Current Highlights from the Global COVID-19 DocMatter Community Newsletter

The International Anesthesia Research Society (IARS), DocMatter, plus many other medical societies with providers on the front lines, and the distinguished physician volunteers on the COVID-19 Scientific Advisory Board (C19SAB) are contributing to this Community dedicated to addressing the COVID-19 pandemic by helping all healthcare professionals access global peer experience and education. Below are publications hand-selected and reviewed by our Scientific Advisory Board for the Global COVID-19 DocMatter Community Newsletter.

Click on a newsletter number or date below to see articles included in that edition. To search by keyword, select Ctrl + F on a PC and Command + F on a Mac. Then, enter keyword and Enter.

Current Highlights from the Global COVID-19 DocMatter Community Newsletter

Newsletter 32, May 28, 2020:
  • 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.
  • 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.
  • 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.
  • 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 Mattew J. Cummings, et al (below) 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.
  • 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.
  • 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.
  • 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.
  • 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.

Previous COVID-19 Newsletters

Newsletter 31, May 26, 2020:

  • 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.
  • Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis
    May 22. Mehra. The Lancet.
    Opinion from SAB Member: Dr. Barry Perlman
    This is a multinational cloud based registry (Surgical Outcomes Collaborative) analysis of 96,032 confirmed COVID-19 patient data from 671 hospitals on 6 continents that explores the effects of hydroxychloroquine or chloroquine with or without macrolide treatment between 12/20/19 and 4/14/20. An additional 2230 patients who received remdesivir, or whose treatment started more than 48 hours after diagnosis or while mechanically ventilated, were excluded.
    • 1868 received chloroquine
    • 3783 received chloroquine with macrolide
    • 3016 received hydroxychloroquine
    • 6221 received hydroxychloroquine with macrolide
    • 81114 were in control group

    The hospital death rate was 11.1%. Age, BMI, being black or hispanic, having coronary artery disease, CHF, a history of arrhythmia, diabetes, HTN, hyperlipidemia, COPD, smoking and immunocompromise were associated with a higher risk of death. Being female, of Asian origin, and ACE inhibitor or statin use were associated with decreased risk of in-hospital mortality. Coronary artery disease, CHF, h/o arrhythmias, and COPD were independently associated with increased risk of ventricular arrhythmias. After using a propensity score matching analysis to control for comorbidities, age, sex, race, ethnicity, cardiac and other antiviral medications, and baseline disease severity, all treatment groups independently had significantly higher (1.5-2.5 x) mortality and > 10x increased risk of de-novo ventricular arrhythmias during hospitalization. The treatment groups also had an approximately 3x incidence of mechanical ventilation as compared with the control group which was not addressed in the discussion but, according to personal communication with the author, reflects the fact that the patients who received the treatment medications got sicker, requiring ventilation. While the discussion does point out that “…a cause-and-effect relationship between drug therapy and survival should not be inferred”, the study does strongly suggest that benefit from these medications could not be confirmed.

  • 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.
  • 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.”

  • 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.
  • 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 (below) 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.
  • 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.
  • 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.
  • 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.
  • 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.”
  • 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.
  • 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 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.

Newsletter 30, May 21, 2020:

  • 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 (below) 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.
  • 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.
  • 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.
  • The Relationship between Status at Presentation and Outcomes among Pregnant Women with COVID-19
    Apr 27. London. American Journal of Perinatology.
    Opinion from SAB Member: Dr. Lydia Cassorla
    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. 55 SARS-CoV-2 positive pregnant women were followed to term and 1 had fetal demise at 17 wks. Among participants 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 cesarean sections for maternal respiratory distress. 12 (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.
  • 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.
  • 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.
  • 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.
  • 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.

Newsletter 29, May 20, 2020:

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Newsletter 28, May 18, 2020:

  • 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 (below) 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.
  • 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.
  • 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.”
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Newsletter 27, May 16, 2020:

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 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.

