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COVID-19 Resources
January – June 2020

Following declarations from the US Department of Health and Human Services and World Health Organization ending the COVID-19 Public Health Emergency, the IARS COVID-19 Scientific Advisory Board (SAB) concluded its review of the scientific literature about SARS-CoV-2 in August. The SAB has reviewed more than 3,100 journal articles and published 1,076 article reviews over the past 42 months. It has been an enormous commitment from the SAB, and the IARS owes our dedicated physician volunteers a huge debt of gratitude for their unwavering participation in this initiative.

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Disclaimer
The material on this website is provided for informational purposes and does not constitute medical advice. New knowledge is added daily and may change over time. Opinions expressed should not be construed as representing IARS policy or recommendations. References and links to third parties do not constitute an endorsement or warranty by IARS.

Retractions:

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.
    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.  VD varies 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.
Subscribe to COVID-19 Newsletter
2021 Resources
July-December 2020 Resources
Disclaimer
The material on this website is provided for informational purposes and does not constitute medical advice. New knowledge is added daily and may change over time. Opinions expressed should not be construed as representing IARS policy or recommendations. References and links to third parties do not constitute an endorsement or warranty by IARS.

Retractions:

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:

  • Audio Interview: Emerging Tools in the Fight against Covid-19. Apr 9. Rubin. NEJM.
    A 20-minute podcast with editors of NEJM, discussing broad topics with COVID, especially serology testing and therapeutics. Little in the way of specifics that will help front-line providers.
  • Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19. Apr 9. Zhang. NEJM.
    Case report and comparison with 2 other COVID-19 patients in Wuhan who presented with coagulopathy, antiphospholipid antibodies, and multiple cerebral infarcts. SARS-CoV-2 was confirmed with RT-PCR or serologic testing. All three patients had histories of multiple co-morbidies. The case report patient was age 69 with a history of HTN, DM, and CVA. He had leukocytosis, thrombocytopenia, elevated PT. aPTT, fibrinogen, and D-dimer. Patients 2 and 3 did not have leukocytosis or as markely elevated D-dimer, and patient 3 had a normal Plt count. All 3 showed presence of anticardiolipin IgA and anti-B2-glycoprotein I IgA and IgG antibodies, and negative lupus anticoagulant.
  • Compassionate Use of Remdesivir for Patients with Severe Covid-19 Apr 10. Grein. NEJM. 
    Opinion from SAB Member: Dr. Louis McNabb
    An uncontrolled, observational study showing the potential benefit of remdesivir (68% of patients had improvement in oxygenation). Larger, controlled studies are necessary to confirm efficacy.
  • Considerations for Drug Interactions on QTc in Exploratory COVID-19 (Coronavirus Disease 2019) Treatment Mar 25. Roden. Circulation. 
    COVID-19 SAB Opinion from: Dr. Barry Perlman
    Hydroxychloroquine and azithromycin have both been associated with QT prolongation and torsades de pointes. The combination on QT prolongation or arrhythmia risk has not been studied. Seriously ill patients can have other risk factors for arrhythmias, such as hypokalemia, hypomagnesemia, fever, and inflammatory state. The authors recommend not using these meds if patient has known congenital long QT syndrome, withholding or withdrawing them if QTc > 500 msec, avoiding other medications that can prolong QTc, and correcting hypokalemia to > 4 mEq/L and hypomagnesemia to > 2 mg/dL. They point out that optimal ECG monitoring may not be possible in critically ill COVID-19 patients.
