95 or similar respirators were more effective than surgical or cotton masks in decreasing risk of infection. Of note, no intervention provided complete protection from infection. The authors suggest the findings from this review of 172 observational (44 comparative) studies from 16 countries regarding COVID-19, SARS, and MERS transmission can be used to guide protection policies for the public and health-care workers.
    However, the analysis was based on non-randomized studies, most involved SARS and MERS, the impact of duration or setting (e.g. ward, ER, OR, ICU) of exposure was not addressed, most studies reported on bundled interventions, the need for appropriate fit and proper use of N95 masks to achieve maximum effectiveness was not considered, only three non-health-care setting studies were included, there was no direct effectiveness comparison of N95 or similar masks to surgical or cotton masks, and the conclusions were rated at a low to moderate degree of certainty.
    Therefore, further research is required to determine optimal protection from COVID-19 infection, and which are most appropriate for health-care versus non-health-care settings.
  • Prevalence of Asymptomatic SARS-CoV-2 Infection: A Narrative Review
    June 3. Oran DP. Annals of Internal Medicine.
    Opinion from SAB Member: Dr. David M. Clement
    A well-written, concise review of 16 studies describing the prevalence and significance of asymptomatic persons infected with SARS-CoV-19. Four of five of the studies that included longitudinal serial testing to distinguish asymptomatic vs. presymptomatic persons showed otherwise healthy asymptomatic persons rarely (0-10%) became symptomatic. On the other hand, 89% of RT-PCR + nursing home patients were presymptomatic. Their conclusion is that asymptomatic infection is a significant factor in the rapid progression of the SARS-CoV-2 pandemic, and that current medical practice and public health measures should be modified to address this challenge.

June 4, 2020:

June 3, 2020:

  • Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series. May 29. Argenziano MG. BMJ.
    Extensive data on demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition. Lacked information on anticoagulation and incidence of VTE.
  • ICU and Ventilator Mortality Among Critically Ill Adults With Coronavirus Disease 2019
    May 26. Auld SC. Critical Care Medicine.
    Opinion from SAB Member: Dr. Philip Lumb, Dr. Jagdip Shah
    PL: Results of an observational cohort study of 217 patients admitted to Emory Healthcare System ICUs between March 6th and April 17th with RT-PCR confirmed COVID-19 disease, 165 of whom required invasive ventilation with a reported mortality rate of 33.9% (56/165) and a hospital mortality of 35.7%. Patient demographics, other supportive therapies (ECMO, RRT, Etc.), laboratory values and pulmonary characteristics well described with clear delineation between survivors and non-survivors. Authors discuss ICU preparation and pre-peak awareness as characteristics promoting more favorable outcomes than previously reported under surge conditions.
    JS: Authors form Emory conducted a retrospective cohort study of critically ill patients with COVID-19 in 6 designated ICUs which were adequately staffed and stocked. 217 patients were admitted to the ICU and 165 were treated with mechanical ventilation in the ICU. A total of 59 died (in the ICU or in hospital) and 88 were discharged out of the hospital. Statistically significant baseline parameters associated with non-survivors were: age > 75, BMI > 40, pre-existing chronic kidney disease. The ICU parameters associated with non-survival were: SOFA score on the day of admission > 7, rise of d Dimer > 1600 ng/dl, C-reactive protein > 183, PaO2:FiO2 < 144, use of mechanical ventilation, use of vasopressors, use of continuous renal replacement therapy, and hospital stay > 11 days. The authors claim that timely start of mechanical ventilation with lung protective strategy likely improves the outcome (the overall mortality in this study was 31%).
  • Nasal Gene Expression of Angiotensin-Converting Enzyme 2 in Children and Adults
    May 20. Bunyavanich S. JAMA.
    Nasal ACE2 Levels and COVID-19 in Children
    May 20. Patel AB. JAMA.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    Why do children seem to have a lower incidence of COVID-19 infection? The authors Bunyavanich, et al studied nasal epithelium samples obtained between 2015-2018 from 305 individuals 4-60 years both with and without asthma as part of a research study on nasal biomarkers of asthma to examine ACE2 gene expression. They found a positive association between ACE2 gene expression and age that was independent of sex and asthma. In the accompanying editorial, the authors note that since ACE2 binds to the receptor binding domain of SARS-CoV-2, by decreasing ACE2 gene expression, that might help mitigate transmission of COVID-19. Patel et al provide a nice editorial on the topic that references the Bunyavanich, et al study.
  • Respiratory Mechanics of COVID-19 vs. Non-COVID-19 Associated Acute Respiratory Distress Syndrome
    Apr 20. Haudebourg AF. American Journal of Respiratory and Critical Care Medicine.
    Opinion from SAB Member: Dr. Robert L. Coffey
    A prospective, observational study comparing the respiratory mechanics and lung recruitability of 30 consecutive COVID-19 ARDS patients and 30 consecutive non-COVID-19 ARDS patients of similar severity. In contrast to other reports, compliance, while ranging widely, was similar in the two groups and did not appear to worsen in COVID patients over the 15 days after their initial symptoms. The lung recruitment measure (R/I ratio) was significantly higher in the COVID-19 ARDS patients. The authors could not discern subgroup phenotypes within these 30 COVID pneumonia patients.
  • SARS-CoV-2 Antibody Testing – Questions to be asked
    May 25. Ozcurumez MK. Journal of Allergy and Clinical Immunology.
    Opinion from SAB Member: Dr. Barry Perlman
    Informative article by the COVID-19 Task Force of the German Society for Clinical Chemistry and Laboratory Medicine addressing the interpretation of antibody testing. Topics discussed include:
    • Possible indications for COVID-19 serology
    • Value of antibody testing in diagnosis
    • Does presence of antibodies indicate end of infectivity?
    • Does presence of antibodies indicate immunity?
    • Comparison of different assay technologies
    • Ensuring assay quality
    • Baseline samples from asymptomatic or healthy individuals
    • Estimating demand for antibody testing

    The paper points out that in a low prevalence setting, even a high specificity test can result in an unacceptable false positive rate, leading to an overestimate of population immunity and a lower estimate of viral mortality. False positive results may be minimized by selecting for higher prevalence with symptom screening or contact tracing.

  • The role of SARS-CoV-2 antibodies in COVID-19: Healing in most, harm at times
    May 20. French MA. Respirology.
    Opinion from SAB Member: Dr. Edward S. Schulman
    This is an excellent commentary that all should read. Though some antibodies to the spike glycoprotein promote virus neutralization and other protective antibody functions, particular IgG antibodies might enhance the infection of immune cells and/or disease progression. One example is antibody‐dependent enhancement of virus uptake by macrophages by enhancing antibodies as described in dengue virus infection that has also been demonstrated for SARS‐CoV‐1. Therefore, current development of antibody-dependent strategies, whether human monoclonal antibodies, convalescent plasma or choosing the right target for vaccine is complex. Depending on the peptide targeted on the spike glycoprotein by the human immune system or the vaccine lab, neutralizing or enhancing activity may result. Simply having a “positive SARS-CoV-2 antibody” on a serological test may not be a license for a “passport.”
  • The Spectrum of Cardiac Manifestations in Coronavirus Disease 2019 (COVID-19) – a Systematic Echocardiographic Study
    May 29. Szekely. Circulation.
    Opinion from SAB Member: Dr. Paul D. Scanlon
    This is a prospective survey of echocardiographic findings in 100 patients admitted with COVID-19–20% had repeat echo during clinical deterioration. At baseline, 61 had mild disease (no O2), 29 had moderate disease (non-inv O2), and 10 had severe disease (intubated). 32 had normal baseline echos, 39 had RV dilatation and dysfunction, 16 had LV diastolic dysfunction only, 10 had LV systolic dysfunction. Of the 20 who deteriorated, 12 (60%) had RV deterioration, of whom 5 (25%) had DVT (possible PE?). 5 (25%) had decrease in LVEF. Lung US was c/w ARDS, without evolution to cardiogenic pulmonary edema.

June 1, 2020:

May 29, 2020:

  • Coagulation changes and thromboembolic risk in COVID-19 pregnant patients
    May 11. Benhamou D. Anaesthesia Critical Care & Pain Medicine.
    Opinion from SAB Member: Dr. Anil Hingorani, Dr. Joseph Anthony Caprini
    AH: A good review of the literature for prophylaxis for pregnant COVID-19 patients.
    JC: This article contains important information for the anesthesiologist including hematologic changes that reflect thrombosis more than an increased incidence of bleeding. I don’t agree with the authors opinion that only selective patients admitted to the hospital should receive prophylactic anticoagulation. Pregnancy is associated with a mild hypercoagulable state, and combining the effects of the virus one would logically conclude that prophylaxis is indicated unless there is an increased risk of bleeding. In my opinion the number one priority is to prevent the patient from developing a thrombotic complication. I would place less emphasis on neuraxial anesthesia. The incidence of thrombosis post discharge in these patients is significant particularly if they have comorbidities. Many of these patients may benefit from prophylaxis for a period of time during the convalescence. A careful detailed thrombosis risk assessment on admission, during hospitalization and updated upon discharge in my opinion should be a standard part of the workup of these patients. The choice of assessment can be whatever is a commonly used in the hospital and may vary widely according to countries.
  • Covid-19, Angiogenesis, and ARDS Endotypes
    May 21. Hariri L. The New England Journal of Medicine.
    Opinion from SAB Member: Dr. Anil Hingorani, Dr. Louis McNabb
    AH: Editorial points out limitations of the Ackermann paper: n=7, none intubated, only 20% with noninvasive ventilation. Exact correlation with the time course of the disease and the findings are not clear.
    LM: Complimentary article to Ackermann’s paper suggesting that the small vessel disruption in COVID-19 may represent a specific ARDS histologic phenotype.
  • Emergence from the COVID-19 Pandemic and the Care of Chronic Pain: Guidance for the Interventionalist. May 21. Deer T. Anesth Analg.
    Chronic pain management took a back seat during the peak of the COVID-19 crisis which resulted in considerable hardship for many chronic pain sufferers. This publication by the American Society of Pain and Neuroscience COVID-19 Task Force provides guidance for chronic pain interventionalists and outlines methods and resources necessary to safely re-introduce essential pain management procedures into daily practice.
  • High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients
    Apr 22. Llitjos JF. Journal of Thrombosis and Haemostasis.
    Opinion from SAB Member: Dr. Anil Hingorani, Dr. Lydia Cassorla
    AH: This French paper is a short communication where the authors describe venous duplex exams in 26 patients in the ICU with COVID-19. 8 patients were on prophylactic heparin doses and 18 were on therapeutic doses. All patients were intubated. The rate of VTE was 100% for the patients on prophylactic doses and 56% for those on therapeutic doses. 8 patients had PE. The authors do not mention the location of lower extremity DVT. This paper is novel and raises questions. It confirms data from a 48 patient series with 84% VTE incidence from China (Extremely High Incidence of Lower Extremity Deep Venous Thrombosis in 48 Patients with Severe COVID-19 in Wuhan).
    LC: This is a French retrospective study from March 19 to April 11, 2020 of 26 consecutive ICU patients from 2 units with severe COVID‐19 who were screened for VTE on ICU admission and at least every 7 days. 8 (31%) were treated with prophylactic anticoagulation, and 18 (69%) were treated with therapeutic anticoagulation. The overall rate of VTE in patients was 69%. The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with therapeutic anticoagulation (100% vs 56%, respectively, P = .03) 6 (23%) had PE. This documents a high incidence of VTE despite prophylaxis and supports trends towards more aggressive anticoagulation.
  • Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19
    May 21. Ackermann M. The New England Journal of Medicine.
    Opinion from SAB Member: Dr. Anil Hingorani, Dr. Louis McNabb
    AH: This is an autopsy study of 7 COVID-19 patients compared to 7 H1N1 patients, age and gender matched with 10 controls. Tests performed: histology, electron microscopy and gene array. Widespread thrombosis with microangiopathy were seen. COVID-19 patients had more alveolar capillary microthrombi and new vessel growth–predominantly through a mechanism of intussusceptive angiogenesis. Gene analysis also showed more angiogenesis.
    LM: This study compared lung histology of 7 patients dying of COVID-19 vs. 7 patients dying of influenza. Key Points: 1) COVID-19 patients had 9 times more capillary micro-thrombi, 2) Disrupted capillary cell membranes with intracellular virus were seen, 3) Perivascular t-cell infiltration was seen, and 4) COVID-19 patients had 2.7 more times new vessel growth through the mechanism of intussusceptive angiogenesis.
  • The association of low serum albumin level with severe COVID-19: a systematic review and meta-analysis. May 26. Aziz M. Crit Care.
    Meta-analysis of 11 studies with 910 patients finding a significantly lower admission serum albumin (3.5 g/dL) in severe COVID-19 patients than in those with non-severe disease (4.0 g/dL). Of note, patient mean age was 48. The primary cause and clinical significance of this difference is not known.
  • Understanding the COVID-19 coagulopathy spectrum
    May 21. Thachil J. Anaesthesia.
    Opinion from SAB Member: Dr. Anil Hingorani, Dr. Lydia Cassorla
    AH: This editorial is a summary article covering the link of the immune system to thrombosis. The paper asks clinical questions concerning the use of additional anticoagulants (beyond heparin) for certain patients and raises the use of thromboelastography for clinical guidance.
    LC: This is a useful editorial that summarizes current trends in management and proposes an algorithm for management of COVID-19 related hypercoagulability. If no contraindications, inpatients should receive prophylaxis with LMWH, or unfractionated heparin if indicated. They propose a low bar for imaging (but not a screening regimen) and ramping up anticoagulation according to findings and potentially thrombolysis if the situation continues to worsen. The potential role of point-of-care TEG or ROTEM viscoelastic testing and questions for the future are addressed. While consideration of antiplatelet therapy and the results of more clinical trials are pending, perhaps the most important message is that each center should have a plan.

May 28, 2020:

  • A simple algorithm helps early identification of SARS-CoV-2 infection patients with severe progression tendency. May 21. Li Q. Infection.
    This study based on over 300 Chinese patients, creates a simple algorithm, named age-LDH-CD4 model, to identify COVID-19 patients with increased likelihood of disease progression.
  • Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization. May 14. Zuo T. Gastroenterology.
    Pilot, prospective comparison of fecal microbiomes in samples from 15 hospitalized COVID-19 patients in Hong Kong with samples from 6 patients hospitalized with community acquired pneumonia and 15 controls. Samples were collected 2-3 times a week until hospital discharge. Samples from COVID-19 patients had increased opportunistic pathogens and decreased beneficial commensals. Bacterial levels remained low and altered from a healthy microbiome even after RT-PCR tests became negative and respiratory symptoms had resolved. COVID-19 patients treated with antibiotics showed a larger change from a healthy microbiome. Baseline (but after admission) Coprobaccillus, Clostriium ramosum, and Clostridium hathewayi correlated with COVID-19 severity, while amounts of the anti-inflammatory Faecalibacterium inversely correlated with severity. Several Bacteroides species, which down regulate ACE2 expression, inversely correlated with viral load, suggesting that it may play a protective role. Study is limited by small sample size, unknown baseline microbiome prior to disease onset, lack of patients with asymptomatic or mild COVID-19.
  • Chloroquine or hydroxychloroquine for COVID-19: why might they be hazardous? May 22. Funck-Brentano C. Lancet.
    A commentary on a Lancet article that retrospectively reviewed the occurrence of significant ventricular arrythmias in 96,032 hospitalized Covid-19 patients from 671 hospitals in six continents. Groups of 1,868 to 6,221 patients each that were given chloroquine or hydroxychloroquine with or without a macrolide were compared to 81,144 control Covid-19 patients who received none of these drugs. While the occurrence of repetitive ventricular arrythmias was much higher in the treated groups (4.3-8.1% versus 0.3%), several lines of reasoning in this commentary suggest that the increase in these arrhythmias was not a major contributor to the increased death rate among these (presumably sicker) patients.
  • COVID-19 and NSAIDS: A Narrative Review of Knowns and Unknowns
    May 24. Pergolizzi Jr. JV. Pain and Therapy.
    Opinion from SAB Member: Dr. Robert L. Coffey
    A brief commentary article reviewing the possible mechanisms for an increase in susceptibility to COVID-19 or for a worsened prognosis in patients taking NSAIDs. The possibility that the anti-inflammatory effects might in fact be helpful is noted. The previously reported association of NSAID use and poor outcome is described, but this may be due to the association of higher NSAID use with increasing age. The review of the literature presented here indicates that “to date there is no strong evidence in favor or disputing the use of NSAIDs in patients diagnosed with COVID-19.”
  • Duration of SARS-CoV-2 viral RNA in asymptomatic carriers. May 24. Yan X. Crit Care.
    Asymptomatic COVID-19 carriers are potentially a significant vector for the spread of SARS-CoV-2, but little is known about asymptomatic carriers. This research letter charts the RT-PCR positivity of 24 asymptomatic RT-PCR positive patients, showing persistent positivity can be lengthy (over 4 weeks). Viral cultures were not performed, so little can be said about infectivity of these asymptomatic carriers.
  • Famotidine Use is Associated with Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Propensity Score Matched Retrospective Cohort Study. May 14. Freedberg DE. Gastroenterology.
    This retrospective cohort study from a single NY institution looked at the relationship between famotidine exposure of Covid-19 patients within 24 hours of hospitalization and death or endotracheal intubation from hospital day 2 to 30. They studied all Covid-19 positive patients from 2/25/20-4/13/20. 84 patients, representing 15% of 1,620 analyzed, were in the famotidine exposed group. Doses and route of adminstration varied. Median length of treatment was 5.8 days. Adjusted hazard risk of death or intubation was 0.42. PPIs did not show a protective effect. Next, 784 patients w/o COVID-19 were analyzed and famotidine exposure did not show a protective effect. A lower peak ferritin value was observed among famotidine-exposed patients, supporting the hypothesis that cytokine release in famotidine exposed patients may be lower in the setting of Covid-19. An untargeted computer modeling analysis identified famotidine as one of the highest-ranked matches for drugs predicted to bind 3CL (3), a SARS-CoV-2 protease.
  • How did we rapidly implement a convalescent plasma program?
    May 25. Budhai A. Transfusion.
    Opinion from SAB Member: Dr. Louis McNabb
    Impressive example of how all interested parties came rapidly together to provide convalescent plasma. Useful tables on their process.
  • Lack of viral clearance by the combination of hydroxychloroquine and azithromycin or lopinavir and ritonavir in SARS-CoV-2-related acute respiratory distress syndrome. May 24. Hraiech S. Ann Intensive Care.
    Letter to the editor that showed a little more than a month after treatment with either hydroxychloroquine and azithromycin or lopinavir and ritonavir or control, that mortality was not different between groups. A retrospective analysis from France.
  • RAAS inhibitors do not increase the risk of COVID-19
    May 22. Fernández-Ruiz I. Nature Reviews Cardiology.
    Opinion from SAB Member: Dr. David M. Clement, Dr. Jay Przybylo
    DC: This editorial briefly reviews 5 recent retrospective studies that all confirm prior speculation that pre-COVID-19 use of ACE2 inhibitors and ARBs is not associated with increased susceptibility to COVID-19 and does not have harmful effects in patients with COVID-19. These results justify prior guideline advice to continue ACE2is and ARBs in the COVID-19 era.
    JP: An editor for Nature combined the results of multiple papers investigating the effect of ACEi and ARB therapy on the susceptibility to COVID-19, concluding that despite the lack of controlled studies, the aggregate of the cited studies provides proof that these drugs do not provide an entry portal for the infection and are safe to continue. This easily understood paper serves as a valuable resource for physicians of any specialty caring for patients on RAAS therapy who are infected with COVID-19.
  • Remdesivir for the Treatment of Covid-19 – Preliminary Report
    May 22. Beigel JH. The New England Journal of Medicine.
    Opinion from SAB Member: Dr. Philip Lumb
    Results from the Adaptive COVID-19 Treatment Trial (ACTT-1), an international, double-blind, placebo-controlled trial of IV remdesivir in adults with documented COVID-19 disease hospitalized with evidence of lower respiratory tract involvement sponsored by the National Institutes of Allergy and Infectious Diseases (NIAID). Patients were randomly assigned to remdesivir or placebo for up to 10 days. It is important to note that “the initial primary outcome measure was the time to recovery, defined as the first day, during the 28 days after enrollment, on which a patient satisfied categories 1, 2, or 3 on the eight-category ordinal scale.”
    Patients were enrolled from February 21 until April 19 at 60 trial sites in the US, Denmark, UK, Greece, Germany, Korea, Mexico, Spain, Japan, and Singapore. Eligible patients were randomized to either study drug or placebo in a 1:1 ratio stratified by study site and disease severity at enrollment; routine therapy in place at the institution was continued. On March 22, the primary outcome was amended by trial statisticians (unaware of the treatment assignments or outcome data) and approved on April 2 prior to any outcome data being available. This change led to the early observation that is now widely recognized as the statement presented by the NIAID sponsors that “remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with COVID-19 and evidence of lower respiratory tract infection.” It is important to read the trial details to understand the reasons for the change and the validity of the results as reported.
    This is an example of a well conducted, adaptive platform clinical trial conducted under difficult circumstances across multiple institutions with appropriate Data Safety Monitoring Board (DSMB) oversight and interim analyses. On April 27, the DSMB reviewed results and because patient enrollment had been completed (patient follow up continuing) at the time of what had been intended to be an interim review, and it was noted that the remdesivir group had a shortened time to recovery when compared to placebo, these results were reported to the NIAID and subsequently made public.
    Hidden in the press coverage but of clinical concern is the now secondary outcome indicating the “odds of improvement were higher in the remdesivir group…than in the placebo group.” The discussion is particularly illuminating regarding the complexities of the study, the enrollment supervision complexity given travel restrictions (lack of study monitors), local and environmental controls and the nature of the study itself; the addition of an experimental therapy supported by routine care across all institutions involved. The authors conclude: “The full statistical analysis of the entire trial population must occur in order to fully understand the efficacy of remdesivir in this trial. These preliminary findings support the use of remdesivir for patients who are hospitalized with COVID-19 and require supplemental oxygen therapy. However, given high mortality despite the use of remdesivir, it is clear that treatment with an antiviral drug alone is not likely to be sufficient.”
    I found this manuscript a fascinating description of an adaptive trial undertaken in difficult circumstances that produced interesting, clinically relevant results that await further analysis for final determination of the remdesivir’s efficacy. However, it stimulated the inclusion of the drug into routine management of COVID-19 patients and suggests that early administration is likely to be of greater benefit.

May 27, 2020:

  • A proposed lung ultrasound and phenotypic algorithm for the care of COVID-19 patients with acute respiratory failure
    May 21. Denault. Canadian Journal of Anesthesia/Journal canadien d’anesthésie.
    Opinion from SAB Member: Dr. Robert L. Coffey
    This is an opinion piece from a group of physicians in Quebec based on a literature review and patient care experience that recommends the use of lung ultrasound and the previously validated ROX index [(SpO2/FiO2)/RR] to better distinguish between the proposed Type L and Type H COVID-19 pneumonia phenotypes. A guide to differentiated ventilator support strategies is offered, but no patient outcome data is presented. While the concepts are interesting and bedside lung ultrasound offers a low risk imaging technique, it is not clear to me that the ventilator strategies suggested differ significantly from standard high quality lung protective ARDS care.
  • Association of renin-angiotensin-aldosterone system inhibitors with COVID-19-related outcomes in Korea: a nationwide population-based cohort study
    May 22. Jung. Clinical Infectious Diseases.
    Opinion from SAB Member: Dr. Jay Przybylo
    In a Korean population of patients taking Renin-angiotensin-aldosterone system (RAAS) inhibitors, the risk of death was higher compared with non-users. However, after adjustment for age, sex, Charlson Comorbidity Index, immunosuppression, and hospital type, the use of RAAS inhibitors was not associated with higher mortality.
  • Chronological Changes of Viral Shedding in Adult Inpatients with COVID-19 in Wuhan, China
    May 23. Huang. Clinical Infectious Diseases.
    Opinion from SAB Member: Dr. Barry Perlman
    This is a retrospective study of 308 COVID-19 inpatients at one hospital in Wuhan between 1/11/20 and 2/21/20 who received > 5 ORF1ab gene RT-PCR tests. Viral loads (based upon cycle threshold) peaked 2-4 days after admission and then decreased with treatment. A rebound seen around 7, 16, and 22 days after admission was more common in non-severely ill patients. 43% of patients had positive tests after 2 negative tests. On day 30 of treatment most patients had undetectable virus by RT-PCR tests. High viral loads (cycle threshold < 30) correlated with critical illness, mortality, decreased serum albumin, decreased Th and Ts cells, lower lymphocyte, eosinophil, and basophil counts, and increased neutrophil counts, serum glucose, corrected calcium, LDH, CKMB, myoglobin, ultra TnI, and NT-proBNP. Sputum viral loads were higher than in nasopharyngeal samples, and respiratory loads were higher than in GI samples. The authors suggest that positive RT-PCR test rebound reflects surviving coronavirus particles.
  • Critically ill patients with COVID-19 in New York City
    May 19. Grasselli. The Lancet.
    Opinion from SAB Member: Dr. Jagdip Shah
    This editorial describes the study by Matthew J. Cummings, et al as a high-quality example of research even when facing an overwhelming clinical workload. The authors claim that further studies are required to improve and personalize patient treatment, with particular attention to the role of initial non-invasive respiratory support strategies, timing of intubation, optimal setting of mechanical ventilation, and efficacy and safety of immunomodulating agents and anticoagulation strategies.
  • Detection of SARS-CoV-2 in human breastmilk. May 21 Groß. Lancet.
    In this study of 2 women with severe COVID-19 disease, one mother shed SARS-CoV-2 RNA from breast milk for 4 days. Interesting but a small study.
  • Distinct phenotypes require distinct respiratory management strategies in severe COVID-19. May 11. Robba. Respir Physiol Neurobiol.
    An opinion piece from Italian physicians based on a literature review and their extensive experience caring for patients with Covid-19 pneumonia. They recommend classifying patients into three phenotypes based on CT scan results (1. Focal ground glass opacities, 2. Atelectasis and peribronchial opacities, 3. Patchy ARDS-like pattern) and provide recommendations for specific support strategies according to the physiology typically associated with each of these CT scan types. Since no patient outcome data is presented, it’s not clear that their strategies are superior to others, and they themselves state that these “might” guide therapy and ventilator settings.
  • Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study
    May 19. Cummings. The Lancet.
    Opinion from SAB Member: Dr. Jagdip Shah
    1150 adults were admitted in this prospective study from 2 hospitals (Columbia, New York). Both hospitals were able to utilize more than double the ICU surge capacity. 257 were critically ill with confirmed COVID-19. The median age of patients was 62 years, 67% were men, 82% of patients had at least one chronic illness, (HTN, DM, BMI > 30). A high incidence of critical illness among racial and ethnic minorities in this pandemic is noted. 39% of patients had died and 37% remained hospitalized, 79% patients had to be mechanically ventilated for 18 days, 66% of 257 patients received vasopressors and 31% RRT. The authors present extensive respiratory and critical illness parameters on the first day of critical illness (medians): SOFA = 11, lowest PaO2:FiO2 = 129 mmHg, plateau airway pressure = 27 cmH2O, highest PEEP = 15 cmH2O.
    In the multivariable Cox model, older age (HR 1.31 per 10-year increase), chronic cardiac disease (HR 1.76), chronic pulmonary disease (HR 2.94), higher concentrations of interleukin-6 (HR 1.11 per decile increase), and higher concentrations of D-dimer (HR 1.10 per decile increase) were independently associated with in-hospital mortality. Univariate and multivariate HRs being somewhat similar suggest a higher confidence in the study and the group composition.
    Patients hospitalized with COVID-19 had a high frequency of invasive mechanical ventilation, extrapulmonary organ dysfunction, and substantial in-hospital mortality.
  • Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019-Induced Acute Respiratory Distress Syndrome: A Multicenter Descriptive Study
    May 18. Yang. Critical Care Medicine.
    Opinion from SAB Member: Dr. David M. Clement, Dr. Jagdip Shah
    DC: Though ECMO was shown to be an effective management choice in H1N1 ARDS, the utility of ECMO in COVID-19 is unclear. This study helps us to understand the use of ECMO with COVID-19 respiratory failure. This is a descriptive, retrospective, uncontrolled study from China of 59 ventilated patients, 21 of whom received ECMO for worsening respiratory failure. Of the 21 treated with ECMO, 12 died (57%), 9 were weaned off ECMO, and 6 were discharged. Of patients ventilated without ECMO, 63% died (NS compared with ECMO). This shows that ECMO is not a hopeless endeavor in certain circumstances with COVID-19 respiratory failure.
    JS: Here, Chinese authors retrospectively review the outcomes from 21 patients (2 hospitals) who received extracorporeal membrane oxygenation support (ECMO). When the optimal lung-protective strategy and prone position were both proven to be ineffective, patients would be considered for ECMO if any one of these criteria were met:
    1. PaO2/FiO2 less than 50 mm Hg over 3 hours;
    2. PaO2/ FiO2 less than 80 mm Hg over 6 hours;
    3. arterial blood gas pH less than 7.25 and PaCO2 greater than 60 mm Hg over 6 hours, as well as RR greater than 35 breaths per minute;
    4. RR greater than 35 breaths per minute, arterial blood gas pH less than 7.2, and Pplat greater than 30 cm H2O;
    5. complicated with cardiogenic shock or cardiac arrest.

    They adopted these doctrine from the H1N1 experience. The results showed a tendency of decline in mortality but with no significant difference. No ECMO 63.2% vs ECMO 57.1%; p=0.782. Noted in the study, 12 patients died and nine survived. The authors imply “we should have started earlier.”

  • Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. May 22. Petrilli. BMJ.
    An extensive prospective outcome study from NYC from 4 Ac Care Hospitals with 394 ICU beds and 1357 non-ICU beds. Out of about 12,000 patients for that period, 5,279 patients were positive for COVID-19: 48.1% were treated as outpatients, and 51.9% required admission to hospital. Out of those who got admitted: 63.4% were discharged, 36.1% experienced critical illness, 24.3% who were discharged to a hospice or among the 990 patients with critical illness, 63.4% required mechanical ventilation, 10.3% required non-ICU care.
    The study involved those admitted without critical illness, and those admitted to ICU, mechanical ventilation, discharge to hospice, or death. Then fitted multivariable logistic regression models with admission and with critical illness as the outcomes to identify factors associated with those outcomes. Authors also looked at admission values objectively for prediction of outcome as well. They found mortality to be 57% among all ICU or ventilated patients slightly higher than ARDS mortality. Some of the markers (either admission or admission to hospital) were common for worse outcome: Admission from March 16 to April 5, age > 55 years, unknown for smoking history, BMI > 40, CHF, O2 Sat % < 92, low Lymphocyte, high normal for C reactive, D Dimers, Procalcitonin, Troponin.
    Overall, they found that age and comorbidities are powerful predictors of requirement for admission to hospital rather than outpatient care; however, the degree of oxygen impairment and markers of inflammation are most strongly associated with poor outcomes during hospital admission. The study has very elaborate, descriptive analysis backed by statistics. It has a self-explanatory graph of several categories of clinical values to outcome.
  • Features of 20‚133 UK patients in hospital with Covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study
    May 22. Docherty. BMJ.
    Opinion from SAB Member: Dr. David M. Clement
    This is a somewhat different twist on the numerous studies describing symptoms, co-morbidities and outcomes with COVID-19 inpatients. It is a prospective, observational cohort study from the UK of 20,100 inpatients who were tracked with a pandemic protocol written before the SARS-CoV-2 pandemic in response to the H1N1 and MERS epidemics. An army of 2,468 research nurses, administrators and medical students collected data using a pre-pandemic standardized form and protocol in 208 hospitals on about a third of RT-PCR positive patients. Of note, symptoms were present in overlapping clusters reflecting organ systems involved (lung, GI, musculoskeletal and musculo-cutaneous). Overall, symptoms, comorbidities and outcomes were somewhat similar to previous studies: 41% of patients were discharged alive, 26% died and 34% were still inpatients. In ICU patients, 32% died and 41% were still admitted. The utility of pre-pandemic preparation for many facets of care was apparent.
  • Incidence, clinical outcomes, and transmission dynamics of severe coronavirus disease 2019 in California and Washington: prospective cohort study
    May 12. Lewnard JA. BMJ.
    Opinion from SAB Member: Dr. W. Heinrich Wurm
    For the practicing clinician, this study represents an epidemiological deep dive using the Kaiser Permanente database of 1840 patients (as of April 22, 2020) in a prospective cohort study aimed to:
    1. Assess population-based rates of COVID-19 disease over time in three distinct geographic areas (Southern CA: 15.6, Northern CA 23.3, WA 14.7)
    2. Model
      • estimated hospital length of stay for survivors (9.3 days) and non-survivors (12.7 days)
      • ICU admission rates and median length of stay for males (48.5% and 10.6 days) and females (32% and 14.9 days)
      • Fatality risk by age group (median 18.9%; >80yrs: 37.3)
    3. Study transmission dynamics by following the effective reproduction number over the study period within each region.

    The authors conclude that hospitalizations have substantial lengths of stay, that probability of ICU stay is high, and that the effective reproduction number has fallen over time, coincident with social isolation regulations.

  • Individual quarantine versus active monitoring of contacts for the mitigation of COVID-19: a modelling study. May 20 Peak. The Lancet Infectious Diseases.
    Two non-pharmaceutical interventions to prevent disease spread include voluntary individual quarantine and voluntary active monitoring. The effectiveness of either strategy depends on the duration of presymptomatic infectiousness, the fidelity of quarantining and contact tracing, and other measures such as physical distancing. This mathematical study provides the statistical foundation for deciding on quarantining or contact tracing once the presymptomatic infectiousness of COVID-19 is established. If the serial interval for COVID-19 (partly determined by presymptomatic infectiousness) is similar to that of SARS, there are few plausible conditions under which individual quarantine would offer a sufficient advantage over active monitoring.
  • Olfactory and gustatory function impairment in COVID-19 patients: Italian objective multicenter-study. May 21. Angelo Vaira. Head Neck.
    A 25 author study from Italy that was based on 345 patients who were either home-quarantined health care workers (161) or hospitalized patients (184), and all patients were swab positive for COVID-19. About 75% reported combined olfactory and taste disorders. Interestingly, of those who did not report any taste or smell disturbance, 30% had objective signs of odor dysfunction and those who had isolated odor or taste dysfunction had 20-30% more taste or odor dysfunction, that is the opposite dysfunction. Also, for 30%, the first sign of COVID-19 infection was chemo-sensitive dysfunction.
  • Predicting infectious SARS-CoV-2 from diagnostic samples
    May 22. Bullard. Clinical Infectious Diseases.
    Opinion from SAB Member: Dr. Barry Perlman
    Many studies have assumed that “viral shedding” based on positive RT-PCR testing suggests presence of infectious virus. This is a retrospective cross-sectional Canadian study to determine whether presence of SARS-CoV-2 RNA by RT-PCR predicts infectivity. 26/90 (29%) samples positive by RT-PCR targeting the 122nt portion of the envelope gene incubated on Vero cells demonstrated viral growth. Only samples with RT-PCR cycle threshold (Ct) < 24 and symptom to test time (STT) < 8 days showed growth. Specificities for the thresholds of Ct > 24 and STT > 8 days were 97% and 96%, respectively. If confirmed by larger studies utilizing additional RT-PCR targets, these results suggest that Ct and STT can predict duration of infectivity with high specificity and would avoid the unnecessary isolation resulting from policies based upon 2 negative RT-PCR results.
  • Proposed Modifications in the 6-minute Walk Test for Potential Application in Patients with mild Coronavirus Disease 2019 (COVID-19): A Step to Optimize Triage Guidelines. May 19. Mantha. Anesthesia & Analgesia.
    The authors propose to have patients perform the 6 minute walk test (while wearing a mask) to better discriminate between Covid-19 patients with mild pneumonia and those with severe pneumonia. They recommend adding this test to the established WHO criteria for severe pneumonia that includes 1) severe respiratory distress, 2) a respiratory rate of >30 breaths/min, or 3) an SpO2 ≤93% on room air. They propose a 1400 foot distance covered as the point of discrimination (approx 3 METS), but do not provide any patient data.
  • Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy
    May 15. George. Lancet Respir Med.
    Opinion from SAB Member: Dr. Louis McNabb, Dr. Edward S. Schulman
    LM: This is an opinion article raising the issue of long-term pulmonary fibrosis in survivors of severe COVID-19 pneumonia/ARDS. The authors discuss the logic for considering anti-fibrotic drugs such as: pirfenidone and nintedanib. They also discuss many other experimental anti-fibrotic drugs and their potential mechanism of action in COVID-19.
    ESS: While it may eventually become pertinent to consider the theoretical role of anti-fibrotic agents in the treatment of COVID-19, it must be noted that we do not yet know the natural history of lung injury in survivors and whether fibrosis is a persistent feature. With regards to pirfenidone and nintedanib, these agents carry significant side-effect profiles including nausea, vomiting, diarrhea and liver injury that may preclude their use in critically ill COVID-19 patients. Furthermore, the authors of this paper acknowledge relationships including “personal fees with the companies marketing pirfenidone and nintedanib.”
  • Pulmonary fibrosis secondary to COVID-19: a call to arms?
    May 15. Spagnolo. Lancet Respir Med.
    Opinion from SAB Member: Dr. Louis McNabb
    This is a short article pointing out the potential for a large population of COVID-19 survivors with residual pulmonary fibrosis and its consequences.
  • Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. May 22. Zhu. The Lancet.
    Early interim results of a dose-escalation, single-centre, open-label, non-randomised, 108 subject, phase 1 trial of an adenovirus vectored COVID-19 vaccine showing some immunogenicity and frequent mild to moderate side effects, (fever, malaise, pain at injection sites) over 28 days of observation. This Ad-5 vector has previously been used for Ebola and HIV vaccine candidates where one of the vaccine candidates appeared to increase HIV acquisition. This study also suggests that a person’s previous exposure to the Ad-5 virus appears to decrease the immunogenicity of this vaccine. The authors plan to continue observing the outcomes of this trial and to proceed to a Phase 2 trial using the lower two of the three vaccine dose levels used in this study.
  • Saving Lives Versus Saving Dollars: The Acceptable Loss for Coronavirus Disease 2019. May 18. Ashkenazi. Crit Care Med.
    This is in response to the previous article “Adult ICU Triage During the Coronavirus Disease 2019 Pandemic. Who Will Live and Who Will Die?” Recommendations to Improve Survival in CCM.
    A thought provoking reply: Care for patient vs. population and simultaneously incorporating a principal of “life for ‘Fittest for a survival’” while accepting the strategic “retrieve” in this pandemic.
    The author questions the article’s recommendation of a triage algorithm based on various criteria—except for the age.
    The formula in question is based on 1. Performance score; 2. ASA score; 3. Number of organ failures; and 4. Predicted survival. Performance score and predicted survival has indirectly incorporated the age of the patient in consideration for “greater good to great number of people / year.”
    The author makes a cerebral argument for a need for strategic pre-planning of the national capacities (based on ICU beds) and capabilities (surge of 100 + Supply + Space) of a pandemic. Here the policy maker should consider as an “acceptable loss,” which represents the ultimate balance between saving lives and keeping life routines. This includes defining the “price” that we are willing to “pay” in order to be able to save the most lives and life-years and to lower the morbidity rate while, at the same time safeguarding the economy and individuals at workplaces and the fabric of social existence. Social distancing, quarantine, tracking and monitoring are medical aspects of a pandemics but does cause a collateral damage in the area with 1. Loss of lives due to suicides; 2. Psychiatry diseases; 3.Delayed chronic treatment; 4. Domestic violence; and 5. Economic losses. An evaluation of the “acceptable loss” is a professional, financial, ethical, legal, social, cultural, and historical dilemma. The COVID-19 pandemic has shown a dichotomy of the society: “the objective element” of the lethal virus and “controlled element” of the overprotective reaction for those who are not at risk, while vulnerable populations are left unprotected.
    ICU Triage needs to be 1. Differential diagnosis with comorbidities – risks stratification of population; 2. International surge – share and care of equipment and valuable resources; 3. Awareness to differential age; and 4. Meta leadership at stages (country, state, city level). The author appeals a medical triage, acceptable loss is based on two basic principles: beneficence and distributive justice.
    In a big country that is fractured at several levels, these suggested principals will need “a well-orchestrated political will” in this pandemic. On the other side, success for a smaller, monolithic, resources poor, undemocratic country from the author’s perspective in this pandemic.
  • Symptom profiles and risk factors for hospitalization in patients with SARS-CoV-2 and COVID-19: A Large Cohort from South America. May 5. Díaz. Gastroenterology.
    A nicely done descriptive, retrospective study from Chile briefly describing all admitting symptoms, but focusing on GI symptoms, in all RT-PCR positive patients (n=7016). The results are similar to similar studies from other areas: cough (53%), myalgia (56%), and fever (44%) were the most common symptoms, with GI symptoms including diarrhea (7%), and abdominal pain (4%). Fifty percent of tested stool samples were RT-PCR positive, and mortality was 1.1%.
  • Therapy with agents acting on the renin-angiotensin system and risk of SARS-CoV-2 infection
    May 22. Gnavi. Clinical Infectious Diseases.
    Opinion from SAB Member: Dr. Jay Przybylo
    This is a study with controls demonstrating that patients treated with ACE inhibitors (ACEi) or Angiotensin II Receptor Blockers (ARBs), in particular those with diabetes or cardiovascular disease, were not more susceptible to SARS-CoV-19 infection due to drug therapy.
  • Training and Fit Testing of Health Care Personnel for Reusable Elastomeric Half-Mask Respirators Compared With Disposable N95 Respirators
    Mar 25. Pompeii LA. JAMA.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    In this research letter, the authors showed that health care workers can be rapidly fit tested and trained to use the reusable Elastomeric Half-Mask Respirators. These have the advantage over N95 respirators in that they are reusable. They cost about $30-$40 and they are used currently in about four major U.S. health systems.