Newsletter 26, May 15, 2020:

  • ORIGINAL ARTICLE: Incidence of thrombotic complications in critically ill ICU patients with COVID-19
    Apr 13. Klok. Thrombosis Research.
    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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.”
  • 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.
  • 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.
  • 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.

Newsletter 25, May 13, 2020:

  • 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.
  • 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.
  • 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.
  • 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.
  • Clinical course of severe and critical COVID-19 in hospitalized pregnancies: a US cohort study
    American Journal of Obstetrics & Gynecology MFM. Apr 27, 2020.
    Rebecca A.M.Pierce-Williams; Julia Burd; Laura Felder; Rasha Khoury; et al
    Opinion from SAB Member: Dr. Jay Przybylo
    This is a data-rich, multicenter study of COVID-19 severe and critically ill women in third trimester of pregnancy. Of the many findings: critically ill women required intubation and 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.
  • 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.
  • 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.

Newsletter 24, May 12, 2020:

  • 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.
  • 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.
  • 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.

  • 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.
  • 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.
  • 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.

Newsletter 23, May 11, 2020:

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • The following 4 articles provide evidence that COVID-19 infection is Kawasaki Disease in an exceptionally small number of children. Regardless of the diagnosis terminology, the treatment of all COVID-19 patients regardless of age includes the administration of immunoglobulin.
  • 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.
  • 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.
  • 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.”

Newsletter 22, May 8, 2020: 

  • 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.

  • 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.
  • 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.”
  • 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.
  • 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.
  • 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.

Newsletter 21, May 7, 2020: 

  • 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.

  • 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.
  • 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.
  • 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.
  • 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.

Newsletter 20, May 6, 2020: 

  • 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.

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Newsletter 19, May 5, 2020: 

  • 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.

  • 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.
  • Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19
    May 1. Mehra. The New England Journal of Medicine.
    Opinion from SAB Member: Dr. David M. Clement, Dr. Jagdip Shah
    DMC: This study, with data from many institutions and three different continents, provides an excellent summary of the patient characteristics most associated with mortality in COVID-19 patients. JS: The authors provide a multivariate, logistical regression model that describes a few independent predictors and their corresponding odds ratios of in-hospital death from COVID-19. The population (N= 8910) comes from 169 hospitals located in 11 countries in Asia, Europe, and North America. Inclusion criteria were that patients must be hospitalized with COVID-19 positive swab test with a reported outcome (discharged alive v. dead) by March 20, 2020. 1536 patients (17.2%) were from North America, 5755 (64.6%) were from Europe, and 1619 (18.2%) were from Asia. The significant, independent predictors (odds ratio for death [>1=more likely to die; <1=less likely to die]) of in-hospital death included: 1) >65 yr of age (1.93); 2) Female (0.79); 3) Coronary Artery Disease (2.7); 4) Congestive Heart Failure (2.48); 5) Arrhythmia (1.95); 6) COPD (2.96); 7) Current Smoker (1.79); 8) Receiving ACEi (0.33); 9) Receiving statin (0.35). Of note, the authors were not able to confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital mortality in this clinical context.
  • 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.
  • 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.
  • 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.

Newsletter 18, May 2, 2020: 

  • 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.

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Newsletter 17, April 30, 2020: 

  • 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.

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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.

Newsletter 16, April 28, 2020: 

  • 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.

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Newsletter 15, April 27, 2020: Special Report from the SAB

  • 95 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.

Newsletter 14, April 25, 2020:

  • 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.

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Newsletter 13, April 24, 2020:

  • 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. 

  • 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.
  • 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.
  • 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.

Newsletter 12, April 23, 2020:

  • 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.

  • 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.
  • 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.

Newsletter 11, April 22, 2020:

  • 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.”

  • 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.
  • 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).
  • 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.
  • 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.
  • 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.

Newsletter 10, April 21, 2020:

  • 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 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.

  • 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%).

  • 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.

  • 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.