  • COVID-19 and the RAAS-a potential role for angiotensin II? Apr 7. Busse. Critical Care. 
    COVID-19 SAB Opinion from: Dr. Jay Przybylo
    The most significant editorial I’ve read that posits the early use of angiotensin II might be beneficial by blocking the entry of the virus through the angiotensin-converting enzyme (ACE) receptor on the cell wall. Proposed that it is best if used early.
  • Inquiring into Benefits of Independent Activation of Non-Classical Renin-Angiotensin System in the Clinical Prognosis and Reduction of COVID-19 mortality. Apr 9. Álvarez Aragón. Clin Infect Dis.
    A speculative letter to the editor with excellent research value, but little to offer the front line provider.
  • Is There an Association Between COVID-19 Mortality and the Renin-Angiotensin System—a Call for Epidemiologic Investigations. Mar 30. Hanff. Clin Infect Dis.
    Is there a relationship between the renin-angiotensin system and mortality due to Covid-19? Indeed, people with cardiovascular disease have a higher incidence of mortality due to the disease. Activation of the renin–angiotensin system (RAS) is significant in the pathogenesis of cardiovascular disease and specifically coronary atherosclerosis. But also, angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2. More study is needed.
  • ISTH interim guidance on recognition and management of coagulopathy in COVID-19 Mar 25. Thachil. Journal of Thrombosis and Haemostasis. 
    Opinion from SAB Member: Dr. Barry Perlman
    Lymphopenia is common with COVID-19, and severely ill patients are likely to have coagulopathy. The following is an interim guidance statement on management of COVID-19 coagulopathy: 1) Upon presentation of COVID-19, the measurements advised, in order of importance, are of d-dimer, prothrombin time, and platelet counts. 2) Increased d-dimers are commonly reported in patients with severe illness and may predict mortality. Three- to four-fold increases in d-dimer may signal the need for admission in patients without other clear indicators of severity. 3) Prolongation in prothrombin times and degree of thrombocytopenia (100–150×109/L) have been modest. 4) In addition to the above parameters, fibrinogen should be monitored; nonsurvivors with severe illness have developed disseminated intravascular coagulation around day 4; significant worsening in these parameters at days 10 and 14 was also reported. 5) The panel advises use of prophylactic dose low-molecular-weight heparin unless there is active bleeding or a platelet count of <25×109/L; it is hoped that this strategy will impact septic-like coagulopathy and protect against venous thromboembolism. 6) Bleeding has been rare, but if present, panelists advise keeping platelet counts >50×109/L (and >20×109/L goal in nonbleeding patients), fibrinogen >2.0 g/L, and the prothrombin ratio <1.5.
  • PCR Assays Turned Positive in 25 Discharged COVID-19 Patients Apr 8. Yuan. Clinical Infectious Diseases. 
    COVID-19 SAB Opinion from: Dr. Lydia Cassorla
    172 patients discharged from a Shenzhen hospital following clinical improvement and 2 consecutive day negative PCR tests for COVID-19 virus. They were then followed at home with nasal and cloacal swab PCR testing every 3 days during a planned 14-day quarantine. 25 patients (14.5%) re-tested positive and were returned to hospital. Some had new symptoms. The authors suggest that the pre-discharge testing may be more reliable in detecting persistent virus carriers if separated by 48 hours.
  • Practice of novel method of bedside postpyloric tube placement in patients with coronavirus disease 2019. Apr 9. Yuan. Critical Care.
    Report of a Chinese version of Dobhoff tube: claims to insert in the second part of duodenum “easier” in Covid patient. No objective evidence.