May 22, 2020:

  • Continuous positive airway pressure to avoid intubation in SARS-CoV-2 pneumonia: a two-period retrospective case-control study. May 19. Oranger. Eur Respir J.
    The use of CPAP has been controversial with COVID-19 respiratory failure. This retrospective, case control research letter/study from France of 66 patients casts some light on this controversy. Two periods of time, one with and the other without CPAP, were analyzed for intubation rate in similar COVID-19 patients in a dedicated pulmonary unit. In the non-CPAP period, 6 intubations and two deaths occurred by day 7 (57%), and in the CPAP period, 9 intubations and no deaths occurred by day 7 (23%). No CPAP patients crashed requiring emergency intubation, and acquisition of COVID-19 by HCW was similar during the two time periods.
  • Factors Associated With Intubation and Prolonged Intubation in Hospitalized Patients With COVID-19
    May 19. Kur. Otolaryngology–Head and Neck Surgery.
    Opinion from SAB Member: Dr. David M. Clement
    A retrospective, observational study from Chicago of 486 adult inpatients with COVID-19 that is nicely written and provides a wealth of clinical data. The focus of the study was on demographics and risk factors associated with intubation and time to extubation. 28% (138) of patients were intubated and of those, 56% were extubated, 15% died and 28% were still intubated. Age, male sex and a history of diabetes were independent risk factors associated with intubation. Age and BMI>30 predicted a longer time to extubation. Among the data are some interesting findings, such as 1/3 of patients were intubated in the ED, SpO2 was below 90 in 12% of non-intubated patients, only one non-intubated patient died, and 4% were treated with ECMO. There are limitations acknowledged (e.g. criteria for intubation), but overall the study provides a useful window into a COVID-19 surge. We feel this paper pairs nicely with a previous paper reviewed by the SAB that covered the timing and indications for tracheostomy Tracheostomy in the COVID-19 era: global and multidisciplinary guidance.
  • Category: Correction
    Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis – published in The Lancet on May 22, 2020, subjected to an expression of concern on June 2, and retracted on June 4.
    Department of Error: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis
    May 29. Mehra MR. The Lancet.
    The Department of Error from the Lancet published the above statement about an article previously cited and summarized by this Scientific Advisory Board in the 26MAY2020 Newsletter.
    “In this Article, in the first paragraph of the Results section, the numbers of participants from Asia and Australia should have been 8101 (8·4%) and 63 (0·1%), respectively. One hospital self-designated as belonging to the Australasia continental designation should have been assigned to the Asian continental designation. The appendix has also been corrected. An incorrect appendix table S3 was included, originally derived from a propensity score matched and weighted table developed during a preliminary analysis. The unadjusted raw summary data are now included. There have been no changes to the findings of the paper. These corrections have been made to the online version as of May 29, 2020, and will be made to the printed version.”
  • Nurturing Morale
    May 8. Vinson. Anesthesia & Analgesia.
    Opinion from SAB Member: Dr. W. Heinrich Wurm
    An “Open Mind” contribution focusing on current pandemic related stressors, but also on the personal impact the “Great Catch-up” phase that we are entering now will have on individual anesthesiologists’ morale. Daily challenges are identified, and remedies suggested. The role compassionate, honest and servient leadership plays under these circumstances is highlighted and leaders are urged to become aware of their crucial role in stressful situations. The author is a pediatric anesthesiologist and chair of the ASA Committee on Physician Well-being.
  • Olfactory Dysfunction and Sinonasal Symptomatology in COVID-19: Prevalence, Severity, Timing, and Associated Characteristics. May 19. Speth. Otolaryngol Head Neck Surg.
    The lead author was from the United States, though the patients were from Sweden. 103 patients were studied. The prevalence of hyposmia or anosmia was 61.2%, the mean onset was 3.4 days after symptoms of COVID-19 first appeared and was severe in nature and was strongly correlated with a concomitant loss of taste. 30% to 50% of participants experienced nasal obstruction or rhinorrhea, which they attributed to COVID-19. However, there was no correlation between these symptoms and OD. Only older age was negatively associated with having OD and female sex was possibly positively associated with having OD.
  • Olfactory Dysfunction in COVID-19: Diagnosis and Management
    May 20. Whitcroft. JAMA.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    This is a study that examines olfactory dysfunction both with and without COVID-19. The basis of olfactory dysfunction, as the authors explain, may be due to disruption of cells in the olfactory neuroepithelium, and that the virus may actually penetrate the brain and then have downstream effects on brain regions that may adversely affect olfactory function. The authors explain also how olfactory dysfunction should be assessed and how it might be treated.
  • Return to work for healthcare workers with confirmed COVID-19 infection. May 20. Zhang. Occup Med (Lond).
    A Canadian Occupational Medicine editorial addressing the confusion created by a discrepancy between guidelines addressing safe return to work for health care workers recovering from COVID-19. The US CDC offers two strategies and requires either two negative naso-pharyngeal swabs taken 24 hours apart or a non-testing approach based on symptom resolution (10 days since symptoms or 72 hrs since recovery). Public Health England recommends return after day 7 of symptom onset, provided clinical improvement has occurred and the health care worker has been afebrile for 48 hours.
    The authors suggest a pragmatic approach that uses cessation of clinical symptoms backed up by serology to prove non-infectivity.
  • Subjective Changes in Smell and Taste During the COVID-19 Pandemic: A National Survey-Preliminary Results. May 19. Coelho. Otolaryngol Head Neck Surg.
    The authors provided statistics on the incidence of olfactory disturbances, which is similar to other studies. Some patients with olfactory disturbances might not actually have COVID-19, but testing isn’t always done, in part because these individuals may have no other suspicious symptoms.
  • Technologies to optimize the care of severe COVID-19 patients for healthcare providers challenged by limited resources
    May 19. Rubulo. Anesthesia & Analgesia.
    Opinion from SAB Member: Dr. Lydia Cassorla
    This excellent and comprehensive summary from multinational European and North American authors reviews techniques and approaches that may be of particular utility in limited-resource settings. Topics discussed: ETT positioning, processed EEG for drug conservation, neuromuscular monitoring, paperless documentation in isolation settings, adaptation of anesthesia machines for the ICU, point-of-care diagnostics including testing for infection, point-of-care US, and thromboelastography. One might think of every medical center as limited in resources, therefore, I suspect most readers will find useful information here.
  • Tracheostomy in the COVID-19 era: global and multidisciplinary guidance
    May 15. McGrath. Lancet Respir Med.
    Opinion from SAB Member: Dr. Jay Przybylo
    Presented by an international, multidisciplinary team, this article attempts to limit “conflicting recommendations” that have arisen in this pandemic regarding tracheostomies. Using COVID-19 as the example, the paper reviews the history of pandemics, searches the literature for guidance, and describes the issues of tracheostomy–in non-COVID-19 patients less than 50% of trached patients survive to leave the hospital and 12% are functional at 1 year while in COVID-19 the statistics are worse, suggesting a longer wait prior to tracheostomy. Using data on the infectious nature of COVID-19, the wait allows the detectable virus to drop below 50% of patients while allowing antibodies to become detectable in most. With this timing, the incidence of trach is 0.5%. The location of the procedure and the optimal procedure are discussed. The care of patients with emphasis on healthcare provider safety is discussed. The paper contains multiple, easily interpretable tables and graphs. Not a science paper with statistics and errors supplied, this paper promotes standards that can (should) be met worldwide.

May 21, 2020:

  • Cardiovascular implications of the COVID-19 pandemic: a global perspective
    May 10. Boukhris. Canadian Journal of Cardiology.
    Opinion from SAB Member: Dr. Jagdip Shah
    Cardiologists from across the world provide a holistic review of the present and future of their acute and chronic issues with clinical practice in this article. The article provides a comprehensive overview with evidence-based input of the pathophysiology and the dynamic cardiovascular implications of COVID-19. The authors have made an excellent effort to explain pathophysiology for noncardiac conditions, drug implication and their interactions as well. They noted that the information in references here is contemporary and relevant. It offers a detailed recommendation of existing pathways of care, the role of modern technologies (AI, social media, smartphones, telemedicine, etc.) to tackle the patient care issues in this pandemic, which other specialties can adopt. This is a practical, realistic proposal of novel management algorithms for the most common acute cardiac conditions with excellent tables and figures that are easy to read and follow.
    Although respiratory symptoms dominate the clinical presentation, COVID-19 is known to have potentially serious cardiovascular consequences, including myocardial injury, myocarditis, acute coronary syndrome, pulmonary embolism, stroke, arrhythmias, heart failure, and cardiogenic shock. The cardiac manifestations of COVID-19 may be related to the adrenergic drive, systemic inflammatory milieu and cytokine-release syndrome caused by SARS-CoV-2, direct viral infection of myocardial and endothelial cells, hypoxia due to respiratory failure, electrolytic imbalances, fluid overload, and side effects of certain COVID-19 medications known to be in practice currently.
  • Cardiovascular phenotypes in ventilated patients with COVID-19 acute respiratory distress syndrome
    May 18. Evrard. Critical Care.
    Opinion from SAB Member: Dr. Philip Lumb
    This is a comparison of TEE findings in 18 COVID-19 patients with 23 seasonal flu (A-H1N1) patients ventilated for flu-associated ARDS from previous 2 years. While COVID-19 patients were older, disease was less severe (SAPSII, SOFA, less vasopressor support). Cardiac findings indicated that left ventricular failure, acute and severe cor pulmonale were higher in flu. Interestingly, the authors report, “Hypovolemic and hyperkinetic phenotypes were similarly observed in both groups. Despite similar tidal volume and PEEP level, COVID-19 patients had significantly higher P/F ratio and respiratory-system compliance, and lower driving pressure than flu patients.” The manuscript includes illustrative tables. This is a preliminary study requiring further investigation to elucidate cardiac phenotypes during COVID-19 disease.
  • Cardiovascular Safety of Potential Drugs for the Treatment of Coronavirus Disease 2019
    May 20. Aggarwal. The American Journal of Cardiology.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    Any drug might have an effect on the heart. The authors have provided a nice summary of the cardiac safety of various drugs used to treat patients with COVID-19, including chloroquine/hydroxychloroquine, azithromycin, remdesivir and lopinavir/ritonavir, interferon-alpha, and briefly concerning some other therapies.
  • Higher solar irradiance is associated with a lower incidence of COVID-19
    May 19. Guasp. Clinical Infectious Diseases.
    Opinion from SAB Member: Dr. Jay Przybylo
    This is an interesting study using statistical evaluation of population density and solar and weather influences on COVID-19 spread that correlates high urban population density and low UV radiation to increased COVID-19 infection rates. The graphs are difficult to interpret.
  • Neurologic complications of COVID-19
    May 10. Bridwell. American Journal of Emergency Medicine.
    Opinion from SAB Member: Dr. W. Heinrich Wurm
    Announced by the authors as, “A practical review of the literature aimed at the emergency medicine clinician”, this review of 60 recent papers dealing with the neurological impact of COVID-19 adds value for the clinician without being superficial. The avenues of direct viral assault via endothelial ACE-2 receptors, retrograde migration via the nasopharynx into the olfactory system, or via transsynaptic transmission, are highlighted, as well as the impact of secondary events like the systemic inflammatory response evoked by the virus and its impact on the blood brain barrier or the effect hypoxia may exert on cerebral autoregulation.
    In addition to highlighting clinical presentations, this review points to pre-existing neurological disease like stroke and Parkinson’s as an important risk factor not only for added neurological complications, but for severity of illness and mortality. A table listing the side effects of various pharmaceuticals used to treat COVID-19 provides another helpful addition for the practitioner.
  • Rationale for Prolonged Corticosteroid Treatment in the Acute Respiratory Distress Syndrome Caused by Coronavirus Disease 2019
    Apr 2020. Villar. Critical Care Explorations.
    Opinion from SAB Member: Dr. Barry Perlman
    This is an opinion piece advocating for the use of corticosteroids in severe COVID-19 outside of trials. The occurrence rate of ARDS with COVID-19 is 17-41%. There is an association between ARDS and dysregulated systemic inflammation, and corticosteroids have been used to down-regulate systemic and pulmonary inflammation in non-viral ARDS due to bacterial pneumonia and sepsis. The 2017 Corticosteroid Guideline Task Force of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine, based on 9 RCTs, found moderate quality/certainty of evidence that corticosteroids decrease duration of conventional mechanical ventilation and improve survival. A subsequent RCT also showed corticosteroid benefit in patients receiving low tidal volume ventilation. The authors opine that the WHO recommendation against the routine use of corticosteroids for viral pneumonia outside of clinical trials is based on incomplete evidence and flawed studies. 2 large studies showing benefit with SARS and H1N1 pneumonia, and small observational studies showing benefit with COVID-19 ARDS, support the viewpoint that there is currently no evidence to “deny the use” of corticosteroids outside of RCTs in COVID-19 patients with life threatening cytokine storm.
  • Simulated Sunlight Rapidly Inactivates SARS-CoV-2 on Surfaces
    May 20. Ratnesar-Shumate. The Journal of Infectious Diseases.
    Opinion from SAB Member: Dr. Jay Przybylo
    This is a biodefense research article proving that simulated sunlight inactivates SARS-CoV-2. 90% of the virus on different surfaces became inactivated in between 7-14 minutes. Lower intensity light containing UV spectra took longer to achieve effect. Different than the article describing the effect of UV light on large populations in geographic regions investigating natural effects of the sun and climate, this article is specific to the actual virucidal effect of the light.
  • The Relationship between Status at Presentation and Outcomes among Pregnant Women with COVID-19. 5/20/20. London V. Am J Perinatol.
    Review by the SAB
    By Dr. Lydia Cassorla, on behalf of the SAB
    This is a single-center retrospective cohort study of pregnant women who tested positive for COVID-19 at one Brooklyn hospital from March 15 to April 15, 2020. Fifty-five SARS-CoV-2 positive pregnant women were followed to term and 1 had fetal demise at 17 weeks. Among parturients with COVID-19 symptoms at presentation (n = 33), 16 (48.5%) had Cesarean delivery, 9 (27.3%) had preterm birth <37 weeks of whom 7 were C/Section for maternal respiratory distress. Twelve (26%) required respiratory support including 1 who required mechanical ventilation. Among those who were asymptomatic at presentation (n = 22), 6 (27%) had Cesarean delivery, and there were no preterm births. Pregnant women who present without symptoms remained asymptomatic to a greater degree than has been reported from cohorts of older individuals. Initially, patients were only tested because of symptoms of potential exposure. Universal testing began during the study period and 13.3% of 76 asymptomatic patients tested after that date were COVID-19 positive. Of 48 neonates tested on day 0 by PCR, none tested positive for COVID-19. Conclusion: Pregnant women with COVID-19-related symptoms have a high rate of severe disease and preterm birth due to Cesarean delivery to treat maternal respiratory distress.

May 20, 2020:

  • A care pathway for the cardiovascular complications of COVID-19: Insights from an institutional response
    Apr 28. Loungani. American Heart Journal.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    Cardiovascular complications may be common in the sickest patients with COVID-19. To that end, the authors present a framework for addressing cardiac complications associated with COVID-19. What’s shown is what to do with myocardial injury, ST segment elevation, heart failure, arrhythmias, and drug considerations.
  • Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic
    May 17. Belhadjer. Circulation.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    A summary of 35 children from France admitted for acute heart failure in febrile cardiogenic shock or left ventricular dysfunction and inflammatory state (all with fever (>38.5°C) and asthenia) that was temporally related to previous exposure to SARS-CoV-2. SARS-Cov-2 infection was confirmed in 31/35 patients (88.5%). 80% of patients were in cardiogenic shock requiring the use of intravenous inotropic drugs. Ten/35 patients (28%) required mechanical circulatory assistance with veno-arterial extracorporeal membrane oxygenation (V-A ECMO) which was weaned and removed in all. All but one patient left the hospital after a median stay of 8 days. The point: not all children have a mild COVID-19 disease.
  • Anticipating and curtailing the Cardiometabolic toxicity of social isolation and emotional stress in the time of COVID-19
    Apr 20. Oren. American Heart Journal.
    Opinion from SAB Member: Dr. David M. Clement
    “Individuals experiencing sustained deficiencies in social interaction attributable to quarantine or physical distancing should be considered at higher risk of cardiovascular disease.” “Understanding social isolation and its public health consequences is key to minimizing the late cardiometabolic burden of COVID-19.” In a well referenced opinion paper, the authors briefly explain this increased risk, and encourage health care providers to address this increased risk by paying more attention to risk modification in individual patients: risk assessment, hypertension, and healthy living habits (diet, exercise, smoking reduction). Though far from flashy, these recommendations are important.
  • Are Gastrointestinal Symptoms Specific for COVID-19 Infection? A Prospective Case-Control Study from the United States. May 19. Chen. Gastroenterology.
    Though this is the first prospective study of GI symptoms in COVID-19 patients, its findings are not surprising. This study from Baltimore was a prospective, case-controlled study of 340 consecutive patients tested by RT-PCR. Symptoms of anorexia and diarrhea, combined with the loss of smell and taste and fever predicted a positive test with 99% specificity. No mention is made of how patients were chosen for RT-PCR testing, no discussion of the influence of false negative test was given, and no patients under 18 yo were included.
  • Clinically Applicable AI System for Accurate Diagnosis, Quantitative Measurements, and Prognosis of COVID-19 Pneumonia Using Computed Tomography
    May 17. Zhang. Cell.
    Opinion from SAB Member: Dr. Barry Perlman
    A variety of projects are investigating how artificial intelligence (AI) tools can be utilized during the COVID-19 pandemic. In this report, CT results from 4154 patients and clinical information from 843 patients in China were used to develop an AI system to diagnose COVID-19 pneumonia and differentiate it from other common (viral, bacterial, and mycoplasma) pneumonias. Data from retrospective and pilot prospective studies were used to validate the system, with sensitivities of 87-95% and specificities of 82-89%. System performance was superior to that of junior radiologists and comparable to mid-senior radiologists. It was found that lung CT findings correlated with clinical and biochemical evidence of disease severity in other organs systems. This AI system may assist in early diagnosis, prognosis prediction, management, evaluation of drug treatment efficacy, and follow up of COVID-19 patients.
  • COVID-19 update: Covid-19-associated coagulopathy
    May 15. Becker. Journal of Thrombosis and Thrombolysis.
    Opinion from SAB Member: Dr. Anil Hingorani, Dr. Lydia Cassorla, Dr. Joseph Anthony Caprini
    AH: This article contains very detailed data on COVID-19 and its effects on coagulopathy that includes basic science.
    LC: This comprehensive and detailed analysis of COVID-19 associated coagulopathy (bleeding and thrombosis phenotypes) is a deep dive into both what is known and speculation about pathophysiology. Overlapping and distinguishing features relative to DIC and thrombotic microangiopathies (including TTP, HUS, pre/eclampsia) are reviewed. Lab features of COVID coagulopathy more resemble DIC, with the exception of the absence of low platelet count. A useful table for comparison is provided. Virchow’s triad of pro-thrombotic factors holds strong. (Abnormal blood flow, vascular injury and abnormalities within the circulating blood). US and international guidelines regarding thromboprophylaxis are reviewed as the world awaits more definitive data from ongoing clinical trials.
    JC: This is an incredibly important paper describing the sophisticated array of changes associated with this viral infection. It is must reading for those interested in learning more about the pathophysiology of the disease. There are too many important points in this paper to repeat otherwise we would rewrite the paper. Most sentences are packed with information. What is important for all of us to understand is that this viral infection is much more than the coagulation system gone wild. In addition, no amount of heparin anticoagulation will be the answer to controlling the morbidity and mortality associated with this disease. The important take away is a concept introduced nearly 50 years ago by the famous hematologist Oscar Ratnoff. He described a “tangled hemostatic web” where contact activation pathways of the blood beginning with factor XII (Hageman factor) resulted in a triggering of platelet, coagulation, fibrinolysis, complement, and kallikrein pathways. The clinical result was not only thrombosis but also systemic vascular changes consistent with activation of both the inflammatory and immunologic pathways. The implications of this work quite clearly involved therapeutic approaches not only involving anticoagulation but also perhaps antiplatelet, anti-fibrinolytic, anti-inflammatory, and anti-immunologic therapy. We know there are various stages of the disease and introducing these modalities at different times may also be important. I personally feel that this knowledge intensifies my zeal for providing early and adequate anticoagulation to these patients along with anti-inflammatory and anti-immunologic therapy to prevent the progression of the disease.
  • Below are three recent literature reviews on neurological manifestations and complications of COVID-19 as well as possible psychiatric and neuropsychiatric effects on patients that are now available. Relying primarily on case reports and pre COVID-19 coronavirus research there is strong suspicion that SARS-CoV-2 gains access to both the central and peripheral nervous system directly and possibly to a larger extent than observed in SARS or MERS. While the etiological mechanisms of anosmia remain unclear, this early sign may be a clue to the neurotropism of the SARS-CoV-2 virus. Separating primary neurologic injury from secondary effects of severe illness, hypoxia, hyper-inflammatory state and multi-organ failure, represents an additional hurdle. While new onset psychiatric illness is unlikely to follow COVID-19 recovery, patients are prone to suffer post-traumatic stress disorder and its complex symptomatology.
    • Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review
      Apr 28. Montalvan. Clinical Neurology and Neurosurgery.
      Opinion from SAB Member: Dr. W. Heinrich Wurm
      This is a systematic review of 67 studies dealing with neurological manifestations of COVID-19, including encephalitis, Guillain Barre, multiple sclerosis, and stroke, but also reviewing available evidence of neurotropism of CoV observed during SARS and MERS. Direct viral access to the CNS through the cribriform plate and olfactory bulb and dissemination via trans-synaptic transfer to the peripheral nervous system remains under investigation, as is the invasion of the medullary cardiorespiratory center as a postulated cause of refractory respiratory failure observed in COVID-19. Future research into the expression of ACE2 receptors in neurological tissues could be the key to some of these questions.
    • Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic
      May 18. Rogers. The Lancet Psychiatry.
      Opinion from SAB Member: Dr. W. Heinrich Wurm
      This systematic review and meta-analysis of 70+ papers deals primarily with psychiatric sequelae of SARS-CoV and MERS-CoV and suggests that among patients admitted to hospital for severe SARS or MERS coronavirus infections, delirium is common acutely, whereas post-traumatic stress disorder, depression, anxiety, and fatigue are common in the following months. COVID-19 patients are likely to experience delirium, confusion, agitation, and altered consciousness, as well as symptoms of depression, anxiety, and insomnia but at this point there is not enough data to determine the overall extent and impact of such sequelae. Based on their review, the authors believe there is no indication that COVID-19 results in new onset mental illness.
    • Neurological manifestations and complications of COVID-19: A literature review
      Apr 24. Ahmad. Journal of Clinical Neuroscience.
      Opinion from SAB Member: Dr. W. Heinrich Wurm
      Narrative review covering the neurological manifestations of COVID-19 based on an English language literature search which at the time of submission (April 24th) consisted of only two series: one retrospective chart review from China (245 patients, 45% neurologic involvement), and one observational study from France (58 patients, 84% neurological involvement). Following a brief discussion of SARS-CoV2’s access to central and peripheral neurons, the authors postulate the two prime mechanisms responsible for neurological injury to be hypoxia and the COVID-19 immune response. What follows are a series of case reports of central and peripheral nervous system effects, including encephalopathies, encephalitis, and strokes, as well as anosmia, myelitis, Guillian Barre syndrome and a poorly defined but not infrequently seen syndrome of skeletal muscle damage accompanied by CPK elevations, severe muscle pain and signs of concomitant kidney and liver injury. The authors conclude with a call for clinicians to track and report more detailed information on neurological manifestations of COVID-19.
  • Should Clinicians Use Chloroquine or Hydroxychloroquine Alone or in Combination With Azithromycin for the Prophylaxis or Treatment of COVID-19?
    May 13. Qaseem. Annals of Internal Medicine.
    Opinion from SAB Member: Dr. Barry Perlman
    Practice points based on evidence review concluded on 4/17/20 by the University of Connecticut Health Outcomes, Policy, and Evidence Synthesis Group and developed by the Scientific Medical Policy Committee of the ACP.
    1. Do not use chloroquine or hydroxychloroquine alone or in combination with azithromycin as prophylaxis against COVID-19 due to known harms and no available evidence of benefits in the general population.
    2. Do not use chloroquine or hydroxychloroquine alone or in combination with azithromycin as a treatment of patients with COVID-19 due to known harms and no available evidence of benefits in patients with COVID-19.
    3. In light of known harms and very uncertain evidence of benefit in patients with COVID-19, using shared and informed decision making with patients (and their families), clinicians may treat hospitalized COVID-19–positive patients with chloroquine or hydroxychloroquine alone or in combination with azithromycin in the context of a clinical trial.

    Additional issues considered:

    1. Chloroquine and hydroxychloroquine are used to manage other major ailments, such as rheumatic diseases, with a known benefit and are in short supply in the United States.
    2. Inappropriate and overuse of antibiotics (e.g., azithromycin) is an important contributor to the antibiotic resistance, an immediate public health threat.
  • Thoracic Anesthesia of Patients With Suspected or Confirmed 2019 Novel Coronavirus Infection: Preliminary Recommendations for Airway Management by the European Association of Cardiothoracic Anaesthesiology Thoracic Subspecialty Committee
    May 17. Senturk. Journal of Cardiothoracic and Vascular Anesthesia.
    Opinion from SAB Member: Dr. Lydia Cassorla, Dr. Joseph Anthony Caprini
    LC: This report is the result of an opinion based survey of anesthesiologists experienced in thoracic surgery (TS) cases regarding management of patients for TS who are known or suspected of being SARS-CoV-2 positive. It is the result of 21 responses from Europe and Canada out of 28 survey requests sent to members of the European Association of Cardiothoracic Anaesthesiology. The report covers all aspects of care. Of interest, it shows a trend towards the choice of a bronchial blocker (BB) over double lumen endotracheal tube (DLT) for lung isolation in both previously intubated and non intubated TS patients. This is related to the potential for reduced aerosolization and reduced tube-changing procedures if the patient is already intubated or is to remain intubated post-op. The flow charts are useful. A nice review of the issues, albeit not data-based. A word of caution: while these practitioners may be rather experienced with the use of BBs, they can be more difficult to place and keep in place than a DLT.
    JC: This publication outlines the consensus recommendations of a group of expert anesthesia specialists who were surveyed regarding the overall approaches to general and specific aspects of airway management, preparations for anesthesia, lung isolation/separation procedures and ventilation itself. It is a very detailed analysis. The authors are quick to point out that the recommendations contained in this document are not claimed to be evidence-based or comprehensive. They do represent the opinion of experts regarding conducting routine daily practice and patience with this serious viral infection.
  • Unique Patterns of Cardiovascular Involvement in COVID-19. May 11. Hendren. J Card Fail.
    The authors described the variable presentations of cardiac involvement in COVID-19 within the broader spectrum of symptomatic SARS-CoV-2 infection, something that has previously been proposed. There are two phenotypes: cardiac involvement superimposed on top of the typical pulmonary predominate symptoms or isolated or predominate cardiac presentation. Though fever is common with typical pulmonary involvement, not so in the predominate cardiac phenotype. The troponin level with an isolated cardiac presentation can be absent or markedly elevated depending on the presentation. Though with a cardiac predominate disease there may be chest pain due to a myocardial infarction, patients with COVID-19 disease superimposed on pulmonary disease. Much speculation.

May 19, 2020:

  • Age and sex differences in soluble ACE2 may give insights for COVID-19. May 14. Edsfeldt. Crit Care.
    Research letter detailing longitudinal study of soluble ACE2 (sACE2) levels by gender and age to determine potential differences and possible determinants of COVID-19 susceptibility for elderly male patients based on observation that disease more prevalent in adults>children and men>women. sACE2 levels analyzed from individuals registered in the pediatric osteoporosis prevention (POP) study; from age 7.7 years to 23.5 years at 2 to 3 year intervals. Results indicated that sACE2 levels increase more as boys age than girls. Authors suggest results support for observations re: age and sex prevalence for COVID-19 susceptibility.
  • Angiotensin II infusion in COVID-19-associated vasodilatory shock: a case series
    May 15. Zangrillo. Critical Care.
    Opinion from SAB Member: Dr. Philip Lumb
    This research letter details a trial of angiotensin II (ANGII) in 16 patients with vasodilatory shock resistant to high dose catecholamine (norepinephrine > 0.25 mcg/kg/min) as either first line or rescue infusion in a compassionate use protocol. Patients demonstrated improvement in oxygenation parameters associated with ANGII infusion; catecholamines were withdrawn or significantly reduced after 24 hours. Small series with interesting and favorable results.
  • Antibody Testing For Covid-19
    May 15. Mathur. American Journal of Clinical Pathology.
    Opinion from SAB Member: Dr. Barry Perlman
    Accurate antibody tests can help with diagnosis, identify those with asymptomatic infections, determine prevalence in a population, aid in contact tracking, and measure progression to herd immunity. The 10 antibody tests that are currently FDA-approved have, on average, a sensitivity of 84.9% and a specificity of 98.6%. Sensitivities of these tests range from 58% to 94%. 90 additional tests are available for use, but are not yet FDA approved and don’t have sensitivity and specificity established. Table 2 demonstrates that positive predictive value varies widely depending on both the accuracy of the tests and local disease prevalence. When prevalence is high, such as in the greater NY area, antibody tests with specificity and sensitivity of 98% or better can be used as reliable screening tools. In areas of low prevalence, a test would need 100% specificity to avoid false positive results that could incorrectly indicate that someone is immune to COVID-19. The authors warn against using serologic tests not yet FDA approved with unknown accuracy to guide decision making.
  • Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19). May 1. Diao. Front. Immunol.
    Lymphopenia is a feature in Covid-19, however the number of T cells marking progressive disease is not known. This retrospective analysis from Wuhan, China examined 522 cases from December 2019 to January 2020. The critical numbers of total T cells, CD4+ and CD8+ T cells indicating more critical illness or impending death were less than 800, 300, or 400/μL, respectively. Also, these T cells expressed enhanced surface PD-1 and Tim-3, so called “exhaustion markers”. T cell numbers are negatively correlated to the “cytokine storm” mediators TNF-α, IL-6, and IL-10. This study suggests low T lymphocyte counts mandates early intervention.
  • Risk Factors of Severe Disease and Efficacy of Treatment in Patients Infected with COVID-19: A Systematic Review, Meta-Analysis and Meta-Regression Analysis. May 14. Zhang. Clin Infect Dis.
    This is an extensive meta-analysis and meta-regression of 45 studies (Asia only) with 4,203 patients, noted rates of intensive care unit (ICU) admission (10.9%), mortality (4.3%) and acute respiratory distress syndrome (ARDS) (18.4%). The investigators followed up with the regression analysis of these patients and studied the associations with the key epidemiological features, clinical characteristics, laboratory investigations, radiological findings, treatment details for outcomes of COVID-19. The investigators have statistically significant proof for their finding that: 1. elevated LDH is a significant predictive marker of ARDS; 2. Both elevated leukocyte count and elevated LDH suggests clinically a secondary infection and its complication on multi-systems which also predict the mortality; 3. Treatment with the anti-retroviral drug lopinavir-ritonavir was not associated (antiviral treatment likely to be all 6, 4 or 2 drugs) with any additional significant benefit on complications or outcome; and 4. corticosteroids were associated with possible harm.
    Strength: Extensive statistical proof while addressing biases. The publications included were GRADE (A method of exclusion) then addressed by several filters for the non-validity, has excellent graphs and tables. The secondary outcome (infection – 8.9% cardiac injury 7.8 %..) noted. Subgroup analysis for antiviral drugs and steroids are also complementary to the investigation.
    Weakness: No mention of -> Prone benefits, convalescent plasma therapy OR HCQ, LDH and its association with shock or antiviral Meds. Asian patients only (High tobacco?).
  • Smell and taste alterations in Covid-19: a cross-sectional analysis of different cohorts
    May 14. Paderno. Allergy & Rhinology.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    In this study of a little over 500 patients who were either hospitalized or in quarantine with laboratory confirmed SARS-CoV-2 disease, whose data was collected between March 27 and April 1 via survey, the prevalence of olfactory and gustatory dysfunction was greater than 50%. There was a higher prevalence in home-quarantined patients (79% vs 72%). Hospitalized patients, though, had more dyspnea and a lower rate of flu-like syndrome. Indeed, because of a severe clinical condition and a decrease in oral intake, the perception of olfactory and gustatory dysfunction in the inpatient setting was likely lower than for outpatients. Outpatients were also younger, healthier, were less likely to smoke, and were more likely female.
  • Understanding pathophysiology of hemostasis disorders in critically ill patients with COVID-19
    May 15. Joly. Intensive Care Medicine.
    Opinion from SAB Member: Dr. Anil Hingorani, Dr. Joseph Anthony Caprini
    AH: This review of the literature of COVID-19 and its effects on coagulation is complete and bridges into the clinical effects of this knowledge.
    JC: This paper describes a number of interesting observations regarding the pathophysiology and clinical manifestations of this disease. The focus of this paper on heparin, while important, does not adequately reflect to the reader what is involved in the correlation between pathophysiology and various treatment modalities. The Becker paper captures more fully the myriad of pathophysiologic mechanisms, and provides a good source for the interested reader regarding these interactions in COVID-19. The bottom line for the treating physician is there is going to be a combination of therapeutic modalities including heparin at various stages of the disease needed to blunt the pathophysiologic changes described in this paper. Thromboelastography is mentioned in this paper as a possible way to measure the sum total of these effects using a global test. I’m a strong proponent of this method, having worked with it for many years, but it is not quite ready for clinical application except in prospective studies correlating the results with known hemostatic tests. Reminding us that evidence-based data is not available for full anticoagulation isn’t very helpful, especially since there are a number of reports showing a variety of beneficial effects with these treatment doses.
  • Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction–Based SARS-CoV-2 Tests by Time Since Exposure
    May 13. Kucirka. Annals of Internal Medicine.
    Opinion from SAB Member: Dr. Barry Perlman
    This analysis illustrates that the predictive value of a negative SARS-CoV-2 RT-PCR test result depends on both pre test probability and test timing relative to exposure or symptom onset. Therefore, it applies more to “ruling out” infection in exposed patients and health care workers, rather than “clearing” asymptomatic patients for elective surgery. Using results from 7 previous studies reporting SARS-CoV-2 RT-PCR results, a Bayesian hierarchical model was created to estimate the false-negative rate by day since symptom onset or virus exposure. The model assumed a typical 5-day incubation period to symptom onset. The probability of RT-PCR false negative decreased from 100% on day 1 of exposure to 20% on day 8 (3 days after typical symptom onset), and then increased again to 66% on day 21. Therefore, the lowest post test probability from 1 negative RT-PCR test is achieved when the test is done on day 8, 3 days after symptoms onset. However, the post test probability from a negative day 8 sample varied from 1.2% to 14% depending on the pretest probability. The model suggests that negative RT-PCR tests early or late in infection should not be used to rule out COVID-19 if suspicion is high based on clinical and epidemiologic information.