  • 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.

Newsletter 9, April 20, 2020:

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

Newsletter 8, April 18, 2020:

  • Corticosteroid Guidance for Pregnancy during COVID-19 Pandemic
    Apr 9. McIntosh. Am J Perinatol.
    Opinion from SAB Member: Dr. Jagdip Shah, Dr. Brian McNabb
    JH: The author compared dose/duration of steroid use during pregnancy with steroid use in ICU for COVID-19 patients and came to the conclusion the maternal risks must be balanced against neonatal benefits. Concludes a cautious & careful consideration with all parties (F/M). BLM: Specific recommendations include no corticosteroids should be administered to COVID-19 positive or suspected gravid patients at > 32 weeks of gestation, MFM consultation to address risks and benefits of corticosteroid use is recommended for COVID-19 positive or suspected gravid patients at < 32 weeks gestation, no tocolysis in COVID-19 positive or suspected gravid patients who are not receiving steroids.

  • 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.

  • 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.

  • 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.

  • Obstetric Anesthesia During COVID-19 Pandemic 
    Apr 14. Bauer. Anesthesia & Analgesia.
    Opinion from SAB Member: Dr. W. Heinrich Wurm
    Well-organized summary of obstetric anesthesia management during the pandemic with emphasis on safe practice methods for patients and providers. Recommend platelet count on admission and isolation of mother and newborn.

Newsletter 7, April 14, 2020:

  • A role for CT in COVID-19? What data really tell us so far Apr 11. Hope. The Lancet 
    Opinion from SAB Member: Dr. Barry Perlman
    Opinion piece from academic radiologists that CT should not be used to diagnose COVID-19, as the described ground-glass opacities and consolidation are not specific. The positive predictive value of CT is low unless pre-test probability is high, and in one study of confirmed COVID-19 patients from the Diamond Princess cruise ship, 1/3 did not have CT lung opacities and 20% of symptomatic patients had negative CT findings. Further, use of CT during the pandemic is “logistically challenging” in terms of resource allocation, cleaning, and potential exposure of COVID-19 to caregivers and other patients.

  • Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19 Apr 9. Chu. Clinical Infectious Diseases. 
    Opinion from SAB Member: Dr. Philip Lumb
    Ex-vivo investigation (excised donor lung segments from surgical patients with lung tumors) inoculated with either SARS-CoV-2 or SARS-CoV preparations. Infection and replication capacity of the two preparations were compared. Excellent methodology section detailing specimen and culture preparation, biohazard security and virology challenge and critical analysis. Results demonstrated that SARS-CoV-2 was more capable of infecting and replicating in lung tissue than SARS-CoV. The discussion includes the statement, “These findings may explain the high viral load in the respiratory secretions of COVID-19 patients during the early days on presentation or even during incubation, and thus the its person-to-person transmissibility.” This is a meticulously conducted experiment with well described methodology and important conclusions that provides insight into why COVID-19 propagates rapidly, has variable penetrance and clinical outcomes, and gives a theoretical rationale for early use of antiviral medication. An important study that could help define future therapeutic intervention and further ongoing research.

  • COVID-19 Guidance for Triage of Operations for Thoracic Malignancies: A Consensus Statement from Thoracic Surgery Outcomes Research Network Mar 24. Thoracic Surgery Outcomes Research Network, Inc. The Annals of Thoracic Surgery
    Opinion from SAB Member: Dr. Jagdip Shah, Dr. Jay Przybylo
    Dr. Jagdip Shah: A working model proposed by a group of surgeons for cancer patients for delayed surgery. Dr. Jay Przybylo: For all specialties, classifying elective versus urgent procedures places the onus of decision making on the person charged with running the procedural schedule. This position would be aided with a uniformed determination of those procedures presently classified differently between institutions. Little disagreement exists with procedures such as cardiac valve failure. Postponing tumor biopsy and therapy has resulted in patients waiting before treatment can begin. A national declaration could be beneficial to afflicted patients.