  • SARS-CoV-2 Vaccines: Status Report Apr 14. Amanat. Immunity. 
    COVID-19 SAB Opinion from: Dr. Barry Perlman
    There are no existing vaccines or production processes for coronavirus vaccines. Studies on SARS-CoV-1 and the related MERS-CoV vaccines suggest that the S protein on the surface of the virus is an ideal target for a vaccine. Antibody titers in individuals that survived SARS-CoV-1 or MERS-CoV infections often waned after 2–3 years or were weak initially, so an effective SARS-CoV-2 vaccine will need to be efficacious longer to protect against recurrent seasonal epidemics. Currently an MRNA-based vaccine, which expresses target antigen in vivo after injection of mRNA encapsulated in lipid nanoparticles is the furthest along and in phase I clinical trials. Several other vaccines (live attenuated, inactivated virus, or focused on the S protein) are in the pre-clinical phase. Safety testing typically takes 3-6 months. Production of live attenuated or inactivated virus vaccines would probably be faster because of existing infrastructure. It is highly likely that more than one dose of the vaccine will be needed, spaced 3–4 weeks apart. Realistically, SARS-CoV-2 vaccines will not be available for another 12–18 months—too late to affect the first wave of this pandemic, but useful if additional waves occur later or in a post-pandemic scenario in which SARS-CoV-2 continues to circulate as a seasonal virus.
  • Special considerations for the management of COVID-19 pediatric patients in the operating room and pediatric intensive care unit in a tertiary hospital in Singapore. Apr 9. Thampi. Pediatric Anesthesia.
    Basically says pediatric COVID patients should be managed same as adults but an interesting read.
  • Structural and molecular modeling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection Apr 3. Fantini. International Journal of Antimicrobial Agents. 
    COVID-19 SAB Opinion from: Dr. Barry Perlman
    Structural and molecular modeling showed that chloroquine can bind to sialic acids and gangliosides with high affinity. A new type of ganglioside-binding domain at the tip of the N-terminal domain of the SARS-CoV-2 spike (S) protein was identified, which may facilitate contact with the ACE-2 receptor. Chloroquine and the more potent hydroxychloroquine block binding of the viral spike to gangliosides, which the authors suggest may be the mechanism of action of these medications against SARS-CoV-2.
  • Use of Hydroxychloroquine and Chloroquine During the COVID-19 Pandemic: What Every Clinician Should Know Mar 31. Yazdany. Annals of Internal Medicine. 
    COVID-19 SAB Opinion from: Dr. Barry Perlman
    Data to support the use of hydroxychloroquine and chloroquine for COVID-19 are limited and inconclusive. Given serious potential adverse effects, the hasty and inappropriate interpretation of the literature by public leaders has potential to do serious harm. 10 trials are under way, and information should be forthcoming within weeks. Treatment interruptions for those with SLE and other rheumatic diseases must be prevented, because lapses in therapy can result in disease flares and strain already stretched health care resources.
  • “We Signed Up for This!” Student and Trainee Responses to the Covid-19 Pandemic. Apr 9. Gallagher. NEJM.
    Well written and thoughtful perspective from the University of Washington providing a status update on the role of medical students (clinical rotations were suspended in mid-March) as well as reporting on and discussion of the results of a survey among residents and medical students on the impact of the current situation. A call for administrators and teachers to communicate, listen and be aware of the duplicity of emotions among young clinicians wishing to serve as well as protect themselves and others and a realization of the multitude of once theoretical dilemmas that now become real in our daily practice.