May 16, 2020:

  • A Game Plan for the Resumption of Sport and Exercise After Coronavirus Disease 2019 (COVID-19) Infection
    May 13. Phelan. JAMA Cardiology.
    Opinion from SAB Member: Dr. Barry Perlman
    Expert consensus opinion from members of the American College of Cardiology’s Sports & Exercise Cardiology Council, with input from national leaders in sports cardiology, regarding when those recovered from COVID-19 can return to recreational or competitive sports. Acute cardiac injury, based on elevated troponin, EKG changes, or ECHO abnormalities, occur in up to 22% of hospitalized COVID-19 patients. After myocarditis, return to play should require “normalization of ventricular function, absence of biomarker evidence of inflammation, and absence of inducible arrhythmias.” ECHO, stress testing, and rhythm monitoring are used to determine risk stratification after 3-6 months of exercise restriction. An algorithm is provided based on COVID-19 testing and symptoms: 1) Asymptomatic COVID-19 positive athletes or those who have detected antibodies indicating prior infection can slowly resume activity after 2 weeks; 2) If mild or moderate symptoms, a minimum of 2 weeks cessation of exercise training after symptoms resolve is recommended, and if cardiovascular evaluation including cardiac biomarkers and imaging reveal evidence of cardiac involvement, myocarditis return-to-play guidelines should be followed; 3) For those who were hospitalized or had more severe COVID-19, myocarditis return-to-play guidelines should be followed, and if cardiac biomarkers and imaging are normal after cardiac reevaluation graded, resumption of exercise can start at a minimum of 2 weeks after symptom resolution.
  • A primer on viral-associated olfactory loss in the era of COVID-19
    Apr 9. Soler. Allergy & Rhinology.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    A nice summary of olfactory loss associated with COVID-19 that helps to answer questions that include presentation and evaluation, natural history, mechanisms of disease and viral pathogens, pharmacologic treatment, olfactory training. The authors then conclude with some practical recommendations including the fact that COVID-19 should be considered if a patient has a sudden loss of smell and/or taste, patients with an acute loss of smell and taste after COVID-19 should assume smell loss is virally associated, oral or topical steroids should not be used to treat acute loss of smell with active COVID-19, olfactory training should be started sooner rather than later, and for persistent loss of smell, consult an otolaryngologist.
  • A serological assay to detect SARS-CoV-2 seroconversion in humans
    May 12. Amanat. Nature Medicine.
    Opinion from SAB Member: Dr. Jay Przybylo
    A dense, technical Brief Communication stating in the first sentence that the authors developed “a serological enzyme-linked immunosorbent assay” that then proceeds to describe the purpose and method culminating in the assay to assess the presence of SARS-CoV-2 spike protein antibody.
  • AGA Institute Rapid Review of the GI and Liver Manifestations of COVID-19, Meta-Analysis of International Data, and Recommendations for the Consultative Management of Patients with COVID-19
    May 1. Sultan. Gastroenterology.
    Opinion from SAB Member: Dr. David M. Clement
    This is an excellent paper from the American Gastroenterological Association for frontline workers wanting to understand and care for patients with GI disease during the COVID-19 pandemic. It starts with a detailed meta-analysis (47 studies with 10,890 patients) of GI symptoms and abnormal LFTs in patients with COVID-19. Overall, 10% of COVID-19 patients had GI symptoms and 15% had elevations of AST and/or ALT. Both GI symptoms and elevated LFTs were more common outside China. Occasionally, GI symptoms presented before other COVID-19 symptoms. Though fecal RT-PCR testing is commonly positive, culture of SARS-CoV-2 is rarely successful. Numerous tables are included, such as the GI side effects of commonly used COVID-19 drugs. Based on all pooled information, guidelines are presented for frontline providers dealing with GI symptoms in the COVID-19 era. These include, among others, checking for other etiologies of GI symptoms in outpatients, following LFTs on COVID-19 inpatients, not testing stool, and following outpatients with GI symptoms alone in case they develop COVID-19.
  • Anaesthesia and intensive care in obstetrics during the COVID-19 pandemic. May 6. Morau. Anaesth Crit Care Pain Med.
    This is a complete recommendation list to all personnel, how to prepare for COVID-19 environments at labor and delivery (L&D) room. The author points out that L&D cannot afford to hold back and has to continue to perform the duty irrespective of the pandemic which is of high transmissibility and infectivity of this virus. The authors have provided management skills required for this disease in detail regarding all system involvements and their complications that pertain to parturient. The authors review the antenatal, post and intra natal care, role of triage, role of testing for COVID-19, anesthetic care, pain treatment, staff training…and stresses the need for PPE but be prepared for telemedicine where it’s possible, infection control, and a need to be vigilant of known complications to mother/fetus and offers practical points. A helpful guide to all L&D staff.
  • Asymptomatic Seroconversion of Immunoglobulins to SARS-CoV-2 in a Pediatric Dialysis Unit
    May 14. Hains. JAMA.
    Opinion from SAB Member: Dr. Jay Przybylo
    This is a Research Letter describing the futility of limiting the spread of SARS-CoV-2 using a pediatric dialysis unit as an example. A single patient presented to the unit and was isolated for therapy. This initiated testing on everyone, patients and staff, in the unit. 38% of patients and healthcare workers who presented repeatedly to this unit seroconverted positive to the virus by serum evaluation over a two-week period, proof that this virus is rapidly spreading in unrecognized ways.
  • Characteristics and Outcomes of Coronavirus Disease Patients under Nonsurge Conditions, Northern California, USA, March-April 2020. May 14. Ferguson. Emerg Infect Dis.
    This report from Stanford presents data from 72 Covid-19 patients in their hospitals over a 4-week period. Their patients had similar risk factors but better outcomes than have generally been reported. Overall death rate was 8.3% with a 14% death rate for ICU patients. The potential explanations are discussed, including non-surge conditions. They observed different standards of care between their two hospitals and call for standardized, well-publicized guidelines for new pathogens early on in an epidemic.
  • Considerations for Assessing Risk of Provider Exposure to SARS-CoV-2 after a Negative Test. May 8. Long. Anesthesiology.
    Decisions will need to be made about how to address airway management and degree of PPE going forward. This is a discussion of the statistical methods necessary to predict the risk of exposure of an anesthesiologist to SARS-CoV-2 if a patient has had a single negative test. The authors discuss the factors including prevalence in the population, volume of surgery, and degree of risk tolerance in the face of uncertainty. They suggest that policies should place a priority on a low threshold of negative predictive value and argue for universal airborne precautions, irrespective of preoperative test results.
  • Corona Viruses and the Chemical Senses: Past, Present, and Future
    May 14. Pellegrino. Chemical Senses.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    In this review of chemosensory ability in patients with COVID-19, the authors sought to determine whether chemosensory dysfunction is the same with COVID-19 as it is with other pandemics including SARS and MERS and whether COVID-19 represents a special case of viral infection attacking the olfactory system. They also discussed whether the taste disturbances with COVID-19 are a misrepresentation of olfactory disturbances rather than the direct impact of SARS-CoV-2 on taste and chemical sensitivity of skin and mucous membrane pathways. First, whether taste disturbance is olfactory-dependent or instead reflects true taste loss in COVID-19 is currently unclear. Second, olfactory disturbances may not be as prominent in SARS and MERS as with COVID-19. Third, the reduction in sensitivity being associated with reduced ability to promote the clearing of pathogenic agents from the nasal cavities can only be speculated. Certainly, distinguishing each aspect of chemo-sensation in patients with confirmed and suspected COVID-19 diagnosis as well as with other respiratory illnesses is needed to determine whether the chemical senses are uniquely affected by COVID-19 infection.
  • Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19. May 12. Liang. JAMA Intern Med.
    Developed a prediction model for composite end point of ICU admit, need for a ventilator, and death based on ten variables: cxray abnormality, age, hemoptysis, dyspnea, unconsciousness, # of comorbidities, cancer hx, neutrophil/lymphocyte ratio, LDH, and direct bilirubin.
  • Editorial: Is the Prone Position Helpful During Spontaneous Breathing in Patients With COVID-19?
    May 15. Telias. JAMA.
    Opinion from SAB Member: Dr. Philip Lumb
    This is an intelligent discussion and summary of related articles that demonstrates interesting observations regarding prone positioning despite small sample sizes, lack of controls and limited outcome benefits in clinical studies. Taken in context of related case studies, this editorial stimulates discussion and further clinical trials.
  • Elective Tracheostomy During Mechanical Ventilation in Patients Affected by COVID-19: Preliminary Case Series From Lombardy, Italy. May 12. Turri-Zanoni. Otolaryngol Head Neck Surg.
    Most interesting statement in paper: “early recommendations worldwide seem to suggest waiting at least 14 days of endotracheal intubation to avoid clinically futile procedures for patients…” Remainder is common sense infectious disease protection.
  • Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population-based cohort study. May 12. Banerjee. The Lancet.
    Opinion from SAB Members: Drs. Barry Perlman and Heinrich Wurm
    BP: To better assess the impact of COVID-19 on mortality, EMR data from 3 862 012 individuals in the United Kingdom > 30 yrs old were used to model 1 yr mortality in excess of baseline and deaths due to underlying conditions. Based on reported prevalence, 1 yr mortality from underlying conditions were estimated. The excess COVID-19 related deaths were then modeled at varying relative COVID-19 mortality risks and suppression related prevalence scenarios. 20% of the study population had at least one high-risk condition and 10% had multiple conditions. Excess deaths from COVID-19 decreased with increasing suppression measures. At a relative risk of 2, full suppression would result in minimal excess mortality. These models could help determine appropriate social distancing and isolation measures, particularly for individuals at highest risk. However, the models don’t take into account non-linear increase in mortality rates if health systems become overwhelmed, the impact of poor compliance with social isolation policies, impact of specific morbidities or multiple co-morbidities on risk of COVID-19 mortality, or impact of social distancing on underlying conditions.
    HW: In this population-based cohort study, a team of authors from the Institute of Health Informatics at the University College of London, used 3.8 million electronic health records as the basis for their modeling. They estimated the excess number of deaths over 1 year under different COVID-19 incidence scenarios based on 4 different levels of transmission suppression and differing mortality impacts based on 3 different relative risk scenarios for the disease. The result is a model and an online tool for understanding mortality – in excess of the expected – due to the COVID-19 pandemic. It signals an urgent need for sustained, stringent suppression measures.
  • Gastrointestinal and Liver Manifestations of COVID-19. Mar 1. Agarwal. J Clin Exp Hepatol.
    A brief literature review of GI symptoms and elevated LFTs in COVID-19 patients. Mostly data from China, somewhat dated.
  • Interferon beta-1b for COVID-19
    May 8. Shalhoub. The Lancet.
    Opinion from SAB Member: Dr. Barry Perlman
    Studies of interferons alpha and beta have shown variable results with SARS-CoV and no significant benefit with MERS-CoV. This comment discusses the accompanying study of triple drug therapy (https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(20)31042-4.pdf) including interferon beta-1b for patients with mild-moderate COVID-19 by Hung et al. While combination therapy with interferon showed benefit as compared to lopinavir-ritonavir alone, further studies with larger patient numbers and use of placebo controls are needed to determine: 1) whether patients with severe disease would benefit; 2) if interferon beta-1b has efficacy alone or in combination with other medications; 3) how best to treat patients when therapy is started more than 7 days after symptom onset; and 4) the optimum number of interferon beta-1b doses.
  • Novel coronavirus (COVID-19) infection: What a doctor on the frontline needs to know. May 14. Down. Ann Med Surg (Lond).
    Slightly outdated review of available knowledge and diagnostic and therapeutic options for COVID-19 without any new insight.
  • Organ procurement and transplantation during the COVID-19 pandemic. May 11. Loupy. Lancet.
    The authors conclude that the COVID-19 pandemic has caused a dramatic loss of organs all across the world. Deceased organs denied means more preventable death likely in coming months. The overall reduction in deceased donor transplantations since the COVID-19 outbreak was 90.6% in France and 51.1% in the USA, respectively. In both France and the USA, this reduction was mostly driven by kidney transplantation, but a substantial effect was also seen for heart, lung, and liver transplants, all of which provide meaningful improvement in survival probability. Leaders of medical institutions will make difficult decisions about how best to deploy limited medical resources. The authors state that the data from public record suggests the only option is living related organ transplant.
  • Potential for Lung Recruitment and Ventilation-Perfusion Mismatch in Patients With the Acute Respiratory Distress Syndrome From Coronavirus Disease 2019
    Apr 28. Mauri. Critical Care Medicine.
    Opinion from SAB Member: Dr. Louis McNabb
    In this article, ventilated patients with COVID-19 were given PEEPs of 5 and 15 cmH2O. The degree of lung recruitment was variable among the participants and most of the V/Q mismatch was attributed to increased dead space ventilation.
    • Dealing With the CARDS of COVID-19
      May 13. Marini. Critical Care Medicine.
      Opinion from SAB Member: Dr. Louis McNabb
      This is an editorial response to above article that describes different phases of COVID-19 lung involvement, which require different ventilator strategies. The author describes the potential pathophysiologic causes of V/Q mismatch.
  • Respiratory disease in rhesus macaques inoculated with SARS-CoV-2. May 12. Munster. Nature.
    An excellent and detailed study of SARS-CoV-19 infection in eight Rhesus Macques, showing by clinical, testing and pathologic means that the disease is similar to that in humans. It is suggested that Rhesus Macques could provide a laboratory model for human infection.
  • Respiratory Parameters in Patients With COVID-19 After Using Noninvasive Ventilation in the Prone Position Outside the Intensive Care Unit
    May 15. Sartini. JAMA.
    Opinion from SAB Member: Dr. Philip Lumb
    This is a research letter describing observations on non-invasive ventilation (FiO2 0.6; 10 cm H2O CPAP) in the prone position (PP) on April 2nd, 2020. Measured outcomes of proning during the observation period included SPO2, respiratory rate, and comfort and tolerance of PP, before, during and after proning. Fifteen patients were identified and during proning, all demonstrated increased oxygenation, decreased RR, and adequate comfort. The clinical status of patients followed up at day 14 (April 16, 2020) included: 9 discharged home, 1 improved, 3 continued pronation, 1 intubated and in ICU, and 1 died. As the authors state, “Limitations include the small number of patients, short duration of NIV in the prone position, and lack of a control group. Comparisons of NIV in the prone position with oxygen by face mask or NIV in the standard position are needed. Importantly, selection bias is possible.”
  • The electronic medical record and COVID-19: is it up to the challenge?
    May 2. Pryor. American Journal of Infection Control.
    Opinion from SAB Member: Dr. Barry Perlman
    This is a discussion of existing EMR barriers during the COVID-19 pandemic. Currently, hospital infection prevention (IP) teamwork and communication with caregivers and other hospital staff involve too many manual processes. Identified areas in need of more EMR assisted automation include: notification and identification of suspected and positive COVID-19 patients, tracking infected and suspected inpatients and inter-facility transfers, and ensuring proper isolation orders are executed. For example, EMR screens should be more standardized across disciplines, improved EMR communication between health systems is needed, and IPs should receive more automated alerts regarding testing and patient disposition.
  • Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. May 8. Hung. Lancet.
    Multicenter, prospective, open-label, randomized phase 2 trial with adult confirmed COVID-19 patients in 6 Hong Kong hospitals. 52 combination medication patients received lopinavir, ritonavir, ribavirin, and Interferon beta-1b. For 34 combination medication patients who started treatment after 7 days of symptom onset, interferon beta-1b was omitted due to concerns of pro inflammatory side effects. 41 controls received just lopinavir and ritonavir. Stress steroids were also given to patients requiring oxygen support, and approximately half the patients in each group received antibiotics. The time to negative nasopharyngeal swab RT-PCR (primary endpoint) was 7 days for the combination medication group and 12 days for the control group. The combination group also had earlier time to negative RT-PCR from other specimen locations, quicker alleviation of symptoms, earlier hospital discharge, and decreased IL-6 levels. One control patient withdrew due to 6x increased alanine transaminase, but there were no differences in mild, self limiting adverse effects between the 2 groups. Of note, for patients who started treatment > 7 days after symptom onset, there were no significant differences in outcome between the combination medication group (minus interferon beta-1b) and the control group, suggesting the beneficial effects of interferon beta-1b. However, it is not known if patients who start treatment after 7 days of symptoms onset would benefit from interferon beta-1B. Further, since severe COVID-19 patients were not included, further studies are needed to determine if these patients would benefit from the combination therapy.
  • Use of Prone Positioning in Nonintubated Patients With COVID-19 and Hypoxemic Acute Respiratory Failure
    May 15. Elharrar. JAMA.
    Opinion from SAB Member: Dr. Philip Lumb
    This research letter includes 24 patients entered into a spontaneous breathing prone positioning trial. Reported outcomes: 1) ability to tolerate position for specified and increasing times; 2) PaO2 increase in prone position (PP); 3) sustained PaO2 increase on resupination; 4) progression of disease. The article notes that of 5 patients requiring intubation, 4 did not tolerate prone position for > 1 hour. Out of 24 patients, 15 (63%) tolerated PP > 3 hours, oxygenation increased in 6 (25%), and sustained following resupination in 3 (12%). As authors note, the study had several limitations–the sample was small, a single episode of PP was evaluated, the follow-up was short, clinical outcomes were not assessed, and causality of the observed changes cannot be inferred.

May 15, 2020:

  • An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study
    May 13. Verdoni. The Lancet.
    Opinion from SAB Member: Dr. Jay Przybylo
    A study of Kawasaki-like illness comparing children presenting over a five-year period prior to SARS-CoV-2 to a group of children presenting in a two-month period after SARS-CoV-2. The disease is further broken down into children presenting with circulatory dysfunction vs immune system disorder. An included table describes in depth all possible variables of the COVID-19 patients. Compared with adults, children have a more benign respiratory illness, yet suffer from vasculitis and cytokine storm. All received immunoglobulin in addition to aspirin. Steroids were administered to a minority of patients. No children were reported to die. The report contains a discussion of Kawasaki Syndrome and links the probable cause to a virus.
  • An Update on Current Therapeutic Drugs Treating COVID-19
    May 11. Wu. Current Pharmacology Reports.
    Opinion from SAB Member: Dr. W. Heinrich Wurm
    A review of common and not-so-common therapeutic agents in current use or under consideration to treat COVID-19 patients, collated by a group from Rutgers School of Pharmacy. Grouped into antivirals, supportive, miscellaneous and traditional herbal medicine, the discussion spans across a wide array of therapies currently used around the globe to deal with COVID-19. Mechanism action and logistics of use in COVID-19 as well as other viral illnesses is addressed, and pros and cons according to recent studies are reviewed. Ongoing trials worldwide are listed. Along with 175 citations, this paper represents a valuable reference for clinicians and investigators.
  • COVID Activated Emergency Scaling of Anesthesiology Responsibilities (CAESAR) ICU
    May 7. Verdiner. Anesthesia & Analgesia.
    Opinion from SAB Member: Dr. Jagdip Shah
    Practitioners from the American Society of Anesthesiologists (ASA), the Society of Critical Care Anesthesiologists (SOCCA), the Society of Critical Care Medicine (SCCM), and the Anesthesia Patient Safety Foundation (APSF), representing more than a dozen universities in the USA, created the COVID Activated Emergency Scaling of Anesthesiology Responsibilities (CAESAR) ICU working group. The specific goal is to address the shortage of critical care medicine (CCM) MDs in this current COVID-19 pandemic when supply is mismatched with demand, by fast-tracking anesthesiologists with short notice. This long article is formatted as a knowledge-based guideline. It addresses all possible potential areas of weaknesses in anesthesiology knowledge as it pertains to practicing in the ICU on day #1. The authors have provided state of the art information about the pathophysiology of COVID-19, pertaining to all the disciplines (respiratory, cardiovascular, renal, inflammation cascades, central nervous system, infection control, endocrinology, coagulation dichotomy, etc.) in a dynamic fashion. The article is a well referenced and complete effort to inform non-ICU physicians in simple formats of an inner working of the ICU regarding: multi-specialty involvement, scoring systems for patients, the ABCDEF Bundle (Assess, prevent, and manage pain, Both spontaneous awakening trials and spontaneous breathing trials, Choice of analgesia and sedation, Delirium: assess, prevent, and manage, Early mobility and exercise, and Family engagement and empowerment), drug therapy / interactions, supply shortages and their implications, managing codes, interpretation of monitors, ventilator synchronizations, proning, CPR, ARDS, glucose control, ECHO, ECMO, CRRT/dialysis/ultrafiltration, ethical philosophy, the role of the triage committee, and role of palliative care and hospice. The authors explain clearly that COVID-19 is a very different disease regarding its transmissibility to the caregivers, and stresses the need for adaptability of the healthcare system for a huge surge of ICU demand while optimizing the patients for greater benefit and greater good without wasting time, effort and resources.
  • Currently available intravenous immunoglobulin contains antibodies reacting against severe acute respiratory syndrome coronavirus 2 antigens. May 12. Díez. Immunotherapy.
    Antibodies against common human coronaviruses are present in the normal population. 2 IVIG products Gamunex-C and Flebogamma DIF were tested with ELISA assays from different manufacturers for crossreactive antibodies to SARS-CoV-2 and other coronaviruses including SARS-CoV and MERS-CoV. While cross reactivity was demonstrated, further research is needed to determine clinical efficacy and safety for COVID-19 treatment.
  • Evaluation of coagulation function by rotation thromboelastometry in critically ill patients with severe COVID-19 pneumonia
    May 11. Pavoni. Journal of Thrombosis and Thrombolysis.
    Opinion from SAB Member: Dr. Lydia Cassorla, Dr. Joseph Anthony Caprini, Dr. Anil Hingorani
    LC: While perhaps not available or familiar to many, ROTEM, a form of thromboelastography (TEG), is a clinically useful point-of-care tool that can help evaluate coagulopathy. It extends diagnostic capability beyond traditional coagulation studies by providing an evaluation of platelet function, clot strength, and fibrinolysis. The test takes about an hour to complete and requires user training. This Italian single center retrospective observational study evaluated ROTEM in 40 consecutive COVID-19 patients admitted to the ICU with multiple measurements over 10 days. In many, hypercoagulability without consumptive coagulopathy or secondary hyperfibrinolysis was detected. The article provides discussion of the potential value of ROTEM over conventional coagulation studies in COVID-19 to guide therapy and calls for prospective studies. JC: This is an interesting article introducing the concept of using viscoelastic measurements to correlate with clinical events in patients with a severe viral infection. This study is small but it does demonstrate the concept of hypercoagulability. I am not sure at this point given the widespread vascular damage associated with this disease how this unique technique is going to be clinically helpful. I’m not discouraging the use of this technique which I have used extensively in the past for other purposes, but realize that we need more work. One interesting thought is that we know many patients following hospitalizations are still at high risk of developing thrombotic complications. Furthermore, there have been attempts to identify patients who would benefit from extended anticoagulation based on risk factors including laboratory parameters such as D dimer. It would be interesting to learn whether this technique might be useful in deciding the length of extended anticoagulant prophylaxis based on the return of the thrombelastographic parameters to normal. AH: This is an evaluation of coagulation function by rotation thromboelastometry in critically ill patients with severe COVID-19 pneumonia (n=40). This is a point-of-care test to assess hypercoaguability for COVID-19, and is NEW data worth reviewing.
  • Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis. May 12. Mao. The Lancet Gastroenterology and Hepatology.
    Lengthy meta-analysis from China detailing the GI symptoms and LFTs in COVID-19 patients. The pooled prevalence of digestive symptoms was 15%, and of abnormal liver functions was 19%. Of note, pediatric patients with COVID-19 had a similar prevalence of gastrointestinal symptoms to those of adult patients. More severe GI symptoms and abnormal liver tests were more common in patients with severe COVID-19 disease.
  • Mechanical Ventilation in COVID-19: Interpreting the Current Epidemiology
    Apr 26. Wunsch. American Journal of Respiratory and Critical Care Medicine.
    Opinion from SAB Member: Dr. Jay Przybylo
    A plea for action using COVID-19, ARDS and ventilatory support for the example of demonstrating the differences in care that exist internationally and regionally. No aspect of the choice to ventilate exists in a rational, prescribed manner. As evidence, the author cites the JAMA article with 88% New York mortality in mechanically ventilated patients, the difference between the 29% mechanically ventilated patients cited in China compared to 89.9% in the U.S., and the difference in ventilatory assistance between 18.6% and 42.0% in California alone. The author cautions that differences in care resulted in differences in outcomes, publications and conclusions. COVID-19 has amplified these differences in care.
  • Medically Vulnerable Clinicians and Unnecessary Risk During the COVID-19 Pandemic
    May 13. Janvier. The American Journal of Bioethics.
    Opinion from SAB Member: Dr. Philip Lumb
    This is an intellectually provocative discussion on appropriate tasks for retired physician volunteers in COVID-19 areas. The article entertains appropriate conflict between “wishing to be in the front line” versus more appropriate and potentially intellectually valuable activities that entertain less risk for volunteers and the health system.
  • Multidisciplinary guidance for safe tracheostomy care during the COVID-19 pandemic: the NHS National Patient Safety Improvement Programme (NatPatSIP)
    May 12. McGrath. Anaesthesia.
    Opinion from SAB Member: Dr. David M. Clement
    Prolonged ventilation necessitating tracheostomy is not uncommon with the COVID-19 pandemic. To address most questions about tracheostomies, UK stakeholder organizations involved in tracheostomy care developed consensus guidelines based on the available literature, expert opinion, and existing multidisciplinary guidelines. These guidelines address infectivity of patients with respect to tracheostomy, indications and timing, aerosol-generating procedures, risks to staff, insertion procedures, and management following tracheostomy. The paper is long but well organized, and starts out with the key points, such as recommending an apnea test, the use of full muscle paralysis for tracheostomy insertion, and plans to define and limit trach care post-insertion to reduce virus exposure to staff.
  • Real-time tracking of self-reported symptoms to predict potential COVID-19
    May 11. Menni. Nature Medicine.
    Opinion from SAB Member: Dr. Lydia Cassorla
    This interesting report may represent a sign of the future of disease prediction models. 2.6M users reported symptoms on a smartphone-based app during a 4 week period beginning 24 March 2020. 93.6% in GB (balance in US). 15,638 UK and 2,763 US app users reported having had an RT-PCR SARS-CoV-2 test, and having received the result. Of the UK cohort with a (+) COVID PCR test, 65% reported a loss of smell and taste, compared with 23% of those with a (-) test result. “We re-ran logistic regressions adjusting for age, sex and BMI to identify other symptoms besides anosmia that might be associated with being infected by SARS-CoV-2. All ten symptoms queried (fever, persistent cough, fatigue, shortness of breath, diarrhea, delirium, skipped meals, abdominal pain, chest pain and hoarse voice) were associated with testing positive for COVID-19 in the UK cohort…In the US cohort, only loss of smell and taste, fatigue and skipped meals were associated with a positive test result.” A prediction model was created including factors of age, sex, loss of smell/taste, cough, fatigue, and skipped meals. “In the UK test set, the prediction model had a sensitivity of 0.65 (0.62–0.67), a specificity of 0.78 (0.76–0.80), an area under the curve (AUC) of the receiver operating characteristic curve (ROC) (that is, ROC-AUC) of 0.76 (0.74–0.78), a positive predictive value of 0.69 (0.66–0.71) and a negative predictive value of 0.75 (0.73–0.77).” Application of the model to the US cohort showed similar sensitivity and increased specificity of 0.83. Limitations include self-selection of cohorts, self-reporting, testing selection bias, and in GB the influence of media reports. The authors recommend adding loss of smell/taste to WHO symptom list for COVID-19.
  • Recruitability and effect of PEEP in SARS-Cov-2-associated acute respiratory distress syndrome
    May 12. Beloncle. Annals of Intensive Care.
    Opinion from SAB Member: Dr. Jay Przybylo
    A follow-up to a previous case report prospective study demonstrating the effect of high vs low PEEP on two groups of mechanically ventilated SARS-CoV-2 patients divided into highly vs poorly recruitable lung mechanics. Determining the R/I ratio, the ratio between the recruited lung compliance and CRS at a PEEP of 5 cmH2O, might lead to better ventilatory management.
  • Risk Factors for Viral RNA Shedding in COVID-19 Patients. May 12. Fu. Eur Respir J.
    Retrospective study of 410 confirmed COVID-19 patients in China who received follow-up RT-PCR testing after symptoms started to improve. 14% had 1 negative test followed by 1 positive test. Median time to 2 consecutive negative tests was 19 days after symptom onset (range 3-44 days) and 7 days after fever resolution. 96% tested negative within 30 days of symptom onset. 40 patients had fever resolution after testing negative. Coronary heart disease, serum albumin < 35 g/L, and initiation of antiviral treatment > 7 days after symptom onset were independent risk factors for prolonged positive tests.
  • Subphenotyping ARDS in COVID-19 Patients: Consequences for Ventilator Management
    May 12. Bos. Annals of the American Thoracic Society.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    As the authors note, there are phenotypes that can be used as a basis to treat patients with ARDS. For example, patients with focal lung pathology respond better for ventilation to prone positioning, though their lungs are not as recruitable. The authors in a retrospective sequential analysis of 70 patients in The Netherlands tried to see if the same was true in patients with COVID-19 and found that that was not the case.

May 14, 2020:

  • Coronavirus Disease 2019, Prothrombotic Factors, and Venous Thromboembolism. May 12. Schulman. Semin Thromb Hemost.
    Nice short review of coagulation abnormalities in COVID-19 patients. States we need randomized clinical trials, before making recommendations advocating more aggressive anticoagulation to prevent VTE in COVID-19 patients.
  • COVID and the Renin-Angiotensin System: Are Hypertension or Its Treatments Deleterious? May 12. Zores. Front Cardiovasc Med.
    Review of the RAAS with implications for COVID-19. A decrease in cell surface ACE2 may reduce binding of SARS CoV-2 but result in greater activation of angiotensin type 1 receptor (AT1R) by angiotensin II, causing more severe tissue damage. Decreased ACE2 may also increase thrombosis development via metabolism to angiotensin IV and activation of the angiotensin type 4 receptor. In contrast, increased ACE2 on the cell membrane due to up regulation by ACEI or ARBs may increase viral binding but result in less the damage due to less AT1R activation by angiotensin II. Studies are needed to determine whether ACEI or ARBs are beneficial or harmful in COVID-19 patients, but current recommendations are to continue these medications if the patient had been taking them for hypertensive management prior to infection.
  • COVID-19 and Racial/Ethnic Disparities
    May 11. Hooper. JAMA.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    In this viewpoint article, the authors highlight the health disparities among African Americans and Latinos. The incidence of COVID-19 disease is higher, and the number of patients who die from the disease is greater in these groups of patients. It’s hard to know why, but social and structural determinants of health, racism and discrimination, economic and educational disadvantages, health care access and quality, individual behavior, and biology may be determinants. This is not the first time, in that pulmonary tuberculosis, for example, disproportionately affects persons of lower socioeconomic status. As the authors note, the “pandemic presents a window of opportunity for achieving greater equity in the health care of all vulnerable populations.”
  • Critical Care During the Coronavirus Crisis: Challenges and Considerations for the Cardiothoracic and Vascular Anesthesia Community. May 12. Augoustides. J Cardiothorac Vasc Anesth.
    Editorial commentary on planning and preparation for ICU utilization during pandemic (COVID-19) with specific reference to surge planning. Notes importance of graded response using a framework leading from conventional through contingency to crisis emphasizing the importance of understanding varying response levels, all of which have been seen during the current crisis; conservation, substitution, adaptation, reuse and reallocation. Discusses importance of developing early and well accepted institutional triage plan. Document geared for hospital and ICU administrative purposes for preparation and planning.
  • Dynamic profile for the detection of anti-SARS-CoV-2 antibodies using four immunochromatographic assays. May 12. Demey. J Infect.
    4 immunochromatographic lateral flow assay tests (LFA) from Asian manufacturers for Sars-CoV-2 IgM and IgG were evaluated and the kinetics of antibody detection in 22 RT-PCR positive patients were determined. Median antibody detection time from onset of symptoms ranged from 8-10 days depending on the manufacturer. Sensitivity range for detecting either IgM or IgG was 60-80% on day 10 but all assays were 100% sensitive on day 15. IgM was not detected in 3 patients with two of the assays and was not reliably detected prior to IgG. 1 cross reaction was seen with other human coronaviruses (other than SARS-CoV).
  • Gastrointestinal, hepatobiliary, and pancreatic manifestations of COVID-19
    Apr 29. Patel. Journal of Clinical Virology.
    Opinion from SAB Member: Dr. David M. Clement
    This paper is a good overview of the current literature on GI disease with COVID-19. A well written, concise review of the GI symptoms, laboratory abnormalities, outcomes, possible mechanisms of GI disease, and outcomes in COVID-19 patients with GI disease are included. The prolonged Rt-PCR positivity of fecal samples is discussed, concluding that this could be a significant mode of viral transmission, and should be taken into account.
  • Hyperinflammatory shock in children during COVID-19 pandemic. May 11. Riphagen. Lancet.
    A Correspondence to Lancet describing a hyperinflammatory shock syndrome in a cluster of children, 8 in a population of 2 million, however a 3-fold increase from normal over the 10-day inclusion period. 1 child died. Confusing, the article states that respiratory involvement did not occur, yet the included table shows 5 children suffered tachypnea. Only 2 of 8 children were proven COVID-19. Prior to publishing, another cohort of children has been admitted. Though not listed, the authors imply the COVID-19 diagnosis approached 50%. All children received immunoglobulin and aspirin.
  • Liver injury is associated with severe Coronavirus disease 2019 (COVID-19) infection: a systematic review and meta-analysis of retrospective studies. May 10. Parohan. Hepatol Res.
    From 212 articles from around the world (English & non-English literature), 20 articles were selected from various sources by Iranian investigators, 3,428 patients were entered in meta-analysis with complete records. They followed by a systematic review and meta-analysis, analyzing the laboratory findings and trying to ascertain the mechanism of liver injury caused by COVID-19 infection. Here is an excellent effort for the collection, analyzing and applying of appropriate statistics for the data by the authors. They noted that a mild to moderate derangement of liver profile (AST, ALT, total Bilirubin and Albumin levels) was associated with severe outcome from COVID-19 infection. But offer a limited inference of mode of injury except to point out a derangement of endothelial ACE2 cells in liver and or in biliary tree, perhaps toxicity of anti-viral drugs and inflammatory cytokine production abnormality or maybe part of MOF.
  • RAAs inhibitors and outcome in patients with SARS-CoV-2 pneumonia. A case series study. May 9. Conversano. Hypertension.
    Retrospective, observational study of 191 confirmed COVID-19 patients from one Italian hospital. 50% had HTN, and 70% of those were on ACEI or ARBs. 28 patients were still hospitalized at the end of the study. Age, HF, and CKD were univariate predictors of mortality, but HTN and ACEI/ARB treatment were not.
  • Taste Changes (Dysgeusia) in COVID-19: A systematic review and metaanalysis
    May 1. Aziz. Gastroenterology.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    The authors performed a retrospective analysis of published articles that reported on ageusia/dysgeusia as a symptom in laboratory-confirmed COVID-19 patients and found that almost half of the patients (49.8%) with COVID-19 have altered taste sensation. Though it is not certain that taste or smell changes can predict COVID-19, certainly the clinical feature can raise the suspicion of COVID-19 and lead to early testing and diagnosis.
  • The tug-of-war between coagulopathy and anticoagulant agents in patients with COVID-19
    May 8. Canonico. European Heart Journal – Cardiovascular Pharmacotherapy.
    Opinion from SAB Member: Dr. Lydia Cassorla, Dr. Anil Hingorani
    LC: This brief report from the pharmacology literature outlines possible drug-drug interactions between anticoagulants and experimental drugs for COVID-19 patients including antivirals and anti-cytokine Rx. Most are due to hepatic metabolism. The interaction with cytochrome P450s and P-glycoprotein are the principal mechanism involved in DDIs. It includes a summary table that pretty much says it all. AH: Useful for listing drug to drug interactions of anticoagulants and other agents used for COVID-19, though I am not sure why they are using the older term NOAC rather than the safer term DOAC.
  • Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients
    May 6. Klopfenstein. Medecine et Maladies Infectieuses.
    Opinion from SAB Member: Dr. Philip Lumb
    Retrospective case-control study demonstrating possible benefit of Tocilizumab prescription (TCZ: recombinant humanized anti-interleukin-6 receptor [IL-6R] monoclonal antibody used in the treatment of rheumatoid arthritis) when combined with standard care. The article describes a small number of cases, but contains a well-referenced discussion that considers the theoretical basis for use; the methodology and results are clearly presented.

May 13, 2020:

  • Adult ICU Triage During the Coronavirus Disease 2019 Pandemic: Who Will Live and Who Will Die? Recommendations to Improve Survival
    May 6. Sprung. Critical Care Medicine.
    Opinion from SAB Member: Dr. Jagdip Shah
    The authors review 3 methods of triage (Andorran Model, Medical Benefit, and Manchester Triage System), in 3 countries (Spain, Ecuador, and the Netherlands). They then compared results with current COVID-19 pandemic ICU care profiles. The Netherlands ICU was able to increase capacity 4-fold and was able to decrease mortality while other ICUs in Ecuador and Spain more than doubled ICU bed capacity and experienced an increased mortality of almost 2- to 3-fold. Triage is to be used only in crisis mode, not in contingency mode (e.g. when demand for ICU bed is increased >100%). Here the authors make an appeal for a flexible, simple and powerful tool implemented by a triage committee that may include doctors with relevant experience (palliative care, critical care, administration), nurses, social workers, and ethicists for ICU admission and discharge. The authors recommend a triage algorithm based on clinical estimations of the incremental survival benefit (saving the most life-years) with “first come, first served” being applied for patients with otherwise equal priorities/benefits. Prognosis is an important factor to consider with emphasis on biologic age being needed for COVID-19, specifically. Fairness by age, gender, race ethnicity, sex preference, financial status, social worth is also recommended. The triage model proposed here is based on the priority (1 to 4) label of all ICU seeking patients. The triage committee will make color coding of each patient seeking ICU based on: 1. performance score (The premorbid baseline condition using the Eastern Cooperative Oncology Group Performance Score + the Clinical Frailty Score + the Karnofsky Performance Scale), 2. ASA class, 3. SOFA score, 4. predicted survival. The triage committee reviews all ICU admitted patients Q24 hrs and also Q14 days for discharge from the ICU. The authors make a plea for health workers to get priority for treatment with a blessing from the government/communities that they serve. Administrators in the committee are likely to guide space, staff and supplies. An excellent graphic clearly written for the current pandemic is included.
  • Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State
    May 11. Rosenberg. JAMA.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    Among 1438 hospitalized patients with a diagnosis of COVID-19 in metropolitan New York, treatment with hydroxychloroquine, azithromycin, or both, compared with neither treatment, was not significantly associated with differences in in-hospital mortality. Although randomized double-blind clinical trials are the optimal study design, given the urgent need to respond to the COVID-19 pandemic in New York, this study was designed as an observational multi-center retrospective cohort study using data from the State Health Information Network for NY (SHIN-NY), the state’s public health information exchange network connecting New York State hospitals, supplemented by medical record reviews by trained chart abstractors to evaluate the clinical outcomes and adverse effects associated with hydroxychloroquine and azithromycin therapies for COVID-19. Of course, the interpretation of these findings may be limited by the observational design.
  • Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019. May 12. Shi. Eur Heart J.
    No real news here, but large number of cases and associated data illustrate that cardiac involvement is an important predictor of death with COVID-19. All consecutive patients admitted to Renmin Hospital of Wuhan University between 1/1/20 and 2/23/20 with laboratory-confirmed COVID-19 were included in this retrospective study. Data from 671/1001 unique severe cases with adequate information was analyzed. Study period ended on a given date, not with definitive outcome. A great deal of data is presented, not only regarding myocardial injury. 62(9.2%) died of whom 75.8% had elevated initial cardiac troponin (cTnl), vs 9.7% of survivors. Among many other factors, (none surprising), elevated cTnI, CK-MB and NT-ProBNP levels were predictors of risk for in-hospital death, along with age, CV morbidities and inflammatory response. cTnI > 0.026 ng/mL was associated with a hazard ratio of 4.56.
  • Characteristics and outcomes of patients hospitalized for COVID-19 and cardiac disease in Northern Italy. May 9. Inciardi. Eur Heart J.
    A retrospective case review of 92 consecutive COVID-19 patients admitted to a single center in Italy. Those with pre-existing heart disease (AF, CHF, CAD) had higher rates of thrombo-embolic and pulmonary complications, and higher death rates.
  • Clinical and histological characterization of vesicular COVID-19 rashes: A prospective study in a tertiary care hospital
    May 8. Fernandez‐Nieto. Clinical and Experimental Dermatology.
    Opinion from SAB Member: Dr. Barry Perlman
    There are now many reports of COVID-19 patients presenting with or having associated cutaneous lesions. This is a prospective observational study of vesicular lesions in 24 COVID-19 patients in Spain. 29% had prior history of dermatologic conditions. 75% had a disseminated pattern with the rest having a more localized one. Median rash duration was 10 days. Rashes developed a median 14 days after COVID-19 diagnosis, prior to COVID-19 treatment in 71%. Skin biopsy in 2 patients showed histology consistent with viral infection. PCR tests performed on vesicular fluid in 4 patients were negative in 4/4 for SARS-CoV-2 and herpes virus.
  • Clinical course of severe and critical COVID-19 in hospitalized pregnancies: a US cohort study. 5/12/20. Pierce-Williams RAM. Am J Obstet Gynecol MFM.
    Review by the SAB
    By Dr. Jay Pryzbylo, on behalf of the SAB
    Data-rich, multicenter study of COVID-19 severe and critically ill women in third trimester pregnancy. Of the many findings, critically ill women required intubation, delivered prematurely mostly for maternal risk, the newborns were COVID-19 negative, 1 of 64 women required a tracheostomy. Matched to a non-pregnant control group, pregnancy did not alter outcome.
  • Coronavirus Disease-2019 with Dermatologic Manifestations and Implications: An Unfolding Conundrum. May 9. Almutairi. Dermatol Ther.
    4 categories of dermatological effects of COVID-19 are discussed:
    1. Cutaneous manifestations. Include urticaria, varicella-like vesicles, transient livedoid eruptions, livedoid vasculopathy, purpuric eruptions, lichenoid photodermatitis, erythroderma, photo-contact dermatitis, and generalized pustular figurate erythema
    2. Skin changes from lifestyle alterations, such as prolonged PPE contact and excessive personal hygiene
    3. Medication adverse cutaneous effects. For example, chloroquine and hydroxychloroquine can aggravate pre-exisitng psoriases or cause potentially severe cutaneous reactions
    4. Effect on primary skin diseases and their treatment. Guidelines recommend continuing immune-modulating treatments despite COVID-19
  • Cutaneous manifestations of the Coronavirus Disease 2019 (COVID-19): a brief review. May 7. Tang. Dermatol Ther.
    Review of 14 PubMed articles on cutaneous manifestations of COVID-19 in 88 patients. Skin lesions were typically erythematous, urticarial, or vesicular. 1 patient had no other symptoms.
  • Cutaneous Signs in COVID-19 Patients: A Review
    May 10. Wollina. Dermatologic Therapy.
    Opinion from SAB Member: Dr. Barry Perlman
    Detailed review describing reported cutaneous symptoms of COVID-19. ACE2 receptors are found in skin and adipose tissue. SARS-CoV-2 associated pulmonary and cutaneous fibrosis both involve transdifferentiation of adipocytes or lipo-fibroblasts into myofibroblasts. Adipocytes can act as a viral reservoir. The different cutaneous manifestations are described, along with differential diagnosis and associated COVID-19 presentation. Chilblain-like acral eruptions, purpuric and erythema multiforme-like lesions have been seen in children and young adult patients with asymptomatic or mild COVID-19. Acro-ischemic lesion and maculopapular rash are often seen in adult patients with more severe disease. Urticaria with pyrexia can be an early symptom of SARS-CoV-2 infection. Attention to cutaneous signs may aid in diagnosis, triage, and risk stratification of COVID-19 patients.
  • EDITORIAL: Hydroxychloroquine, Coronavirus Disease 2019, and QT Prolongation
    May 1. Bonow. JAMA Cardiology.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    Hydroxychloroquine has been advocated and even politicized as a promising therapy because of its anti-inflammatory and potential antiviral properties. However, hydroxychloroquine prolongs the QT interval because of blockade of inward cellular potassium current and is known to be proarrhythmic, especially in the setting of other drugs that also prolong the QT interval. Azithromycin has also been increasingly recognized for risks of QT interval prolongation and sudden death. Excessive prolongation of QTc was observed in 14 of 40 patients (36%) in an intensive care unit, and 37 of 40 patients (93%) manifested an increase in QTc with hydroxychloroquine alone or in combination with azithromycin. In another study, 18 of 90 patients (20%) treated with hydroxychloroquine alone or in combination with azithromycin developed QTc prolongation of 500 milliseconds or more. As noted in the editorial, there’s a potential risk associated of QT prolongation with widespread use of hydroxychloroquine and the combination of hydroxycholoquine and azithromycin in ambulatory patients with known or suspected COVID-19.
  • Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19? May 10. Panigrahy. Cancer Metastasis Rev.
    Discusses inflammatory process and potential development of stimulation of inflammatory resolution as an adjunctive, novel, host-centric mechanism to clear inflammatory debris and aid recovery. Mechanisms of inflammation and dysregulated host response in disease states described and theoretical basis for therapeutic development advanced.
  • Our recommendations for acute management of COVID-19. May 10. Mojoli. Crit Care.
    A 16 step narrative on “how we do it” from an Italian critical care team. Listing of current practice ranging from “do not trust a negative nasal swab” to “we prefer lung ultrasound over other imaging techniques”.
    While much is familiar, there are surprises: “we introduce hydroxychloroquine 200 mg TID and azithromycin 500mg daily”, but no mention of anticoagulation, or proning.
    A quick and interesting read for anyone interested to explore how other units operate.
  • Prognostic Value of Leukocytosis and Lymphopenia for Coronavirus Disease Severity. May 8. Huang. Emerg Infect Dis.
    In this meta-analysis report from Los Angeles CA and Winston-Salem NC investigators analyzed data from 8 English-language studies representing 1280 unique adult cases of COVID-19 from China and Singapore, of which 46% were classified severe. “Pooled data across early studies validate a significant correlation between elevated leukocyte count and decreased lymphocyte count among patients with severe cases of COVID-19 compared with those with mild cases. Why lymphopenia is associated with severe illness remains unclear.”
  • Prolonged Persistence of SARS-CoV-2 RNA in Body Fluids. May 9. Sun. Emerg Infect Dis.
    This prospective study from China reports on the results of serial PCR tests for hospitalized SARS-CoV-2 RNA from 49 patients, beginning with onset of symptoms. 43 mild and 6 considered severe cases. They sampled throat, sputum, NP, and feces every 3d. 95% of severe patients had clearance of RNA in all samples 7-8 days later than for mild cases, on average. Throat swab cleared first in mild but not severe cases. It is difficult to comment on their statistical findings as they collected only 32.75% of their desired samples for a variety of reasons. No asymptomatic patients included.
  • SARS-CoV-2 in pregnancy: symptomatic pregnant women are only the tip of the iceberg. May 11. Khalil. Am J Obstet Gynecol.
    A dramatically titled UK article testing all pregnant women presenting for delivery for COVID-19. During a 3-week period ending early in April, of the 129 pregnant women tested, only 1 presented with symptomatic infection. However, 7% tested asymptomatic positive. None of these women developed symptoms and all were discharged with healthy infants at ~2 days.
  • The impact of respiratory protective equipment on difficult airway management: a randomised, crossover, simulation study. Apr 26. Schumacher. Anaesthesia.
    This study from the U.K. examines intubation times and comfort in simulated difficult airway intubations using PAPR, “standard respirators” and normal surgical masks. Various intubating equipment was used. No significant differences were found for intubation times between the respirators, and PAPR had better vision, were cooler, and noisier. Though reassuring, the availability of different sorts of respirators is highly institution and individual specific, and the results of this investigation may be difficult to apply to all settings.