  • Medically-Necessary, Time-Sensitive Procedures: A Scoring System to Ethically and Efficiently Manage Resource Scarcity and Provider Risk During the COVID-19 Pandemic Apr 9. Prachand. Journal of the American College of Surgeons. 
    Opinion from SAB Member: Dr. W. Heinrich Wurm
    A resource and safety conscious scoring system, created by surgeons at the University of Chicago to identify medically-necessary, time-sensitive procedures and facilitate surgical treatment of non-COVID-19 related disease during the height of the pandemic in an efficient and ethical manner. Taking into consideration perioperative outcome, likelihood of virus transmission to health care personnel and utilization of hospital resources, the authors identified 21 factors related to procedural complexity, aspects of disease and patient co-morbidities. As proof of concept, the scoring system was applied retrospectively to cases done in the week of March 20th and performed well. A few limitations were identified, particularly in factor weight assignment, and may require adjustments as the pandemic runs its course.

  • Pain Management Best Practices from Multispecialty Organizations during the COVID-19 Pandemic and Public Health Crises Apr 7. Cohen. Pain Medicine.
    Opinion from SAB Member: Dr. Jagdip Shah
    This is a long, detailed article with blessings from various societies and government agencies including the VA administration who stress the need to treat chronic pain. The COVID-19 pandemic represents an unprecedented global health crisis that requires carefully weighing the dynamic balance between access to pain care, which can have long-term personal and socioeconomic benefits, with the immediate goal of minimizing exposure risk for frontline healthcare providers and vulnerable patients. It is important to recognize that these recommendations are meant to serve as guidelines. Authors explore a variety of opportunities of safe practice while following all the prescribed guidelines in current COVID-19 pandemic.

  • Point-of-care lung ultrasound in patients with COVID-19 – a narrative review Apr 10. Smith. Anaesthesia.
    Opinion from SAB Member: Dr. Barry Perlman
    Review on the use of ultrasound imaging for the diagnosis and management of COVID-19 patients with associated lung injury and respiratory failure. Ultrasound can detect COVID-19 associated pleural line irregularities and B-line artifacts caused by interstitial thickening, inflammation, and small consolidations. These changes increase with severity of disease, so point-of-care ultrasound can be used to follow disease progression and aid in clinical decision making. The authors make recommendations regarding a standardized ultrasound lung exam, scoring system, and training of additional providers in the use of lung ultrasound.

  • 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.

  • The Role of Chest Imaging in Patient Management during the COVID-19 Pandemic: A Multinational Consensus Statement from the Fleischner Society Apr 3. Rubin. CHEST. 
    Opinion from SAB Member: Dr. Barry Perlman
    Recommendations from a multidisciplinary panel of radiologists, pulmonologists, and other disciplines from 10 countries on the use of chest X-ray (CXR) and CT for managing COVID-19 patients. Ultrasound was not considered due to the panel member’s limited experience with ultrasound in COVID-19 patients at the time of the meeting. They recommend that chest imaging should not be used for patients with suspected COVID-19 and mild clinical features. Rather, it is useful when patients are at risk for disease progression, develop worsening respiratory status, or have moderate-severe disease and high pre-test probability of COVID-19 infection. CT is more sensitive than CXR in mild or early COVID-19 infection, and for alternative diagnoses such as acute heart failure or pulmonary thromboembolism. However, local resources, expertise, infection control issues, and clinical judgment impact the decision as to which modality should be used. Table 2 provides a nice summary of the recommendations.

Newsletter 6, April 13, 2020:

Newsletter 5, April 11, 2020:

  • Alert for SARS-CoV-2 infection caused by fecal aerosols in rural areas in China Apr 7. Meng. Infection Control & Hospital Epidemiology. 
    COVID-19 SAB Opinion from: Dr. Jagdip Shah
    SARS-CoV-2 can be detected in feces and urine of COVID-19 cases, especially the asymptomatic cases. SARS-CoV can persist in feces from infected people for as long as four days, and SARS-CoV-2 may persist in feces for a longer time. The feces may form high concentrations of viral aerosol and travel through the air to cause infection. Close the lid & then flush, ventilation system, spray disinfectant/wash floor weekly, skeptic to a smell in pumping station.