April 9, 2020:

April 8, 2020:

April 7, 2020:

April 6, 2020:

April 5, 2020:

April 4, 2020:

  • Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis. Apr 4. Lippi. Progress in Cardiovascular Diseases.
    Troponin levels should be measured as a marker of infection severity. Patients with severe SARS-CoV-2 infection experience significant cardiac injury.
  • Dysregulation of immune response in patients with COVID-19 in Wuhan, China Mar 21. Qin. Clinical Infectious Diseases. 
    COVID-19 SAB Opinion from: Dr. Barry Perlman
    Study of 452 Wuhan, China COVID-19 patients showed severe cases tended to have lower lymphocyte counts, higher neutrophil-lymphocyte ratios, lower monocytes, eosinophils, and basophils, decreased memory helper and regulatory T-cells.
  • Race to find COVID-19 treatments accelerates Mar 27. Kupferschmidt. Science. 
    COVID-19 SAB Opinion from: Dr. Jay Przybylo
    Remdesivir, developed by Gilead Sciences to combat Ebola and related viruses, shuts down viral replication by inhibiting a key viral enzyme, the RNA polymerase. It didn’t help patients with Ebola in a test during the 2019 outbreak in the Democratic Republic of the Congo. But in 2017, researchers showed in test tube and animal studies that the drug can inhibit the SARS and MERS viruses. As compassionate use, which required Gilead to review patient records; some doctors have reported anecdotal evidence of benefit, but no hard data. Remdesivir may be much more potent if given early. Chloroquine and hydroxychloroquine decrease acidity in endosomes, compartments that cells use to ingest outside material and that some viruses co-opt during infection. But SARS-CoV- 2’s main entryway is different: It uses its so-called spike protein to attach to a receptor on the surface of human cells. Studies in cell culture have suggested chloroquine can cripple the virus, but the doses needed are usually high and could cause severe toxicity. “Researchers have tried this drug on virus after virus, and it never works out in humans.” Hydroxychloroquine might actually do more harm than good. It has many side effects and can, in rare cases, harm the heart-and people with heart conditions are at higher risk of severe COVID-19. Lopinavir-ritonavir combination. Abbott Laboratories developed the drugs to inhibit the protease of HIV, an enzyme that cleaves a long protein chain during assembly of new viruses. The combination has worked in marmosets infected with the MERS virus, and has also been tested in patients with SARS and MERS, though those results are ambiguous. But the first trial with COVID-19 was not encouraging. SOLIDARITY combines these two antivirals with interferon-beta, a molecule involved in regulating inflammation that has lessened disease severity in marmosets infected with MERS. But interferon-beta might be risky for patients with severe COVID-19, Herold says. “If it is given late in the disease it could easily lead to worse tissue damage, instead of helping patients,” she cautions. Other approved and experimental treatments are in testing against coronavirus or likely soon to be. They include drugs that can reduce inflammation, such as corticosteroids and baricitinib, a treatment for rheumatoid arthritis. Some researchers have high hopes for camostat mesylate, a drug licensed in Japan for pancreatitis, which inhibits a human protein involved with infection. Other antivirals will also get a chance, including the influenza drug favipiravir and additional HIV antiretrovirals. Researchers also plan to try to boost immunity with “convalescent” plasma from recovered COVID-19 patients or monoclonal antibodies directed at SARS-CoV-2.
  • Ten Weeks to Crush the Curve. Apr 1. Fineberg. NEJM.
    Editorial advocating 6 steps to “defeat” Covid-19 by early June: Establish united command, increase diagnostic test availability for everyone with symptoms, supply health workers with PPE and equip hospitals to care for surge, differentiate population based on presence or absence of current infection and treat accordingly, inspire and mobilize public, research.
  • The Italian coronavirus 2019 Outbreak: Experiences and Recommendations From Clinical Practice. Mar 27. Sorbello. Anaesthesia. 
    COVID-19 SAB Opinion from: Dr. Barry Perlman
    Recommendations based on Italian COVID-19 clinical experience including airway management, team roles, and PPE use. 

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February 19, 2020:

  • NIH clinical trial of remdesivir to treat COVID-19 begins Feb 25. NIH News Release. NIH 
    Opinion from SAB Member: Dr. Jay Przybylo
    A small uncontrolled study from China suggested the drug demonstrated some efficacy. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro cell research from Feb. 4, 2020. This study intends to document the drug’s efficacy. Remdesivir is currently available to some patients through an NIH (National Institute of Allergy and Infectious Diseases) sponsored study being conducted through the Univ. of Nebraska Medical Center (NCT4280705), as well as several other clinical trials and expanded access programs (NCT04292730, NCT04292899, 2020-000936-23). Hopefully results soon.

February 13, 2020:

February 12, 2020:

February 3, 2020:

February 2020:

  • Practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-nCoV) patients. Wax and Christian.
  • Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19) Feb 16. WHO. 
    Opinion from SAB Member: Dr. Barry Perlman
    Joint Mission was a series of meetings and field visits from February 16-24, 2020 by 25 Chinese and international experts, headed by Dr. Bruce Aylward of WHO and Dr. Wannian Liang of the People’s Republic of China. The major objectives: 1) To enhance understanding of the evolving COVID-19 outbreak in China and the nature and impact of ongoing containment measures; 2) To share knowledge on COVID-19 response and preparedness measures being implemented in countries affected by or at risk of importations of COVID-19; 3) To generate recommendations for adjusting COVID-19 containment and response measures in China and internationally; and 4) To establish priorities for a collaborative program of work, research and development to address critical gaps in knowledge and response and readiness tools and activities. It was recommended that “uncompromising and rigorous” non-pharmaceutical measures to contain transmission, proactive surveillance, rapid diagnosis and isolation, and tracking and quarantine of close contacts should be employed globally.

November 13, 2006:

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