May 12, 2020:

  • Angiotensin-Converting Enzyme 2 and Antihypertensives (Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors) in Coronavirus Disease 2019. Mar 26. Sanchis-Gomar. Mayo Clin Proc.
    Nice review of renin-angiotensin-aldosterone system (RAAS) and interaction with angiotensin converting enzyme inhibitors (ACEI) and potential adverse outcomes with COVID-19 patients. Reviews current literature and mechanisms with recommendation to continue ACE inhibitors and angiotensin receptor blockers (ARB).
  • COVID-19 Convalescent Plasma; Phase 2
    May 6. Knudson. Transfusion.
    Opinion from SAB Member: Dr. Louis McNabb
    This article discusses methodological issues in using convalescent plasma for COVID-19 patients, such as: donor selection, the fact that some donors have over ten times the antibody level of other donors, the existence of many different antibody tests, factoring in the weights of recipients, and pre- and post-antibody measurements in recipients.
  • In-hospital cardiac arrest outcomes among patients with COVID-19 pneumonia in Wuhan, China
    Apr 2. Shao. Resuscitation.
    Opinion from SAB Member: Dr. David M. Clement
    This study documents the poor outcomes for in-hospital cardiac arrest (IHCA) in severe COVID-19 patients. It is a retrospective, observational study from China, of 136 patients with IHCA. Most were monitored, had witnessed arrests, and received CPR in under a minute. Most IHCA had respiratory causes, 94% had asystole or PEA, and only 6% had shockable rhythms. Return of spontaneous circulation was achieved in 13%, with 3% surviving at least 30 days and only one patient surviving with an acceptable neurologic outcome at 30 days.
  • Misinformation During the Coronavirus Disease 2019 Outbreak: How Knowledge Emerges From Noise
    Apr 1, 2020. Rochwerg. Critical Care Explorations.
    Opinion from SAB Member: Dr. Lydia Cassorla
    This well articulated narrative review by authors from Canada, New Zealand, and the US outlines the challenges and opportunities for both the media and researchers to develop knowledge in the face of an information storm. Much of the media is driven by corporate interests rather than a desire to meticulously vet sources and research quality, fanning hysteria. There are important benefits to the “live update” culture, however, consumers are advised to carefully consider the reliability of their sources in both lay press and medical publications. During a pandemic, conventional research and publishing practice are out of synch with the need for rapid information and dissemination, as they require months to years. Major publications have prioritized and made accessible COVID-19 related work to help overcome barriers to rapid, peer-reviewed work and combat misinformation. Nonetheless, some reports remain questionable. The concept of “living guidelines”, frequently updated as evidence emerges, is discussed. The authors highlight the benefit of advance planning to accelerate clinical trials, governmental support, targeted funding and collaboration with industry to optimize the reliability of research output when pandemics occur.
  • Nonsedation or Light Sedation in Critically Ill, Mechanically Ventilated Patients. Mar 19. Olsen. NEJM.
    The study involves 710 patients from 7 ICUs of 3 Scandinavian countries from 2014 – 2017. Randomized, retrospective, propensity score match (several exclusion) for ventilated patients with light sedation and no sedation. The sedation protocol involves Propofol, midazolam, M, clonidine (not dex.) …. The characteristics of the patients at baseline were similar in the two trial groups, except for the score on the Acute Physiology and Chronic Health Evaluation (APACHE) II, which was 1 point higher in the nonsedation group (RASS -1.3 to – 2.3). The difference of Delirium 1 day less, Thrombotic event 2.5%, Primary outcome 90 days mortality – sedation group lower than nonsedation ? Secondary: 1 day less of delirium, Thrombotic event 2.5% higher and Mech. Vent – one day less in nonsedation group. Most other were no different or statistically not significant.
  • Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials. Dec. 18, 2003. Smith. BMJ.
    Parachute use to prevent death and major trauma when jumping from aircraft: randomized controlled trial. The study highlights a. The importance of the conclusion when writing and reading a manuscript and b. Randomization might not always be possible: in designing studies, investigators must always consider equipoise.
  • Seven alternatives to evidence based medicine. Dec. 19, 1999. Isaacs. BMJ.
    A short, easy to read, tongue in cheek (maybe) analysis of decision making styles when there is inadequate evidence on which to base a clinical decision. Cheer up! We have all been there in the past, and frequently find ourselves in this situation with COVID-19.
  • Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions
    Apr 26. Jamilloux. Autoimmunity Reviews.
    Opinion from SAB Member: Dr. Philip Lumb
    Reviews current literature and knowledge of COVID-19 pathophysiology and focuses on following question: “How can antiviral immunity be reinforced and hyperinflammatory damages be avoided?” The authors provide a detailed overview of the immunopathology of various presentations of COVID-19 from mild to progressive respiratory and multi-organ system failure, and death. Subsequently, the authors discuss the rationale for targeted and non-targeted, supportive therapies. They conclude with, “Therefore, factors to predict progression toward severe forms of the disease are, at present, the most urgently needed and awaited determinants. A highly-structured approach, which includes immune monitoring, would thus be of utmost importance.”

May 11, 2020:

  • Acute respiratory failure in COVID-19: is it “typical” ARDS? May 6. Li. Crit Care.
    A review of the mostly earlier Chinese literature, describing the differences between classic ARDS and COVID-19 respiratory failure. Differences in compliance, time course, hypoxemia and imaging suggest COVID-19 pulmonary disease can be different than classic ARDS, and that some patients will respond well to HFNO.
  • Association between ABO blood groups and risk of SARS-CoV-2 pneumonia. May 7. Li. Br J Haematol.
    In this brief study report of 265 COVID-19 patients from Wuhan, China, “The ABO blood group … showed a distribution of 39.3 %, 25.3 %, 9.8 % and 25.7 % for A, B, AB and O, respectively. The proportion of blood group A in patients infected with SARS-CoV-2 was significantly higher than that in healthy controls (39.3 % versus 32.3 %, P= 0.017), while the proportion of blood group O in patients infected with SARS-CoV-2 was significantly lower than that in healthy controls (25.7 % versus 33.8 %, P< 0.01).” The theory that adhesion of SARS-CoV-2 to ACE-2 receptor is inhibited by human natural anti-A antibodies is discussed.
  • Association Between Hypoxemia and Mortality in Patients With COVID-19. Apr 6. Xie. Mayo Clin Proc.
    Single center retrospective study of 140 patients with moderate to critical suspected or confirmed COVID-19 pneumonia in Wuhan, China. Those with SpO2 90% or less were more likely to be older, male, have HTN, and present with dyspnea. 26% died. Cutoff SpO2 of 90.5% showed a 85% sensitivity and 97% specificity for survival. Hypoxemia (SpO2 < 90%) despite O2 or dyspnea were independently associated with increased risk of death.
  • Co-infection and Other Clinical Characteristics of COVID-19 in Children. May 1. Wu. Pediatrics.
    Chinese study, data rich on children from infancy through teen age. Briefly virus transmitted from adult. 40% asymptomatic. When symptomatic, mostly upper respiratory. Only 1 of 74 children, a teen, severely ill and recovered without intubation.
  • Considerations for Assessing Risk of Provider Exposure to SARS-CoV-2 after a Negative Test
    May 8. Long. Anesthesiology.
    Opinion from SAB Member: Dr. Barry Perlman
    The SARS-CoV-2 RT-PCR test is not 100% sensitive and, therefore, can result in a false negative. It has been questioned whether 1 negative test preop can be used to guide the level of PPE needed to adequately protect an anesthesiologist during an intubation or other aerosol generating procedure. Negative predictive value (NPV) and post test probability of SARS-CoV-2 infection were calculated based upon estimated prevalence in the population and test sensitivity and specificity. Using a “most likely” prevalence estimate of 1.0%, post test probabilities ranged from 1 in 89 to 1 in 1,636 with a median of 1 in 338. Based on the results: 1) If prevalence is uncommon, 1 negative test should provide “reassurance” regarding risk of exposure from an asymptomatic patient; 2) If surgical volume is high, exposure to aerosolized SARS-CoV-2 from asymptomatic, 1 test negative patients might occur on a regular basis; 3) If prevalence is high, full PPE should be used for test negative patients; 4) Due to estimate uncertainty in prevalence and testing sensitivity, there is a wide range in the calculated negative predictive value. The authors recommend that a lower threshold of NPV to justify use of universal airborne precautions regardless of preop test results be determined but be re-evaluated if prevalence estimates change.
  • Convalescent Plasma To Treat Coronavirus Disease 2019 (Covid-19): Considerations For Clinical Trial Design
    May 6. Barone. Transfusion.
    Opinion from SAB Member: Dr. Louis McNabb
    This article discusses many of the issues in collecting and administering convalescent plasma, and outlines the clinical trials in the USA currently in progress.
  • Evidence for and against vertical transmission for SARS-CoV-2 (COVID-19). May 3. A A. Am J Obstet Gynecol.
    Maternal-neonatal transmission of COVID-19 is discussed through evaluating previous published articles. The data presented is biased in two ways. In China, the bulk of deliveries is through C-section, 94%. Conclusions are drawn between delivery method of which there are too few vaginal deliveries. The data is also skewed by the authors evaluating neonatal results from 12 papers, but one paper supplies 50% of the data. Still, the paper provides an excellent description of IgG and IgM involvement post-delivery.
  • Pathogenesis and Treatment of Kawasaki’s Disease
    Sept. 17, 2005. Yeung. Opinion in Rheumatology.
    Opinion from SAB Member: Dr. Jay Przybylo
    This article defining Kawasaki Disease (“…an infectious trigger leads to massive activation of the immune system, resulting in a prolonged self-directed immune response at the coronary arteries”) equates COVID-19 as Kawasaki Disease in a small number of young children.
  • Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in severe patients with COVID-19. May 1. Sciascia. Clin Exp Rheumatol.
    Pilot, prospective, open, single arm, multi center study of off-label tociliuzamab, a humanized anti Il-6 receptor antibody, with 63 patients hospitalized with severe COVID-19 in Italy. Patients also received either lopinavir/ritonavir or darunavir/cobicistat. There was no significant survival difference with oral versus IV tociluzamab. D-dimer and CRP significantly decreased by day 1 of treatment. Administration within 6 days of hospital admission was associated with a 2x increased likelihood of survival. There were no severe-to-moderate adverse events from tociluzamab infusion.
  • Rapid development of an inactivated vaccine candidate for SARS-CoV-2. May 6. Gao. Science.
    Chinese equivalents of the CDC are sharing their latest efforts to prophylactic treatment of COVID 19 in absence of clear therapeutic modalities. The authors claim to have developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies neutralized 10 representative SARS-CoV-2 strains (may address other Corona / RNA SARS & MERS +/-), suggesting a possible broader neutralizing ability against SARS-CoV-2 strains. Three immunizations using two different doses (3 μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support clinical development of SARS-CoV-2 vaccines for humans. The authors, in development of the vaccine, isolated SARS-CoV-2 strains from the bronchoalveolar lavage fluid (BALF) samples of 11 hospitalized patients (including 5 patients in intensive care), among which 5 are from China, 3 from Italy, 1 from Switzerland, 1 from UK and 1 from Spain. The vaccine noted to elicit attenuated clinical, histopathologic, and bio chemical response. A smaller controlled double arm animal study to evaluate “Cytokine storm” response was encouraging as well. Phase I, II, and III will occur later this year!!
  • Respiratory advice for the non-respiratory physician in the time of COVID-19
    May 4. Bennett. Clinical Medicine Journal.
    Opinion from SAB Member: Dr. David M. Clement
    A pre-print review from the British Thoracic Society mostly describing one approach to the pre-ICU respiratory care of hospitalized COVID-19 patients. The emphasis is on coordinated assessments, cooperation between personnel, and the systematic alteration of respiratory treatments as patient parameters hit certain thresholds. Healthcare worker safety and efficiency, do-not-intubate preferences (“ceilings of care”), proning before intubation, oxygen therapy (esp. CPAP) and triggers for transfer to the ICU are reviewed. Several tables and diagrams help explain this strategy.
  • Sample Pooling as a Strategy to Detect Community Transmission of SARS-CoV-2. Apr 6. Hogan. JAMA.
    In this research letter, a group of Stanford pathologists replicated a study done to determine the prevalence of trachoma in a population using RT-PCR in pooled samples to determine whether community transmission was in fact active during the early phases of SARS-CoV-2 arrival in the US when routine testing was done only on travelers and their contacts. There were two positives among 2888 nasal and lower respiratory samples tested both late in February when COVID-19 prevalence increased sharply. The pooled screening method is a lower cost method to test large populations quickly, using less reagents, and increase overall testing efficiency at an expected slight loss of sensitivity. The result is early detection of community transmission and timely implementation of appropriate infection control measures to reduce spread.
  • Severe acute respiratory syndrome coronavirus 2 detection in the female lower genital tract. Apr 29. Cui. Am J Obstet Gynecol.
    Case series from China of 35 COVID-19 + female patients, 37-88 yo, who had careful PCR testing of anal and vaginal sites, all negative.
  • Should COVID-19 take advice from rheumatologists?
    May 7. Kernan. Lancet Rheumatology.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    Anakinra is a drug that has had success treating patients with auto-inflammatory diseases and now, there is evidence that the drug may also be useful in managing patients with COVID-19 disease who also have acute respiratory distress syndrome. The authors summarized the results seen in the study “Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study” (below). As the authors note: “these and other emerging data rightly focus more attention on the host inflammatory response and might herald a shift in how we approach the host-virus relationship.”
  • Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study
    May 7. Cavalli. Lancet Rheumatology.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    The authors first noted that of 16 patients treated between March 10 and March 17, 2020 with COVID-19, ARDS, and hyper-inflammation who were managed with CPAP outside of the ICU, that 21-day survival was 56%. Another similar group of patients receive low dose anakinra (100 mg twice a day) and did not do much better. But when instead high-dose intravenous anakinra (5 mg/kg twice daily) was used, survival increased to 90% at 21 days.
  • Targeting the inflammatory cascade with anakinra in moderate to severe COVID-19 pneumonia: case series. May 6. Aouba. Ann Rheum Dis.
    When some people are fighting a COVID-19 infection, it may not be the virus itself that’s causing distress, but the exaggerated host response in the form of a cytokine storm the body uses to fight off the infection. In this letter to the editor, the authors used anakinra, an anti-IL-1 blocking drug, in this study administered subcutaneously for 9 consecutive patients with SARS-CoV-2 infection confirmed by reverse transcription-PCR on nasopharyngeal swabs hospitalized in a non-ICU, with oxygen flow of ≤6L/min, and C reactive-protein levels ≥50mg/L. One patient developed acute respiratory failure 6 hours after the first and only dose of anakinra, leading to premature treatment cessation and ICU admission. The other 8 patients had good outcomes and C reactive protein (CRP) levels decreased steadily but only partially by 6 days in all, and normalized in 5/8 patients by day 11. In addition, at last followup, all patients were alive. The study was not randomized, but the results are promising.
  • The Role of Antibody Testing for SARS-CoV-2: Is There One?
    Apr 29. Theel. Journal of Clinical Microbiology.
    Opinion from SAB Member: Dr. W. Heinrich Wurm, Dr. Barry Perlman
    WHW: This well-written correspondence presents a deep dive into the state-of-the-art SARS-CoV-2 serology as of mid-April 2020. While outlining the usefulness and applicability of serologic testing, the authors shed light on the absence of FDA oversight of a burgeoning industry of 91 manufacturers. This is a must read for anyone looking for: 1) A tutorial on the optimal use and interpretation of currently available serological testing; 2) verification studies used by laboratories; or 3) the role serologic testing plays in: a) Developing population immunity; b) Development of vaccine; c) Identifying convalescent plasma donors; d) Monitoring the response of vaccines. BP: Richly detailed commentary regarding the current state of SARS-CoV-2 serology testing. It points out the current lack of FDA oversight for serologic testing, which has resulted in a variety of approaches that differ in assay format, antibody detected, target antigen, and specimen type. In addition, it is not yet known whether antibody detection indicates clinical immunity. While some may decide not to read the entire article, the abstract provides a nice summary and useful information.
  • Tocilizumab for the Treatment of Severe COVID-19. May 5. Alattar. J Med Virol.
    Retrospective review of 25 ICU patients in Doha, Qatar with confirmed severe COVID-19 who received tociluzamab and were followed for 14 days. Patients received a median of 5 other antiviral medications. 92% had at least 1 adverse event, including anemia, increased ALT, or QT prolongation. Tociluzamab was associated with a rapid decrease in oral temperature and serum CRP. Significant radiologic improvement and decreased invasive ventilation were seen on days 7 and 14.

May 9, 2020:

  • Lupus Anticoagulant and Abnormal Coagulation Tests in Patients with Covid-19
    May 5. Bowles. The New England Journal of Medicine.
    Opinion from SAB Member: Dr. Philip Lumb
    Authors note that while a prolonged aPTT may indicate caution in prescribing anticoagulants, they report a coagulation screening series of 216 patients positive for COVID-19 of which 44 (20%) had a prolonged aPTT. Lupus anticoagulant assays were performed in 34 patients and 31 (91%) tested positive. Authors suggest that a persistent presence of Lupus anticoagulant can be associated with a “thrombotic tendency within the antiphospholipid syndrome” and that a prolonged aPTT in the presence of COVID-19 should not “withhold use of anticoagulants for thrombosis while awaiting further investigation of a prolonged aPTT, nor withhold thrombolytic therapy in the face of high risk PE on the basis of a prolonged aPTT alone.”

May 8, 2020:

  • Acute Physiology and Chronic Health Evaluation II Score as a Predictor of Hospital Mortality in Patients of Coronavirus Disease 2019
    May 7. Zou. Crit Care Med.
    Opinion from SAB Member: Dr. David M. Clement, Dr. Jagdip Shah
    DC: Especially in healthcare settings with overextended resources, accurately predicting mortality may or may not be useful for frontline providers. In this retrospective, single referral hospital study from China of 154 ICU patients with COVID-19, an admitting Acute Physiology and Chronic Health Evaluation (APACHE) II score of equal to or greater than 17 predicted mortality with a sensitivity of 96% and a specificity of 86%, better than other predictive indices.
    JS: This single, tertiary center, retrospective, small study (N= 154) in China compared three ICU scoring systems on day one of ICU admission to decide which one is a better predictive tool for survival (e.g. a futility index) with COVID-19 patients with MOF. The three scoring systems compared were APACHE II (age, Glasgow Coma Scale, vital signs, oxygenation, chemistry values, hematology values & organ insufficiency [0 to 71]; used for general critical illness), Sequential Organ Failure Assessments (PaO2:fiO2 ratio, mean arterial pressure, creatine, GCS, platelet count, bilirubin [0 – 24]; used for general critical illness), and Confusion, Urea, Respiratory rate, Blood pressure, Age 65 (CURB65; used for pneumonia). Their aim was to describe the difference of epidemiologic and clinical characteristics between survivors and deaths in an attempt to provide an effective clinical tool to predict the probability of death among patients with COVID-19 based on data about admission and the first day in the ICU. The APACHE II score performed better to predict hospital mortality in patients with COVID-19 compared with SOFA and CURB65 scores. APACHE II scores greater than or equal to 17, serve as an early warning indicator of death, which may help to provide guidance for making further clinical decisions. The authors’ conclusion is useful and applicable when you have a tremendous surge of ICU admissions in a short time, shortage of equipment, manpower (DRs & RNs), and patients with comorbidities. The authors capture a few hallmark comorbidities: hypoxic encephalopathy, abnormal Na & K, abnormal hepatic panel, a higher platelet:lymphocyte ratio, (an index of inflammatory process?). ROC & AUC is a tool for sensitivity/specificity index: AUC FOR APACHE II = 0.966, SOFA = 0.867, CURB65 = 0.844.
  • Autoimmune hemolytic anemia associated with Covid-19 infection. May 7. Lazarian. Br J Haematol.
    Opinion from SAB Members: Drs. Philip Lumb and Joseph Anthony Caprini
    PL: Series of 7 Covid-19 positive patients from six different French and Belgian hospitals who developed autoimmune hemolytic anemia during admission. Patient demographics presented with associated co-morbidities; timeframe consistent with development of cytokine storm. Authors recommend screening for presence of a lymphoid clone in patients with Covid-19 infections and autoimmune cytopenias.
    JAC: The abstract states it well and I include it here- “Although the pathophysiology underlying severe Covid‐19 remains poorly understood, accumulating evidence argue for hyperinflammatory syndrome causing fulminant and fatal cytokines release associated with disease severity and poor outcome (Mehta et al, 2020).
    However, the spectrum of complications is broader and include among others various autoimmune disorders such as autoimmune thrombocytopenia, Guillain-Barré and antiphospholipid syndrome (Zhang et al, 2020; Zulfiqar et al, 2020; Toscano et al, 2020). In this report we describe 7 patients from 6 French and Belgian Hospitals who developed a first episode of autoimmune hemolytic anemia (AIHA) during a Covid-19 infection.”
  • Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study
    May 6. Wichmann. Annals of Internal Medicine.
    Opinion from SAB Member: Dr. Lydia Cassorla, Dr. Joseph Anthony Caprini
    LC: This fascinating report from Hamburg Germany describes the findings of complete autopsy reports, as mandated by law, of the first 12 consecutive known COVID-19 deaths in their city. “In all cases the cause of death was in the lungs or the pulmonary vascular system”. Unsurprisingly, patients were older (10/12 >60 yrs) and all had pre-existing co-morbidities and pneumonia at death. They trended obese with BMI of >30 in 5 and nearly 30 in a sixth. The focus of the report is on the high incidence (7/12 or 58%) of venous thrombosis with 4/12 dying of PE. D-dimer was measured in 5 patients on admission, all elevated. 3/5 of those with elevated D-dimer had venous thrombosis including 2 PE deaths. 3 patients had some form of anticoagulation therapy, including 2 PE deaths. There is a trove of additional information in this report as each death resulted in a full autopsy, a post mortem total body CT in all but 2, histopathology and virology. SARS–CoV-2 RNA was present in high titers in the lungs in all, and in the blood in 6/10. The authors suggest that their findings support proactive anticoagulant therapy for hospitalized patients as well as potentially for outpatients. JC: In this autopsy study of 12 consecutive patients who died of COVID-19, we found a high incidence of deep venous thrombosis (58%). One third of the patients had a pulmonary embolism as the direct cause of death. Furthermore, diffuse alveolar damage was demonstrated by histology in 8 patients (67%). The CT images of the ground glass appearance in the lungs is chilling. They indicate the need for more than heparin and some have raised the possibility of steroids. The association between fatal outcomes and pre-existing risk factors, particularly CV disease is also striking.
  • COVID-19 and Kawasaki Disease: Novel Virus and Novel Case
    May 1. Jones. Hospital Pediatrics.
    Opinion from SAB Member: Dr. Jay Przybylo
    Case report with more specifics about Kawasaki treatment in conjunction with COVID-19.
  • Effect of regular intravenous immunoglobulin therapy on prognosis of severe pneumonia in patients with COVID-19
    Apr 25. Xie. Journal of Infection.
    Opinion from SAB Member: Dr. Jay Przybylo
    This article shows that the use of IVIG reduces the length and severity of hospitalization in COVID-19 patients.
  • Infection prevention and control compliance in Tanzanian outpatient facilities: a cross-sectional study with implications for the control of COVID-19. May 6. Powell-Jackson. The Lancet.
    Researchers from the Dept of Global Health and Development at the London School of Hygiene and Tropical Medicine set out to find studies investigating health care workers’ compliance with infection prevention and control practices in low-income countries. They found a few papers and decided to focus on data collected in 2018 in Tanzania as part of a randomized trial comparing private for profit dispensaries vs. health centers in faith-based dispensaries. The result was uniformly disappointing with only 7% compliance with hand hygiene and 5% with disinfection of reusable equipment. Nurses and midwives performed uniformly better than physicians and other health care workers.
    In a pandemic, this result will have implications on SARS-CoV-2 transmission among health care workers around the globe.
  • Interpreting Diagnostic Tests for SARS-CoV-2
    May 6. Sethuraman. JAMA.
    Opinion from SAB Member: Dr. Barry Perlman
    Viewpoint from authors in India and Japan discusses interpretation of RT-PCR and ELISA serology testing. There are a variety of RT-PCR tests. Most target envelope, nucleocapsid, spike, RNA-dependent RNA polymerase (RdRp), or ORF1. Most have comparable sensitivities with the RdRp test showing lower sensitivity. RT-PCR nasal swab testing becomes positive as early as day one of symptom onset, peaks within the first week, and starts to decline by week 3. Sputum and fecal sample positivity persists longer than for nasopharyngeal samples. Of note, a positive result reflects presence of viral RNA and does not necessarily mean viable virus. IgM and IgG ELISA testing may be positive as early as day 4 of symptom onset, and rises in weeks 2 and 3. IgM declines by week 5 and disappears by week 7, while IgG persists beyond week 7. Antibody detection to NC protein is most sensitive, while antibody testing to the S receptor-binding domain is more specific and might indicate neutralizing antibodies. Paired testing with initial RT-PCR and then 2 weeks later can increase diagnostic accuracy. It is not known how long neutralizing antibodies will persist and provide protection.
  • Missed or Delayed Diagnosis of Kawasaki Disease During the 2019 Novel Coronavirus Disease (COVID-19) Pandemic
    Apr 21. Harahsheh. The Journal of Pediatrics.
    Opinion from SAB Member: Dr. Jay Przybylo
    Brief Letter to Editor reminds caregivers that although COVID-19 is rare in children, an even more rare complex of symptoms in this age group, Kawasaki Syndrome, predisposes to long-term coronary artery involvement that might be prevented with immunoglobulin therapy.
  • Strategies for daily operating room management of ambulatory surgery centers following resolution of the acute phase of the COVID-19 pandemic. May 7. Dexter. J Clin Anesth.
    Opinion from SAB Members: Drs. J. Lance Lichtor and David Clement
    JLL: Strategies for daily operating room management of ambulatory surgery centers following resolution of the acute phase of the COVID-19 pandemic. Excessive detail for that which is obvious. Though not stated the percent of operations that use Bovie, surely a high percentage and not discussed but that also can produce an aerosol.
    DC: Practical suggestions for maintaining safety while increasing volume of elective surgeries as ORs gradually ramp up. Suggestions include maximizing regional anesthesia and MAC anesthesia, designating different ORs for AGPs and non-AGPs, minimizing PACU use, alternating a pair of ORs for each surgical team etc. Though mostly common sense, these approaches are different than traditional OR practice, and will be useful for front-line workers to consider.
  • Unexpected severe thrombocytopenia in the COVID-19 positive parturient. May 7. Kim. Anesthesia & Analgesia.

May 7, 2020:

  • A Trial of Lopinavir-Ritonavir in Covid-19: Letter Series with Author Response
    May 5. Dalerba. The New England Journal of Medicine.
    Opinion from SAB Member: Dr. W. Heinrich Wurm
    This investigation from Wuhan, China, published in early April, elicited a number of responses which culminated in the following message: Abandoning an available antiviral at this stage of the pandemic based on a statistically under-powered trial is unwise. Larger cohorts, earlier enrollment and control for secondary therapies might yet point towards a role for these drugs in the management of the SARS-CoV-2 virus. Larger studies are currently underway.
  • ACE2, COVID-19, and ACE Inhibitor and ARB Use during the Pandemic: The Pediatric Perspective. May 6. South AM. Hypertension.
    A thorough description of the effect of COVID-19 on renin-angiotensin including perspective particular to pediatrics including small percentage of affected patients. The significance is that pediatrics is the focus with the conclusion: At this time, there is no evidence that children with hypertension, cardiovascular disease, or chronic kidney disease, and/or those who are taking ACE inhibitors or ARBs, are at increased risk of SARS-CoV-2 infection or more-severe COVID-19.
  • An Italian programme for COVID-19 infection in multiple sclerosis
    Apr 30. Sormani. The Lancet Neurology.
    Opinion from SAB Member: Dr. Barry Perlman
    This article describes a program developed by the Italian MS Society, Italian MS Foundation, and MS Study Group of the Italian Neurological Society to help guide management of patients with multiple sclerosis during the COVID-19 pandemic. Case report forms were sent to >200 neurologists in Italy and data was collected on 232 patients with known or suspected COVID-19. 96% had mild infection. Of the 3% with critical infection, 1 recovered and 5 died. Further data collection is needed to determine if MS disease or treatment impacts COVID-19 infection.
  • Anesthesia Considerations and Infection Precautions for Trauma and Acute Care Cases During the COVID-19 Pandemic. Apr 24. Gong Y. Anesthesia & Analgesia.
    Recommendations from The Task Force of the Chinese Society of Anesthesiology for Trauma and Acute Care about surgery in a hospital during the Covid-19 pandemic. The article looks like it is from high-powered anesthesiologists in Beijing. Somewhat repetitive information in this long review article. It’s complete information regarding the subject.
  • Application of Lung Ultrasound during the COVID-19 Pandemic: A Narrative Review
    Apr 30. Convissar. Anesthesia & Analgesia.
    Opinion from SAB Member: Dr. David M. Clement
    An excellent review of the literature on the use of point of care ultrasound (POCUS) with the current COVID-19 pandemic and previous viral epidemics. Typical POCUS findings (thick irregular pleural lines, B lines, A lines during recovery) are as good or better for diagnosis and followup compared with CXR or CT, and are nicely shown on accompanying videos. “Lung ultrasound may be preferred over chest radiography or computed tomography in the diagnosis and monitoring of COVID-19 patients due to its ease of bedside use, low associated cost, and reduced risk of infectious spread.”
  • Can N95 Respirators Be Reused after Disinfection? How Many Times?
    May 5. Liao. ACS Nano.
    Opinion from SAB Member: Dr. Lydia Cassorla
    Due to shortages of PPE, individuals and groups are seeking effective methods to decontaminate N95 masks designed for single use. While this report in the basic science literature from the Stanford-4C Air group does not include confirmatory testing of SARS-CoV-2 decontamination, it adds to current information about the effects of decontamination methods on the fabric of N95 masks. Based on their work, heat in a range of 70-85 degrees C in a static air oven for 30 min with varying degrees of relative humidity does not degrade the structure and function of the filter layer of masks up to 50 cycles. These are temperatures that have been shown in referenced work to be effective in inactivating SARS-CoV-2. The authors suggest that this is a potentially safe and relatively simple technique to decontaminate N95 masks for re-use by the same individual during the current pandemic. UVGI was a secondary option, with adequate retention of function for up to 10 cycles. Their work mostly involved fabric samples, using only a few whole masks due to shortages, and highlights the importance of ongoing fit evaluation, especially after 5 rounds of donning and doffing.
  • Coronavirus disease 2019 (COVID-19) and the renin-angiotensin system: a closer look at angiotensin-converting enzyme 2 (ACE2)
    May 5. Zemlin. Annals of Clinical Biochemistry: International Journal of Laboratory Medicine.
    Opinion from SAB Member: Dr. Barry Perlman
    In depth review of SARS-CoV-2, COVID-19, the renin-angiotensin system, the relationship between ACE2 and COVID-19, use of ACE-I and ARB with COVID-19, and possible RAS related targets for COVID-19 treatment.
  • COVID-19 and Trauma Care: Improvise, Adapt and Overcome!
    May 1. Dutton. Anesthesia & Analgesia.
    Opinion from SAB Member: Dr. Jagdip Shah
    This article outlining the approach to trauma care in the era of COVID-19 emphasizes: PPE for the whole anesthesia team, use of negative pressure ORs, blood conservation, video laryngoscopy and safety precautions during extubation, the role of lung protective ventilation strategies–frequent manual breaths, a need to expand use of multimodal analgesia (regional techniques), care for multi-organ failure intra op, restrictive goal-directed fluid therapy, standard ASA monitoring and frequent laboratory values–especially the coagulation profile to guide patient care, guidelines that address the shortage of drug and equipment on the horizon, healthcare worker protection including donning and doffing, and the current chaos surrounding emergency and acute care surgery. It has guidelines on when to operate in the ER. It references useful resources for those practicing trauma care, including the COVID-19 Global DocMatter Community, the Trauma Anesthesiology Society DocMatter Community, and www.Intubatecovid.org — a website for like-minded trauma anesthesiologists. The authors wish lung ultrasound would be more frequently included in acute surgery / trauma, with less emphasis on CT scans in emergency care.
  • Early recovery following new onset anosmia during the COVID-19 pandemic – an observational cohort study. May 6. Hopkins C. J Otolaryngol Head Neck Surg.
    Post-viral loss of sense of smell accounts for up to 40% of anosmia cases. Nasal respiratory and epithelial cells and olfactory epithelial cells have high levels of ACE2. Survey of 382 patients with presumed COVID-19 — only 15 had been tested and of those 80% were positive. 86% had complete anosmia and 12% had severe anosmia. For 17% this was their only symptom. 80% reported improvement in 1 week. Recovery plateaued after 3 weeks. Limitation of study was low rate of confirmatory COVID-19 testing.
  • High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study
    May 4. Helms. Intensive Care Medicine.
    Opinion from SAB Member: Dr. Louis McNabb, Dr. Joseph Anthony Caprini
    LM: Study of 150 patients in an ICU setting. The main clinical threat was PE at 16%. There was a high incidence of catheter clotting, particularly for patients on dialysis (28/29). Most of patients were on at least prophylactic anticoagulation. 67% of patients were still intubated at time of data analysis, which may have led to underestimation of thrombotic risk, Lupus anticoagulant was found in 50/57 patients. No DIC was noted, but this result may reflect early termination of the study. Curiously, non-COVID-19 patients with ARDS had higher D-dimer levels. JC: In a prospective cohort study, we have shown that sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients with COVID-19 ARDS during their ICU stay, mainly pulmonary embolisms (25 patients, 16.7%). Despite anticoagulation, a high number of patients with COVID-19 ARDS developed life-threatening thrombotic complications, meaning that higher anticoagulation targets than in usual critically ill patients should probably be considered.
  • Incidence of venous thromboembolism in hospitalized patients with COVID-19
    May 5. Middeldorp. Journal of Thrombosis and Haemostasis.
    Opinion from SAB Member: Dr. Louis McNabb
    This is an article describing 198 hospitalized patients of which 38% were in the ICU. 20% were diagnosed with VTE, of which 13% were symptomatic. Most patients were on prophylactic anticoagulation in the medical units. Patients in the ICU received BID prophylactic anticoagulation (double standard regimen). The key point to this paper is that clinicians need to be vigilant looking for VTE in patients with less severe COVID-19 disease.
  • Interim Guidance for Basic and Advanced Life Support in Children and Neonates With Suspected or Confirmed COVID-19. May 6. Topjian A. Pediatrics.
    A prepublication Scientific Statement from the American Association of Critical Care Nurses and including authorship of physicians across North America. A step by step guide to resuscitating children from time of birth on with special attention to COVID-19.
  • Molecular testing for acute respiratory tract infections: clinical and diagnostic recommendations from the IDSA’s Diagnostics Committee. May 6. Hanson KE. Clin Infect Dis.
    Diagnostics Committee of the Infectious Diseases Society of America recommendations for respiratory molecular testing based on comprehensive literature review. Highly sensitive and specific nucleic acid amplification tests (NAAT) are the diagnostic gold-standard in clinical virology and also has utility for bacterial pneumonia testing. Rapid testing may decrease unnecessary antibiotic use, improve antiviral prescribing, limit additional testing, shorten hospital and ED lengths of stay, and optimize infection control, but factors such as study design, sample sizes, and test accuracy, performance and resulting negatively impact ability to combine study results to demonstrate benefits. May be most useful clinically with intermediate pre-test probability and intermediate disease severity. Questions posed by the IDSA:
    • To test or not to test. Whether test result will impact therapy depends upon illness severity, symptom duration, comorbidities, possible immunosuppression, choices of testing and their availability, result turn-around time, and disease prevalence. Multiplex bacterial pneumonia panels are too new to evaluate test performance and clinical impact.
    • Which test. For influenza, CDC and IDSA recommend testing. For SARS-CoV-2, there are more than 24 NAATs authorized for emergency use, and results can be impacted by sampling site (nasal, oral, or lower airway) and when in the illness the sample is obtained. Optimal approach for COVID-19 testing has not been defined. Use of multiplex NAAT with or without bacterial testing needs further study.
    • Interpretation of bacterial DNA in lower resp. tract sample. Issues include colonization versus pathogen, false positive due to dead or impaired organisms, significance of organism quantitation.
    • Improved antibiotic stewardship due to NAAT testing. Rapid test results may allow antibiotics to be stopped, but false positives may increase antibiotic use.
    • Recommendations for future studies shown in Table 2.
  • Olfactory Dysfunction: A Highly Prevalent Symptom of COVID-19 With Public Health Significance. May 6. Sedaghat AR. Otolaryngol Head Neck Surg.
    In this state of the art review, the scientific evidence that relates to olfactory dysfunction in the face of COVID-19 is reviewed. A high prevalence of olfactory dysfunction is noted in patients with COVID-19 using objective measures of olfactory testing. Also, the presence of olfactory dysfunction might also be useful to predict patients who might develop COVID-19. Most patients with olfactory dysfunction will note improvement after 1-2 weeks just as symptoms of COVID-19 improve.
  • The Prevalence of Olfactory and Gustatory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-analysis. May 6. Tong JY. Otolaryngol Head Neck Surg.
    In this meta-analysis of 10 studies, all published in 2020, that included patients from studies in North America, Europe, and Asia, 1600 patients were analyzed. Over 50% of patients had some level of olfactory dysfunction and almost 50% had some level of gustatory dysfunction. For many patients also, olfactory dysfunction was a presenting symptom. Screening patients for olfactory dysfunction may be indicative of COVID-19 infection.
  • Understanding Observational Treatment Comparisons in the Setting of Coronavirus Disease 2019 (COVID-19)
    May 5. Thomas. JAMA Cardiology.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    In this editorial, concerning patients with COVID-19, hypertension, diabetes, and cardiovascular disease may be vulnerable and are more likely to be taking angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs). Based on the Mehta study (below), patients taking those drugs can continue taking the drugs given the current pandemic given the fact that these patients are not more likely to be susceptible to the disease, though based on a secondary analysis, the severity of disease might be greater in terms of need for hospitalization and ICU admission. Yet, it’s possible also that the presence of cardiovascular disease and other comorbidities lowers the threshold on the part of referring clinicians to hospitalize and move to the ICU those individuals considered to be at higher risk than the general population. These secondary findings, though real, should not be considered as causal.
    • Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19)
      May 5. Mehta. JAMA Cardiology.
      Opinion from SAB Member: Dr. J. Lance Lichtor
      As has been discussed in previous articles this newsletter has referenced, SARS-CoV-2 binds to the extracellular domain of the transmembrane angiotensin-converting enzyme 2 (ACE2) receptor to gain entry into host cells; patients who are taking angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers are theoretically at an increased risk for becoming infected with SARS-CoV-2 or may have worse outcomes; upregulation of angiotensin-converting enzyme 2 may improve outcomes in infection-induced acute lung injury in patients with SARS-CoV or SARS-CoV-2 infections; and in certain high-risk patients, the withdrawal of ACEIs or ARBs may be harmful. In this retrospective analysis of 18,472 patients tested for SARS-CoV-2, taking either an angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers was not associated with an increase in the likelihood of testing positive for SARS-CoV-2 infection.
  • Utility of Tracheostomy in Patients with COVID-19 and Other Special Considerations
    May 5. Mecham. Laryngoscope.
    Opinion from SAB Member: Dr. Jay Przybylo
    A concise prepublication article describing the options for prolonged airway support in COVID-19. Begins with statistics on this pandemic vs earlier SARS-CoV. Provides pros and cons of OR vs bed space, positive pressure vs negative pressure rooms, and percutaneous vs open tracheostomy. The authors imply a percutaneous tracheostomy at the bedside prevents transporting the patient and exposing many people to the virus and might be the best solution in complex patients who are likely to require an artificial airway for a prolonged time.
  • Venous thromboembolism and heparin use in COVID-19 patients: juggling between pragmatic choices, suggestions of medical societies
    May 4. Profidia. Journal of Thrombosis and Thrombolysis.
    Opinion from SAB Member: Dr. Lydia Cassorla, Dr. Joseph Anthony Caprini
    LC: This editorial states that while most guidelines are currently recommending antithrombotic prophylaxis for all hospitalized COVID-19 patients, and full anticoagulation for a subset, questions remain about which population may benefit from therapeutic doses of anticoagulation. It is a call to share data via registries and arrive at a consensus at a time when randomized controlled clinical trials may not be able to answer the question in a timely manner. JC: This is a very good discussion from the data driven point of view including extrapolation of pre-existing data to the clinical presentation and course of patients with COVID-19. Unfortunately, it is a whole new ball game and we need to learn on the job.
  • What’s new in lung ultrasound during the COVID-19 pandemic. May 6. Volpicelli G. Intensive Care Med.
    A highly technical description from Europe of the differential diagnosis and possibly unique lung ultrasound findings in patients with COVID-19. Good videos and excellent table. This would be helpful for a provider in the ICU or ED already trained in lung ultrasound.