  • 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.

  • COVID-19 pneumonia manifestations at the admission on chest ultrasound, radiographs, and CT: single-center study and comprehensive radiologic literature review Apr 7. Lomoro. European Journal of Radiology Open.
    COVID-19 SAB Opinion from: Dr. Lydia Cassorla
    A retrospective review of findings on chest imaging (CXR, CT and US) from 58 COVID-19 patients at time of admission to a single Northern Italian hospital within 1 month. This report includes a summary of data from 3886 patients reported from international literature reports of >10 COVID-19 patients, through March 15, 2020. Bilateral and multifocal lesions, with likely progress from ground glass opacities to later consolidation are most common. The lesions are predominantly peripheral. This report includes illustrations of typical findings and may be useful for those assessing patients with possible COVID-19 illness.

  • Effectiveness of Surgical and Cotton Masks in Blocking SARSCoV-2: A Controlled Comparison in 4 Patients Apr 6. Bae. Annals of Internal Medicine. 
    COVID-19 SAB Opinion from: Dr. Barry Perlman
    BP-Brief study of 4 infected patients coughing into petri dishes while wearing no mask, surgical mask, or cotton mask showed that neither surgical nor cotton masks effectively filtered SARS–CoV-2 during coughs. This is in contrast to the influenza virus which has been shown to be effectively filtered by surgical masks. It is hypothesized that the ineffectiveness with the SARS-CoV-2 virus is due to its small particle size. In addition, greater contamination by virus particles were found on the outside than the inside of the masks, demonstrating the importance of hand hygiene after touching the outer surface of masks.

  • Kidney diseases in the time of COVID-19: major challenges to patient care Apr 6. Rabb. The Journal of Clinical Investigation. 
    COVID-19 SAB Opinion from: Dr. Jagdip Shah
    Short concise article related to COVID-19 and its impact on several conditions: ACE2 receptor/HBP, erythropoietin production, vitamin D metabolism, presence of urinary viral load for a long time in urine after recovery, dialysis: altering systemic-inflammatory markers/infection risk, kidney transplant related practical issues: consideration to only transplant high quality organs, a need to change the immunosuppressant regime and its implication in this pandemic.

  • 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.

  • Prone Positioning in Severe Acute Respiratory Distress Syndrome June 6, 2013. Guérin. NEJM. 
    SAB COVID-19 Opinion from: Dr. Jay Przybylo
    Title is self-explanatory.

  • 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.

  • 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.

  • The use of high-flow nasal oxygen in COVID-19 Apr 4. Lyons. Anaesthesia.
    COVID-19 SAB Opinion from: Dr. David M. Clement, Dr. Jack Lance Lichtor
    David Clement: A summary of the studies of high flow nasal oxygen (HFNO), a review of various conflicting guidelines for its use with COVID-19 patients, and a common sense approach (mainly to avoid rigid thinking) that may help front line workers decide whether to use it or not. PPE, negative pressure rooms, modification of flow rate are advised if HFNO is used. Jack Lance Lichtor: Though high-flow oxygen therapy may have some benefit in patients with acute hypoxaemic respiratory failure, aerosolization may result in COVID-19 virus spread. Yet, if the use of this form of oxygen therapy is felt to be useful, then it should be used in a negative pressure room.

  • 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.

Newsletter 4, April 8, 2020:

Newsletter 3, April 7, 2020:

Newsletter 2, April 4, 2020:

Newsletter 1, April 3, 2020:

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Thank you COVID-19 DocMatter Scientific Advisory Board and Content Reviewers!