May 6, 2020:

  • Association Between Clinical Manifestations and Prognosis in Patients with COVID-19. May 5. Yu. Clin Ther.
    This is a chart review study from China. Older age and higher BMI were independent risk factors associated with COVID-19 patients with pneumonia.
  • COVID-19 patients with respiratory failure: what can we learn from aviation medicine?
    May 5. Ottestad. British Journal of Anaesthesia.
    Opinion from SAB Member: Dr. Jay Przybylo
    A short editorial with an interesting observation that the symptoms of hypoxia of COVID-19 might be masked by hypocapnia, as demonstrated by previous flight altitude experiments.
  • Establishment and Management of Mechanical Circulatory Support During the COVID-19 Pandemic. May 4. Pham. Circulation.
    This short report from a multinational group of cardiac surgeons suggests that planning and an algorithmic approach to ECMO may assist decision making and resource allocation in centers with capability. While meaningful outcome data is not yet available, there are survivors and a joint registry between North America and Europe. VV Ecmo is recommended for isolated respiratory failure and VA ECMO for cardiac or cardiopulmonary failure. The argument is made to make establishing a criteria a priority.
  • Management of acute ischemic stroke in patients with COVID-19 infection: Report of an international panel
    May 3. Qureshi. International Journal of Stroke.
    Opinion from SAB Member: Dr. Barry Perlman
    Multinational expert consensus for management of acute ischemic stroke in COVID-19 patients. 5% incidence of acute ischemic stroke is noted in COVID-19 patients, and such events are associated with older age, hepatic and renal dysfunction, HTN, DM, cerebrovascular disease, and elevated D-dimers. Mortality rate of 38% dependent on severity of COVID-19 infection. Possible undiagnosed COVID-19 infection should be suspected in patients with acute stroke, as some may have difficulty communicating due to the stroke. Since renal insufficiency is common with COVID-19 infection, risk of contrast-induced nephropathy should be considered prior to neuroimaging. Coagulation assessment can help determine risk benefit of IV rt-PA. Mechanical thrombectomy with low threshold for intubation and general anesthesia may be considered on case-by-case basis. Single or dual antiplatelet therapy may be considered for patients who do not receive IV rt-PA or mechanical thrombectomy. Risk of healthcare provider infection and mitigation strategies are also discussed.
  • Medical treatment options for COVID-19. May 4. Delang. Eur Heart J Acute Cardiovasc Care.
    There is an urgent need for treatment for this COVID-19 pandemic from all quarters of the world. Several clinical trials with COVID-19 patients are evaluating “repurposed drugs”, but there is no uniformity in timing, duration of treatment and study endpoints. Currently, there are registered clinical trials pertaining to one or more clinical outcomes in 66% of the studies, virological in 23%, radiological in 8%, or immunological in 3%. Repurposing of existing antiviral and immunomodulating drugs is an important strategy, because the safety profile of these drugs is well known. In the solidarity (started in April worldwide), a clinical trial launched by the WHO, is appealing due to simplicity. On 7 March 2020, the most frequently evaluated antiviral therapies were lopinavir/ritonavir (LPV/r) (n=15), chloroquine (n= 11), arbidol (n= 9), hydroxychloroquine (n= 7), favipiravir (n=7) and remdesivir (n= 5). Immune modulating drugs: IL-6 inhibitors – receptor antagonist – Tocilizumab (Actemra) and Granulocyte-macrophage colony-stimulating factor. Both critical role immune response and/or macrophage activation syndrome (MAS).
  • Pediatric Multi-System Inflammatory Syndrome Potentially Associated with COVID-19. May 4. New York City Health Department.
    Based on 2020 Health Alert #13 from the New York City Health Department, multi-system inflammatory syndrome, recently reported by authorities in the United Kingdom, is also being observed among children and young adults in New York City and elsewhere in the United States and includes features of Kawasaki disease or features of shock. If a patient is less than 21 years old, with persistent fever (four or more days), and either incomplete Kawasaki disease, typical Kawasaki disease, and/or toxic shock syndrome-like presentation; and there is no alternative etiology identified that explains the clinical presentation, the patient should be presented to the New York City Health Department. The findings have been published: Jones VG, Mills M, Suarez D, et al. COVID-19 and Kawasaki disease: novel virus and novel case. Hosp Pediatr. 2020; doi: 10.1542/hpeds.2020-0123; and Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020 Mar 28;395(10229): 1033-1034. DOI: 10.1016/S0140-6736(20)30628-0.
  • Randomized Clinical Trials and COVID-19: Managing Expectations
    May 4. Bauchner. JAMA.
    Opinion from SAB Member: Dr. Jagdip Shah
    Today there are more than 1,000 studies addressing various aspects of COVID-19 registered on ClinicalTrials.gov, including more than 600 interventional studies and randomized clinical trials (RCTs). It has become common practice to report the glimpses of preliminary results in social media and the popular press. The authors question how we (clinicians, press, public, politicians) should understand the results. The authors appeal to investigators to be strict on control groups, statistical power, proper selection of clinical endpoints, and blinding methods, and strongly advocates merging smaller trials for better robust outcomes. This article was open for comments and an excellent comment from Bhatt A. from Oxford points out that the International Committee of Medical Journal Editors (ICMJE) should be firmer in its proactive stance and guidance to ethics committee verdicts than simply relying on ethics approvals, which all small and uncontrolled studies will have, but which may not have meaning or purpose.
  • Severe ARDS in COVID-19-infected pregnancy: obstetric and intensive care considerations. Apr 14. Schnettler. Am J Obstet Gynecol MFM.
    Single case report in a high-risk pregnancy (age 39, mild myotonic dystrophy, and hx of prior cva on BCP). Patient did require ventilator and proning. Although patient had improved, still on vent at time of writing the article. Suggested algorithms for management at different gestational ages. Some outdated recommendations for treatment. Main interesting point is proning in pregnancy.

May 5, 2020:

  • Acute myocardial injury is common in patients with Covid-19 and impairs their prognosis
    Apr 6. Wei. Heart.
    Opinion from SAB Member: Dr. Philip Lumb
    101 patient prospective study from January to March 10, 2020 in Sichuan, China with primary endpoints including cardiac injury defined by above normal high-sensitivity troponin T (hs-TnT) levels. Study confirms that myocardial involvement in COVID-19 is common and that elderly and patients with underlying cardiovascular disease at increased risk.
  • Antibody Detection and Dynamic Characteristics in Patients with COVID-19
    Apr 19. Xiang. Clinical Infectious Diseases.
    Opinion from SAB Member: Dr. Barry Perlman
    Serologic study of 85 SARS-CoV-2 RT-PCR test confirmed COVID-19 patients, 24 patients with symptoms but negative RT-PCR testing, and 60 controls. Serologic test was an ELISA for IgM and IgG against the SARS-CoV-2 nucleocapsid N protein. COVID-19 patients showed IgM by 4 days after symptom onset with peak by day 9. IgG increased sharply 12 days after symptom onset, with all COVID-19 patients positive for both IgG and IgM by day 30. For symptom positive but test negative patients, 88% had IgM and 71% had IgG, demonstrating false negative RT-PCR results. 3 controls had IgG but not IgM, which represent either false positives or asymptomatic infection. For RT-PCR confirmed patients: IgM sensitivity 77%, specificity 100%, PPV 100%, NPV 80%. IgG sensitivity 83%, specificity 95%, PPV 95%, NPV 84%. The authors suggest that IgG can be used to diagnose COVID-19 in pneumonia patients, and if negative, serology testing should be repeated 10 days after onset.
  • Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing. May 3. Rawson. Clin Infect Dis.
    “Despite the extensive reporting of broad-spectrum empirical antibiotic prescribing in patients with coronavirus respiratory infections, there is a paucity of data to support their association with bacterial/fungal co-infection.” No important findings to help guide untargeted antimicrobial treatment in this UK meta-analysis of previously reported data. The authors suggest that better studies are required to guide antimicrobial therapy in COVID-19 patients.
  • Cardiac considerations in patients with COVID-19
    May 1. Calvillo-Argüelles. CMAJ.
    Opinion from SAB Member: Dr. Louis McNabb
    Five key points on cardiac considerations for COVID-19 in a convenient one-page summary.
  • Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the Coronavirus Disease 2019 (COVID-19) Pandemic
    Mar 17. Driggen. JACC.
    Opinion from SAB Member: Dr. Jay Przybylo
    An exhaustive State-of-the-Art Review with complete recommendations concerning every phase of COVID-19 cardiac involvement from presentation by phone through hospitalization and including all forms of cardiac pathology to healthcare worker precautions. Multiple tables with reviews from previous studies and 100+ references included.
  • Cardiovascular manifestations and treatment considerations in Covid-19. May 2. Kang. Heart.
    A review article nicely summarizing the current theories and studies on the cardiovascular manifestations of COVID-19.
  • Characteristics, treatment, outcomes and cause of death of invasively ventilated patients with COVID-19 ARDS in Milan, Italy. May 1. Zangrillo. Crit Care Resusc.
    Many with COVID-19 end up requiring critical care and then die. It might be useful to better predict who might die to better plan critical care resources. Of 73 invasively ventilated patients with COVID-19 ARDS in a referral centre in Milan, Italy male sex and hypertension were disproportionately common; one in 15 patients was treated with ECMO; and one in five with RRT. Most patients received vasopressors and neuromuscular blocking agents, three out of four patients were treated with prone positioning, and three in ten received a tracheostomy. After a medical followup of 20 days, about 15% died. This was a single center study, and though more granular data was provided, this was not really a guide concerning who should or should not receive intensive care.
  • Clinical and laboratory predictors of in-hospital mortality in patients with COVID-19: a cohort study in Wuhan, China. May 4. Wang. Clin Infect Dis.
    Are there factors that might predict mortality? Based on this study of almost 300 patients, age, history of hypertension, and coronary heart disease were predictive and another analysis that included high-sensitivity C-reactive protein, higher D-dimer and thrombin time and lower activated partial thromboplastin time also predicted a higher incidence of death. All interesting findings, but again, what is the practitioner to do with such a study based on only 1 hospital.
  • Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan, China. May 2. Wang. Crit Care.
    Retrospective study of 107 COVID-19 patients discharged from 2 hospitals in Wuhan, China.
    Week 1 after onset — fever, though dyspnea, lymphopenia, multi-lobar pulmonary infiltrates. In severe cases, thrombocytopenia, acute kidney injury acute myocardial injury and ARDS.
    Week 2. Fever, cough, systemic symptoms, and thrombocytopenia began to resolve with persistent lymphopenia in mild cases, while in severe cases leukocytosis, neutrophilia, and multi-organ dysfunction were seen.
    Week 3. Mild cases clinically resolved with persistent lymphopenia. Severe cases showed persistent lymphopenia, severe ARDS, refractory shock, anuria, coagulopathy, thrombocytopenia, and death.
    88 survived. Duration of active viral shedding in survivors was 13 days. Non-survivors were older, predominantly male, had more co-morbidites such as HTN or CV disease, and were more likely to present with with dyspnea, diarrhea. They had higher neutrrophil count, D-dimer, BUN, creatinine, HS-troponin I, CK, CK-MB, LDH, ALT, and AST and had lower platelets. Causes of death included refractory ARDS, septic shock, sudden cardiac arrest, hemorrhagic shock and AMI.
  • Coagulopathy associated with COVID-19
    May 4. Lee. CMAJ.
    Opinion from SAB Member: Dr. Louis McNabb
    5 key points in a concise one-page summary on where we are in our understanding of coagulopathy issues for COVID-19.
  • COVID-19 and acute myocardial injury: the heart of the matter or an innocent bystander?
    Apr 30. Cheng. Heart.
    Opinion from SAB Member: Dr. Philip Lumb
    Short but valuable review of myocardial involvement in COVID-19 with relevant literature reviews, and a useful table of potential mechanism and diagnostic limitations in myocardial injury. Recognizes the current therapeutic dilemmas facing clinicians in order to maximize myocardial preservation and/or recovery.
  • COVID-19 and Neonatal Respiratory Care: Current Evidence and Practical Approach. May 3. Shalish. Am J Perinatol.
    An international group of perinatologists reviewed reports of COVID-19 infections under 10 y/o noting the incidence is rare, less than 1% of all cases. In newborns the number is lower. Recommendations for care are listed.
  • COVID-19 Illness and Heart Failure: A Missing Link. May 4. Mehra. JACC Heart Fail.
    Very good summary of pathophysiology of multisystem with a table irrespective of heart failure. Somewhat repetitive but clear statements describe phases of COVID-19 and addresses optimization of each system (respiratory, fluid, anti inflammatory).
  • COVID-19, superinfections and antimicrobial development: What can we expect? May 4. Clancy. Clin Infect Dis.
    Authors are concerned about superinfection of Covid-19 (700,000 deaths/year), drug resistance and no new drugs in the pipeline, a weak government response, a counterproductive regulation of prescription model, raw material for antibiotics coming from China and India, market forces drying out due to stakeholders…
    Coronavirus disease 2019 (COVID-19) arose at a time of great concern about antimicrobial resistance (AMR). No studies have specifically assessed COVID-19-associated superinfections or AMR. Based on limited data from case series, it is reasonable to anticipate that an appreciable minority of patients with severe COVID-19 will develop superinfections, most commonly pneumonia due to nosocomial bacteria and Aspergillus.
    Microbiology and AMR patterns are likely to reflect institutional ecology. Broad-spectrum antimicrobial use is likely to be widespread among hospitalized patients, both as directed and empiric therapy. Stewardship will have a crucial role in limiting unnecessary antimicrobial use and AMR. Congressional COVID-19 relief bills are considering antimicrobial reimbursement reforms and antimicrobial subscription models, but it is unclear if these will be included in final legislation. Prospective studies on COVID-19 superinfections are needed, data from which can inform rational antimicrobial treatment and stewardship strategies, and models for market reform and sustainable drug development. A plea for rational antimicrobial treatment and stewardship strategies, and models for market reform and sustainable drug development.
  • Inhibitors of the Renin-Angiotensin-Aldosterone System and Covid-19
    May 1. Jarcho. The New England Journal of Medicine.
    Opinion from SAB Member: Dr. David M. Clement
    Editorial reviewing the theoretical concerns for the use of ARB/ACEI drugs during the COVID-19 epidemic, and three observational clinical studies that conclude these drugs seem not to influence the course of the disease. This is consistent with other studies and guidelines from pertinent organizations; that ARB/ACEI drugs should be continued if a patient develops COVID-19 disease.
  • Olfactory and Gustatory Dysfunction in Coronavirus Disease 19 (COVID-19)
    May 1. Luers. Clinical Infectious Diseases.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    72 patients with polymerase chain reaction confirmed COVID-19 agreed to participate and were enrolled in this study. Reduced olfaction was noted in 74% and a reduced sense of taste was noted in 69%. 68% reported both symptoms. Both symptoms occurred on average on the 4th day after first symptoms were noted, though 13% noted reduced olfaction and taste on the first day of COVID-19 symptoms.
  • Preliminary observations of anaesthesia ventilators use for prolonged mechanical ventilation in intensive care unit patients during the COVID-19 pandemic. May 4. Gouel-Cheron. Anaesth Crit Care Pain Med.
    Letter discussing positive experience using anesthesia ventilators during the first twenty days of use in a critical care unit when Patient care initiated with an anesthesia ventilator. Two patients required change to an ICU specific ventilator; one after 6 hours, the second after 70 hours due to inability to resolve high plateau pressures and hypercarbia with setting adjustments. Critique that lung compliance could not be measured, but ABG’s and clinical assessment noted acceptable. Water trap emptying and filter changes noted every two days, similar to ICU ventilator routine.
    Interesting observations; however, anesthesia ventilators are not identified, and it is difficult to interpret results in absence of basic anesthesia machine characteristics.
  • Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19. May 2. Reynolds. N Engl J Med.
    A retrospective, observational study from New York of 12,594 patients on various anti-hypertensive medications. Sophisticated statistical analysis showed no association of any class of drugs (including ARBs/ACEIs) and the presence or severity of COVID-19 disease.
  • Risk Factors Associated with Clinical Outcomes in 323 COVID-19 Hospitalized Patients in Wuhan, China. May 4. Hu. Clin Infect Dis.
    The authors analyzed over 300 patients, cared for in Wuhan, China, to identify some risk factors with outcome. The authors found 27 risk factors associated with COVID-19 clinical outcomes. Unlike some other studies, the authors found that smoking was an independent factor for poor outcome. Hypnotic administration was significantly associated with favorable outcomes and higher hypersensitive troponin I were found to predict poor clinical outcomes. So many factors were considered and with such studies, any factor can be found significant. If the study had been more focused, the findings would have been more credible.
  • Role of serology in the COVID-19 pandemic
    May 1. Stowell. Clinical Infectious Diseases.
    Opinion from SAB Member: Dr. Barry Perlman
    Editorial of serologic study by Xiang et al. which demonstrated ability to measure IgG and IgM in COVID-19 patients with good sensitivity and specificity. The editorial points out that variability in kinetics and magnitude of the serologic response, especially early in infection, can result in false negative results, and IgM results may be false positive. In addition, it is not known if positive serology correlates with disease immunity. Suggested uses for serologic testing: 1) COVID-19 symptoms but RT-PCR negative; 2) Populations to determine degree of community exposure; 3) Frontline healthcare workers; 4) Convalescent plasma donation.
  • SARS-CoV-2 asymptomatic and symptomatic patients and risk for transfusion transmission. May 4. Corman. Transfusion.
    German authors caution on blood donor poll getting contamination by COVID-19. They noted low risk transfusion risk, but avoid all donor that + RN – PCR. 18 Patient with PCR positive, RNAemia (Actual RNA of virus) was neither detected in 3 patients without symptoms nor in 14 patients with flu‐like symptoms, fever or pneumonia (Mild to moderate symptoms). The only one patient with RNAemia suffered from acute respiratory distress syndrome (ARDS). Risk for SARS‐CoV‐2 transmission through blood components in asymptomatic SARS‐CoV‐2 infected individuals therefore seems negligible but further studies are needed to decease contamination. RNAemia is closely linked to IL 6. RNAemia is NOT considered as infectivity. Stresses need of standardization of RN – PCR all across the world. Male had higher incidence of + RNAemia.
  • Soluble urokinase plasminogen activator receptor (suPAR) as an early predictor of severe respiratory failure in patients with COVID-19 pneumonia. May 2. Rovina. Crit Care.
    Endothelial urokinase plasminogen activator receptor (uPAR) may be cleaved early during COVID-19 infection, causing an increase of its soluble counterpart, suPAR. Studies suggest that suPAR may be a biomarker for risk of death, sepsis outcome, and kidney disease. To determine whether suPAR can be used as a predictor of COVID-19 severe respiratory failure, the Hellenic Sepsis Study Group is collecting clinical information and serum samples within the first 24 hours of admission. Preliminary findings — 57 COVID-19 patients with pneumonia were followed for 14 days. Admission levels of suPAR were significantly greater in patients who progressed to severe respiratory failure, with levels > 6ng/ml having a sensitivity of 86% and specificity of 92%. Male gender was also a risk factor for severe respiratory failure. There was an association between admission suPAR and D-dimers. How elevated suPAR levels can be used to guide therapy will require further study.
  • The Renin-Angiotensin-Aldosterone System in Coronavirus Infection-Current Considerations During the Pandemic. May 4. Augoustides. J Cardiothorac Vasc Anesth.
    An editorial reviewing what is known, being studied, and speculated about the RAAS system’s contributions to the clinical spectrum of COVID-19 disease.
  • The Use of Bronchoscopy during the COVID-19 Pandemic: CHEST/AABIP Guideline and Expert Panel Report
    Apr 29. Wahidi. Chest.
    Opinion from SAB Member: Dr. Louis McNabb
    Lengthy article with very little data summarized in a table at end of article. There is a nice table detailing which patients need emergency vs. elective bronchoscopies. Unsurprisingly, the article recommends that operators and health care workers should wear PAPR or N-95 masks with eye shields, gloves, and gowns for most if not all bronchoscopy situations.
  • Use of drugs with potential cardiac effect in the setting of SARS-CoV-2 infection. May 2. Sacher. Arch Cardiovasc Dis.
    French editorial for mitigating risk of arrhythmias due to COVID-19 treatment. Preliminary studies do not document QT prolongation related deaths from hydroxychloroquine/azithromycin, although in one study acute renal failure was a strong predictor of extreme QTc prolongation. Risk factors for QT prolongation and Torsades de pointes:
    1. Modifiable. Hypokalemia, hypocalcemia, hypomagnesemia, bradycardia.
    2. Non-modifiable. Congenital long QT syndrome, female, age > 65, baseline QTc>460 ms, cardiac disease, history of kidney or liver disease, sepsis.
    3. Related to COVID-19 infection. Myocarditis, arrhythmias, hypokalemia, ARF Cardiac workup and optimization prior to initiation of COVID-19 medication treatment should be guided by risk factors (Figure 1). ECG is required before starting drug combinations that can both cause QT prolongation. QTc < 460ms is considered low risk, while if > 500 ms QT prolonging drugs should be avoided or stopped.
    The importance of determining QTc accurately and methods for correctly calculating it are discussed.
  • When the game changes: Guidance to adjust sarcoidosis management during the COVID-19 pandemic
    Apr 27. Sweiss. Chest.
    Opinion from SAB Member: Dr. Jay Przybylo
    An international Rheumatology panel makes recommendations regarding sarcoidosis care including lowering the dose of most medications as necessary to protect against viral infection. The Hydroxychloroquine dose should be maintained if the drug is available. Patients should be followed closely and medication doses adjusted as needed.

May 2, 2020:

  • Cardiovascular Consequences and Considerations of Coronavirus Infection – Perspectives for the Cardiothoracic Anesthesiologist and Intensivist During the Coronavirus Crisis
    May 1. Augoustides. Journal of Cardiothoracic and Vascular Anesthesia.
    Opinion from C19SAB: Dr. Barry Perlman
    Editorial discussing causes of cardiovascular collapse in patients with severe COVID-19, focusing on Cardiogenic shock, vasoplegic shock, acute coronary ischemia, and right ventricular failure.
  • Category: Expression of Concern
    Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 – published in the New England Journal of Medicine on May 1, 2020, subjected to an expression of concern on June 2, and retracted on June 4. 
    Expression of Concern: Mehra MR et al. Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19. N Engl J Med. DOI: 10.1056/NEJMoa2007621.
    June 2. Mehra MR. The New England Journal of Medicine.
    The Lancet published the following Expression of Concern about an article previously cited and summarized by this Scientific Advisory Board in the 5MAY2020 Newsletter.
    ‘On May 1, 2020, we published “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19,” a study of the effect of preexisting treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) on Covid-19. This retrospective study used data drawn from an international database that included electronic health records from 169 hospitals on three continents. Recently, substantive concerns have been raised about the quality of the information in that database. We have asked the authors to provide evidence that the data are reliable. In the interim and for the benefit of our readers, we are publishing this Expression of Concern about the reliability of their conclusions.
    Studies of ACE inhibitors and ARBs in Covid-19 can play an important role in patient care. We encourage readers to consult two other studies we published on May 1, 2020, that used independent data to reach their conclusions.’

  • COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options
    Apr 30. Guzik. Cardiovascular Research.
    Opinion from C19SAB: Dr. Philip Lumb, Dr. Lydia Cassorla
    PL: Detailed, research-oriented discussion on cardiovascular implications of COVID-19 infection. Mechanisms of infection described with experimental justification for potential interventions; recognizes supportive care required for most cases. Discusses (albeit briefly) progression to invasive therapies including ECMO. Basic science oriented with clearly described mechanisms and exhaustive review of available literature with references to match. LC: This comprehensive review of COVID-19 illness with a particular eye toward cardiovascular ramifications may raise more questions than it answers. However, it is well written and thoroughly referenced to be consumed when time permits careful reading. Regarding CV complications: “The most common cardiac complications include arrhythmia (AF, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury (elevated hs-cTnI and CK), fulminant myocarditis, and heart failure.” The authors point out that since cardiac manifestations often occur >15 d after onset of symptoms, they are possibly a result of host-driven phenotypes and/or secondary effects of medications. They mention that inclusion bias may result from specific factors in the area where a pandemic begins and expect data to differ as the disease population changes. Surprisingly, a history of smoking or chronic lung disease is less of a risk for poor outcomes than with SARS-CoV (2003) or MERS. HTN/CV disease are risk factors for advanced disease and death but not for infection and may partly be a proxy for age. When acute myocardial injury occurs, PCI may not always benefit patients as their ischemia may be due to Type 2 MI or myocarditis.
  • Institution of a Novel Process for N95 Respirator Disinfection with Vaporized Hydrogen Peroxide in the setting of the COVID-19 Pandemic at a Large Academic Medical Center. May 1. Grossman. J Am Coll Surg.
    A multi-disciplinary team from Washington University School of Medicine, Barnes Jewish Hospital, and BJC Healthcare created a vaporized hydrogen peroxide (VHP) disinfection facility within their institution and developed a logistical framework to provide just-in-time large volume disinfection of N95 masks, returning each mask to its original wearer. In-house experience with the technique was leveraged, using Bioquell VHP and aeration equipment. They built a designated facility with separate areas for receiving used masks, disinfection, and off-gassing. Their first facility processes up to 1500 masks per cycle. Subsequent facilities were created in affiliated medical centers, scaled to local needs. Organizational and operational details are well described, including control processes to verify both sterilization and off gassing. Each user bags and labels his or her own mask, and masks from each work unit remain grouped throughout the process to facilitate timely return of batches to each work site for individuals to retrieve.
  • Renin–Angiotensin–Aldosterone System Blockers and the Risk of Covid-19
    May 1. Mancia. The New England Journal of Medicine.
    Opinion from SAB Member: Dr. David M. Clement
    This is the first large study confirming smaller studies and various recommendations on ACEI and ARBs use in COVID-19 patients. A case-control study from Italy of 6,272 COVID-19 patients looking for an association between ACEI or ARB use and the risk of COVID-19 disease. No association was found between pre-infection ARB/ACEI use and susceptibility or severity of SARS-CoV-2 infection. Starting ACEI or ARB drugs during infection was not studied.
  • Return to normal—prioritizing elective surgeries with low resource utilization. Apr 29. Wilson. Anesthesia & Analgesia.
    In an effort to commence elective surgery without overburdening their ICU, a large hospital in NYC did a statistical analysis of pre-COVID-19 elective surgeries, looking at ICU admission and ventilator use. Cardiac, abdominal and spine surgeries in patients with a high co-morbidity burden were at greatest risk. Such an organized approach to determining how to open to elective surgery is commendable, and is likely to vary in different institutions. Ventilation and ICU care may not be the limiting resource to make such decisions.
  • Testing an Old Therapy Against a New Disease: Convalescent Plasma for COVID-19. Apr 30. Rubin. JAMA.
    A Medical News article written more for general consumption than presenting scientific and clinical results. I first thought to go to the referenced articles that contained only a handful of patients with encouraging results. Then, I noticed a well-developed article summarizing all that has been done so far with transfused plasma including references into the 1890s. Puts the use of transfused plasma into a rational perspective.
  • Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy
    Apr 23. Lodigiania. Thrombosis Research.
    Opinion from SAB Member: Dr. J. Lance Lichtor, Dr. Joseph Anthony Caprini
    JLL: Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. The study is based on retrospective data for 388 admitted hospitalized patients with COVID-19. All ICU patients received thromboprophylaxis and 75% of those admitted to general wards also had thromboprophylaxis. Thromboembolic events occurred in almost 8% of patients which included pulmonary embolism. A little over half of the patients with PE did not receive anticoagulant treatment. Hospital mortality was associated with a high rate of thromboembolic complications. Rapidly increasing D-dimer levels were observed in non-survivors. A true incidence is difficult to determine since, as the reader is told in the discussion, a low number of specific imaging tests were performed. JC: The low incidence of thrombotic events on the ward compared to the ICU is one feature of this series. The fact that 58% of thrombotic events were not on anticoagulation is telling. We know all patients should be on anticoagulation. That has not been their routine practice in the past in many medical patients not in ICU. The paper sends the wrong message advocating for more tests which exposes scanners and machines to risks that may be avoided. Giving everyone anticoagulation and adjusting the dose based on co-morbidities and when the D-dimers skyrocket using full dose anticoagulation. We are learning as we go along but more heparin or LMWH is the developing trend.

May 1, 2020:

  • A Marker of Systemic Inflammation or Direct Cardiac Injury: Should Cardiac Troponin Levels be Monitored in COVID-19 Patients? 4/29/2020. Atallah. Eur Heart J Qual Care Clin Outcomes.
    Detailed discussion of potential evolution of cardiac injury during COVID-19 demonstrating increased mortality in patients developing cardiac dysfunction. Discusses enzymatic increases that aid in prognosis and risk classification. Troponin level increases associated with other markers of inflammation (IL-6). Also noted were increases in D-dimer and indications of a procoagulant state that could lead to ischemia, thrombosis and subsequent cardiac injury.
    “In summary, there are several mechanisms that could be at play to explain myocardial injury in relation to COVID-19 infection, that include but are not limited to: Myocarditis, sepsis and associated systemic inflammatory response, pro-coagulant condition, destabilization of coronary plaque, and hypoxia.”
    Manuscript concludes with 7 recommendations and is published on behalf of the European College of Cardiology.
  • A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Apr 30. Gordon. Nature.
    332 SARS-CoV-2 human protein interactions were identified by cloning virus proteins in human cells and then identifying associated human proteins. 40% are associated with endomembrane compartments or vesicle trafficking pathways. 66 interactions are targeted by 29 approved drugs, 12 in clinical trials, and 28 preclinical compounds. Viral assays at Mt Sinai in NY and the Institut Pasteur in Paris identified 2 sets of agents with antiviral activity — those affecting translation (e.g. hydroxychloroquine and the more effective PB28) and those modulating Sigma1 and 2 receptors (e.g. haloperidol and dextromethorphan). Intriguing methodology for identifying existing compounds for clinical trials.
  • Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases
    Apr 29. Casas. British Journal of Dermatology.
    Opinion from C19SAB: Dr. Barry Perlman
    Description of 5 clinical patterns of cutaneous lesions associated with 375 COVID-19 cases in Spain, in order of associated severity of disease: 1. Acral areas of erythema with vesicles or pustules (Pseuo-chilblain). Appears late, more common in younger patients; 2. Other Vesicular eruptions. More common in middle aged patients; 3. Urticarial lesions; 4. Maculopapular eruptions. Most common; 5. Livedo or Necrosis. Consistent with occlusive vascular disease.
  • Correlation between Heart fatty acid binding protein and severe COVID-19: A case-control study. Apr 30. Yin. PLoS One.
    In patients who had measurements of heart fatty acid binding protein (HFABP), a serum cardiac specific biomarker for myocardial injury, the authors found a correlation between elevated HFABP and progression to severe COVID-19 illness. However only 46 of 245 patients had the test and the study had no control group. During hospitalization, severe illness was observed in 87.5% of HFABP positive patients vs. 40% in those who were HFABP negative (P = 0.002). We do not know why some patients had HFABP measured, making the results difficult to interpret.
  • COVID-19 and One Lung Ventilation. Apr 27. Tryphonopoulos. Anesthesia & Analgesia.
    Here the author addresses one lung anesthesia techniques to reduce aerosolization and airborne COVID-19 particles to reduce exposure for healthcare workers (airway managers) for: Induction, intubation, double lumen tube, suctioning, fiberoptic bronchoscopy, (all aerosol – generating procedure). Main focus of recommendations: complete paralysis, create no flow = silent airway. No open airway. No flow = no aerosol of secretion or due to cough of patient means less exposure.
  • COVID-19 Pandemic ARDS Survivors: Pain after the Storm?
    Apr 27. Vittori. Anesthesia & Analgesia.
    Opinion from C19SAB: Dr. W. Heinrich Wurm
    A look beyond the acute phase of COVID-19 by an international panel of specialists in pediatric critical care, pain management and anesthesiology, alerting us of the challenges ahead as survivors will have to deal with the after effects of ARDS, severe illness, isolation, PTSD, and the altered reality of post-COVID-19 society. Specifically, the panel calls for a multidisciplinary commission of experts to issue recommendations on monitoring symptoms, create best practices to prevent sequelae, establish a registry for survivors (both patients and care givers), and embark on multicenter studies to track chronic pain and other physical and psychological sequelae of the disease and the impact it has on health care workers and families.
  • COVID-19 Related Genes in Sputum Cells in Asthma: Relationship to Demographic Features and Corticosteroids
    Mar 27. Peters. American Journal of Respiratory and Critical Care Medicine.
    Opinion from C19SAB: Dr. Louis McNabb, Dr. Jay Przybylo
    LM: African Americans, males, and diabetics have increased expression of ACE2 and TMPRSS2 which might theoretically explain why these groups are at increased risk for COVID-19. Inhaled corticosteroids decreased expression of ACE2 and TMPRSS2 and theoretically might favorably modify the risk from COVID-19. JP: Thorough study demonstrating asthmatics taking inhaled corticosteroids might be at lower risk of significant COVID-19 infection via activity on the ACE2 receptor.
  • COVID-19: ICU delirium management during SARS-CoV-2 pandemic
    Apr 28. Kotfis. Critical Care.
    Opinion from C19SAB: Dr. W. Heinrich Wurm
    Well referenced review of central nervous system effects of the corona virus with special focus on current available data on delirium–direct and indirectly caused by SARS-CoV-2 infection. While direct CNS invasion is likely originating from the nasopharynx, there is insufficient data on CNS pathophysiology and resulting delirium in severely ill patients. Secondary neural pathology caused by inflammatory mediators affecting the blood brain barrier may be contributing as are metabolic factors secondary to organ dysfunction, social isolation, sedation and pre-existing disease. These concepts are summarized in a well-organized graph and management advice is given using the Society of Critical Care Medicine’s ABCDEF Safety Bundle framework.
  • Current perspectives on Coronavirus 2019 (COVID-19) and cardiovascular disease: A white paper by the JAHA editors
    Apr 29. Gupta. Journal of the American Heart Association.
    Opinion from C19SAB: Dr. David M. Clement
    A “White Paper” from the international editorial board of the Journal of the American Heart Association, thoroughly addressing the important aspects of cardio-vascular disease during the COVID-19 pandemic. Very long, but well organized to highlight the important conclusions on troponin elevations, hypertension (RAS), vascular events (including hypercoagulability), arrhythmias (i.e. long QT with some drugs), myocardial injury, ECMO, healthcare worker protection and ethics. Of note, explanations of the pathophysiology of CV disease usually circle back to the inflammatory response to COVID-19. Statins and antiplatelet therapy recommended. A thorough overview of the current knowledge.
  • Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation
    Apr 28. Leisman. Intensive Care Medicine.
    Opinion from C19SAB: Dr. W. Heinrich Wurm
    A literature review aiming to classify COVID-19 as a vascular disease characterized by “a confluence of vascular dysfunction, thrombosis and dysregulated inflammation.” The author’s argument is based on the divergence of lung injury seen in the early stages of COVID-19 from typical ARDS, the elevation of pro-thrombotic markers and histopathological findings of endothelial injury. They consider the evidence of a cytokine storm as an underlying mechanism weak and propose “vasculopathy and dysregulated inflammation” to be the underlying cause leading to thrombotic microangiopathy in pulmonary, renal and other organ systems. A graphic demonstration of the SARS-CoV-2 infection of an endothelial cell initiating a cascade of ACE-2 mediated events, strengthens the argument: loss of angiotensin 2 results in loss of autoregulation and vasoconstriction leading to the hypoxic compliant lung injury described by Gattinoni.
    The author’s closing argument is to focus less on cytokine modulation and more on anticoagulation as a therapeutic measure and to investigate the use of angiotensin 2 therapy.
    This paper created a lively discussion among the members of the SAB as to its clinical relevance and applicability. It is hoped that it will do the same among our readers. Most importantly, we look forward to future multi-disciplinary research leading to a consensus on the mechanisms of COVID-19’s attack on multiple organ systems.
  • Factors associated with mortality in patients with COVID-19. A quantitative evidence synthesis of clinical and laboratory data. Apr 20. Martins-Filho. Eur J Intern Med.
    For this meta-analysis a literature search performed January 1- April 06, 2020 led to screening 8692 titles and abstracts among which 73 full-text articles were assessed for eligibility and 69 were excluded, 11 due to potential overlapping data. Data in the report is from only four retrospective Chinese studies encompassing 852 unique patients (489 male and 363 female) with confirmed SARS-CoV-2 infection by RT-PCR: 603 survivors and 249 non-survivors. The study reports increased risk for in-hospital death in older patients (MD= 13.8, 95%CI 8.0 to 19.7), male gender (RR= 1.3, 95%CI 1.1 to 1.4), with comorbidities (RR= 1.6, 95%CI 1.4 to 2.0) and dyspnea (RR= 1.8, 95%CI 1.4 to 2.2). The report details the relative risk for death of dozens of clinical and laboratory findings. There are no surprises.
  • Hypercoagulation and Antithrombotic Treatment in Coronavirus 2019: A New Challenge. Apr 30. Violi. Thromb Haemost.
    The authors analyzed variables regarding clotting and fibrinolysis along with platelet count in COVID-19 patients, according to disease severity and survival. Tables and algorithms are clearly presented.  The conclusion of this report is to treat those with pneumonia that is severe or associated with elevated D-dimer levels but not those with mild disease without additional risk factors for thrombosis. In contrast, opinion in the US appears to be swinging toward prophylaxis in most if not all hospitalized COVID-19 patients.  
  • Inhaled Nitric Oxide and COVID-19. Apr 28. Ignarro. Br J Pharmacol.
    In this letter to the editor, the authors note that NO may have an antiviral effect and in patients with SARS-CoV, reversed pulmonary hypertension, improved severe hypoxia and shortened the length of ventilatory support. Whether the same will improve hypoxia in patients with COVID-19 infection with moderate to severe COVID-19 with pneumonia and under assisted ventilatory support is being studied.
  • Neuraxial anaesthesia and peripheral nerve blocks during the COVID-19 pandemic: a literature review and practice recommendations. Apr 29. Uppal. Anaesthesia.
    “Regional anaesthesia may be the preferred choice for providing anaesthesia care when possible, as it can provide an alternative safe anaesthetic care plan by avoiding the need for aerosol- generating procedures.” This paper provides recommendations for performing regional anesthesia during the COVID-19 pandemic.
  • Obesity could shift severe COVID-19 disease to younger ages. Apr 30. Kass. The Lancet.
    A Lancet “Correspondence” from Johns Hopkins describing a negative correlation between age and BMI in 265 COVID-19 patients.
  • Patients with cancer appear more vulnerable to SARS-COV-2: a multi-center study during the COVID-19 outbreak
    Apr 29. Dai. Cancer Discovery.
    Opinion from C19SAB: Dr. J. Lance Lichtor
    Based on a retrospective analysis of patient information collected from 14 hospitals in Hubei Province, China, patients affected by the SARS-CoV-2 coronavirus for 105 hospitalized patients with cancer and 536 patients without cancer were compared. Patients with hematological cancer (1st), lung cancer (2nd), and cancers in metastatic stages demonstrated higher rates of severe events compared to patients without cancer. In addition, patients who underwent cancer surgery showed higher death rates and higher chances of having critical symptoms. In addition, patients on immunotherapy had the highest death rate and the most severe illness. It is expected that people with systemic disease should do less well. Unfortunately, the authors did not compare the two groups to hospitalized patients with cancer but without COVID-19.
  • Persistent hiccups as an atypical presenting complaint of COVID-19. Apr 30. Prince. Am J Emerg Med.
    A case report of a patient who presented with hiccups, for which a CT was obtained. This was abnormal and SARS-CoV-2 testing was positive. Hiccups resolved on hydroxychloroquine.
  • Pulmonary Embolism and Increased Levels of d-Dimer in Patients with Coronavirus Disease. Apr 29. Griffin. Emerg Infect Dis.
    All patients on 40 mg lovenox SC q day. SX’S occurred after cytokine storm. All patients survived to clear discharge.
  • Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Apr 29. Wang. The Lancet.
    2:1 randomized, placebo controlled double blind controlled study on 237 patients in Hubei province China on patients with confirmed COVID-19 disease of 10 days duration or less. No statistically significant results reported although trend to shorter time to clinical improvement requires confirmation in larger studies.
  • Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia
    Apr 30. Pei. Journal of the American Society of Nephrology.
    Opinion from C19SAB: Dr. Barry Perlman
    Retrospective study of EMR data from 333 COVID-19 patients hospitalized with pneumonia in China. Patients with CKD or on dialysis were excluded. 75% had hematuria, proteinuria, or acute kidney injury. 82% had suspected intrinsic AKI. Severity of pneumonia was an independent risk factor for AKI. 46% with AKI had complete recovery of kidney function within 3 weeks of illness onset. Renal involvement correlated with a 9X increased rate of mortality. No deaths occurred in patients with pre-renal AKI, or in whom hematuria or proteinuria resolved.
  • Respiratory Pathophysiology of Mechanically Ventilated Patients with COVID-19: A Cohort Study
    Apr 16. Ziehr. American Journal of Respiratory and Critical Care Medicine.
    Opinion from C19SAB: Dr. Jay Przybylo
    A small study submitted as a letter to the editor that describes the characteristics of patients presenting with respiratory failure requiring mechanical ventilation. The study demographics confirm other reports and further describes ventilatory management using measurements of oxygenation and compliance. Prone positioning improved the pulmonary status of patients in this study.
  • Variation in COVID-19 Hospitalizations and Deaths Across New York City Boroughs. Apr 29. Wadhera. JAMA.
    New York City has emerged as the epicenter of the COVID-19 outbreak. New York City is composed of 5 boroughs (the Bronx, Brooklyn, Manhattan, Queens, and Staten Island), each with unique demographic, socioeconomic, and community characteristics. Prior analyses have shown health inequities across these boroughs. The author relied on available public records from the recent past (census, age, M: F, race / ethnicity, education level, annual average income, available hospital bed, etc.) & current death rate from Covid-19 for each borough. Graphs & table suggests – Bronx: highest hospitalization & death rate, black population, lowest education, poverty & lowest income population of all the boroughs of NYC.
    The author provides raw data for comparison. Author provided table numbers but failed to make any conclusion for important health policy answers. Assumption people did not travel to another borough? Surge capacity for each hospital was not taken in account. The study is ongoing?