The IARS would like to recognize the COVID-19 DocMatter Scientific Advisory Board and the Content Reviewers for sharing their expertise and time to help curate and evaluate the most relevant information coming out about COVID-19 for our members. The COVID-19 DocMatter SAB meet daily to discuss articles, provide reviews and determine what information would be most valuable to those on the frontline. The Content Reviewers review a list of articles daily to determine their topic areas and relevance to the audience. We greatly appreciate the commitment they have made to help during this major health crisis!

DocMatter Scientific Advisory Board

Joseph Anthony Caprini, MD, MS, FACS, RVT
Specialty: Vascular Surgery, Hematology (Clinical)
Senior Clinician Educator
University of Chicago Pritzker School of Medicine

Lydia Cassorla, MD, MBA
Specialty: Anesthesiology
Professor Emerita, Department of Anesthesia and Perioperative Care, University of California, San Francisco

Stephen Cecil, MD*
Specialty: Anesthesiology
Wayne County Anesthesia Associates, Wayne Memorial Hospital

David M. Clement, MD
Specialty: Anesthesiology
St. Joseph Hospital

Robert L. Coffey, MD
Specialty: Pulmonology
Retired Physician

David C. Henry, MD
Specialty: Anesthesiology
Jackson Anesthesia Associates

Anil Hingorani, MD
Specialty: Vascular Surgery, General Surgery
Vascular Institute Of New York

Jack Lance Lichtor MD
Specialty: Anesthesiology
Yale University

Philip Lumb, MBBS, MD, MCCM
Specialty: Anesthesiology, Critical Care Medicine
Professor of Anesthesiology, Keck School of Medicine of USC

Louis McNabb, MD
Specialty: Pulmonology and Critical Care Medicine, Sleep Medicine
St. Jude Medical Center

Barry Perlman, MD, PhD, CMI
Specialty: Anesthesiology
Chair, Informatics Committee, Oregon Society of Anesthesiologists

Jay Przybylo, MD, FAAP, MFA
Specialty: Anesthesiology
Associate Professor, Department of Anesthesiology, Northwestern University Feinberg School of Medicine

Elin A. Rowley, ScD, MSc, IDHA*
Specialty: Infectious Diseases, Public Health/Epidemiology
Assistant Professor of Clinical Sciences, William Carey University College of Osteopathic Medicine

Paul D. Scanlon, MD
Specialty: Internal Medicine, Pulmonology
Professor of Medicine (Retired)
Mayo Clinic College of Medicine and Science - Rochester

Edward S. Schulman, MD
Specialty: Allergy and Immunology; Pulmonology and Critical Care Medicine
Professor of Med and Division Chief
Division of Pulmonary, Critical Care & Sleep Medicine, Drexel University College of Medicine

Jagdip Shah, MD, MBA
Specialty: Anesthesiology
Associate Professor of Anesthesiology and Critical Care Medicine, Department of Anesthesiology, Medical College of Virginia - Virginia Commonwealth University School of Medicine

W. Heinrich Wurm, MD
Specialty: Anesthesiology
Chair Emeritus, Tufts Medical Center

*Drs. Cecil and Rowley have been deployed to the frontlines to help address the influx of COVID-19 patients and have had to leave their post on the SAB.

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Nancy Kenepp, MD
Specialty: Anesthesiology
Associate Professor Emeritus, Temple University, Katz School of Medicine, Department of Anesthesiology

Jonathan V. Roth, MD
Specialty: Anesthesiology
Chairman Emeritus, Department of Anesthesiology; Staff Anesthesiologist, Albert Einstein Medical Center

Robert N. Sladen MBChB, FCCM 
Specialty: Anesthesiology, Critical Care Medicine
Allen Hyman Professor Emeritus of Critical Care Anesthesiology, Columbia University Vagelos College of Physicians and Surgeons

Eugene I. Tolpin, MD, PhD
Specialty: Anesthesiology
ChristianaCare Health Systems, Newark, Delaware

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