April 30, 2020:

  • ABO blood group predisposes to COVID-19 severity and cardiovascular diseases. Apr 29. Dai. Eur J Prev Cardiol.
    The authors state “Although ABO blood type and/or cardiovascular diseases are prognostic of COVID-19 patient severity, they are not risk factors predisposing to the risk of getting SARS-CoV-2 infection”. However, their report is of a proposed theory that relative differences in ACE and ACE2 receptor activity in persons with differing ABO blood types results in higher Covid-19 severity in A-type individuals, with no data or citations to back up the idea.
  • Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals. Apr 27. Yuan. Nature.
    Unedited manuscript accepted for publication by Nature.
    RNA fragments of the virus were trapped in ambient air using gelatine filters and droplet digital PCR in several areas of 2 Wuhan hospitals (one a converted stadium) during the height of the crisis (mid-February to early March 2020). It is important to note, that these samples were not analyzed for viability as contagions. Particle size were measured and mechanisms of resuspension of particles is described. Resuspension of RNA fragments was observed when used PPE was moved for disposal. The study demonstrates the need for wearing masks in public spaces, the effectiveness of meticulous disinfectant measures, particularly the surface disinfection of PPE before doffing and the advantage of naturally vented buildings (stadiums) for non-critical patient care and quarantine.
  • Battle Buddies: Rapid Deployment of a Psychological Resilience Intervention for Healthcare Workers during the COVID-19 Pandemic
    Apr 24. Albott. Anesthesia & Analgesia.
    Opinion from SAB Member: Dr. David M. Clement
    A very detailed overview of a program implemented at the University of Minnesota, designed to preserve “the psychological health of the medical workforce” through “pre-emptive resilience-promoting strategies” during the COVID-19 pandemic. Their program included three levels of support: 1. A “Battle Buddy” peer support strategy based on a US Army program. 2. A mental health consultant assigned to every clinical unit. 3. Confidential one-on-one additional help for HCW with additional needs. Excellent tables and graphic support. No outcome information.
  • Clinical phenotypes of SARS-CoV-2: Implications for clinicians and researchers
    Apr 11. Rello. European Respiratory Journal.
    Opinion from C19SAB: Dr. Barry Perlman
    Discussion of COVID-19 clinical experience in Italy and Spain. Lymphocytopenia, low procalcitonin, and elevated LDH and CRP are characteristic. Hypercoagulability is common, with increased risk of thrombotic and embolic events. Severe cases have elevated D-Dimer and INR, and low fibrinogen and platelet count. Use of prophylactic unfractionated heparin is suggested for all hospitalized COVID-19 patients. 5 phenotypes of COVID-19 infection are described to guide individualized therapy (Table 2): 1. Most common is benign, with fever, headache, mild respiratory symptoms, malaise. Normal CXR and no hypoxemia; 2. 80% of hospitalized patients. Hypoxemia or small CXR opacities. Should be monitored closely due to risk of rapid deterioration. Typically hypovolemia and hyper-inflamed. Good candidates for clinical trials of anti-virals, anti-inflammatories, or anti-fibrotics; 3. 15% of China hospitalizations. Greater hypoxemia and high respiratory rates. High IL6. Also candidates for clinical trials. Prone position may help avoid intubation. Consider intubation if respiratory alkalosis with increasing hyperventilation on high O2; 4. Severe hypoxemia requiring intubation. Pulmonary hypoxic vasoconstriction with normal lung compliance. Probably due to pulmonary microvascular thrombosis. Advise no delay in intubation, especially when BB coalescent lines are present in more than 3 fields. Nitric oxide or prostacyclin may be helpful. PEEP typically should be 8-10 cm H2O with tidal volumes 6-9 mL/kg. Avoid recruitment maneuvers, prone positioning; 5. Less common. Advanced disease with acute lung injury or co-infection causing high procalcitonin. More common when intubation is delayed by non-invasive ventilation treatment. Low lung compliance < 40 mL/cm H2O. Suggest ARDS strategy with high PEEP and prone positioning.
  • Covid-19 may present with acute abdominal pain. Apr 29. Saeed. Br J Surg.
    This is a report of evolving understanding of the range of presenting symptoms of Covid-19 patients. Of 76 patients presenting to the ER in Oslo, Norway, during a 15-day period with a chief complaint of abdominal pain, 9 were found to be positive for coronavirus. All 9 had other GI symptoms – 3 nausea, 5 nausea+vomiting and 1 diarrhea. 5 had fever. None complained of respiratory problems. When coronavirus infection was diagnosed, pulmonary evaluation revealed 6 had ground glass opacities on CT. The diagnoses included cholecystitis in 1 and appendicitis in 1 however the report indicates that all were discharged home for self-quarantine and none required ICU care. This led to modifications in their institutional protocols. “Droplet isolation and testing for COVID-19 are now performed on all patients with abdominal pain.”
  • COVID-19-related myocarditis in a 21-year-old female patient
    Apr 13. Kim. Eur Heart J.
    Opinion from SAB Member: Dr. Barry Perlman
    Report of 21-year-old South Korean patient with COVID-19 and elevated Troponin I of 1.26 ng/ml and NT-proBNP of 1929 pg/ml. Chest CT showed multifocal consolidation and bilateral peripheral lower lobe ground-glass opacification. EKG showed NSIVCD and multiple PVCs. ECHO showed severe LV systolic dysfunction. Cardiac CT showed normal coronary arteries but myocardial edema and hypertrophy with lateral LV subendocardial perfusion defect. Cardiac MRI was also consistent with myocardial edema with extensive transmural late gadolinium enhancement. Her treatment or clinical course were not discussed.
  • Fatal Invasive Aspergillosis and Coronavirus Disease in an Immunocompetent Patient. Apr 29. Blaize. Emerg Infect Dis.
    The gold standard to prove invasive disease is to show fungal invasion in tissue samples. Although at least 4 out of 6 reported patients died, there was no corroboration with autopsy findings. Also the “immunocompetent patient” had asymptomatic and untreated myelodysplastic syndrome.
  • Mild versus severe COVID-19: laboratory markers. Apr 29. Velavan. Int J Infect Dis.
    Discusses biochemical markers as an index of severity in COVID-19 patients. Concludes that low lymphocyte count and elevated serum levels of CRP, D-dimers, ferritin and IL-6 may help in stratifying risk.
  • Objective evaluation of anosmia and ageusia in COVID-19 patients: a single-center experience on 72 cases
    Apr 27. Vaira. Head & Neck.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    Among 72 COVID-19 patients, almost 75% had chemosensory dysfunctions during the course of their COVID-19 disease, with taste disorders in 12%, 14% with olfactory dysfunction, and 41% with combined dysfunction. 66% had recovery of chemosensitive dysfunction, with recovery in <5 days in 19 patients. Using an objective test, 80% of these patients still revealed a certain degree of residual hypoosmia or hypogeusia after resolution of their illness.
  • PICS Statement: Increased number of reported cases of novel presentation of multisystem inflammatory disease. Apr 27. Paediatric Intensive Care Society.
    Notice of a small increase in children presenting in the UK with “overlapping features of toxic shock syndrome and atypical Kawasaki disease with blood parameters consistent with severe COVID-19″ — elevated CRP, ESR, ferritin, troponin, and pro BNP. Abdominal pain, GI symptoms, and cardiac inflammation have been common. In some cases, COVID-19 test was negative. Suggestion to consider COVID-19 if pediatric patients present with toxic shock or atypical Kawasaki Disease.
  • Reduced Rate of Hospital Admissions for ACS during Covid-19 Outbreak in Northern Italy. Apr 29. De Filippo. N Engl J Med.
    Higher death rate not accounted for by Covid-19 disease may indicate patients dying at home from untreated ACS.
  • Sex-specific clinical characteristics and prognosis of coronavirus disease-19 infection in Wuhan, China: A retrospective study of 168 severe patients. Apr 29. Meng. PLoS Pathog.
    In this single center retrospective analysis of 168 severe or critically ill patients with COVID-19, men had a higher trend toward a risk of mortality and a lower hospital discharge rate.
  • The Role of the Renin-Angiotensin System in Severe Acute Respiratory Syndrome-CoV-2 Infection. Apr 29. Alfano. Blood Purif.
    Interesting discussion of ACE and ACE 2 receptors and related interactions and detailed explanation of logic to continue ACE inhibitors in patients with COVID-19. This is despite early concerns that ACE inhibitors and angiotensin II receptor blockers could affect ACE2 actions and exacerbate disease. While this recommendation is well-publicized, the explanation provides a good summary of the interactions and logic behind the recommendation.
  • Troponin and BNP Use in COVID-19
    Mar 18. Januzzi. American College of Cardiology.
    Opinion from SAB Member: Dr. Barry Perlman
    Discussion of troponin and BNP elevations in COVID-19 patients. While increased levels of both biomarkers are common in these patients and are associated with an unfavorable course, the mechanism is not clear as severe respiratory illness can cause both to rise. Cardiomyocytes have abundant distribution of ACE2, which suggests that the troponin rise may be due to direct, nonischemic myocardial damage due to myocarditis. It is recommended that troponin and BNP be measured in COVID-19 patients only if acute MI or heart failure are suspected clinically. ECHO or coronary angiography should only be performed if results are expected to impact outcome.
  • Understanding the Renin-Angiotensin-Aldosterone-SARS-CoV-Axis: A Comprehensive Review
    Apr 18. Ingraham. European Respiratory Journal.
    Opinion from SAB Member: Dr. Jay Przybylo
    “Comprehensive Review” is an understatement. A basic science article that ties together the RAS to COVID-19 clinical implications. Addresses the infection and many of the symptoms that result. The article needs time to consume.
  • Updates on What ACS Reported: Emerging Evidences of COVID-19 with Nervous System Involvement. Apr 29. Baig. ACS Chem Neurosci.
    Author claims that there is a CNS connection with COVID-19. Anosmia, dysgeusia, ataxia, and altered mental status could be early signs of the neurotropic potential of this virus. There are reported cases of acute necrotizing hemorrhagic encephalopathy (was reported in a female with a 3 day history of cough, fever, and altered mental status who was COVID-19 positive), Acute G, B & Encephalitis. This is a view point.
  • Use of tocilizumab for COVID-19 infection-induced cytokine release syndrome: A cautionary case report
    Apr 20. Radbel. CHEST.
    Opinion from SAB Member: Dr. Philip Lumb
    The article reviews experimental rationale for use of tocilizumab (IL-6 receptor antagonist) as COVID-19 therapy based on cytokine release syndrome (CRS) and subsequent secondary hemophagocytic lymphohistiocytosis which may add/cause to lung pathologies. Syndromes characterized by production of inflammatory cytokines including IL-6, IL-10 and TNF alpha providing therapeutic rationale for tocilizumab which is commonly used to treat CRS secondary to CAR T-cell therapy. 2 case reports detailing patient deterioration and death following tocilizumab therapy despite a decrease in CRP (IL-6 surrogate) following therapy. While no direct correlation to tocilizumab and mortality is suggested, authors caution against use.

April 29, 2020:

  • Caution Needed on the Use of Chloroquine and Hydroxychloroquine for Coronavirus Disease 2019
    Apr 24. Fihn. JAMA.
    Opinion from SAB Member: Dr. Jay Przybylo
    Data from Brazilian researchers previously discussed now published. Study stopped when high dose chloroquine was found to result in more deaths in a group of patients with concurrent heart disease and associated other diseases. Of great interest is the accompanying editorial that addresses multiple issues associated with COVID-19 and chloroquine use.
  • COVID-19 and its implications for thrombosis and anticoagulation
    Apr 27. Connors. Blood.
    Opinion from C19SAB: Dr. Anil Hingorani, Dr. Louis McNabb
    AH: This article reviews the worldwide literature regarding the effects of COVID-19 on the hematologic system and proposes prophylaxis and treatment options for these patients that is clinically relevant and well organized. LM: Good overview on mechanisms of sepsis-induced coagulopathy. Concludes no data at this time for full anticoagulation of COVID-19 patients in the ICU setting unless proven or suspected VTE. The authors note that COVID-19 do not have propensity to bleed. Many centers are using moderate dosing of anticoagulation, i.e., BID LMWH in the ICU.
  • COVID-19 Associated Pulmonary Aspergillosis. Apr 27. Koehler. Mycoses.
    The authors performed a chart review of patients in 2 separate ICUS with COVID-19 and acute respiratory distress syndrome and noted that in 5/19 patients, with moderate to severe acute respiratory distress syndrome without underlying immunocompromising disease, they had invasive pulmonary aspergillosis. Whether this represented invasive disease or colonization is not clear.
  • Early risk factors for the duration of SARS-CoV-2 viral positivity in COVID-19 patients. Apr 27. Lin. Clin Infect Dis.
    Study from China on 137 COVID+ (PCR) patients, looking at lab and clinical characteristcs that correllated with duration of PCR positivity. Older age, lower lymphocyte counts, eosinophils, CD8+ T cells and higher levels of IL-6 and IL-10 correlated with longer PCR positivity.
  • Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial
    Apr 24. Borba. JAMA.
    Opinion from SAB Member: Dr. Jay Przybylo
    Data from Brazilian researchers previously discussed now published. Study stopped when high dose chloroquine was found to result in more deaths in a group of patients with concurrent heart disease and associated other diseases. Of great interest is the accompanying editorial that addresses multiple issues associated with COVID-19 and chloroquine use.
  • Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study
    Apr 27. Bi. The Lancet Infectious Diseases.
    Opinion from SAB Member: Dr. Barry Perlman
    Retrospective epidemiologic analysis demonstrating the benefits of contact surveillance, adequate availability of testing, and quarantines. There were 391 confirmed cases of COVID-19 Jan 14-Feb 12 and 1286 close contacts confirmed before Feb 9 in Hubei province. Suspected cases and contacts were tested by RT-PCR nasal swabs. Asymptomatic close contacts who tested positive were quarantined at central facilities, while those who tested negative were quarantined at home or a central facility. Infection rate did not differ significantly by age, with on average 7% of close contacts becoming infected, 77% of these contacts having any symptoms, and 3% of infections having severe disease at initial assessment. Median time to recovery was 22 days with older patients and those with severe disease having a longer time to recovery. Contact-based surveillance reduced the duration an infected person could spread disease in the community by 2 days as compared with symptom-based surveillance.
  • Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Apr 27. Bhimraj. Clin Infect Dis.
    This publication serves as “Guidelines 1.0” from the IDSA, put together from a panel in the US, Canada, and China. There is lack of knowledge and uncertainty regarding all therapies. Chloroquine with or without Azithromycin, lopinavir+ritonavir, tocilizumab, and convalescent plasma are recommended to hospitalized patients only in the context of a clinical trial. Corticosteroids are of uncertain value for pneumonia due to COVID-19 and recommended only in the context of a clinical trial for patients with associated ARDS. The document will be updated as new data emerges and will remain posted on the IDSA website.
  • Innovative ICU Physician Care Models: Covid-19 Pandemic at New York-Presbyterian
    Apr 28. Kumaraiah. NEJM Catalyst.
    Opinion from SAB Member: Dr. W. Heinrich Wurm
    Stunning description of the strategy, innovation, collaboration and compassion that propelled NYC health care providers to rise to the challenge of creating and staffing 550 additional critical care beds as the COVID-19 pandemic surged. The ingredients for success were flexibility, sharing best practices and deploying teams across a vast enterprise. A must read for all of us.
  • Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young
    Apr 28. Mocco. NEJM.
    Opinion from SAB Member: Dr. W. Heinrich Wurm
    Report of 5 patients under 50 presenting with large vessel arterial occlusion and stroke symptoms and testing positive for COVID-19. Clinical characteristics are presented and delay in seeking medical care due to fear of contracting the virus is highlighted.
  • Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China
    Apr 10. Mao. JAMA.
    Opinion from SAB Member: Dr. Jay Przybylo
    This article lists some of the neurologic findings that occur in 36+% of patients admitted in China. Includes disrupted mentation and vascular insults and adds musculoskeletal injury caused by the disease.
  • Patient blood management during the COVID-19 pandemic – a narrative review. Apr 27. Baron. Anaesthesia.
    Expert international consensus statement providing blood management recommendations during the COVID-19 Pandemic. Recommendations include management of the supply chain, donation precautions, elective surgery management and other important aspects of blood utilization. While designed to aid practitioners during the COVID-19 pandemic, nonetheless the recommendations may be considered more generally applicable for future use.
  • Profile of IgG and IgM antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Apr 27. Qu. Clin Infect Dis.
    Analysis of serological responses to SARS-CoV-2 nucleocapsid protein and spike glycoprotein in 41 patients in Shenzhen China. Serum from 10 influenza patients and 28 patients having routine checkups were used as control. Most patients developed antibody responses 1-23 days after illness onset. Critically ill patients had delayed but stronger antibody responses. Median time of seroconversion was 11 days for IgG and 14 days for IgM. Of note, 5 patients had not developed IgM antibodies by the end of serum collection period, suggesting a longer study is needed.
  • Rational Use of Tocilizumab in the Treatment of Novel Coronavirus Pneumonia
    Apr 26. Zhang. Clinical Drug Investigation.
    Opinion from SAB Member: Dr. Jagdip Shah
    Key Points: 1) Cytokine storm is an important factor in the rapid deterioration of patients with COVID-19, 2) Tocilizumab, an IL-6 receptor antagonist, is hypothesized to be used in the treatment of cytokine storm caused by COVID-19 and is recommended as an immunotherapy drug for critical COVID-19 patients in China, 3) Tocilizumab should be used cautiously in patients with serious infections, neutropenia, thrombocytopenia, and liver damage, 4) Clinical studies are ongoing, making use outside of clinical studies premature for recommendation. This article includes a nice graphical representation of the cytokine storm pathways and potential mechanism of action for IL-6 receptor antagonists.
  • Regional Planning for Extracorporeal Membrane Oxygenation Allocation During COVID-19
    Apr 20. Prekker. CHEST.
    Opinion from SAB Member: Dr. Lydia Cassorla
    This pre-proof review from the University of Minnesota and the Mayo Clinic provides a well thought out and succinctly described framework for regional ECMO resource planning and operational deployment. Their approach involves regional situation awareness, a high degree of coordination between centers with ECMO capability, clinical decision support tools, involvement of expert clinicians in decision making and triage of resources to those most likely to benefit. It also addresses the ethical and practical aspects of not continuing to offer ECMO during a disaster, a decision best based upon a pre-existing framework. Priority for ECMO, which is described as a “trial of support rather than an indefinite resource assignment”, is based upon probability of survival, expected duration of ECMO, illness severity and patient age. A table outlines their framework for prioritization. Acute respiratory failure due to infection including flu and corona viruses is expected to require a “long” duration of >5 days with anticipated survival >60% if all other organ systems are intact. The authors anticipate that when more data of sufficient quality is available for COVID-19 patients treated with ECMO, it may become clearer how to optimally leverage this limited resource.
  • The role of adipocytes and adipocyte-like cells in the severity of COVID-19 infections. Apr 27. Kruglikov. Obesity (Silver Spring).
    Fascinating discussion regarding potential role of adipocytes and adipocyte-like cells (e.g. pulmonary lipofibroblasts) in the pathogenic response to COVID-19 leading to an additional mechanism for development of severe pulmonary fibrosis. Detailed pathways described that provide credible evidence for the severity of the disease appearing disproportional in diabetic and obese patients. Potential therapies suggested requiring future controlled trials.

April 28, 2020:

  • Addressing the corona virus outbreak: will a novel filtered eye mask help? Apr 26. Douglas. Int J Infect Dis.
    Hermetically sealed eye masks tend to fog up in a few minutes. By modifying such a mask to allow filtered air entry laterally or above the eyes using N-95 or N-100 filter material, the authors create a Filtered Eye Mask (patent pending) which did not fog during a one hour experiment. Only prototypes were tested on one of the authors. No definitive investigation into virus penetration was performed.
  • Association of Inpatient Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients With Hypertension Hospitalized With COVID-19. Apr 17. Zhang. Circulation Research.
    Wuhan area 9 hospitals Covid 19 + (PCR OR CT) all HBP patients identified = 3430. 1128 patients included in the study, includes 188 were Rx with either ARB OR ACE I. 940 were Rx for HBP with non ARB / ACE I medications. Outcome death rate : 3.7% (with ARB/ ACEI ): 9.8%. Retrospective, multicenters, power +/- , role of Chinese herbals medicine ?, no comparison with other anti HBP medicine.
  • Cardiac injury is associated with mortality and critically ill pneumonia in COVID-19: A meta-analysis. Apr 26. Santoso. Am J Emerg Med.
    A retrospective, cardiac injury causes death. Conclusion unable to link the deaths to cytokine storm or myocarditis, but able to state all who died had elevated troponin.
  • Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019. Apr 26. Zhu. Int J Infect Dis.
    Pre-proof retrospective study from China of 127 in-patients with COVID-19. IL-6, CRP and hypertension were the best predictors of severe disease.
  • COVID-19 in long-term liver transplant patients: preliminary experience from an Italian transplant centre in Lombardy. Apr 9. Bhoori. Lancet Gastroenterol Hepatol.
    A Lancet GI “Correspondence” from Italy. 3/111 liver transplant patients on minimal immunosuppression died of COVID-19, whereas the 3/40 recent liver transplant patients on higher dose immunosuppression that became COVID-19 + survived with quarantining only. Because not all transplant patients were tested, denominators are unknown. The idea is raised, but in no way proven, that an intact immune system may not be beneficial for all patients. Several co-morbidities were more common in the severe patients.
  • COVID-19 in Pregnancy: Consider Thromboembolic Disorders and Thromboprophylaxis. Apr 26. Di Renzo. Am J Obstet Gynecol.
    Pregnant patients who normally present with altered coagulation parameters (increased thrombin generation, prothrombotic state, increased intravascular inflammation) can be at increased risk for thrombosis if infected with COVID-19. Prophylaxis with low molecular weight heparin should be considered in caring for these patients.
  • Determining risk factors for mortality in liver transplant patients with COVID-19
    Apr 24. Webb. The Lancet Gastroenterology & Hepatology.
    Opinion from SAB Member: Dr. Barry Perlman
    A previous correspondence of liver transplant patients in Italy reported that 3 of their 111 long-term liver transplant survivors (on minimal immunosuppression) died from severe COVID-19, while 3 of 40 more recent liver transplant patients (on full immunosuppression) who had COVID-19 experienced an “uneventful course.” The long-term survivors were older, and had significantly higher incidence of obesity, DM, HTN, kidney disease, cardiovascular disease, and hyperlipidemia. Asymptomatic patients were not tested, so the incidence of SARS-CoV-2 in each group was not known. To address whether co-morbidities contributed to the higher death rate in the long-term transplant patients, the current correspondence reports the outcome of 39 liver transplant recipients with COVID-19 submitted to the COVID-Hep and SECURE Cirrhosis international registries. 9 (23%) died of respiratory failure. Frequency of co-morbidities between fatal and non-fatal cases was not significantly different. A study with larger case numbers will be needed to identify risk factors for severe COVID-19 in liver transplant patients.
  • How Could This Happen? Narrowing Down the Contagion of COVID-19 and Preventing Acute Respiratory Distress Syndrome (ARDS)
    Apr 25. Alaerts. Acta Biotheor.
    Opinion from SAB Member: Dr. W. Heinrich Wurm
    A biologist’s deeply scientific but also philosophical review of the history, epidemiology and the viral genomics of the Corona virus family. The author provides a helpful template for understanding the present pandemic outbreak and focuses on the role of the renin-angiotensin system in acute lung injury and ARDS and SARS-CoV action during infection. His suggestions for future research list: 1) The correlation and interaction with previous medication, particularly ACE-inhibitors; 2) Creating immunologic profiles, particularly for patients at risk for ARDS; and 3) The influence of viral genomic differences on infectivity, virus reproduction and shedding and biochemical entry routes with host cells. In addition, the range of immunological reactions to the virus by the host deserves further scrutiny and will be of great importance in the vaccine development. A valuable contribution to both clinician scientists and investigators searching to contribute to solve the COVID-19 puzzle.
  • Hypertension prevalence in human Coronavirus: The role of ACE system in infection spread and severity. Apr 27. Ruocco. Int J Infect Dis.
    Review of Angiotensin, associated second messengers and inflammation mediators, effects of ACE-I and ARBs, and possible implications with SARS-CoV2 infection.
  • Incidence of thrombotic complications in critically ill ICU patients with COVID-19
    Apr 13. Kloka. Thrombosis Research.
    Opinion from C19SAB: Dr. Anil Hingorani, Dr. Lydia Cassorla
    AH: This paper presents real world data on thromboembolism with COVID-19 patients in the ICU. It gives the clinician realistic expectations of the incidence of thromboembolism in these critically ill patients and explores prophylaxis strategies.
    LC: The incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital was observed for 4 weeks. (March 7-April 5, 2020). Among 184 ICU patients with proven COVID-19 pneumonia, 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still in the ICU at the conclusion of the observation period. All patients received at least standard doses of thromboprophylaxis. The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CT pulmonary angiography and/or ultrasonography confirmed venous thrombosis in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%). PE was the most frequent thrombotic complication (n = 25, 81%). Age (adjusted hazard ratio 1.05/per year) and coagulopathy were independent predictors of thrombotic complications. None developed DIC. The findings were all the more striking given that ¾ of the study patients were still in ICU at the end of the observation period. The authors recommend low molecular weight heparin prophylaxis in higher dose ranges in all ICU patients, vigilance, and a low bar for diagnostic tests to confirm thrombosis but not full therapeutic anticoagulation for all ICU patients with COVID-19 illness “even in the absence of randomized evidence”. There have been many other reports regarding the high incidence of thrombotic complications in COVID-19 patients. The question of when to use prophylactic or therapeutic anticoagulation in severely ill patients that will likely be further clarified as data and studies emerge.
    • UPDATE: Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis
      May 9. Klok. Thrombosis Research.
      Opinion from SAB Member: Dr. Louis McNabb, Dr. Anil Hingorani
      LM: This article reported on 184 COVID-19 patients in the ICU. The initial evaluation demonstrated a thrombotic rate of 31%. Follow up 17 days later showed a thrombotic rate of 49%. The PE rate was 65/184, and most patients were on prophylactic anticoagulation. Given the high risk of VTE in COVID-19 patients, we need immediate trials on regimens of anticoagulation to reduce thrombotic complications.
      AH: A review of 184 ICU COVID-19 patients in the Netherlands. The patients had a high incidence of VTE despite prophylaxis and 3% had arterial thrombosis. Patients with thrombotic complications had five-fold increased risk of all-cause death.
  • It’s Not the Heat, It’s the Humidity: Effectiveness of a Rice Cooker-Steamer for Decontamination of Cloth and Surgical Face Masks and N95 Respirators. Apr 26. Li. Am J Infect Control.
    This study from Case Western University Medical School and the Cleveland VA Medical Center studied the inactivation of test organisms on surgical face masks (Precept; Arden, NC), 3M 1860 N95 respirators (3M; Saint Paul, MN), and cotton and quilting fabric cloth face masks using a rice cooker. Authors demonstrated that a short cycle of steam treatment (13-15 minutes total including heating and 5 min steam) applied via a commonly used kitchen rice cooker-steamer was effective for decontamination of methicillin-resistant Staphylococcus aureus (MRSA) and RNA virus bacteriophage MS2. Dry heat at the same temperature levels was much less effective.
  • Management of COVID-19 Respiratory Distress
    JAMA. Apr 24, 2020.
    John J. Marini; Luciano Gattinoni
    Opinion from SAB Member: Dr. Louis McNabb
    Discusses the differences in the lung mechanics and approaches to treatment in the early vs. the late phase of lung injury in COVID-19. Primary goal is to prevent patient self-induced lung injury from increased transpulmonary pressures from patient’s hypoxic drive.
  • Myocarditis in a patient with COVID-19: a cause of raised troponin and ECG changes. Apr 27. Doyen. Lancet.
    Case report of COVID-19 related myocarditis. 69 yr old with history of HTN on b-blocker admitted in Nice with COVID-19 ARDS. EKG showed LVH and diffuse inverted T waves. HSTI was 9000 nl/L. ECHO showed LVH with normal wall motion and EF. Initially started on antiplatelet therapy but coronary angiography was negative. MRI was consistent with apical and inferolateral myocarditis. Negative workup for other causes of myocarditis. He was treated with hydrocortisone for 9 days and discharged from ICU after 3 weeks. Suggestion for measuring troponin and ruling out myocardial infarction if myocarditis is suspected in COVID-19 patients.
  • N95 Mask Decontamination Information
    Apr 27. Cassorla L; Przybylo JH; Clement DM; Perlman B. IARS Coronavirus (COVID-19) Resources.
    Opinion from SAB Member: Dr. Lydia Cassorla
    Interest in decontamination and re-use of N95 and similarly rated particle filtering masks (e.g. Filtering Face Piece grades 2,3 [FFP2, FFP3]–Euro standards for N95 type masks) designed for single use has skyrocketed due to extraordinary demand that cannot be met during the current COVID-19 pandemic. For a decontamination technique to be considered worthy it must satisfy at least 4 criteria: 1) Effective in inactivating the targeted pathogen; 2) Preserve desired particle filtration after decontamination; 3) Preserve mask fit; 4) Be safe for reuse. The most promising techniques appear to involve heat (wet or dry), hydrogen peroxide, and ultraviolet light. Other decontamination techniques such as alcohols, high heat, and bleach were shown by multiple investigators to destroy the filtering properties of the masks. Readers should note constraints and limitations for each study. Not all assessed masks fit after processing. Decontamination was assessed using established norms or by the inactivation of pathogens other than SARS-CoV-2, due to tests being performed before the current pandemic or the risks that would have been incurred. How many times the fabric or whole masks were re-sterilized also varies. Some websites, such as those from the Centers for Disease Control and the industry-academic consortium N95Decon.org are being continuously updated with new information and potential recommendations as they become available. We have assembled potentially useful resources and references on this topic.
  • No SARS-CoV-2 detected in amniotic fluid in mid-pregnancy. Apr 26. Yu. Lancet Infect Dis.
    In this letter to the editor, 2 pregnant women developed COVID-19 infection early during their pregnancy and in the second trimester, the two women were both positive for SARS-CoV-2 total antibodies in their serum and negative for SARS-CoV-2 RNA in throat swabs. RT-PCR tests of the patients’ amniotic fluid collected during their second trimester were negative, and tests for SARS-CoV-2 IgM and IgG in amniotic fluid were also negative. As the authors admit, the virus might not have been detectable due to gestation age, ideally performed after 18–21 weeks’ gestation, based on Zika virus data. The sample size was also very small.
  • Personal protective equipment (PPE) for both anesthesiologists and other airway managers: principles and practice during the COVID-19 pandemic
    Apr 23. Lockhart. Canadian Journal of Anesthesia/Journal canadien d’anesthesie.
    Opinion from SAB Member: Dr. W. Heinrich Wurm
    A call to arms from several Canadian anesthesia departments stressing the fact that protecting health care personnel from infection is the most important factor determining the success of a prolonged campaign against COVID-19. Their exhaustive recommendations exceed WHO standards in the area of high risk aerosol generating medical procedures (AGMPs) like endotracheal intubation and include head, neck and wrist protection. A sobering table highlights the odds-ratio of transmission for a number of anesthesia related procedures including AGMPs, but a reminder to avoid self-contamination during the doffing procedure is of equal importance. This guide is a valuable reference for practitioners, students and instructors.
  • Prevalence and Characteristics of Gastrointestinal Symptoms in Patients with SARS-CoV-2 Infection in the United States: A Multicenter Cohort Study
    Apr 20. Redd. Gastroenterology.
    Opinion from SAB Member: Dr. Jay Przybylo
    A brief but substantial article constructing a link between SARS-CoV-2, angiotensin converting enzyme 2 receptors as the cellular entry portal, and the abundance of the receptor in the GI tract. GI symptoms were associated with taste and smell disorders but not associated with blood, liver or heart involvement.
  • SARS-Cov-2 (human) and COVID-19: Primer 2020
    Apr 24. Ramakrishna. Hepatology International.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    This is a pictorial original paper that illustrates basics concerning where the disease came from, what the virus looks like, how it enters the body, disease prognosis, how it replicates in the lung and the liver, and generally how it replicates.
  • SARS-CoV-2 infection and the upper limbs deep vein thrombosis risk. Apr 27. Bozzani. Ann Vasc Surg.
    3 patient series of patients requiring HcPAP developed upper limb DVT despite initiation of antithrombotic prophylaxis (not described). “D-dimer values were increased at the admission (mean 11572.7 mcg/L; range 6226-18552 mcg/L)”. Note “However, should be considered that, in our clinical series, long-term bed rest, severe dehydration secondary to fever, tachypnea and sometimes diarrhea, and the compressive action on the axillary veins by the hood straps of the HcPAP also increase the risk of DVT.”
  • Sensitivity to angiotensin II dose in patients with vasodilatory shock: a prespecified analysis of the ATHOS-3 trial
    June 3, 2019. Ham. Annals of Intensive Care.
    Opinion from SAB Member: Dr. Jay Przybylo
    This extends beyond a case report in an 88y/o who died. Angiotensin II provided stabilization of blood pressure and allowed decrease of other vasopressors.
  • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vertical Transmission in Neonates Born to Mothers With Coronavirus Disease 2019 (COVID-19) Pneumonia. Apr 26. Hu. Obstet Gynecol.
    In this research letter, the authors describe 7 pregnant women diagnosed with COVID-19, who were otherwise healthy during pregnancy and who after pregnancy recovered from COVID-19. 6/7 mothers underwent C-section and for one, the baby was delivered vaginally before the C-section could be performed. 1/7 infants was positive for COVID-19, but that infant as well as the other children subsequently were without symptoms of the disease. What’s not clear is if the mothers were chosen sequentially, if there were inclusion and exclusion criteria, when the mothers acquired COVID-19 and when they recovered.
  • The role of extracorporeal life support for patients with COVID-19: Preliminary results from a statewide experience
    Apr 25. Sultan. Journal of Cardiac Surgery.
    Opinion from SAB Member: Dr. Jagdip Shah
    Preliminary report of ECMO from Pittsburgh/Pennsylvania describing their experience of the first 10 patients on ECMO. All patients were cannulated in a venovenous configuration. As of 9Apr2020, 2 patients were successfully liberated from ECMO support after 7 and 10 days, 1 patient was on a weaning course, 1 death occurred after 9 days on ECMO due to multiorgan dysfunction, and all other patients were still on ECMO with a median time of support of 11 days (IQR, 4‐14).
  • Updated diagnosis, treatment and prevention of COVID-19 in children: experts’ consensus statement (condensed version of the second edition)
    Apr 24. Shen. World Journal of Pediatrics.
    Opinion from SAB Member: Dr. Lydia Cassorla
    This review provides guidance in the form of an updated consensus statement regarding COVID-19 in children. In early February 2020, an expert committee with more than 30 Chinese experts from 11 academic medical organizations formulated the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children. According to the 28 February 2020 WHO COVID-19 situation report, pediatric cases in China accounted for 2.4% of 55,924 confirmed cases. Close contact with infected persons with or without symptoms is the main transmission route of SARS-CoV-2 to children, resulting in mostly clustered cases. “There is no direct evidence of vertical mother-to-child transmission, but newborns can be infected through close contact.”
    Risk factors, diagnosis, severity classifications, early warning indicators, differential diagnosis, and treatment are discussed. Risk factors for severe disease include underlying diseases, immunosuppressant Rx and age<3 months. Most manifestations and laboratory findings are similar to adults, with atypical symptoms such as GI manifestations and listlessness noted. The group recommends antipyretics such as ibuprofen and acetaminophen if T>38.5 degrees C, and nebulizer treatments to manage mucus plugs. “Antiviral drugs without clear evidences of safety and efficiency are not recommended to be used in pediatric patients. The revised antiviral drug therapy remains interferon-alpha (IFN-alpha) sprays and aerosol inhalation. We do not recommend using lopinavir/ritonavir, ribavirin or chloroquine phosphate in pediatric patients.” Intubation and controlled ventilation is recommended if non-invasive mechanical ventilation does not result in clinical improvement after 2 hours. Plasma exchange to treat cytokine storm, immunoglobulin and anticoagulation are mentioned. 27 references provided, including the group’s initial statement.

April 25, 2020:

  • Acute Pulmonary Embolism Associated with COVID-19 Pneumonia Detected by Pulmonary CT Angiography. Apr 24. Grillet. Radiology.
    Retrospective study of patients that received contrast CT’s of chest. 23 of 100 positive for PE. Patients with PE tended to be sicker and more likely on ventilators. No data on treatment of PTS with PE or their outcome.
  • Acute Pulmonary Embolism in COVID-19 Patients on CT Angiography and Relationship to D-Dimer Levels
    Apr 23. Leonard-Lorant. Radiology.
    Opinion from SAB Member: Dr. Philip Lumb, Dr. Louis McNabb
    PL: Reports 32/106 (30% [95%CI 22-40%]) COVID-19 positive patients were diagnosed positive for acute PE on pulmonary CT angiography between March 1st and March 31st. Noted in this series incidence correlated with increased D-dimer levels; sensitivity 32/32 positive PE with D-dimer >2660 mcg/L (100% [95%CI 88-100]) with a specificity of 49/74 (67% [95%cI 52-79]) on CT angiography. Authors confirm higher incidence of PE in COVID-19 patients with elevated D-dimer, suggested secondary to COVID induced activation of blood coagulation secondary to systemic inflammatory response and recommend increased awareness of and surveillance for PE complications. LM: The results of this article give a theoretical basis for routine use of full dose anticoagulation in COVID-19 patients. The efficacy of such a practice should be explored in controlled studies with prophylactic anticoagulation as a comparator.
  • All Hands on Deck: How UW Medicine Is Helping Its Staff Weather a Pandemic
    Apr 24. Kim. NEJM Catalyst.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    University of Washington Medicine was one of the first U.S. health systems to treat COVID-19 patients in large numbers. The article describes how they helped their workforce during the crisis by providing free testing for COVID-19 infection, that included liberalizing history and symptom elements so that more employees would be free to ask for the test; counseling on how to quarantine and when to return to work safely; and then open communication through regular community-wide virtual (Zoom) Friday afternoon town hall meetings and facilitation of peer-to-peer support both emotional and practical.
  • Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China. Apr 24. Li J. JAMA Cardiol.
    In this single-center retrospective study of hospitalized COVID-19 patients from Wuhan, China, although in-hospital mortality of those with hypertension (21.3%) was 3x that of non-hypertensive patients, ACEI/ARB treatment was not independently associated with disease severity or outcomes. Of 1178 patients, 30.7% had hypertension of which 31.8% were taking ACEI/ARBs. There was no difference in the percentage of severe vs. non-severe infections, survivors vs. non-survivors, or ACEI vs. ARB treatment. In the data table, death of those with hypertension was significantly associated with male sex, age over 60, diabetes, cerebrovascular disease, coronary artery disease, and chronic kidney disease. These results support current guidelines and recommendations for treating hypertension.
  • Barrier Shields: Not Just for Intubations in Today’s COVID-19 World? Apr 24. Tsai. Anesthesia & Analgesia.
    Instead of using shields just to prevent aerosol exposure during intubation, the author suggests leaving the shield in place throughout the case to provide protection during other aerosol generating procedures, such as suctioning, extubation, high flow oxygen delivery, or upper endoscopy. For rigid plastic barrier with arm ports, a clear drape can be used to cover the ports.
  • COVID-19 in Children in the United States. Intensive Care Admissions, Estimated Total Infected, and Projected Numbers of Severe Pediatric Cases in 2020. Apr 16. Pathak. J Public Health Management and Practice.
    This study projects the number of children with COVID-19 that will need hospitalization in the US by the end of 2020, based on US PICU admission data from Virtual PICU Systems (VPS) March 18 through April 6, 2020 and studies from China. For every COVID-19 PICU admission, there are an estimated 2400 infected children in the community — 176,000 nationwide as of April 6. Modeling scenarios projected 11% of children hospitalized for COVID-19 will require PICU care. The authors caution that real-time surveillance of US COVID-19 cases need to be improved.
  • How does coronavirus kill? Clinicians trace a ferocious rampage through the body, from brain to toes. Apr 17. Wadman. Science.
    A summary article about the biology of the COVID-19 pandemic, written by staff members of Science Magazine. An excellent overview that touches on some of the controversial aspects of the infection (i.e. cytokine storm and hypercoagulability).
  • How to Rapidly Deploy Intubation Practice Changes in a Pediatric Hospital During the COVID-19 Pandemic. Apr 22. Brown. Anesthesia & Analgesia.
    Authors from Seattle Children are sharing the protocol for intubation for Covid-19 and unknown patients, anywhere in the hospital irrespective of age/HT/WT or comorbidity of these patients. It has good illustrations. Since Seattle is where Covid-19 started its journey in this country, they had to think fast, act, create something “out of box which will fit across the facility. They practiced on simulation to” perfect it “in the era of intubation and age of social distancing, aerosol, inline HEPPA filters, inline suctioning, video laryngoscope, covers for it, drugs, dirty / clean tray… the list looks complete. It’s worth following for those still trying to address the issue.
  • Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19
    medRxiv. Apr 23, 2020.
    Joseph Magagnoli; Siddharth Narendran; Felipe Pereira; Tammy Cummings; et al
    Opinion from SAB Member: Dr. Jay Przybylo
    Non-peer reviewed study. Hydroxychloroquine (HC) failed to reduce the need for mechanical ventilation but did result in more deaths when compared to a control group. This correlates with a study from Brazil stopped early because HC resulted in heart rhythm abnormalities.
  • Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility
    Apr 24. Arons. NEJM.
    Opinion from SAB Member: Dr. W. Heinrich Wurm
    Second epidemiological analysis of institutional spread of COVID-19 in a Kings County, WA Skilled Nursing Facility. Triggered by just one symptomatic patient who came in contact with an infected health care worker, this meticulous study highlights the spread of the virus over the next 23 days resulting in 57 (65%) additional infections. Most notably, 89% of asymptomatic residents testing positive one week into the outbreak, were symptomatic 4-7 days later. These findings underscore the role asymptomatic and pre-symptomatic patients play in spreading the virus, as well as the need for low threshold serial institutional testing.
  • What the Great Pandemic Novels Teach Us
    Apr 23. Pamuk. The New York Times.
    Opinion from SAB Member: Dr. J. Lance Lichtor, Dr. David M. Clement
    JLC: Though not really a science paper, this piece shows, based on literary history, how eerily similar the current pandemic is compared to what has happened over the last 400 years in terms of initial response (denial); the carelessness, incompetence and selfishness of those in power that infuriates the masses; how institutions are unsure how to deal with many of the issues; how rumor and the spread of false information has been a universal and unprompted response, including how the disease is foreign, and is brought in with malicious intent; the intensity of suffering; and finally the terror all of us feel which shows how fragile our lives are and how we all share the same humanity. Fear may cause us to withdraw, but it also teaches us to be humble and practice solidarity.
    DC: One may question the historical accuracy of novels. During the current pandemic some countries (New Zealand, Australia and Taiwan for example) have largely avoided baseless rumors and false information. But the human tendency for such dysfunctional approaches to pandemics are wonderfully illustrated in this article.

April 24, 2020:

  • Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection. Apr 23. Spinato G. JAMA.
    Retrospective phone assessment of alteration in taste and smell among 202 consecutive patients who presented to an Italian outpatient facility. Using a symptom-based rhino-sinusitis outcome measure called Sino-Nasal Outcome Test-22 (SNOT-22), degree of impairment was assessed. 50% of patients had moderate to complete loss of taste and smell but only 12% found this to be an early symptom. There is strong evidence that the density of ACE2 receptors in the nasal mucosa is linked to this symptomatology and that it is specific to COVID-19 infection, but neither loss of taste or smell was assessed objectively in this study.
  • COVID-19 and diabetes mellitus: what we know, how our patients should be treated now, and what should happen next. Apr 23. Angelidi AM. Metabolism.
    Wanders between basic science and clinical implications in a number of organ systems and occasionally mentions diabetes. Provides no new or novel treatments but encourages further research.
  • COVID-19 therapeutic options for patients with kidney disease
    Apr 23. Izzedine. Kidney International.
    Opinion from SAB Member: Dr. Jay Przybylo
    An editorial, but one of significance. Contains a table of antiviral drugs that might currently be used. For international use.
  • D-dimer Levels on Admission to Predict In-Hospital Mortality in Patients With Covid-19. Apr 19. Zhang L. J Thromb Haemost.
    D-dimer >= 2 ug/ml on admission may be an early predictor for COVID-19 in-hospital mortality. Retrospective study of 343 RT-PCR confirmed COVID-19 patients in Wuhan, China. A D-dimer cutoff of 2 ug/ml (4x normal) correlated with increased risk of in-hospital mortality with a sensitivity of 92% and specificity of 83%. Patients with D-dimer levels >= 2 ug/ml had a higher incidence of co-morbidities — DM, HTN, CAD, and stroke. They also had higher incidence of other abnormal lab values — lower lymphocyte count, hemoglobin, and platelet count, and higher neutrophil count, CRP, and PT — but D-dimer showed the highest concordance index.
  • Early Self-Proning in Awake, Non-intubated Patients in the Emergency Department: A Single ED’s Experience during the COVID-19 Pandemic
    Apr 22. Caputo. Academic Emergency Medicine.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    In patients with non-COVID-19 related ARDS, having a patient in the prone position while awake while also using high-flow nasal cannula (HFNC) can decrease the risk of intubation and improve outcome. After 50 patients with hypoxia (SpO2<90%) were asked to position themselves in the prone position, before treatment but with supplemental oxygen (not with HFNC), SpO2 was 84% and increased to 94% after 5 minutes in the prone position. 13 patients were intubated within 24 hours in the ED and 5 more were intubated more than 24 hours after arrival in the ED. Interesting, and though the study did not have a control group, the initial effect was significant.
  • Epidemiological and clinical characteristics of 26 asymptomatic SARS-CoV-2 carriers. Apr 23. Pan Y. J Infect Dis.
    Retrospective analysis of 26 persistently asymptomatic patients with positive test results for SARS-CoV-2 nucleic acid to determine the clinical characteristics and asymptomatic carrier transmission of COVID-19 infection.
  • Ethnicity and COVID-19: an urgent public health research priority. Apr 21. Pareek. The Lancet.
    A Lancet Correspondence stressing the need to collect and report ethnic data when reporting on the pandemic. It seems there may be differences in the way SARS-CoV-2 infects people of different ethnicity, and accurate reporting of ethnicity could be important.
  • Liver injury in COVID-19: management and challenges. Mar 4. Zhang. The Lancet Gastroenterology and Hepatology.
    Review of “available cases” from medical center in Beijing reporting liver co-morbidities in 2-11% of COVID-19 patients with 14-53% cases showing elevated transaminase levels. Suggestion that liver damage is greater in severe cases. Theoretical discussion about potential causes and further observations about global burden of liver disease. No therapeutic options defined. Further research recommended.
  • Lung Ultrasound in Children With COVID-19. Apr 23. Denina M. Pediatrics.
    Study involves a US application of 8 pediatric patients in Italy. The author concludes: practical, PoC application may be superior concurrent confirmation with radiological for hard evidence and superior for one patient who was recovering who had a clear X-ray but a presence of a Curly B line. None of them were ventilated, 2 patients were on oxygen. No pictures in the article, and a small number. US can replace X-ray in pediatrics.
  • Multicenter initial guidance on use of antivirals for children with COVID-19/SARS-CoV-2
    Pediatric Infectious Diseases Society. Apr 22, 2020.
    Kathleen Chiotos; Molly Hayes; David W Kimberlin; Sarah B Jones; et al
    Opinion from SAB Member: Dr. Barry Perlman
    Recommendations from a multidisciplinary panel of infectious disease physicians and pharmacists from 18 North American institutions regarding the use of antiviral treatment for severe COVID-19 infection in children.
    The panel addressed the following questions:
    1. Are antiviral agents indicated in children with COVID-19?
    2. What criteria define the pediatric population in whom antiviral use may be considered?
    3. Does presence of any underlying medical condition or characteristic warrant different criteria for antiviral use based on increased risk of COVID-19-related morbidity or mortality?
    4. What agents are preferred if antiviral therapy is offered to children with COVID-19?
    The panel concluded that most pediatric COVID-19 patients have mild disease and just require supportive care. A small proportion develop severe illness requiring respiratory support. Most of these, and some children with critical illness, also only require supportive care. In the absence of available data, possible risk factors for severe COVID-19 in children were discussed–cardiovascular or pulmonary disease, diabetes, cancer, obesity, young age, immunocompromise. On a case by case basis, if antiviral medication is used, remdesivir is recommended as the preferred agent, with hydroxychloroquine as an alternative if remdesivir is contraindicated or not available. Hydroxychloroquine/azithromycin combination and lopinavir-ritonavir are not recommended. Preferably, antivirals should be used as part of a clinical trial, but as of 4/14/20 no US trials are enrolling children < age 12. Of note, subsequent to acceptance of this manuscript, preliminary results from a hydroxychloroquine retrospective analysis and a remdesivir clinical trial, both involving adult COVID-19 patients, did not show benefit. Additional studies are ongoing.
  • Patient Self-Proning with High-Flow Nasal Cannula Improves Oxygenation in COVID-19 Pneumonia
    Apr 21. Slessarav. Canadian Journal of Anesthesia.
    Opinion from SAB Member: Dr. Philip Lumb
    Single case report of successful patient management utilizing HFNC on 68 year old patient instructed to self-prone in a negative pressure room. Discussion includes concept of two types of respiratory failure in COVID-19 paralleling the work of Gattinoni and others.
  • Points to consider in the preparation and transfusion of COVID-19 convalescent plasma. Apr 23. Epstein J. Vox Sang.
    This summary was prepared by The Working Party on Global Blood Safety of the International Society of Blood Transfusion. Convalescent plasma may be used as a possible treatment for patients with COVID-19. The plasma is collected using apheresis so the person donating the blood loses a minimal amount of red cells. Otherwise, collection and administration is no different than other types of transfusion.
  • Potential association between COVID-19 mortality and health-care resource availability. Feb 25. Ji. The Lancet Global Health.
    A Lancet “Correspondence” from February documenting an association in China between increased COVID-19 mortality and the “healthcare burden” of Hubei vs. other provinces. The graphs are dramatic, but not proof, that Hubei has higher mortality (2.9% vs. 0.7% outside Hubei) because of an overextended healthcare system.
  • Potential for Lung Recruitment and Ventilation-Perfusion Mismatch in Patients With the Acute Respiratory Distress Syndrome From Coronavirus Disease 2019
    Apr 28. Mauri. Critical Care Medicine.
    Opinion from SAB Member: Dr. Louis McNabb
    In this article, ventilated patients with COVID-19 were given PEEPs of 5 and 15 cmH2O. The degree of lung recruitment was variable among the participants and most of the V/Q mismatch was attributed to increased dead space ventilation.
  • Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. April 2020. Shi. The Lancet Infectious Diseases.
    Another chest CT article, this time with 81 patients.
  • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children and Adolescents: A Systematic Review. Apr 23. Castagnoli R. JAMA Pediatr.
    Italian authors, retrospective, metanalysis of literature (PUBMD, Cochrane…) from all China except one Singapore, Pediatric population with + PCR. They Identified 815 articles, selected 18 studies (Bias, exclusion criteria addressed with a referee author). N= 1065 includes 444 < 10 years age and 553 >10 but < 19. Slightly higher M >: F ratio. Software assistance, tightness of statistics – but no mention. Majority had mild symptoms, moderate < 20 patient & 1 kid < Shock. No vertical transmission but mainly contact from family. Asymptomatic manifestation for majority noted. 8 patients with rectal swab + ve in spite of – ve NP. Author concludes weakness of study: 3 month window, China factor, no adult comparison, no viral load to clinical picture or viral to immunity….
  • Sonographic signs and patterns of COVID-19 pneumonia
    Apr 21. Volpicelli. The Ultrasound Journal.
    Opinion from SAB Member: Dr. Barry Perlman
    This paper describes the use of lung ultrasound (LUS) for diagnosis of COVID-19 pneumonia, and discusses signs that distinguish it from classic ARDS. Sonographic signs with COVID-19 are similar to those seen with ARDS–clusters of B lines and small peripheral consolidations. More particular to early COVID-19 pneumonia is “a shining band-form artifact spreading down from a large portion of a regular pleural line, often appearing and disappearing with an on–off effect in the context of a normal A-lines lung pattern visible on the background.” It is important to also consider clinical presentation, symptom timing, laboratory findings and co-morbid diseases when using LUS for diagnosis or following progression of COVID-19. The use of LUS in the pediatric COVID-19 population is not discussed, but at the time of this review one small preliminary study of 8 pediatric patients showed LUS utility for both diagnosing and following the resolution of disease.
  • Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. Apr 23. Zheng S. BMJ.
    In this retrospective cohort study, 3497 respiratory, stool, serum, and urine samples were collected from 96 hospitalized Covid-19 patients and evaluated for SARS-CoV-2 RNA viral load. Disease severity was mild in 22 and severe in 74. Infection confirmed in all patients by sputum and saliva testing. RNA was detected in the stool of 55 (59%) and in the serum of 39 (41%) patients. The urine was positive in 1 patient. The median duration of virus in stool (22 days, interquartile range 17-31 days) was longer than in respiratory (18 days, 13-29 days; P=0.02) and serum samples (16 days, 11-21 days; P<0.001). The median duration of virus in the respiratory samples of patients with severe disease (21 days, 14-30 days) was longer than in patients with mild disease (14 days, 10-21 days; P=0.04). In the mild group, the viral loads peaked in respiratory samples in the second week from disease onset, whereas viral load continued to be high during the third week in the severe group. Virus duration was longer in patients > 60 yrs old and in males. 78 (81%) patients received glucocorticoids and 33 (34%) antibiotic treatment. All patients received antiviral Rx with interferon α inhalation, lopinavir-ritonavir combination, arbidol, favipiravir, and darunavir-cobicistat combination. The authors claim no deaths in this group. The main conclusions were that the virus persists for a longer time in stool than in respiratory or serum samples and that patients with more severe disease have a longer respiratory viral persistence with a greater load. This potentially affects their ability to transmit disease to others.

April 23, 2020:

  • A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. Mar 18. Cao. NEJM.
    Randomized 199 patients to receive lopinavir-rotonavir vs standard care. No difference in clinical improvement, mortality, or viral shedding.
  • Central Nervous System Involvement by Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2). Apr 22. Paniz-Mondolfi. J Med Virol.
    In this case report of 1, a 74 yo patient with Parkinson’s with a positive nasopharyngeal swab test for SARS-CoV-2 by real-time reverse-transcription-polymerase-chain-reaction amplification was noted to be confused when admitted. He expired on day 11 and at post-mortem, was noted to have viral particles in brain capillary endothelium and actively budding across endothelial cells, though the nature of the virus in the brain was not otherwise defined.
  • Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Feb 24. Huang. The Lancet.
    Detailed review of clinical features of COVID-19 presentation and progression from Wuhan; patient data collected prospectively on 41 patients with COVID-19 confirmed by real-time RT-PCR and next-generation sequencing admitted between December 16th, 2019 and January 2nd, 2020. Analysis and information well presented.
  • Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study. Apr 21. Chu. The Lancet Microbe.
    A science study with little clinical significance. A comparison of SARS-CoV-2 vs COVID-19 for entry and replication into numerous human and nonhuman cell lines. The authors state the article might be of pertinence to further cell studies on optimization of antiviral assays but not necessarily to human organs in the physiologic state — life.
  • Comparison of nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 detection in 353 patients received tests with both specimens simultaneously. Apr 22. Wang. Int J Infect Dis.
    Using negative RT-PCR testing as criteria for hospital discharge after COVID-19 infection is hampered by the test’s false negative rate. Retrospective comparison of simultaneous nasopharyngeal and oropharyngeal swab RT-PCR tests from 353 Wuhan, China patients. Consistency was poor with nasopharyngeal testing having a 2.5 x higher positive rate overall and 3.5 x higher rate for inpatients. However, 33% of nasopharyngeal tests were negative when the simultaneous oropharyngeal test was positive, demonstrating false negatives with either technique.
  • Connecting clusters of COVID-19: an epidemiological and serological investigation
    Apr 21. Yong. The Lancet Infectious Disease.
    Opinion from SAB Member: Dr. Heinrich Wurm
    Fascinating account of a successful epidemiological disease tracking operation using RT-PCR and serologic testing to identify COVID-19 transmission among 3 clusters – 2 churches and a New Year’s gathering – in Singapore between mid-January and the end of February. While initial testing of all patients presenting with pneumonia using RT-PCR led to the diagnosis of overtly infected patients who were shedding virus, serologic testing played an important role in identifying convalescent cases or people with minimal symptoms, allowed assessment of disease penetration among the population and guidance towards containment efforts.
    • An accompanying editorial by Johns Hopkins epidemiologists, stresses the value of broad testing strategies to assess and contain the spread of COVID-19, particularly by measuring SARS-CoV-2-specific IgG antibody titers. It enumerates 4 distinct and valuable concepts gained from serological testing, including identifying potential candidates for donation of reconvalescent serum. It also points out several remaining challenges, among those sensitivity and specificity of the test, excluding cross reactivity to other viruses resulting in false positives, antibody kinetics determining the duration of immunity, as well as cost and portability of the test.
  • COVID-19 and African Americans. Apr 15. Ingraham. JAMA.
    A very important social/cultural aspect of the pandemic, with preliminary data clearly laid out by author. But this will not help front-line workers, and as the author states, what to make of the disparities is not clear: “Data fully adjusted for comorbidities have not been reported but it is likely that some, if not most, of these differences in disease rates and outcomes will be explained by concomitant comorbidities.”
    Blacks have disproportionately been victims of COVID-19. Evidence of potentially egregious health care disparities is now apparent. Persons who are African American or black are contracting SARS-CoV-2 at higher rates and are more likely to die. COVID-19 has become the herald event that now fully exposes the deep and chronic social wounds in US communities. The Johns Hopkins University and American Community Survey indicate that to date, of 131 predominantly black counties in the US, the infection rate is 137.5/100,000 and the death rate is 6.3/100,000.5. This infection rate is more than 3-fold higher than that in predominantly white counties. Moreover, this death rate for predominantly black counties is 6-fold higher than in predominantly white counties. Comorbidities (HBP, DM, Obesity……) and preventive measures may not be able to be practiced, health care access…author claims many unstated factors are playing out. Public health is complicated and social reengineering is complex, but change of this magnitude does not happen without a new resolve.
  • CT imaging features of 4,121 patients with COVID-19: a meta-analysis. Apr 22. Zhu. J Med Virol.
    Meta-analysis of 34 retrospective studies that describes the lung CT characteristics of patients with COVID-19. The most common charachteristics were bilateral and multi-lobar ground glass opacities. 8% of CTs were normal. Analysis did not include any clinical or outcome information, and suggested CT could help with diagnosis.
  • Faecal calprotectin indicates intestinal inflammation in COVID-19. Apr 22. Effenberger. Gut.
    Austrian PAP Letter to the Editor of GUT noting that fecal calprotectin levels are elevated in 40 COVID-19 inpatients with active diarrhea.
  • Is Adipose Tissue a Reservoir for Viral Spread, Immune Activation and Cytokine Amplification in COVID-19. Apr 22. Ryan. Obesity (Silver Spring).
    Obesity has been recognized as a risk factor for poor outcome with COVID-19 infection. The paper theorizes that adipose tissue may act as a reservoir for increased viral spread, immune activation, and cytokine amplification. Nice review of adipose tissue cytokine pathways. Areas of research are suggested.
  • Kidney disease is associated with in-hospital death of patients with COVID-19. Mar 20. Cheng. Kidney International.
    A retrospective study, regression analysis, single center 701 (600 + 101 with possibly raised baseline serum creatinine, BUN & low GFR) patient in Wuhan with a possible renal insuffiency and one without. Preexisting renal compromise will progress to acute kidney injury and to a higher mortality. In this cohort, approximately 13% of patients had underlying kidney disease. More than 40% had evidence of abnormal kidney function and 5.1% had acute kidney injury (AKI) during their hospital stay. There was a dose dependent relationship between AKI stages and death, with an excess risk of mortality by at least 4 times among those with stage 3 AKI. Kidney disease is a major complication of COVID-19 and a significant risk factor of death. Nonetheless, the study findings suggest that early identification of those at risk, interventions to provide appropriate support, and avoidance of nephrotoxins, vigilance may help to improve the prognosis of patients with COVID-19. Sudden loss of kidney function, ACE2 association are part of hypothesis. Hazard ratio (3 to 8) with increasing proteinuria, hematuria, AK Stage 3, rising kidney markers.
  • Lung–kidney interactions in critically ill patients: consensus report of the Acute Disease Quality Initiative (ADQI) 21 Workgroup. Dec. 9, 2019. Joannidis. Intensive Care Medicine.
    Consensus report summarizing findings of a June 2018 conference on lung and kidney interactions in critical illness (18 pages, 123+ references). Using ADQI 21 methodology, including critical review of available clinical and research evidence, an international panel of pulmonologists, nephrologists and critical care specialists created clinical recommendations and suggestions for future research.
    Clinical recommendations with high quality evidence included lung protective ventilation, conservative fluid management and early recognition and treatment of pulmonary infections. Consensus statements linking AKI and ARDS were developed and the effect of ECMO and RRT on either organ system was explored.
    COVID-19 attacks both organ systems and much of this work applies to clinical scenarios clinicians face daily in critical care units around the globe. Despite its volume, this report (18 pages, 123 references), may be of value to clinicians dealing with the impact of COVID-19 on the front lines today.
  • Preliminary therapeutic drug monitoring data of β-lactams in critically ill patients with SARS-CoV-2 infection. Apr 22. Novy. Anaesth Crit Care Pain Med.
    In this letter to the editor, the authors describe their use of β-lactams to treat 20 critically ill patients with a confirmed SARS CoV-2 viral infection.
  • Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized with COVID-19 in the New York City Area
    Apr 22. Richardson. JAMA.
    Opinion from SAB Member: Dr. David M. Clement, Dr. J. Lance Lichtor
    DC: This is a case review of a 12 hospital system in New York City, detailing the characteristics and outcomes of 5,700 patients admitted between March 1 and April 4. Besides the usual co-morbidities (hypertension, obesity and diabetes), only 31% of patients were febrile at triage, 14% needed ICU admission, 12% were intubated and of those intubated, 88% died. This provides an early window into the US experience. The supplementary tables provide a wealth of clinical data. JLL: In this review of 5700 patients admitted between March 1, 2020, and April 4, 2020 to any of 12 Northwell Health acute care hospitals, some clinical characteristics and outcomes were described. The median time to obtain polymerase chain reaction testing results was 15.4 hours, and common morbidities included hypertension, obesity and diabetes. 30% were febrile, almost 20% had a respiratory rate greater than 24 and almost 30% needed supplemental oxygen. The overwhelming majority had a positive COVID-19 test result on the first attempt. About 15% were treated in the ICU; 12% were treated with mechanical ventilation and 3% were treated with kidney replacement. About 20% died. Patients between 18 and 65 were more likely to be treated in the ICU, receive mechanical ventilation, compared to patients older than 65 years. Mortality rates were lower than reported in China.
  • Symptom Screening at Illness Onset of Health Care Personnel with SARS-CoV-2 Infection in King County, Washington. Apr 17. Chow. JAMA.
    Typical symptom screening for Covid-19 will miss 20 percent of health care workers with the virus. Perhaps more alarming is that health care personnel worked a median of two days with symptoms.
  • The important role of serology for COVID-19 control
    Apr 21. Winter. The Lancet Infectious Diseases.
    Opinion from SAB Member: Dr. W. Heinrich Wurm
    This accompanying editorial by Johns Hopkins epidemiologists stresses the value of broad testing strategies to assess and contain the spread of COVID-19, particularly by measuring SARS-CoV-2-specific IgG antibody titers. It enumerates 4 distinct and valuable concepts gained from serological testing, including identifying potential candidates for donation of reconvalescent serum. It also points out several remaining challenges, among those: sensitivity and specificity of the test, excluding cross reactivity to other viruses resulting in false positives, antibody kinetics determining the duration of immunity, and cost and portability of the test.
  • The need for urogenital tract monitoring in COVID-19. Apr 22. Wang. Nat Rev Urol.
    COVID-19 patients may develop AKI requiring RRT and male reproductive hormone changes have been reported suggesting gonadal function impairment in addition to other and more reported symptoms. Early proteinuria and developing AKI requiring support predictors of higher mortality. Possible mechanisms discussed including observation that during recovery, adaptive immune cells may attack renal parenchymal cells further damaging not only the kidney but potentially compromising reproductive function. Conclusions support renal monitoring and possible post recovery fertility consultation for recovered males. Possible mechanisms discussed with references.

April 22, 2020:

  • Audiological profile of asymptomatic Covid-19 PCR-positive cases. Apr 21. Mustafa MWM. Am J Otolaryngol.
    Viral infections can cause hearing loss. 20 confirmed positive but asymptomatic COVID-19 patients were compared with 20 controls with normal hearing. The COVID-19 patient group had significantly worse high frequency pure-tone thresholds and transient evoked otoacoustic emission amplitudes, suggesting damage to cochlea hair cells. The paper recommends further research to determine the mechanism of this effect.
  • COVID-19: consider cytokine storm syndromes and immunosuppression. Mar 16. Mehta. The Lancet.
    Jay: Letter to Editor. Authors from a medical society (HLH Across Specialty Collaboration) use data from China to redefine Cytokine Storm as Haemophagocytic LymphoHistiocytosis (sHLH). No advance in therapy is advocated.
    Cassorla: “Secondary haemophagocytic lymphohistiocytosis (sHLH) is an under-recognised, hyperinflammatory syndrome characterised by a fulminant and fatal hypercytokinaemia with multiorgan failure. Cardinal features of sHLH include unremitting fever, cytopenias, and hyperferritinaemia; pulmonary involvement (including ARDS) occurs in approximately 50% of patients.” The authors raise the question of whether mortality from COVID-19 could be reduced by identifying the subset of patients with severe disease who have sHLH (using a scoring calculator), and treating with immunosuppression therapy.
  • COVID-19: impact on cancer workforce and delivery of care. Apr 20. Mayor. The Lancet Oncology.
    A Lancet “News” piece stressing the adaptations being made to care for cancer patients during COVID-19. Centralization of cancer care, telemedicine, modifying chemo and radiation treatments and splitting teams of cancer care workers are mentioned.
  • Category: Emerging Clinical Data and Guidelines 
    Diarrhea is associated with prolonged symptoms and viral carriage in COVID-19 
    Apr 13. Wei. Clinical Gastroenterology and Hepatology.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    In this retrospective analysis of 84 patients with SARS-CoV-2, diarrhea occurred in 31% of patients, and patients with diarrhea had a higher incidence of headache, myalgia or fatigue, cough, sputum production, nausea and vomiting and duration of symptoms and hospital stays were longer for patients who had diarrhea. The digestive system is also a potential pathway for SARS-CoV-2 infection. Though the diarrhea could have been due to antibiotic use–all patients received antibiotics (46% used two antibiotics) and intestinal probiotics relieved diarrhea, which is consistent with diarrhea secondary to antibiotic use.
  • Dynamic profile of RT-PCR findings from 301 COVID-19 patients in Wuhan, China: a descriptive study. Apr 11. Xiao. J Clin Virol.
    More than 2 negative RT-PCR tests may be needed to document viral clearing. Retrospective study of of 301 Wuhan COVID-19 patients with mild – moderative symptoms. Average contagious period (positive RT-PCR test) was 20 days, with 26% still testing positive after 4 weeks. Patients < 65 converted on average earlier than older patients. 23% of the 70 patients with 3 documented consecutive RT-PCR tests had a positive test after 2 negative tests. Throat swab tests had a higher flare negative rate of 41%.
  • Category: Treatment / Prevention of COVID-19 
    Endothelial cell infection and endotheliitis in COVID-19 
    Apr 20. Varga. The Lancet.
    Opinion from SAB Member: Dr. Philip Lumb
    Interesting discussion exploring angiotensin converting enzyme 2 (ACE2) receptors on developing pathophysiology of organ failure in COVID-19 infection. 3 case reports of multi-organ failure with detailed postmortem histology demonstrating endotheliitis in multiple organs (lung, heart, kidney, GI tract), all of which express ACE2 receptors as do endothelial cells. While the mechanism of vascular derangement in COVID-19 is unknown, the possibility of endothelial cell involvement by the virus is explored. Pathology indicated direct viral infection of endothelial cells and diffuse endotheliitis in examined necropsy specimens. The authors conclude that their findings support treatment with “therapies to stabilize the endothelium while tackling viral replication, particularly with anti-inflammatory anti-cytokine drugs, ACE inhibitors, and statins.” (References supplied).
  • NIH COVID-19 Treatment Guidelines 
    Apr 21. NIH
    Opinion from SAB Member: Dr. David M. Clement
    A panel of U.S. physicians, statisticians, and other experts has developed treatment guidelines for coronavirus disease 2019 (COVID-19). These NIH guidelines, intended for healthcare providers, are based on published and preliminary data and the clinical expertise of the panelists, many of whom are frontline clinicians caring for patients during the pandemic. Using a familiar and standardized rating scheme, recommendations are made for, among other topics, prophylaxis, treatment modalities (oxygen, ICU ventilation, drugs, etc), pregnancy, children and dealing with concomitant medications. Ongoing drug treatment trials are summarized. Of note, the panel recommends against any drug prophylaxis pre- or post-exposure, and states “no drug has been proven to be safe and effective for treating COVID-19.”
  • Planning and provision of ECMO services for severe ARDS during the COVID-19 pandemic and other outbreaks of emerging infectious diseases. Mar 20.
    Jay: In essence, the original article described ensuring ECMO services around the world meet the guidelines as listed for service development but did not go into direct patient care, ie. pump flow rates or patient determinants of success, labs and vital signs. The first LOE enters the discussion of a single measurement of patient success, HGB levels. Still left out of the discussion is actual scientifically derived recommendations on the entire process of patient management…Lancet Respir Med…
    An article by an international authorship neither a LOE or research article, rather a “how to” recommendation for the world to implement ECMO when needed. Discusses in depth the team, equipment and patient transfer, but does not list recommendations of patient management.
  • What Has the COVID-19 Pandemic Taught Us so Far? Addressing the Problem from a Hepatologist’s Perspective. Apr 21. Méndez-Sánchez. J Clin Transl Hepatol.
    Editorial with 12 international authors.
    The authors outline that hepatic injury during COVID-19 illness may be due to systemic inflammation, liver ischemia and hypoxia, exacerbation of pre-existing liver diseases, and drug-related liver injury. ACE2 is expressed in the epithelial cells of bile ducts “however, in the studies conducted so far, no increase in bile duct injury markers, such as gamma-glutamyl transferase and alkaline phosphatase, has been observed.” “It is a matter of debate whether COVID-19 is directly responsible for the development of liver injury, or whether the observed changes are secondary to the systemic inflammation triggered by infection.“ The authors make no specific recommendations other than to emphasize adherence to general recommendations such as social distancing and appropriate hand washing to curtail spread of the virus until treatment or vaccines are available.

April 21, 2020:

  • Airway management in COVID-19: in the den of the beast. Apr 18. Sorbello. Anesthesia & Analgesia.
    In this letter to the editor, the authors encourage healthcare providers should be protected and should undergo training in using personal protective equipment.
  • Category: Infection Control: An Interim Solution to the Decreased Availability of Respirators against COVID-19 
    Apr 15. Saggese. Anesthesia & Analgesia.
    Opinion from SAB Member: Dr. Barry Perlman
    In NYC, N95 respirator shortages have led healthcare workers to use substandard or unapproved options. Letter from NYC oral/maxillofacial surgeons in response to “Utility of Substandard Face Mask Options for Health Care Workers During the COVID-19 Pandemic” http://dx.doi.org/10.1213/ANE.0000000000004841 describes a do-it-yourself reusable respirator made from an anesthesia mask, inline ventilator or HEPA filter, and elastic straps. This has minimal leakage around the edge and N100 filtration efficiency. It can be washed with soap and water or disinfectant. For non-aerosol generating procedures, they suggest eye protection and a Level 3 surgical mask with a “surgical mask brace” using rubber bands or tourniquets to create a better seal.
  • Barrier System for Airway Management of COVID-19 Patients. Apr 18. Brown. Anesthesia & Analgesia.
    UW and Seattle Children’s Hospital report on using a low cost, flexible, clear barrier drape that protects from aerosolized virus during airway manipulations. Advantage over bulky acrylic alternatives are patient tolerance, lower cost, and access for an assistant.
  • Binding of SARS-CoV-2 and angiotensin-converting enzyme 2: clinical implications. Apr 18. Murray. Cardiovasc Res.
    Literature review, mostly on a molecular cell-biology level, of the RAAS system as it may interact with SARS-CoV-2. Nothing new, and the conclusion is to follow the guidelines of many organizations to continue ACEI and ARBs in patients already on such drugs.
  • Blood transfusion strategies and ECMO during the COVID-19 pandemic. Apr 20. Koeckerling. Lancet Respir Med.
    A response to an article on ECMO during this COVID-19 epidemic. This LOE extends beyond the purpose of the original article and calls for using transfusion restrictive strategies of HGB levels during ECMO at 7g/dl to reduce blood transfusion requirements.
  • Blood transfusion strategies and ECMO during the COVID-19 pandemic – Authors’ reply. Apr 20. Ramanathan. Lancet Respir Med.
    “We believe” HGB at 7 g/dl, 8-10 g/dl when needed.
  • Calculate the COVID-19 equation with the people’s energy as key variable. Apr 19. Boggs. Anesth Analg.
    Editorial covering 1 Swiss study dealing with manpower modeling for ICUs, a correspondence paper from Beijing on HCP protection and an editorial accompanying an article on burnout from Zambia.
    The previously reviewed critical care staffing simulation was felt to be somewhat flawed as it assumed a fixed rate of infection as well as mortality. The Chen article describes the various stages the Chinese HCS went through as the pandemic accelerated: Lack of knowledge, lack of PPE, Knowledge restored, PPE available.
  • Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Mar 1. Liang. The Lancet Oncology.
    In this letter to the editor, the authors note that COVID-19 patients can have cancer and note that patients with cancer might have a higher incidence of COVID-19 than the general population and that patients with cancer may also have a worse outcomes with COVID-19 disease.
  • Chest X-Ray Findings in 636 Ambulatory Patients with COVID-19 Presenting to an Urgent Care Center: A Normal Chest X-Ray Is no Guarantee 
    Apr 13. Weinstock. Journal of Urgent Care Medicine.
    Opinion from SAB Member: Dr. Barry Perlman
    This retrospective, observational, non-blinded study demonstrates that a normal CXR cannot be used to rule out COVID-19 infection. Of 636 CXR of PCR-confirmed COVID-19 NYC and NJ urgent care patients, 58% were re-read as normal and 89% were normal or mildly abnormal. The most common abnormal findings were lower lobe interstitial changes and ground glass opacities. Of note, pleural effusions and lymphadenopathy were uncommon. It is not known whether patients with negative CXR findings developed changes later during their illness.
  • Clinical characteristics and risk assessment of newborns born to mothers with COVID-19. Apr 18. Yang. J Clin Virol.
    Small prospective study of 7 newborns delivered by cesarean section at 36 weeks or greater from COVID-19 infected women in Wuhan, China. 6 mothers had symptoms prior to delivery, and the 7th developed fever post delivery. 2 of 5 neonates admitted to NICU received nCPAP for mild respiratory distress. Their CXRs showed bilateral ground-glass opacities and granular high density shadows. All 7 were isolated from their mothers post delivery and after discharge from the hospital were isolated at home. Of the 6 newborns tested, no throat swabs, amniotic fluid, or umbilical cord blood were RT-PCR positive.
  • Clinical Implications of SARS-Cov2 Interaction with Renin Angiotensin System 
    Apr 16. Brojakowska. Journal of the American College of Cardiology.
    Opinion from SAB Member: Dr. Jay Przybylo
    A data-rich review for physicians/scientists describing what is known to date and what is proposed for study of the complex interactions of COVID-19 and the Renin Angiotensin System activity. A combination of animal and human findings covers multiple body organs with an emphasis on the cardiopulmonary system. The virus needs the Angiotensin Converting Enzyme to enter the cell. ACE inhibitors upregulate the receptor but are integral in inactivating anti-inflammatory pathways. At present the recommendation is to continue the ACE inhibitors. More to follow, hopefully in time to have an effect.
  • COVID-19 pandemic: Greater protection for healthcare providers in the hospital hot zones? Apr 18. Ip. A&A.
    In this letter to the editor, the authors recommend that even in the OB suite, health care workers should be protected.
  • COVID-19 pneumonia: ARDS or not? 
    Apr 16. Gattinoni. Critical Care.
    Opinion from SAB Member: Dr. Jay Przybylo
    Editorial and yet an incredible review in an extremely short article of the pneumonic process associated with COVID-19.
  • COVID-19 putting patients at risk of unplanned extubation and airway providers at increased risk of contamination. Apr 19. Berkow. Anesthesia & Analgesia.
    Discusses increased likelihood for unplanned extubation in COVID-19 mechanically ventilated patients and precautions to decrease risk for UE and to personnel: e.g. sedation protocols, assigned airway/ETT manager during proning; full PPE + PAPR during intubations and reintubation; recognize patient surges decrease desirable staffing ratios-reassign staff for critical procedures. Common sense approach to airway management and potential pitfalls from experts in field.
  • Diabetic patients with COVID-19 infection are at higher risk of ICU admission and poor short-term outcome 
    Apr 9. Roncona. Journal of Clinical Virology.
    Opinion from SAB Member: Dr. Jagdip Shah
    A detailed, retrospective meta-analysis from 3 centers in northern Italy. 9 articles were included, which notably included data from China. This meta-analysis demonstrated that diabetic patients with COVID-19 infection have a higher risk to be admitted to the ICU during the infection. Moreover, diabetes increased the risk of mortality during the infection. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in abstracting data and assessing validity. Quality assessment was performed using the Newcastle-Ottawa quality assessment scale. The main outcome was the risk of ICU admission in diabetic patients with COVID-19 infection while the second was the overall mortality risk in COVID-19 patients with diabetes. Data was pooled using the Mantel-Haenszel random effects models reporting odds ratio (OR) and 95% confidence interval (CI). Statistical heterogeneity between groups was measured using the Higgins I-squared statistic. Results: Among 1382 patients (mean age 51.5 years, 798 males), diabetes was the second most frequent comorbidity. Diabetic patients had a significantly increased risk of ICU admission (OR: 2.79, 95% CI 1.85–4.22, p < 0.0001, I-squared=46%). In 471 patients (mean age 56.6 years, 294 males) analyzed for the secondary outcome, diabetic subjects had higher mortality (OR 3.21, 95% CI 1.82–5.64, p < 0.0001, I-squared=16%).
  • Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes. Apr 18. Han. Am J Gastroenterol.
    Patients with mild Covid-19 illness may present with GI symptoms. This study from Wuhan China identified 206 Covid-19 patients with mild disease of whom 48 had GI symptoms (nausea, vomiting, or diarrhea) alone, 69 had both GI and Respiratory symptoms, and 89 had only respiratory symptoms. All were followed until they had two consecutive daily PCR tests for SARS-CoV-2. Those who presented with GI symptoms waited longer on average to seek treatment, (16 vs. 11.6 days) a longer duration of illness until PCR tests were negative, and a greater likelihood to have positive stool tests.
  • Endoscopy in inflammatory bowel diseases during the COVID-19 pandemic and post-pandemic period 
    Apr 16. Iacucci. The Lancet.
    Opinion from SAB Member: Dr. W. Heinrich Wurm
    This is an international consensus paper by 9 academic centers and 4 societies on the management of inflammatory bowel disease (IBD) and the indications for urgent endoscopy during and after the COVID-19 pandemic. The panel identified 4 clinical scenarios requiring urgent endoscopy and provides well-organized algorithms for each situation. If urgent endoscopy is indicated, ruling out COVID-19 infection and a diagnosis of irritable bowel syndrome (IBS) are high priorities, as COVID-19 infection frequently starts with GI symptomatology (52% in one study). Strict precautions are advised to protect providers and the environment from aerosolized transmission during an endoscopy. An algorithm dealing with post-pandemic gridlock in the endoscopy suite is helpful in prioritizing postponed diagnostic and therapeutic interventions.
  • Extubation of patients with COVID-19. Apr 19. D’Silva. Br J Anaesth.
    Post-anesthesia technique to reduce exposure to Covid-19 aerosol/droplets, could also be used in ICU extubations.
  • Flash survey on severe acute respiratory syndrome coronavirus-2 infections in paediatric patients on anticancer treatment. Apr 20. Hrusak. Eur J Cancer.
    Retrospective, 25 countries, 10,000 pediatric patients on anti cancer treatment (immune compromised). 200 patients identified as likely victims were given COVID-19 Test. 8 patients were asymptomatic only 1 had mild respiratory symptoms. The author shares the attributes to “preventive measures” for success in the height of the outbreak in Europe.
  • Flooded by the torrent: the COVID-19 drug pipeline 
    Apr 18. Mullard. The Lancet.
    Opinion from SAB Member: Dr. Louis McNabb
    There are 180 currently enrolling trials with 150 trials pending. Many of these trials will not have enough patients enrolled to give reliable data. A potentially better model is WHO SOLIDARITY trials which enroll large numbers of patients in several countries. WHO SOLIDARITY is currently investigating remdesivir, hydroxychloroquine, lopinavir/ritonavir, and lopinavir/ritonavir in combination with interferon beta-1a. Results are expected to be coming out from the first trials to complete in the next 12 to 16 weeks.
  • Guillain–Barré Syndrome Associated with SARS-CoV-2. Apr 18. Toscano. N Engl J Med.
    The article review: A rare neurologic disorder became slightly less rare in Northern Italy. 5 cases are presented with two on prolonged ventilation after the article was published.
  • Inflammatory bowel diseases and COVID-19: the invisible enemy. Apr 20. D’Amico. Gastroenterology.
    More of an opinion paper than anything, reviewing past literature on infections in IBD patients on immunosuppresives and biologics. Will not help those treating COVID-19 much.
  • Interim considerations for obstetric anesthesia care related to COVID-19. Apr 5. SOAP. 
    This is interim guidance based on expert opinion of a group of SOAP representatives and differs from SOAP’s more formal consensus statements based on systematic reviews and delphi processes. This content will be updated regularly and integrates information and links to recommendations from the WHO and CDC. Has guidelines for L&D, pre-hospital screening, OB suite training, neonatal, staff, training, and simulation.
  • Laryngeal oedema associated with COVID-19 complicating airway management. Apr 18. McGrath. Anaesthesia.
    This is a letter to the editor. The authors noted that they could not intubate 1 patient due to airway edema and that 2/8 patients had stridor after extubation and their tracheas had to be reintubated. But laryngeal edema is not uncommon for critically ill patients whose tracheas have been extubated.
  • Managing COVID-19 in the oncology clinic and avoiding the distraction effect. Mar 19. Cortiula. Annals of Oncology.
    Authors plea to not unduly delay oncologic treatments including surgery and chemotherapy as the SARS CoV 2 virus is likely to remain a risk for a considerable time.
  • Managing patients with cancer in the COVID-19 era. Apr 18. Peng. Eur J Cancer.
    Editorial In press:
    Authors point out that ACE2 receptor expression is abnormally high or low in many solid malignant tumors of various origins. Their conclusion is “The identification of effective interventions for patients with cancer infected with COVID-19 remains a major challenge. Given the available knowledge of possible mechanisms, clinical trials of drugs are still warranted and individuals with cancer should be studied.”
  • Neuroanesthesia Practice During the COVID-19 Pandemic: Recommendations from Society for Neuroscience in Anesthesiology & Critical Care (SNACC) 
    Apr 15. Flexman. Journal of Neurosurgical Anesthesiology.
    Opinion from SAB Member: Dr. Lydia Cassorla
    These timely guidelines from the Society for Neuroscience in Anesthesiology and Critical Care (SNACC) are recommended reading for those providing neuroanesthesia and neurocritical care during the COVID-19 pandemic. This document was created by a SNACC appointed task force to provide a focused overview of the COVID-19 disease relevant to neuroanesthesia practice through consensus-based expert guidance. This article provides information on the neurological manifestations of COVID-19, advice for neuroanesthesia clinical practice during emergent neurosurgery, interventional radiology (excluding endovascular treatment of acute ischemic stroke), transnasal neurosurgery, awake craniotomy and electroconvulsive therapy, as well as information about healthcare provider wellness. “Guidelines for the anesthetic management of endovascular therapy for acute ischemic stroke during the COVID-19 pandemic” are available in separate guidance from the SNACC. This report from a global group of neuroanesthesiologists reports on indications that CNS manifestations of COVID-19 such as lack of smell/taste and altered mental status may be due to direct invasion of the CNS. There are suggestions of an increased incidence of acute ischemic stroke as well. The authors review measures to establish urgency of procedures and decrease healthcare worker exposure to the virus from patients who nonetheless may require emergent/urgent neurosurgical and neuroradiologic procedures and ECT. 2 Printable graphics summarizing considerations for neurosurgical and ECT procedures are included.
  • Planning and provision of ECMO services for severe ARDS during the COVID-19 pandemic and other outbreaks of emerging infectious diseases. Mar 30. Ramanathan. Lancet Respir Med.
    An article by an international authorship neither a LOE or research article, rather a “how to” recommendation for the world to implement ECMO when needed. Discusses in depth the team, equipment and patient transfer, but does not list recommendations of patient management.
  • Profile of RT-PCR for SARS-CoV-2: a preliminary study from 56 COVID-19 patients. Apr 20. Xiao. Clin Infect Dis.
    Preliminary RT-PCR study on 56 recovering COVID-19 patients in Wuhan, China showed that virus shedding continued up to 6 weeks after symptom onset, with a mean time to negative RT-PCR conversion of 24 days. Patients with positive RT-PCR tests more than 24 days after symptom onset tended to be older and more likely to have HTN or DM. Of note, all patients had mild-moderate illness, none required ICU admission, and all recovered. Also, a second negative test was used for confirmation, although 4 patients tested RT-PCR positive after 2 consecutive presumably false negative results.
  • Pulmonary and Cardiac Pathology in Covid-19: The First Autopsy Series from New Orleans. Apr 10. Fox. medRxiv.
    As of March 31, 2020, New Orleans has had the highest death rate per capita in the US. This is a non-peer reviewed report of the cardiopulmonary findings of the first 4 autopsies performed. The patients were African Americans with obesity and HTN. 3 had IDDM and 2 had chronic kidney disease. Lung parenchyma was edematous and firm, consistent with ARDS. 3 had areas of lung hemorrhage. Only the lung from the patient who had been on methotrexate showed focal consolidation. All cases showed evidence of diffuse alveolar damage with DC4+ aggregates around thrombosed small vessels. Heart tissue showed atypical myocyte degeneration but no myocarditis. The findings suggest that in addition to targeting the virus itself, therapy should also focus on the thrombotic and microangiopathic effects and the maladaptive immune response.
  • Response to COVID-19 in Taiwan: Big Data Analytics, New Technology, and Proactive Testing. Mar 3. Wang. JAMA Network.
    The rapid, coordinated and aggressive Taiwanese response to the pandemic threat that was quite successful through Feb 24. Dated article, not useful to front-line providers.
  • Risk Factors Associated with Disease Severity and Length of Hospital Stay in COVID-19 Patients. Apr 20 Liu. J Infect.
    Pre-Proof article from China which reptrospectively studied 99 patients who recovered from COVID-19 and identified risk factors for severe disease. Since study was retrospective, did not include deaths, and had nothing new.
  • Risk of COVID-19 for patients with cancer. Mar 3. Wang. The Lancet Oncology.
    Lancet Correspondence Letter by Chinese authors, dated March 3, calling into question some of the assertions in article 276.
  • SARS-CoV-2 shedding and infectivity. Apr 19 Atkinson. Lancet.
    The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
  • Category: Clinical Care / Prevention; Anesthesia Care 
    Sedation of mechanically ventilated COVID-19 patients: challenges and special considerations 
    Apr 15. Hanidziar. Anesthesia & Analgesia.
    Opinion from SAB Member: Dr. Jagdip Shah
    A plea from MGH–guidelines are needed for sedation for COVID 19. The authors rationalize in an excellent way of all practical bed side issues for this subset of patients, covering each sedative agent and its pros & cons, prone positioning, drug shortages, staff preference for deeper sedation to avoid emergent re-intubations (which can expose staff to SARS-CoV-2), high sedation requirements, monitoring difficulties, drug interactions.
  • Smell and taste dysfunction in patients with COVID-19. Apr 19. Xydakis. Lancet Infect Dis.
    As the authors note in their first sentence of this letter to the editor: “The plural of an anecdote is not evidence,” and indeed, they provide little more evidence concerning taste and smell dysfunction than what’s already been described.
  • Category: Diagnosis of Infection or Immunity 
    Testing for SARS-CoV-2: Can We Stop at Two? 
    Apr 19. Lee. Clinical Infectious Diseases.
    Opinion from SAB Member: Dr. Lydia Cassorla
    This report from Singapore highlights data as of Feb. 29, 2020 from a set of patients hospitalized with typical symptoms and a history of travel or contacts suggestive of COVID-19 illness. 72/80 (88.6%) tested negative on their first upper respiratory PCR, 5 were positive on the second day, and 3 turned positive on the third daily test. The authors stress that single or even two consecutive daily negative tests may not detect all infected patients. Their PCR test was developed and commercialized in Singapore, targeting N and ORF1ab genes. This report highlights an important point that repeated testing is often required to confirm infection. Readers should keep in mind that PCR tests are not all alike, and implementation such as swabbing location and technique vary. Therefore, sensitivity data can be expected to vary as well.
  • The performance of chest CT in evaluating the clinical severity of COVID-19 pneumonia: identifying critical cases based on CT characteristics. Apr 19. Lyu. Invest Radiol.
    Retrospective study from a single center in China regarding utility of CT scan in diagnosis of COVID19. N= 51. Three groups: mild, moderate, and severe. All groups were tested and scored on: 1. clinical score, 2. qualitative score, 3. quantitative, 4. AI score. Don’t know who were excluded. Stastics had fitness test besides standard tests (P…… ) Comparing mild to severe. Their conclusion: “The combined use of qualitative and quantitative indicators could distinguish cases at different clinical stages, might provide help to facilitate the fast identification and management of critical cases, thus reducing the mortality rate. Critical cases had higher total severity score (>10) and total score for crazy-paving and consolidation (>4) than ordinary cases, and had higher mean lung density (>-779HU) and full width at half maximum (>128HU) but lower relative volume of normal lung density (≦50%) than ordinary/severe cases. CT imaging findings could help to continuously monitor the treatment effects objectively in the follow-up as well as provide guidance for clinical management and treatment.”
  • The Untold Toll – The Pandemic’s Effects on Patients without Covid-19. Apr 18. Rosenbaum. NEJM.
    An articulate, appropriately emotional and well written article on the peripheral and usually undocumented costs of COVID-19’s effects on other (frequently emergency) patient care priorities. Details experiences with delayed coronary angiography, rushed decisions to perform bilateral mastectomy, and inadequate post procedural follow-up. Timely, thoughtful and obvious future implications when “routine” access to medical care resumes.
  • Well-aerated Lung on Admitting Chest CT to Predict Adverse Outcome in COVID-19 Pneumonia. Apr 18. Colombi. Radiology.
    Retrospective study of 236 ED patients in Italy admitted with positive RT-PCR tests and chest CT findings consistent with COVID-19 pneumonia. Lower zone predominance of ground-glass opacities and consolidations were most common findings. > 27% of lung with decreased aeration on admit CT was associated with 5x greater risk of ICU admission or death. Concomitant emphysema was about 2x more common in patients who were admitted to ICU or died.

April 20, 2020:

  • A conceptual and adaptable approach to hospital preparedness for acute surge events due to emerging infectious diseases. Apr 20. Anesi. Crit Care Explor.
    This narrative review provides a framework for factors that must be incorporated into an effective response to an epidemic or pandemic. The focus is on bringing order to what might otherwise be a chaotic situation. Graphics and definitions are useful in conceptualizing the many stressors and optimal responses to a surcharged system. Causes of healthcare capacity strain are defined as increased volume, increased acuity, special care requirements and resource reduction (relative to demand), and the “4 Ss” of surge preparation discussed: Space, Staff, Stuff, Systems. Perhaps most useful for clinical leaders, policy experts and healthcare administrators.
  • A Tool to Early Predict Severe Corona Virus Disease 2019 (COVID-19) : A Multicenter Study using the Risk Nomogram in Wuhan and Guangdong, China. Apr 17. Gong J. Clin Infect Dis.
    A nomogram was developed to help predict which COVID-19 patients are at increased risk of progression to severe disease. Retrospective 3 center study of 372 Covid-19 patients. 19% developed severe COVID-19 within 15 days of admission, as defined by: (1) Shortness of breath, Respiratory rate ≥ 30/min, (2) Resting O2 saturation ≤ 93%, or (3) PaO2/ FiO2) ≤ 300mmHg. A nomogram based on data from 189 patients and then validated with 2 additional patient groups consisting of older age, higher LDH, CRP, RDW, DBIL, and BUN, and lower ALB on admission correlated with higher odds of progression to severe COVID-19. Increased RDW as a risk factor for progression to severe COVID-19 is a new finding.
  • Clinical Characteristics of Covid-19 in New York City. Apr 17. Goyal. NEJM.
    A prelude to what’s coming to us
    NEJM article about experience of 2 NYC Hospitals of first 393 patients with COVID 19.
    Comorbidity was noted to be higher in NYC as compared to China. NYC outcomes were noted different as well with regard to: Higher number of patients were ventilated, lower oxygen earlier, renal replacement, fluids, need for vaso active drugs to maintain hemodynamic stability. 33% required ventilators, 10.2% Mortality, 33% extubated, 66% were discharged – these numbers were higher than China data all across.
  • COVID-19: the case for health-care worker screening to prevent hospital transmission. Apr 16. Black. The Lancet.
    Lancet Letter to the Editor from the UK, urging universal RT-PCR testing of hospital-based HCW in an effort to limit nosocomial infection by asymptomatic or presymptomatic HCW, prevent unnecessary quarantine (which depletes an already stretched workforce) and protect HCWs. Several studies are cited to support such efforts.
  • Death from Covid-19 of 23 Health Care Workers in China. Apr 15. Zhan. NEJM.
    NEJM Letter to the Editor from China, describing the epidemiology of the 23 healthcare workers who died from COVID-19 through April 3. Of note, nearly half (11) were HCW rehired after retirement, and only 2 were respiratory physicians assigned to COVID units. Many deaths were early, suggesting better precautions later were effective. Zero of 42,600 HCW who travelled to Hubei Provence to care for patients with COVID-19 were known to have been infected.
  • Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome 
    Apr 16. Hendren. Circulation.
    Opinion from SAB Member: Dr. Louis McNabb
    Good article outlining the potential causes of myocardial dysfunction in COVID-19, i.e. myocarditis, microvascular injury, cytokine mediated injury, and stress induced cardiomyopathy.
  • Fact versus science fiction: fighting coronavirus disease 2019 requires the wisdom to know the difference 
    Apr 2020. Ingraham. Critical Care Explorations.
    Opinion from SAB Member: Dr. Jay Przybylo
    An editorial plea to avoid the popular fiction enveloping us and to stick to science and facts. A wake up to those falling prey to mass media.
  • High flow nasal cannula is a good treatment option for COVID-19. Apr 17. Geng S. Heart Lung.
    Limited study of 8 patients with COVID-19 induced mild to moderate respiratory compromise. Discussion focuses on HFNC benefits in early disease without mention of aerosolization precautions or negative pressure isolation. Oxygenation indices and patient progress well documented; all patients survived to discharge. The authors note HFNC cannot be substituted for invasive ventilation in severe respiratory failure.
  • Hospital Preparedness for COVID-19: A Practical Guide from a Critical Care Perspective. Apr 17. Griffin KM. Am J Respir Crit Care Med.
    This detailed report from Cornell outlines the adaptations implemented at a large university medical center in one of the epicenters of the SARS CoV2 pandemic. Topics include evolving indications for O2 therapy, intubation and ECMO, PPE, team models, physician staffing and expansion of duties, multidisciplinary care including infectious disease, critical care medicine (CCM), cardiology, anesthesiology, respiratory care, physical therapy, palliative care, and nursing. ICU care was standardized under supervision of CCM specialists regardless of patient location or provider background. Many adaptations in care were designed to limit opportunities for infection of workers, such as dedicated smart phones within ICU care rooms, monitors and care information outside rooms when feasible (compliant due to restricted visitors), bundled care, and dedicated or defined teams for many aspects of care such as invasive procedures and proning. Education, triage, and ethical considerations and wellness are also discussed.
  • Joint statement on safely resuming elective surgery after the COVID-19 pandemic 
    Apr 17. American College of Surgeons; American Society of Anesthesiologists; Association of periOperative Registered Nurses; American Hospital Association.
    Opinion from SAB Member: Dr. Jagdip Shah
    In response to the COVID-19 pandemic, the Centers for Medicare and Medicaid Services (CMS), the U.S. Surgeon General and many medical specialties such as the American College of Surgeons and the American Society of Anesthesiologists recommended interim cancelation of elective surgical procedures. Physicians and health care organizations have responded appropriately and canceled non-essential cases across the country. Many patients have had their needed, but not essential, surgeries postponed due to the pandemic. When the first wave of this pandemic is behind us, the pent-up patient demand for surgical and procedural care may be immense, and health care organizations, physicians and nurses must be prepared to meet this demand. Facility readiness to resume elective surgery will vary by geographic location. The following is a list of principles and considerations to guide physicians, nurses and local facilities in their resumption of care in operating rooms and all procedural areas.
  • Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China. Mar 20. Zeng. JAMA Pediatrics.
    A research letter that describes transmission of COVID-19 from mother to neonate. Three neonates out of 33 virus positive mothers suffered clinical symptoms of the virus. All 3 were born by C-section.
  • Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period 
    Apr 14. Kissler. Science.
    Opinion from SAB Member: Dr. Barry Perlman
    Viral, environmental, and immunologic data from other corona viruses were used to project SARS-CoV-2 transmission and determine social distancing measures that may be needed through 2025. Models suggest that SARS-CoV-2 could cause outbreaks in any season, exhibiting annual, biennial, or sporadic patterns depending on duration of immunity after infection. If similar to other coronaviruses, recurrent SARS-CoV-2 winter outbreaks are likely. Incidence through 2025 will depend on duration of immunity and cross immunity with other coronaviruses. In all models, infection resurgence occurred when social distancing measures were lifted, but restrictive social distancing could also decrease development of population immunity. In the absence of increased critical care capacity and effective new treatments or vaccines, intermittent social distancing will be needed through 2022. Increased critical care capacity, testing, and surveillance are needed to better determine what intermittent social distancing policies may maintain critical care availability while building population immunity.
  • Sequential analysis of viral load in a neonate and her mother infected with SARS-CoV-2. Apr 17. Han MS. Clin Infect Dis.
    An interesting manuscript: 27-day old neonate, born almost at 39 wks and her mother were diagnosed with COVID-19. About a month after the baby was born, her mother and father developed symptoms of COVID-19 and the baby and mother both tested positive and were hospitalized. Though at its early stage, the viral load was highest in the nasopharynx, up until the 18th day it was high in the infant’s stool, when respiratory specimens were negative. It’s not clear if virus detected in stool and urine was viable, still important to wash hands after changing a diaper.
  • Spread of SARS-CoV-2 in the Icelandic Population 
    Apr 14. Gudbjartsson. The New England Journal of Medicine.
    Opinion from SAB Member: Dr. J. Lance Lichtor
    In this study of corona virus spread in Iceland, using targeted testing of persons at high risk for infection and population screening, the frequency of coronavirus infection in the overall Icelandic population was stable from March 13 to April 1, which showed that containment measures in Iceland were working. Testing was a critical component and is a model for other countries.
  • The clinical presentation and immunology of viral pneumonia and implications for management of coronavirus disease 2019. Apr 20. Darden. Crit Care Explor.
    A review article on viral respiratory tract infections with a section on COVID-19. Sections include cytokine activation, genetics, and vaccination with no present therapy. 
  • The use of UV fluorescent powder for COVID-19 airway management simulation training. Apr 17. Gardiner C. Anaesthesia.
    A simulation demonstrating the dispersal of infectious material during airway management.
  • The Utah Model: mental bandwidth and strategic risk generation in COVID-19 airway management. Apr 17. Runnels S. Anaesthesia.
    Correspondence regarding the Consensus guidelines for managing the airway in patients with COVID-19 by Cook et al.
    Two points are raised: “First, failure to minimise aggregate airway management risk poses a strategic threat to our medical systems, and two, it is critical to include the risk of mental bandwidth saturation as a risk for contamination.” They feel that protecting providers is the first principle of the current resource-constrained system. The authors provide a graph which shows that increasing aerosolization risk due to increasing airway management complexity correlates with increasing provider stress.

April 17, 2020:

  • Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Apr 16. Arachchillage DR. J Thromb Haemost.
    This is a pre-proof editorial. 11.5 % patients in Wuhan had consumptive coagulopathy -> DIC with PT, D Dimer, FSP high. Platelets – either N or low N. Caution with VV ECMO & ARDS Careful anti coagulation, ICH with Plt. Even if Platelet N be vigilant.
    DIC prognostic marker for COVID-19. A rise of D Dimer & Reduction of Platelet on VV ECMO = pump failure.
  • Assessing Viral Shedding and Infectivity of Tears in Coronavirus Disease 2019 (COVID-19) Patients. Apr 16. Seah IYJ. Ophthalmology.
    The nasolacrimal system can act as a conduit for viruses to travel from the upper respiratory tract to the eye. The authors measured the presence of SARSCoV-2 with viral isolation and quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis. As the 17 patients in the study were being monitored clinically via routine nasopharyngeal swabs, these results were compared with those of tears to understand further patterns of viral shedding. Of the 17 patients recruited, none demonstrated ocular symptoms. However, 1 patient developed conjunctival injection and chemosis during the stay in the hospital. Fourteen patients showed upper respiratory tract symptoms at presentation, including cough, rhinorrhea, and sore throat. No evidence was found of SARS-CoV-2 shedding in tears through the course of the disease even for the one patient with conjunctival injection.
  • COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals 
    Apr 9. Breslin. American Journal of Obstetrics & Gynecology MFM.
    Opinion from SAB Member: Dr. Jay Przybylo
    A data-complex article from a small geographic area that demonstrates 33% of COVID-19 + pregnant women remained asymptomatic and of those with symptoms, 86% were mild. 60% measured obese and 42% identified as comorbid. Of those with severe and critical illness, there were no deaths. 91% of the newborns tested negative while the remainder were indeterminate. This might be a representative prediction of a larger population. Also warns healthcare personnel of overall infection penetration.
  • COVID-19 pneumonia: different respiratory treatments for different phenotypes? Apr 16. Gattinoni L. Intensive Care Med.
    Clinical observations from experienced researchers conclude two types of lung disease exist variably in COVID-19 patients; patient presentation may depend on severity of infection, initial patient response to hypoxemia and the time from symptom onset to hospital admission. Type L is described as low elastance with retained lung compliance, low VA/Q ratio and normal lung weight. As hypoxemia worsens, patient generated large tidal volumes increase negative intrathoracic pressure which may cause further lung damage. Type H is defined as high elastance due to increased pulmonary edema, high shunt, high lung weight and high lung recruitability. Excellent discussion and physiologic explanation for managing patients with different lung support strategies and ventilatory assistance in both stages. Important discussion for all physicians engaged in treating COVID-19 patients who may present at different stages of the disease which require different ventilatory strategies which may prevent deterioration if treated early in the course.
  • Does COVID-19 Disprove the Obesity Paradox in ARDS? Apr 16. Jose RJ. Obesity (Silver Spring).
    A disporportionate number of non-survivors of COVID-19 patients are obese. The authors postulate that factors may include a chronic pro-inflammatory status, difficult airway, pulmonary elastance, compliance, potential pulmonary hypertansion and RV function may be contributing factors.
  • Gastrointestinal Symptoms and COVID-19: Case-Control Study from the United States 
    Apr 8. Nobel. Gastroenterology.
    Opinion from SAB Member: Dr. Barry Perlman
    Retrospective, case-control study of COVID-19 associated gastrointestinal symptoms, including diarrhea and nausea/vomiting, in NYC patients and essential personnel who had nasopharyngeal swab testing for respiratory symptoms. 278 COVID-19 positive and 238 negative patients were included. Patients with GI symptoms at time of testing had a 70% increased risk of testing positive for COVID-19, while absence of GI symptoms did not impact the likelihood of a positive test result. Increasing BMI also correlated with increased risk of a positive test result. 35% of patients who tested positive had GI symptoms, and these patients were more likely to have illness lasting one week or greater. However, they had a significantly lower death rate and a non-significant lower rate of ICU admission. Of note, the paper does not discuss follow-up testing or the final diagnosis of the patients who had negative testing on presentation but went on to hospital admission (171), ICU admission (30) or death (3), so presumably a significant number of these patients had initial false negative tests and were actually COVID-19 positive.
  • Immune Thrombocytopenic Purpura in a Patient with Covid-19. Apr 16. Zulfiqar AA. N Engl J Med.
    Single case which responded to rxn with steroids, ivg, and eltromopag.
  • Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China. Mar 20. Zeng. JAMA Pediatrics.
    A research letter that describes transmission of COVID-19 from mother to neonate. Three neonates out of 33 virus positive mothers suffered clinical symptoms of the virus. All 3 were born by C-section.
  • Neurologic Features in Severe SARS-CoV-2 Infection 
    Apr 15. Helms. The New England Journal of Medicine.
    Opinion from SAB Member: Dr. Louis McNabb
    Observational study describing neurologic deficits such as agitation (69%), cortical spinal tract signs (67%), confusion (65%), and dysexecutive syndrome post discharge (33%). MRI demonstrated frontotemporal hypoperfusion in 11/11 pts with perfusion imaging. Curiously, all 7 pts with CSF samples tested negative for SARS-CoV-2 infection. Many of the findings would be anticipated in elderly patients (median age 63) in average ICU census without COVID-19 infection.
  • Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19) A review. Apr 13. Sanders. JAMA.
    JAMA review detailing currently reported COVID-19 therapeutic strategies; cautions there is no cure and no specific therapies can be recommended. Reinforces basic medical care, treatment of infection and associated complications, etc. Therapeutic options well defined and described across categories. Recognition that future controlled trials necessary to define more appropriate management options.
  • Prediction models for diagnosis and prognosis of covid-19 infection: systematic review and critical appraisal. Apr 7. Wynants, L. BMJ.
    A review and appraisal of 27 prediction model studies for diagnosis, prognosis, and risk of hospital admission due to COVID-19. Age, temperature, and signs/symptoms were the most reported predictors of suspected disease. Age, sex, CT, CRP, LDH, and lymphocyte count predicted severe prognosis. However, all studies had high risk of bias due to reporting and methodology flaws, such as small sample sizes, non-representative control patients, exclusion of those who had not reached the clinical event of interest by the conclusion of the study, and model overfitting. The authors warn against using prediction models based on questionable data, and recommend that better and more standardized data collection and reporting methodologies are needed to determine the predictors that could be used to guide clinical decisions during the COVID-19 pandemic.
  • Suspected myocardial injury in patients with COVID-19: Evidence from front-line clinical observation in Wuhan, China. Apr 16. Deng Q. Int J Cardiol.
    This article from Wuhan n= 112 patients. ITS pre proof. Retrospective study. Comparison was 2 group of 4 patients with COVID 19 + VE: A: Those who survived and possibly d/c home to B: those who didn’t survive. Excluded 5 patient with pre existing cardiac conditions (CHF, MI 4 days ago ). Stastic believable: p, fitness test.…Lot of redundant numbers / lab….No biopsy or Nuclear study. Extensive data collection of these patients. Ongoing as patient (61) are still in hospital. Troponin & BNP not remarkable until 1 week before the death both of them rises, CPK & LDH late elevation. Covid-19 caused myocarditis – no solid evidence. Inflammatory process/hypoxia are likely cause of myocarditis. 5 Patients had pericardial effusion. TR Flow velocity.., PUM PR, CVP, stiffness of RT/ LT vent , wall motion ……. All Normal to high Normal. No other ECHO / EKG – All non specific. Hypoxia on vent support , ECMO (14), MOF, Cytokine Strom (no inflammatory markers – IL Panel), Met. Acidosis, renal/ liver failure, Abnormal coag. Profile …before Death. Pulm. Hypertension -> ARDS related? From the clinical standpoint and front-line data analysis in our study, though there was evidence of myocardial injury and 12.5% COVID-19 patients had cardiac abnormalities similar to myocarditis, the characteristic changes of cardiac troponin I over time and the absence of typical signs on echocardiography and ECG have suggested that myocardial injury is more likely related to systemic consequences rather than direct damage by the 2019 novel coronavirus. The elevation in cardiac markers was probably due to secondary and systemic causes and can be considered as the warning sign for recent adverse clinical outcomes of the patients.
  • The Science Underlying COVID-19: Implications for the Cardiovascular System. Apr 16 Liu PP. Circulation.
    This is a review article that is published ahead of print. It is well written and detailed and describes the relationship between COVID-19 and the cardiovascular system. Briefly, whereas COVID-19 is primarily a respiratory infection, it has important systemic effects including on the cardiovascular and immune systems. Between 8-28% of patients with COVID-19 infections will manifest troponin release early in the course of the disease, reflecting cardiac injury or stress. The presence of troponin elevation, or its dynamic increase during hospitalization, confers up to 5 times the risk of requiring ventilation, increases in arrhythmias such as VT/VF, and 5 times the risk for mortality. One feature of the virus is that it has enhanced ACE2 receptor binding affinity. Given that ACE2 receptors are located in the human oral pharynx and upper airway, this allows for person-to-person transfer. ACE2 has been confirmed recently as the SARS-CoV-2 internalization receptor that helps to facilitate cell entry. TMPRSS2 and ACE2 are co-expressed in lung, heart, gut smooth muscle, liver, kidney, neurons and immune cells35. Their distribution may help to explain patient symptoms or laboratory findings in COVID-19. And there is more described in the article.
  • Towards aerodynamically equivalent COVID-19 1.5 m social distancing for walking and running. Blocken. Urban Physics.
    Social distancing guidelines are based upon distances that droplets from coughing, sneezing, or exhaling can travel from patients standing still. A previous study showed that deep inhalation and exhalation increases aerosol concentration several fold. Wind tunnel experiments simulated the airflow and droplet dispersion around two walkers or runners breathing moderately deeply side by side 1 meter apart, and in line or staggered at various distances apart. The simulations showed that the largest droplet exposure occurs when a trailing person is behind and in the slipstream of the lead person. Separation of 5 meters when walking or 10 meters when running is needed to provide the same droplet exposure protection as standing 1.5 meters apart. Staggered positioning minimized droplet exposure, but the simulations were done in the absence of cross, head, or tail winds, which might allow droplets to escape the slipstream. Further studies will be needed to validate the findings and determine if this exposure poses infection risk.
  • Visualizing speech-generated oral fluid droplets with laser light scattering. Apr 15. Anfinrud, P. NEJM.
    NEJM letter to the editor, from the NIH, explaining and demonstrating sprays of secretions from speaking. The included graphic video illustrates the degree of droplet/aerosol formation from speech alone.

April 16, 2020:

  • Balancing Supply and Demand for Blood during the COVID-19 Pandemic. Apr 13. Gehrie E. Anesthesiology.
    Thoughtful discussion on COVID-19 impact on disruption of normal sources to maintain national blood supply highlights decreased donations due to elimination of mobile blood drives at schools, universities and other public locations contrasting with continuing demand and overall decrease in donation which parallels other efforts to decrease demand over past decade. Further mitigation discussion recognizes cancellation of elective surgeries (living donor transplantation, etc.), “keeping the blood in the patient”, single unit transfusions in order to keep blood available for other needs. Recommendations: encourage healthy donors to go to donation centers and optimize currently available and practice recommended blood management techniques.
  • Emergency Open-source Three-dimensional Printable Ventilator Circuit Splitter and Flow Regulator during the COVID-19 Pandemic. Apr 10. Lai B. Anesthesiology.
    In this letter to the editor, the authors show how they constructed, using a 3-D printer, a splitter that would allow more than one patient to be ventilated using a single ventilator. The problem with this study is that, as the authors admit, there could be cross-contamination. But the other problem is that this was never actually tested on any patient, so the user has no idea what happens when it is used.
  • Prediction models for diagnosis and prognosis of Covid-19 infection: systematic review and critical appraisal. Apr 9. Wynants L. BMJ.
    Reviews 31 predictive models for risk of Covid-19 pneumonia, risk of hospital admission, and risk of disease severity/death. The author didn’t recommend any of them because of poor design, bias, and poor patient follow-up. Accompanying editorial points out explosion of poorly written articles on Covid-19. Asks the question? Do we really need anymore “case studies” on CT imaging of covid-19, when there are over 250 artilcles already published.
  • Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. Apr 13. Gordan C. Journal of Biological Chemistry.
    No antiviral agents are currently approved to treat COVID-19. This study shows a probable mechanism of antiviral action for remdesivir and supports continued evaluation of its clinical effectiveness and safety.
    SARS-CoV-2 replication depends on viral RNA-dependent RNA polymerase (RdRp). Remdesivir (RDV) is a prodrug that when triphosporylated resembles ATP. It has been shown to have broad in vitro and animal model antiviral activity including SARS-CoV and MERS-CoV. The presumed mechanism of action is competition of remdesivir triphosphate for ATP, causing delayed chain-termination (termination after 3-5 more nucleotide incorporations). Human mitochondrial RNA polymerase has high selectivity for ATP over RDV-TP, consistent with low cytotoxicity of remdesivir. In this in vitro study of purified SARS-CoV, MERS-CoV, and SARS-Cov-2 RdRp, remdesivir triphosphate was efficiently incorporated into RNA, causing delayed termination of RNA synthesis after 3 additional nucleotides were incorporated (i+3). In comparison, chain termination did not occur with Lassa virus RdRp, which is consistent with its higher binding affinity for ATP over RDV-TP. The other antivirals sofosbuvir and ribavairin, and several nucleostide analogs, showed less competition with ATP in this model.
  • Setup of a Dedicated Coronavirus Intensive Care Unit: Logistical Aspects. Apr 7. Mojoli F. Anesthesiology.
    This is a blueprint for re-organizing an existing ICU to accommodate infectious disease patients safely within an ICU environment. Valuable but not unique as a concept.
  • Towards aerodynamically equivalent COVID-19 1.5 m social distancing for walking and running. Blocken. Urban Physics.
    Social distancing guidelines are based upon distances that droplets from coughing, sneezing, or exhaling can travel from patients standing still. A previous study showed that deep inhalation and exhalation increases aerosol concentration several fold. Wind tunnel experiments simulated the airflow and droplet dispersion around two walkers or runners breathing moderately deeply side by side 1 meter apart, and in line or staggered at various distances apart. The simulations showed that that the largest droplet exposure occurs when a trailing person is behind and in the slipstream of the lead person. Separation of 5 meters when walking or 10 meters when running is needed to provide the same droplet exposure protection as standing 1.5 meters apart. Staggered positioning minimized droplet exposure, but the simulations were done in the absence of cross, head, or tail winds, which might allow droplets to escape the slipstream. Further studies will be needed to validate the findings and determine if this exposure poses infection risk.

April 15, 2020:

April 14, 2020:

April 13, 2020:

April 11, 2020:

April 10, 2020: