COVID-19 Resources by Topic

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

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

Click on a phrase below to see resources on that topic. To search by keyword, select Ctrl + F on a PC and Command + F on a Mac. Then, enter keyword and Enter.

III. Clinical Care / Prevention

February 12, 2021

  • Perspectives of Ketamine Use in COVID-19 Patients. 1/1/21. Weinbroum A. J Korean Med Sci.
    This article is a brief review from Israel of the use of ketamine sedation in the context of COVID-19. It includes the rationale, practical aspects and potential benefits such as evidence of reduced IL-6 and CRP following infusion. Advantages include minimal hemodynamic suppression, bronchodilation, and lack of respiratory depression during spontaneous or assisted ventilation. Authors also discuss a potentially lower incidence compared with other sedatives of psychological complications including acute anxiety and post-traumatic stress and depression following illness.

April 24, 2020

  • Anesthesia ICU Transition Materials. University of Utah.
    Four videos lasting over three hours, from the University of Utah, designed to update the ICU knowledge of anesthesiologists (and others) in preparation for a COVID-19 surge. These are well done, thorough and very clinically applicable. Discussions cover most topics from PPE to self-care and sustainable staffing, to specifics of ventilator management and more.

April 7, 2020

April 2, 2020

April 1, 2020

March 11, 2020

March 7, 2020

    1. Pulmonary Management
      December 20, 2021

      December 6, 2021

      October 25, 2021

      • Bacterial Superinfection Pneumonia in Patients Mechanically Ventilated for COVID-19 Pneumonia. 8/17/21. Pickens CO. ATS.
        This Northwestern University single-center study examined the prevalence and etiology of bacterial superinfection (bacterial infection in addition to SARS-CoV-2) in severe SARS-CoV-2 pneumonia at intubation and subsequent ventilator-associated pneumonia (VAP). All patients had bronchoalveolar lavage (BAL) analyzed by quantitative cultures and multiplex PCR. In 179 patients, initial superinfection was detected in 21%; 44.4% developed 1 or more VAP episode(s). Initial VAP pathogens were usually CAP-type and not requiring broad spectrum coverage. Clinical criteria could not distinguish patients with or without superinfections. BAL-based management resulted in significantly reduced antibiotic use. Current guidelines, which advocate empirical antibiotics in severe SARS, results in antibiotic overuse at intubation. Forty-four percent VAPs suggests widespread under-recognition yet overtreatment with unnecessarily broad antibiotics.

      October 18, 2021

      • Beneficial Effect of Prone Positioning During Venovenous Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019. 9/28/2021. Zaaqoq AM. Crit Care Med.
        In this paper the authors attempt to determine if prone positioning has a survival benefit in patients with Covid-19 who are placed on venovenous ECMO. This is an observational report involving 232 patients from 72 participating institutions in multiple countries. During ECMO, 67 (29%) of these Covid-19 patients were placed at times in the prone position. Survival to hospital discharge was 33% in the extracorporeal membrane oxygenation prone group versus 22% in the extracorporeal membrane oxygenation supine group suggesting a benefit. This report seems to be the largest reporting in this specific patient population and suggests the need for a RCT.

      October 4, 2021

      • Antifungal prophylaxis for prevention of COVID-19-associated pulmonary aspergillosis in critically ill patients: an observational study. 9/16/21. Hatzl S. Crit Care.
        This retrospective, observational study reviewed the clinical course of all 132 consecutive patients admitted between September 1, 2020, and May 1, 2021, 75 of whom received antifungal prophylaxis (98% posaconazole). Antifungal prophylaxis was recommended in this medical center, but ordering it was left up to the discretion of individual intensivists. The authors noted that COVID-19-associated pulmonary aspergillosis (CAPA) was diagnosed in 17.5% of patients who did not receive antifungal prophylaxis, versus only in 1.4% of those receiving prophylaxis. They also noted that despite the efficacy shown for antifungal prophylaxis against aspergillosis infection in these patients, this prophylaxis did not have a significant impact on overall survival.

      September 20, 2021

      • High-Flow Nasal Cannula and COVID-19: A Clinical Review. 9/15/21. Crimi C. Respir Care.
        This review is a succinct and thorough description of the value of high flow nasal cannula (HFNC) for moderate-to-severe acute hypoxemic respiratory failure. The published studies on the use of HFNC during the pandemic are reviewed, and ongoing randomized clinical trials are described. Evidence to date finds HFNC (generally 50-60 l/min) to be a valuable and feasible treatment option for patients with COVID-19 pneumonia, with clinical advantages (i.e., it is simple, well tolerated, available outside the ICU, and likely effective at reducing intubations). The current evidence shows that HFNC is no worse than conventional oxygen delivery devices or NIV in terms of dispersion of patient-generated bioaerosols.
      • Investigation of the optimal method of oxygen administration with simultaneous use of a surgical mask: a randomized control study. 9/7/21. Matsui Y. J Anesth.
        In this small (n=24) healthy volunteer study, three methods to deliver supplemental oxygen along with surgical masking were assessed by oxygen reserve index* (ORi) and end-tidal oxygen (EtO2). The goal was to determine the best method to limit aerosol dispersal while transporting patients, using 4 L/M supplemental O2 for consistency. A surgical mask over nasal cannula provided the best results of the 3 methods tested, resulting in an ORi of 0.50 and EtO2 of 33%. The other tested methods were oxygen mask over surgical mask and oxygen mask under surgical mask.
        *SAB Comment: ORi is a relatively new method using multi-wavelength co-oximetry. Incorporated within some pulse oximeters, it provides a noninvasive method to assess changes in the moderately hyperoxic range, (PaO2100-200 mmHg) one within which SpO2 is insensitive. With decreasing PaO2, ORi will decline before SpO2.
      • The use of head helmets to deliver noninvasive ventilatory support: a comprehensive review of technical aspects and clinical findings. 9/9/21. Coppadoro A. Crit Care.
        Helmets have been in use since the early 2000s albeit mostly in a few countries, particularly Italy. Their use has increased with the COVID-19 epidemic. This excellent, brief review notes that helmet therapy can be safely and effectively used to provide NIV (non-invasive ventilation) during hypoxemic respiratory failure, improving oxygenation better than standard oxygen mask treatment and possibly leading to superior patient-centered outcomes than other NIV interfaces. The authors point out issues related to helmet NPPV (non-invasive positive-pressure ventilation) including slow helmet pressurization, reduced CO2 washout and patient–ventilator asynchrony. They state, however, that helmet NPPV is superior to face mask NPPV for patients with ARDS, can be successfully used to treat hypoxemia and is an excellent mode for immunocompromised patients. Helmet NPPV is, however, inferior in patients with COPD exacerbations.

      September 13, 2021

      • Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial. 8/23/21. Ehrmann S. Lancet Respir Med.
        In this multicenter, international, randomized, open-label meta-trial, awake prone positioning (APP) decreased the incidence of intubation in patients with acute severe hypoxemic respiratory failure due to COVID-19 supported with high-flow nasal cannula. From April 2020 through January 2021, 1,121 patients from six countries were randomized to APP as long as possible, or to standard care. The number needed to treat with APP to prevent one intubation was 14. Though not designed to evaluate the duration of APP on outcomes (median daily duration was 5 hours), patients achieving longer durations had better outcomes. Adverse effects were mild, infrequent, and occurred at similar rates between the APP and standard care groups.
        SAB Comment: This is the first large, randomized study of APP, commonly used empirically during the pandemic. The results reinforce the safety and utility of APP for averting intubations. Other randomized studies are underway, as discussed in the accompanying Comment.

      June 28, 2021

      • Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial. 6/15/21. Rosén J. Crit Care.
        In this small, randomized, controlled study from Sweden, the efficacy of awake prone positioning (APP) was evaluated in 75 patients with COVID-19 in moderate to severe respiratory failure. Compared with standard care, implementation of a 16 hour/day protocol for APP increased the duration of prone positioning but did not affect the rate of intubation. The study was halted early due to futility. When secondary outcomes were analyzed, the only difference between groups was a reduction of pressure sores in the APP group.
        SAB Comment: Though small, this is a well-designed prospective and randomized trial of APP in COVID-19 patients and confirms retrospective studies that question the efficacy of APP.
      • Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis. 6/23/21. Verweij PE. Intensive Care Med.
        This is a thorough and lengthy review by an international group of 28 experts prompted by the relatively high incidence of COVID-associated pulmonary aspergillosis (CAPA) seen in severely ill COVID-19 patients. The prevalence of CAPA varied between 0 and 33%. Bronchoscopy and bronchoalveolar lavage (BAL) remain the cornerstone of CAPA diagnosis. Most patients diagnosed with CAPA lack traditional host factors, but pre-existing structural lung disease and immunomodulating therapy may predispose to CAPA risk. Computed tomography seems to be of limited value to rule CAPA in or out, and serum biomarkers are negative in 85% of patients. As the mortality of CAPA is around 50%, antifungal therapy is recommended for BAL-positive patients, while the authors recommend against routinely stopping concomitant corticosteroid or IL-6 blocking therapy in CAPA patients.

      June 14, 2021

      • Closed-Loop Versus Conventional Mechanical Ventilation in COVID-19 ARDS. 6/8/21. Wendel Garcia PD. J Intensive Care Med.
        Closed-Loop (C-Loop) is an automated/autopilot ventilation mode which integrates key patient respiratory parameters into automatic ventilator adjustments that provide a high degree of lung protective ventilation (LPV) and result in a reduced frequency of hypoxemic episodes. This randomized, prospective study compares ventilator support for COVID-19 ARDS patients using either C-Loop (n= 23) or conventional mechanical ventilation (Con-V, n= 17). The C-Loop group showed a statistically significant improvement in the dynamic mechanical power necessary, higher total lung compliance and PF ratio and lowered VD/ VT, PEEP, and Fio2 while maintaining adequate PaO2. This suggests that C-Loop ventilation may decrease the risk of ventilator induced lung injury while reducing the number of necessary human ventilator adjustments. The paper describes an impressive tool with a convincing radar graph for its practical utility but provides limited outcome data.
        SAB Comment: This is a small, futuristic, innovative, and intriguing pilot study of the feasibility of an automated ventilator-adjustment device to better provide lung protective ventilation.
      • The year in review: mechanical ventilation during the first year of the COVID-19 pandemic. 5/7/21. Kallet R. Respiratory Care.
        This thoughtful, well-written, and thorough narrative review of COVID-19 ARDS (C-ARDS) includes 201 references and covers the evolution of best respiratory care practices to date. The overarching question is whether C-ARDS is significantly different from ARDS. Longstanding debates regarding phenotypes and taxonomy are discussed. The evolution of C-ARDS management and physiologic evidence for respiratory care are presented. Topics include phenotypic differences, mechanisms of hypoxia, noninvasive ventilation, timing of intubation, ventilation practices, PEEP, pathologic and radiologic findings, self-inflicted lung injury, lung mechanics, and cross infection. The author concludes that from a respiratory management perspective, C-ARDS differs little from ARDS of other etiologies.

      June 4, 2021

      • Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort. 5/26/21. Wendel Garcia PD. Crit Care.
        Propensity matching was performed on an initial group of 1,421 COVID-19 ARDS patients from the large European RISC-19-ICU cohort resulting in propensity matched patients in cohorts treated initially in the ICU with standard O2 therapy (SOT) (n=85), high-flow oxygen therapy (HFNC) (n=87), non-invasive ventilation (NIV) (n=87) and invasive mechanical ventilation (IMV) (n=92). The ICU intubation rate was lower in patients initially supported with HFNC and NIV compared to those who received SOT. Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). The authors recommend a closely observed trial of HFNC for ICU patients not immediately requiring IMV.
        SAB Comment: This retrospective analysis may best be thought of as a recommendation to perform an RCT to support or challenge these conclusions.

      May 24, 2021

      May 10, 2021

      • A molecular single-cell lung atlas of lethal COVID-19. 4/29/2021. Melms JC. Nature.
        Single-nucleus RNA-sequencing of 19 Covid-19 and 7 control decedents’ lungs was performed after rapid autopsies. Highly inflamed Covid-19 lungs showed activated monocyte-derived macrophages, alveolar macrophages but impaired T cell responses. Monocyte/macrophage-derived IL-1β and epithelial cell-derived IL-6 were unique features of SARS-CoV-2 infection vs other viral/bacterial pneumonias. Transition failure from alveolar type-2 cells to type 1 alveolar cells impaired lung regeneration. They identified expansion of recently described CTHRC1+ pathological fibroblasts contributing to rapid pulmonary fibrosis in COVID-19. This atlas identifies a road map of pathological proteins and cell interactions useful for putative drug targets to disrupt deleterious circuits.

      April 14, 2021

      • Integrative respiratory follow-up of severe COVID-19 reveals common functional and lung imaging sequelae. 4/11/2021. Froidure A. Respir Med.
        Researchers from Belgium evaluated 126 survivors of severe and critical COVID-19 with pulmonary function tests (PFTs), high resolution CT scans (HRCT) and clinical evaluation three months after discharge. At follow-up, 25% of patients complained of dyspnea and 35% of fatigue; lung diffusion capacity (DLCO) was decreased in 45%; 17% had HRCT abnormalities affecting more than 5% of their lung parenchyma while signs of fibrosis were found in 21%. The number of days in ICU were related to the extent of persisting lesions on HRCT, while intubation was associated with signs of fibrosis at follow-up (P = 0.0005). The severity of lung imaging or PFT changes were not predictive of fatigue and dyspnea.

      April 7, 2021

      • Association between pre-existing respiratory disease and its treatment, and severe COVID-19: a population cohort study. 4/4/21. Aveyard P. Lancet Respir Med.
        This retrospective review of medical records from late January through April 2020 of 8,256,161 people registered in 1205 primary care practices in the English NHS showed that people with some respiratory diseases were at an increased risk of hospitalization or death due to COVID-19 compared with those without these diseases with hazard ratios for hospitalization or death respectively as follows: asthma 1·18, 0.99; severe asthma 1·29, 1.08; COPD 1·54, 1.54; bronchiectasis 1·34, 1.12; sarcoidosis 1·36, 1.41; idiopathic pulmonary fibrosis 1·59, 1.47; and lung cancer 2·24, 1.77. The study also provides evidence that the use of inhaled corticosteroids is not associated with a substantially increased risk of severe COVID-19, but nor does it appear to be associated with reduced risk.

      April 2, 2021

      • Functional status of mechanically ventilated COVID-19 survivors at ICU and hospital discharge. 4/1/2021. Musheyev B. J Intensive Care.
        This retrospective single hospital study from New York investigated the functional status of 118 COVID-19 invasive mechanical ventilation (IMV) survivors at ICU and hospital discharge. Mental status, mobility and activities of daily living were assessed near discharge, and showed that half needed discharge oxygen, and most were not functionally independent (22% used cane or walker, 49% needed durable medical equipment, and 14% went to a rehabilitation facility). Worse functional status at hospital discharge was associated with longer IMV duration, older age, male sex and a higher number of comorbidities.
        SAB Comment: This functional status impairment after invasive ventilation with COVID-19 should be compared to that of invasive ventilation from other causes (not detailed in the article).
      • Pulmonary Rehabilitation in Patients Recovering from COVID-19. 3/30/2021. Zampogna E. Respiration.
        This is an observational study reviewing the improvement in 140 previously severely ill hospitalized patients (mean acute care LOS, 47 days; 46% had required mechanical ventilation) who were then admitted to an in-patient pulmonary rehab center. Details of the specific interventions are provided. Patients’ physical status was assessed upon admission to rehab and upon discharge using the Short Physical Performance Battery for lower extremity function, the Barthel Index for general motor function and the six minute walk test. All measures improved for all patients. There was no control group, and rehab LOS average was not noted.

      March 29, 2021

      March 24, 2021

      March 22, 2021

      • Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method. 3/17/21. Nasa P. Crit Care.
        This article discusses the Delphi structured communication process used with 39 international experts, which yielded strong suggestions for use of systemic corticosteroids for critical COVID-19. The suggestions include awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16–24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator desynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end-expiratory pressure titration or the choice of personal protective equipment.

      March 15, 2021

      • COVID-19 Associated Pulmonary Aspergillosis in Mechanically Ventilated Patients. 3/11/2021. Permpalung N. Clin Infect Dis.
        Of 396 mechanically ventilated patients, 39 developed probable or possible COVID-19 associated pulmonary aspergillosis (CAPA). Compared to people without CAPA (controls), people with CAPA had significantly lower median BMI (26.6 vs 29.9, p=0.04), but more underlying pulmonary vascular disorders, which included pulmonary hypertension and chronic pulmonary emboli (41% vs 21.6%, p=0.010), liver disease (35.9% vs 18.2%, p=0.018), coagulopathy (51.3% vs 33.1%, p=0.033), solid tumors (25.6% vs 10.9%, p=0.017), and multiple myeloma (5.1% vs 0.3%, p=0.027). People with CAPA were intubated twice as long as those without, but there was no significant mortality difference between the two groups.
      • Difficult Airway Management in Adult COVID-19 Patients: Statement by the Society of Airway Management. 3/12/2021. Foley LJ. Anesth Analg.
        This statement represents recommendations by the Society for Airway Management task force for the difficult airway management of adults with COVID-19 with the goal to optimize successful airway management while minimizing the risk of clinician exposure. Extensive discussion of almost all aspects of difficult intubations is summarized by three pages of tables, which outline, among other things, an emphasis on preparedness, proper PPE, awake intubation, extubation, equipment and drugs.
      • Severe covid-19 pneumonia: pathogenesis and clinical management. 3/11/21. Attaway AH. BMJ.
        The authors reviewed COVID-19 publications from 1/2020 to 2/2021 and collated the conclusions into a succinct review of major topics descriptive of the disease and its treatment. Concise overviews by topic include mechanism of infection, immunology, pulmonary injury, treatment, outcomes, etc. A table summarizes results of 27 studies regarding respiratory support including high flow nasal cannula, non-invasive ventilation, and invasive mechanical ventilation. Long-term morbidity is also discussed.

      March 12, 2021

      • Transpulmonary pressure measurements and lung mechanics in patients with early ARDS and SARS-CoV-2. 3/7/21. Baedorf Kassis E. J Crit Care.
        To further explore respiratory mechanics in COVID-ARDS, this cohort study from Boston analyzed 40 ventilated patients with chest wall and transpulmonary pressures measured using esophageal pressure monitoring. Lung and respiratory system compliance varied widely over the entire cohort. Elevated basal pleural pressures correlated with increased BMI. Respiratory system and lung mechanics were similar to known existing ARDS cohorts. The wide range of respiratory system mechanics illustrates the inherent heterogeneity that is consistent with typical and COVID-19 ARDS. This information reinforces the practice of treating patients individually, rather than trying to treat with general algorithms.
        SAB Comment: Esophageal pressure monitoring, not usually part of routine ventilator care, provides an indirect measurement of intrapleural pressure, which allows one to determine the compliance/elastance of the chest wall separately from transpulmonary pressure.

      February 26, 2021

      • Intracerebral Hemorrhage in COVID-19 Patients with Pulmonary Failure: A Propensity Score-Matched Registry Study. 2/23/21. Lang CN. Neurocrit Care.
        Some reassurance comes from this retrospective study of all patients 18 years old and older admitted to a tertiary care hospital from 2018 to May 2020 comparing the incidence of intracerebral hemorrhage (ICH) between COVID-19 and non-COVID-19 ARDS patients. The authors found that the 19% incidence of ICH in the 47 COVID-19 ARDS patients was not significantly higher than the 11% incidence in the 116 non-COVID-19 ARDS patients despite higher rates of therapeutic anticoagulation and antiplatelet therapy in the COVID-19 patients.
      • The Pathophysiology and Dangers of Silent Hypoxemia in COVID-19 Lung Injury. 2/23/21. Swenson KE. Ann Am Thorac Soc.
        COVID-19 patients who develop minimally symptomatic hypoxemia are at risk for rapid decompensation, but the pathophysiology of silent hypoxemia in COVID-19 lung injury remains inadequately explained. This review describes the mechanisms, either viral-induced or within the broad normal range of hypoxic sensitivity in the lung and nervous system in healthy people, which could lead to profound hypoxemia without apparent dyspnea, based on what is currently known about SARS-CoV-2 and normal respiratory physiology and pathophysiology in other forms of ARDS. Three aspects are addressed: differences in lung compliance, pulmonary vascular responses to hypoxia, and nervous system sensing and response to hypoxemia. All could be inextricably linked to the phenomenon of silent hypoxemia.

      February 19, 2021

      • Medium-term impact of COVID-19 on pulmonary function, functional capacity and quality of life. 2/12/2021. Anastasio F. Eur Respir J.
        After a median of 135 days, 260 (68.6%) of 379 patients had on average one persistent symptom. Patients who developed pneumonia during COVID-19 showed lower SpO2 at rest (p<0.001), SpO2 during 6-min walking test (p<0.001), total lung capacity (p<0.001), airway occlusion pressure after 0.1 s [P0.1] (p=0.02), P0.1/maximal inspiratory pressure [MIP] ratio (p=0.005) and higher Borg category-ratio scale (p=0.006) and modified Medical Research Council breathlessness scale (p=0.003), compared to patients without pneumonia. SpO2/FiO2 ratio and pneumonia severity index during SARS-COV-2 pneumonia were directly associated with mid-term alteration of partial oxygen saturation at rest (p<0.001), SpO2 during 6-min walking test (p<0.001), residual volume (p<0.001), total lung capacity (respectively p<0.001 and p=0.003) and forced vital capacity (respectively p=0.004, p=0.03).
      • Static compliance of the respiratory system in COVID-19 related ARDS: an international multicenter study. 2/9/21. Vandenbunder B. Crit Care.
        This multicenter, prospective observational study in 21 ICUs in France and Belgium in early Spring compared respiratory mechanics in 372 ventilated COVID-19 patients on Day 1 and Day 14 (when possible) in an effort to predict outcome at 28 days. The mean respiratory system compliance (Crs) on day 1 was 38 +/- 13 ml/cmH2O, with a monomodal distribution, similar to ARDS of other causes. Crs decreased between Day 1 to Day 14 but the decrease was not associated with Day 28 outcome. Higher compliance values on Day 1 were not associated with faster weaning of mechanical ventilation nor with improved survival.
        SAB Comment: Despite reporting a median compliance of 38 ml/cm H2O, we treat individuals according to their own specific physiology that may not reflect the median. As recommended in multiple guidelines, respiratory therapy should be tailored at an individual level.

      February 12, 2021

      February 3, 2021

      • Association of Serum Mannose With Acute Respiratory Distress Syndrome Risk and Survival. 1/27/2021. Wei Y. JAMA Netw Open.
        This two-phase study initially used Mendelian randomization to analyze gene variations in an historical population of 1630 ICU patients at risk for ARDS and found that genes for high mannose level were associated with a lower risk for, and better outcome from, ARDS. They used that outcome to then compare risk and outcomes in a different population of 83 patients with ARDS and 83 matched at-risk patients in the ICU without ARDS and found a protective association of higher mannose levels with a reduction of ARDS risk (OR, 0.67) and, within the ARDS group, a lower 60-day mortality (OR, 0.36). The authors note that these findings could inform prevention and clinical intervention in ARDS.

      February 1, 2021

      • Occurrence of Invasive Pulmonary Fungal Infections in Severe COVID-19 Patients Admitted to the ICU. 1/22/21. Fekkar A. Am J Respir Crit Care Med.
        A careful clinical review of 145 severely ill (72 on ECMO), intubated COVID-19 patients in March and April 2020 where suspicion of ventilator acquired pneumonia led to evaluation for invasive fungal infection. 475 respiratory samples were submitted to direct examination/culture, galactomannan index determination, and PCR targeting. In addition, 532 sera were tested for galactomannan, beta-D-glucan, and/or A. fumigatus PCR. Only 4.8% of these patients were felt to have invasive fungal disease while another 17.2% were considered to have clinically irrelevant colonization. Most were not being treated with steroids. Patients on long-term high-dose steroids and recipients of solid organ transplants were at highest risk.
      • Residual symptoms and lower lung function in patients recovering from SARS-CoV-2 infection. 1/22/21. Trinkmann F. Eur Respir J.
        This is a study of persistent symptoms and PFT abnormalities 2 months after PCR-proven infection in 246 consecutive initially symptomatic patients (median age 48). Only 9% required hospital admission or received specific therapy, and only 2 of the 22 hospitalized patients required ICU treatment. However, at follow up, 46% still had 1-3 symptoms, particularly those initially more symptomatic. Symptom frequencies at presentation vs. 2 month follow-up were olfactory loss (66% vs. 4%), cough (65% vs 14%), fever (59% vs <1%), dyspnea (31% vs 32%), sore throat (26% vs <1%), rhinitis (25% vs 1%), headache (16% vs <1%), and fatigue (6% vs 1%). Mild spirometry and DLCO reductions were found in persistently symptomatic patients.

      January 19, 2021

      • Lung ultrasound score predicts outcomes in COVID-19 patients admitted to the emergency department. 1/11/21. de Alencar JCG. Ann Intensive Care.
        Lung ultrasound (LUS) was performed in the emergency department (ED) on 180 patients who were PCR positive for COVID-19. The protocol involved the examination of 12 lung regions, was performed at bedside by experienced ED physicians, and typically required five minutes. LUS scores correlated with findings from chest commuted tomography (CT) (when performed) and predicted the estimated extent of parenchymal involvement, death, endotracheal intubation, and ICU admission. The authors believe that LUS is more sensitive than chest radiography, requires less resource and infection risk than CT, and could be used as an effective evaluation tool, particularly in resource-constrained settings.
      • Ventilator-associated pneumonia in critically ill patients with COVID-19. 1/12/21. Maes M. Crit Care.
        This retrospective observational study from the UK studied ventilator-associated pneumonia (VAP) in mechanically ventilated COVID-19 (n=81) and non-COVID-19 (n=144) patients at a single hospital. All patients were studied between March and August 2020, and VAP was defined by the European Center for Disease Control using clinical and microbiological criteria. COVID-19 was associated with an increased risk of VAP (28 per 1,000 ventilator days) compared with non-COVID-19 patients (13 per 1,000 ventilator days). Although the distribution of organisms causing VAP was similar between the two groups, aspergillosis was only found in COVID-19 patients (n=3, none on steroids), though one patient without COVID-19 was borderline positive and met clinical criteria.

      January 15, 2021

      January 6, 2021

      December 16, 2020

      • Feasibility and Safety of Prone Position Transport for Severe Hypoxemic Respiratory Failure Due to Coronavirus Disease 2019. 12/9/20. Seethala RR. Crit Care Explor.
        This is a retrospective review of 25 COVID-19 patients, transported and ventilated while prone from outlying hospitals to tertiary medical centers in Boston. Using ground transportation with a median transport time of 38 minutes, and specially trained nurse and paramedic critical care teams, this transport agency developed a protocol to transport prone patients. These patients were quite sick, with a median intubation duration of 5 days before transport. The condition of the patients, the protocols, and events during transport are carefully documented. All patients successfully arrived at their destination. This study provides evidence that when carefully implemented, prone transport may be safe and facilitate otherwise impossible transfers for potentially life-saving tertiary care.

      December 11, 2020

      • Controversies in airway management of COVID-19 patients: updated information and international expert consensus recommendations. 12/1/20. Wei H. Br J Anaesth.
        This editorial by a panel of international experts summarizes the COVID-19 airway management literature on the effectiveness of personal protective equipment (PPE), transmission of the virus during high flow nasal oxygen therapy (HFNO), and the debate over early vs. late intubation. Tables nicely summarize the examined literature. Their consensus includes:
        • The higher the PPE level, the better the protection.
        • There is no convincing evidence that HFNO increases the risk of COVID-19 cross-infection to healthcare workers.
        • Timing of intubation will depend upon individual pathophysiology, the trajectory of the illness, and the response to trials of noninvasive airway management.
        • More study is needed.

      December 7, 2020

      December 2, 2020

      • Veno-venous extracorporeal membrane oxygenation allocation in the COVID-19 pandemic. 11/21/20. Murugappan KR. J Crit Care.
        This is a well-researched and referenced discussion regarding appropriate allocation and utilization of VV-ECMO based on institutional practice. It includes ethical, practical and decision-maker considerations as well as preemptive end-of-life care discussions in severe cases. It introduces the concept of a “bridge to nowhere,” i.e., when the decision to prolong life mechanically has no future alternative/resolution. The article discusses the importance of clear communication between the health care team and patient/family consortium. It highlights the importance of clear understanding of ethical and practical implications of initiation and utilization of a scarce resource.

      November 30, 2020

      • SARS-CoV-2 has displaced other seasonal respiratory viruses: results from a prospective cohort study. 11/15/20. Poole S. J Infect.
        This is a study performed in a county in South East England on the English Channel coast of viral PCR results of tests done from March through May on patients with respiratory symptoms in the emergency department or acute care ward in most of years from 2015 through 2020. Before 2020, a non-SARS-CoV-2 virus was detected in 54% patients (202/371) compared to only 4.1% (20/485) in 2020. SARS-CoV-2 was associated with asthma or COPD exacerbations in a smaller proportion of infected patients compared to other viruses (1.0% vs 37%).

      November 23, 2020

      • Diaphragm Pathology in Critically Ill Patients With COVID-19 and Postmortem Findings From 3 Medical Centers. 11/16/20. Zhonghua S. JAMA Internal Med.
        This research letter describes evaluation of autopsy specimens of diaphragm muscle obtained from 26 consecutive deceased COVID-19 patients, 24 of whom had been on mechanical ventilation for a mean of 12 days. Specimens from 8 deceased non-COVID-19 patients mechanically ventilated for a similar amount of time were used as a control group. ACE-2 receptors were present on diaphragm myofiber membranes in all patients. Viral RNA was found in the myofibers of 4 of the 26 COVID-19 patients. Significantly more fibrosis was present in the diaphragms of the deceased COVID-19 patients than in the diaphragms of the control patients predicting more diaphragmatic weakness in the COVID-19 patients.

      November 16, 2020

      • Analgesia and sedation in patients with ARDS. 11/10/2020. Chanques G. Intensive Care Med.
        A “state of the art“ narrative review by an international panel of experts written to support clinicians in their management of ARDS patients. Proper ventilator settings, followed by analgesia, then sedation, then neuromuscular blockers form the heart of suggested approaches to analgesia and sedation. Separate sections address ARDS and COVID-ARDS, and several flow diagrams suggest various treatments. An “ABCDEF-R” approach is suggested.
      • Current and evolving standards of care for patients with ARDS. 11/6/20. Menk M. Intensive Care Med.
        Written by an international group of experts, this narrative review is a succinct and up-to-date review of caring for ARDS and COVID-ARDS patients, and is very useful for a frontline worker wanting a broad overview. It briefly explains the studies that establish the current standards and discusses therapies of promising interest (evolving standards). Nicely summarized in a table and discussed in the text are: ventilatory management (tidal volume, PEEP, driving pressure, mechanical power, etc.), ventilation adjuncts (proning, neuromuscular blockade, ECMO, etc.) and pharmacotherapy (steroids, fluid therapy, etc.).
      • Prone position in ARDS patients: why, when, how and for whom. 11/10/20. Guérin C. Intensive Care Med.
        This is a thorough and excellent review of the use of prone position in ARDS including a detailed explanation of its effects on pulmonary physiology, gas exchange and hemodynamics. The significant benefits in mortality are discussed. As noted in many studies, the improvement in mortality does not correlate with the degree of oxygenation improvement but appears more likely to be related to a decrease in ventilator-induced lung injury. Specific recommendations and cautions for practical application are provided. The use of prone positioning in spontaneously breathing, non-intubated patients is commonly used with COVID-19, and studies are planned to verify if this strategy can reduce the rate of intubation and improve survival.

      November 9, 2020

      • Combining lung ultrasound and Wells score for diagnosing pulmonary embolism in critically ill COVID-19 patients. 11/4/20. Zotzmann V. J Thromb Thrombolysis.
        This article presents the results of a retrospective evaluation of 20 ICU COVID-19 patients who had all undergone CT pulmonary angiography and lung ultrasound for suspected pulmonary emboli in a tertiary referral ARDS/ECMO center. The study showed that subpleural consolidations ≥ 1cm detected in lung ultrasound were found frequently in COVID-19 ARDS patients with pulmonary embolism. By combining a Wells score ≥ 2 and a lung ultrasound showing subpleural consolidations, PE could be predicted with a sensitivity of 100% and a specificity of 80% in these 20 patients, 12 of whom were found to have pulmonary emboli by CT pulmonary angiography.

      October 28, 2020

      • What have we learned ventilating COVID 19 patients? 10/12/20. Trahtemberg U. Intensive Care Med.
        These leaders in ARDS research provide a crisp review of ventilatory management of COVID-19-induced ARDS (CARDS), based on the underlying pathophysiology and contend that the similarities in the spectrum of CARDS versus that of non-COVID ARDS outweigh the differences. They find a paucity of data exists to justify early intubation. They favor lung protective ventilation for all patients, and they argue for prone positioning for patients with moderate-to-severe ARDS (PaO2/FiO2 ratio < 150 mmHg). In summary they write, “ventilatory management of patients with COVID-19 ARDS should be similar to that for other causes of ARDS, tailored to the specific patient.”

      October 26, 2020

      • Physiological and quantitative CT-scan characterization of COVID-19 and typical ARDS: a matched cohort study. 10/21/20. Chiumello D. Intensive Care Med.
        This detailed Italian physiologic study compared 32 COVID-19 ARDS (CARDS) patients with two other matched historical groups of typical ARDS patients; one matched with the CARDS patients by SpO2/FiO2, and one matched by respiratory compliance. As noted previously by this group (but not some studies by other groups), they found CARDS patients to have higher compliance than the group of non-COVID ARDS patients who were matched for SpO2/FiO2. They also found the CARDS patients had lower SpO2/FiO2 than non-COVID ARDS patients who were matched for compliance. Increasing PEEP from 5 to 15 improved oxygenation in CARDS patients but did not improve respiratory mechanics or CO2 clearance as usually seen in ARDS. These authors continue to recommend low PEEP and low driving pressure in early CARDS.

      October 19, 2020

      October 9, 2020

      October 7, 2020

      October 2, 2020

      September 23, 2020

      September 14, 2020

      September 2, 2020

      • Respiratory physiology of COVID-19-induced respiratory failure compared to ARDS of other etiologies. 8/28/20. Grieco DL. Crit Care.
        This article provides a detailed comparison of the respiratory mechanics of 30 COVID-19 ARDS patients measured within 24 hours of initial intubation with 30 non-COVID matching ARDS patients based on PaO2/FiO2, FiO2, PEEP, and tidal volume. The average compliance and ventilatory ratio were slightly higher in COVID-19 patients. Inter-individual variability of compliance was similar in both groups. In COVID-19 patients, PaO2/FiO2 was linearly correlated with respiratory system compliance. High PEEP improved PaO2/FiO2 in both cohorts, but more remarkably in COVID-19 patients. Recruitability was not different between cohorts. The authors conclude that overall the respiratory mechanics were similar in the two groups but were marked by prominent intra-group variability in both.

      August 31, 2020

      August 25, 2020

      August 19, 2020

      August 12, 2020

      August 10, 2020

      August 5, 2020

      July 27, 2020

      • Pulmonary embolism in hospitalised patients with COVID-19. 7/10/20. Whyte MB. Thromb Res.
        A single center retrospective review of the results of 214 computer tomography pulmonary angiography studies performed on hospitalized Covid-19 patients with suspected pulmonary emboli. 31% of studies were positive for pulmonary emboli which represents 5.4% of all patients admitted during the study’s time interval. Elevated Wells score greater or equal to 4 did not predict results. Median D-dimer was 8000 ng/ml for patients with a positive study versus 2060 ng/ml for patients with a negative study, but low D-dimer had limited utility excluding patients with pulmonary emboli.

      July 24, 2020

      • Personalized Ventilation to Multiple Patients Using a Single Ventilator: Description and Proof of Concept. 7/17/20. Han JS. Crit Care Explor.
        A proof of concept: the authors used components readily available in their hospital to assemble two “bag-in-a-box” breathing circuits. This shared ventilator function is proposed as a “last ditch” ventilatory assist device and not as a preferred ventilation mode. In a time of crisis where resources are limited, they introduced a system of multiple secondary breathing circuits driven by a ventilator in preference to that of simply splitting the breathing circuits. The authors hope, though, that this will not be needed. But these were all test conditions, not actually used on a patient.
      • The role of chest radiography in confirming Covid-19 pneumonia. 7/18/2020. Cleverley J. BMJ.
        An introductory summary of chest X-ray findings in COVID-19 pneumonia for the non-radiologist. Characteristic findings are illustrated however none is diagnostic. Studies show that X-ray imaging may initially appear normal or lag behind disease progression. Chest CT has been shown to be more sensitive however its initial use varies among countries. Includes no mention of chest ultrasound.

      July 21, 2020

      July 20, 2020

      July 13, 2020

      July 10, 2020

      • Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion. 6/22/20. Verweij PE. Intensive Care Med.
        Review by the SAB
        Although the number of COVID-19-associated aspergillosis (CAPA) cases that have been reported is a small number, in two series, similarities and differences with Influenza with Invasive Aspergillosis (IAP) and COVID-19 are pointed out. Here a group of authors (EU, USA and Taiwan) are seeking to change the definition of IAP (inclusive of clinical and radiological signs). They make a point that an under-estimation of IAP requires a need for vigilance for IAP in the ICU, an early diagnosis, holding steroids, judicious use of antiviral to avoid a fatal outcome due to an IAP patient in comparison to Influenza with IAP.
        For CAPA:
        • 85% host factors are -ve but Lymphopenia/monocyte hyperimmune response is present
        • IPA tracheobronchitis is not known
        • The entry point ACE 2 – anti-fungal immunomodulation by antifungal not likely?
        • Serum GM + ve – need a study in COVID-19 to understand the implication.
        • No specificity of secondary infection organism types.

      July 8, 2020

      July 6, 2020

      June 8, 2020

      June 4, 2020

      June 3, 2020

      • ICU and Ventilator Mortality Among Critically Ill Adults With Coronavirus Disease 2019
        May 26. Auld SC. Critical Care Medicine.
        Opinion from SAB Member: Dr. Philip Lumb, Dr. Jagdip Shah
        PL: Results of an observational cohort study of 217 patients admitted to Emory Healthcare System ICUs between March 6th and April 17th with RT-PCR confirmed COVID-19 disease, 165 of whom required invasive ventilation with a reported mortality rate of 33.9% (56/165) and a hospital mortality of 35.7%. Patient demographics, other supportive therapies (ECMO, RRT, Etc.), laboratory values and pulmonary characteristics well described with clear delineation between survivors and non-survivors. Authors discuss ICU preparation and pre-peak awareness as characteristics promoting more favorable outcomes than previously reported under surge conditions.
        JS: Authors form Emory conducted a retrospective cohort study of critically ill patients with COVID-19 in 6 designated ICUs which were adequately staffed and stocked. 217 patients were admitted to the ICU and 165 were treated with mechanical ventilation in the ICU. A total of 59 died (in the ICU or in hospital) and 88 were discharged out of the hospital. Statistically significant baseline parameters associated with non-survivors were: age > 75, BMI > 40, pre-existing chronic kidney disease. The ICU parameters associated with non-survival were: SOFA score on the day of admission > 7, rise of d Dimer > 1600 ng/dl, C-reactive protein > 183, PaO2:FiO2 < 144, use of mechanical ventilation, use of vasopressors, use of continuous renal replacement therapy, and hospital stay > 11 days. The authors claim that timely start of mechanical ventilation with lung protective strategy likely improves the outcome (the overall mortality in this study was 31%).
      • Respiratory Mechanics of COVID-19 vs. Non-COVID-19 Associated Acute Respiratory Distress Syndrome
        Apr 20. Haudebourg AF. American Journal of Respiratory and Critical Care Medicine.
        Opinion from SAB Member: Dr. Robert L. Coffey
        A prospective, observational study comparing the respiratory mechanics and lung recruitability of 30 consecutive COVID-19 ARDS patients and 30 consecutive non-COVID-19 ARDS patients of similar severity. In contrast to other reports, compliance, while ranging widely, was similar in the two groups and did not appear to worsen in COVID patients over the 15 days after their initial symptoms. The lung recruitment measure (R/I ratio) was significantly higher in the COVID-19 ARDS patients. The authors could not discern subgroup phenotypes within these 30 COVID pneumonia patients.

      May 27, 2020

      • A proposed lung ultrasound and phenotypic algorithm for the care of COVID-19 patients with acute respiratory failure
        May 21. Denault. Canadian Journal of Anesthesia/Journal canadien d’anesthésie.
        Opinion from SAB Member: Dr. Robert L. Coffey
        This is an opinion piece from a group of physicians in Quebec based on a literature review and patient care experience that recommends the use of lung ultrasound and the previously validated ROX index [(SpO2/FiO2)/RR] to better distinguish between the proposed Type L and Type H COVID-19 pneumonia phenotypes. A guide to differentiated ventilator support strategies is offered, but no patient outcome data is presented. While the concepts are interesting and bedside lung ultrasound offers a low risk imaging technique, it is not clear to me that the ventilator strategies suggested differ significantly from standard high quality lung protective ARDS care.
      • Distinct phenotypes require distinct respiratory management strategies in severe COVID-19. May 11. Robba. Respir Physiol Neurobiol.
        An opinion piece from Italian physicians based on a literature review and their extensive experience caring for patients with Covid-19 pneumonia. They recommend classifying patients into three phenotypes based on CT scan results (1. Focal ground glass opacities, 2. Atelectasis and peribronchial opacities, 3. Patchy ARDS-like pattern) and provide recommendations for specific support strategies according to the physiology typically associated with each of these CT scan types. Since no patient outcome data is presented, it’s not clear that their strategies are superior to others, and they themselves state that these “might” guide therapy and ventilator settings.
      • 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.”

      May 22, 2020

      • Continuous positive airway pressure to avoid intubation in SARS-CoV-2 pneumonia: a two-period retrospective case-control study. May 19. Oranger. Eur Respir J.
        The use of CPAP has been controversial with COVID-19 respiratory failure. This retrospective, case control research letter/study from France of 66 patients casts some light on this controversy. Two periods of time, one with and the other without CPAP, were analyzed for intubation rate in similar COVID-19 patients in a dedicated pulmonary unit. In the non-CPAP period, 6 intubations and two deaths occurred by day 7 (57%), and in the CPAP period, 9 intubations and no deaths occurred by day 7 (23%). No CPAP patients crashed requiring emergency intubation, and acquisition of COVID-19 by HCW was similar during the two time periods.
      • Factors Associated With Intubation and Prolonged Intubation in Hospitalized Patients With COVID-19
        May 19. Kur. Otolaryngology–Head and Neck Surgery.
        Opinion from SAB Member: Dr. David M. Clement
        A retrospective, observational study from Chicago of 486 adult inpatients with COVID-19 that is nicely written and provides a wealth of clinical data. The focus of the study was on demographics and risk factors associated with intubation and time to extubation. 28% (138) of patients were intubated and of those, 56% were extubated, 15% died and 28% were still intubated. Age, male sex and a history of diabetes were independent risk factors associated with intubation. Age and BMI>30 predicted a longer time to extubation. Among the data are some interesting findings, such as 1/3 of patients were intubated in the ED, SpO2 was below 90 in 12% of non-intubated patients, only one non-intubated patient died, and 4% were treated with ECMO. There are limitations acknowledged (e.g. criteria for intubation), but overall the study provides a useful window into a COVID-19 surge. We feel this paper pairs nicely with a previous paper reviewed by the SAB that covered the timing and indications for tracheostomy Tracheostomy in the COVID-19 era: global and multidisciplinary guidance.
      • 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.

      May 16, 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 that demonstrates interesting observations regarding prone positioning despite small sample sizes, lack of controls and limited outcome benefits in clinical studies. Taken in context of related case studies, this editorial stimulates discussion and further clinical trials.
      • Elective Tracheostomy During Mechanical Ventilation in Patients Affected by COVID-19: Preliminary Case Series From Lombardy, Italy. May 12. Turri-Zanoni. Otolaryngol Head Neck Surg.
        Most interesting statement in paper: “early recommendations worldwide seem to suggest waiting at least 14 days of endotracheal intubation to avoid clinically futile procedures for patients…” Remainder is common sense infectious disease protection.
      • Potential for Lung Recruitment and Ventilation-Perfusion Mismatch in Patients With the Acute Respiratory Distress Syndrome From Coronavirus Disease 2019
        Apr 28. Mauri. Critical Care Medicine.
        Opinion from SAB Member: Dr. Louis McNabb
        In this article, ventilated patients with COVID-19 were given PEEPs of 5 and 15 cmH2O. The degree of lung recruitment was variable among the participants and most of the V/Q mismatch was attributed to increased dead space ventilation.
        • Dealing With the CARDS of COVID-19
          May 13. Marini. Critical Care Medicine.
          Opinion from SAB Member: Dr. Louis McNabb
          This is an editorial response to above article that describes different phases of COVID-19 lung involvement, which require different ventilator strategies. The author describes the potential pathophysiologic causes of V/Q mismatch.
      • Respiratory 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.”
      • Use of Prone Positioning in Nonintubated Patients With COVID-19 and Hypoxemic Acute Respiratory Failure
        May 15. Elharrar. JAMA.
        Opinion from SAB Member: Dr. Philip Lumb
        This research letter includes 24 patients entered into a spontaneous breathing prone positioning trial. Reported outcomes: 1) ability to tolerate position for specified and increasing times; 2) PaO2 increase in prone position (PP); 3) sustained PaO2 increase on resupination; 4) progression of disease. The article notes that of 5 patients requiring intubation, 4 did not tolerate prone position for > 1 hour. Out of 24 patients, 15 (63%) tolerated PP > 3 hours, oxygenation increased in 6 (25%), and sustained following resupination in 3 (12%). As authors note, the study had several limitations–the sample was small, a single episode of PP was evaluated, the follow-up was short, clinical outcomes were not assessed, and causality of the observed changes cannot be inferred.

      May 15, 2020

      • 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.
      • 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.
      • 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.
      • Subphenotyping ARDS in COVID-19 Patients: Consequences for Ventilator Management
        May 12. Bos. Annals of the American Thoracic Society.
        Opinion from SAB Member: Dr. J. Lance Lichtor
        As the authors note, there are phenotypes that can be used as a basis to treat patients with ARDS. For example, patients with focal lung pathology respond better for ventilation to prone positioning, though their lungs are not as recruitable. The authors in a retrospective sequential analysis of 70 patients in The Netherlands tried to see if the same was true in patients with COVID-19 and found that that was not the case.

      May 12, 2020

      • Nonsedation or Light Sedation in Critically Ill, Mechanically Ventilated Patients. Mar 19. Olsen. NEJM.
        The study involves 710 patients from 7 ICUs of 3 Scandinavian countries from 2014 – 2017. Randomized, retrospective, propensity score match (several exclusion) for ventilated patients with light sedation and no sedation. The sedation protocol involves Propofol, midazolam, M, clonidine (not dex.) …. The characteristics of the patients at baseline were similar in the two trial groups, except for the score on the Acute Physiology and Chronic Health Evaluation (APACHE) II, which was 1 point higher in the nonsedation group (RASS -1.3 to – 2.3). The difference of Delirium 1 day less, Thrombotic event 2.5%, Primary outcome 90 days mortality – sedation group lower than nonsedation ? Secondary: 1 day less of delirium, Thrombotic event 2.5% higher and Mech. Vent – one day less in nonsedation group. Most other were no different or statistically not significant.

      May 11, 2020

      May 7, 2020

      • 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.”

      May 6, 2020

      May 5, 2020

      May 1, 2020

      April 29, 2020

      • COVID-19 Associated Pulmonary Aspergillosis. Apr 27. Koehler. Mycoses.
        The authors performed a chart review of patients in 2 separate ICUS with COVID-19 and acute respiratory distress syndrome and noted that in 5/19 patients, with moderate to severe acute respiratory distress syndrome without underlying immunocompromising disease, they had invasive pulmonary aspergillosis. Whether this represented invasive disease or colonization is not clear.

      April 28, 2020

      • 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.
      • 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).

      April 25, 2020

      • Acute Pulmonary Embolism Associated with COVID-19 Pneumonia Detected by Pulmonary CT Angiography. Apr 24. Grillet. Radiology.
        Retrospective study of patients that received contrast CT’s of chest. 23 of 100 positive for PE. Patients with PE tended to be sicker and more likely on ventilators. No data on treatment of PTS with PE or their outcome.
      • Acute Pulmonary Embolism in COVID-19 Patients on CT Angiography and Relationship to D-Dimer Levels
        Apr 23. Leonard-Lorant. Radiology.
        Opinion from SAB Member: Dr. Philip Lumb, Dr. Louis McNabb
        PL: Reports 32/106 (30% [95%CI 22-40%]) COVID-19 positive patients were diagnosed positive for acute PE on pulmonary CT angiography between March 1st and March 31st. Noted in this series incidence correlated with increased D-dimer levels; sensitivity 32/32 positive PE with D-dimer >2660 mcg/L (100% [95%CI 88-100]) with a specificity of 49/74 (67% [95%cI 52-79]) on CT angiography. Authors confirm higher incidence of PE in COVID-19 patients with elevated D-dimer, suggested secondary to COVID induced activation of blood coagulation secondary to systemic inflammatory response and recommend increased awareness of and surveillance for PE complications. LM: The results of this article give a theoretical basis for routine use of full dose anticoagulation in COVID-19 patients. The efficacy of such a practice should be explored in controlled studies with prophylactic anticoagulation as a comparator.

      April 24, 2020

      April 22, 2020

      • Planning and provision of ECMO services for severe ARDS during the COVID-19 pandemic and other outbreaks of emerging infectious diseases. Mar 20.
        Jay: In essence, the original article described ensuring ECMO services around the world meet the guidelines as listed for service development but did not go into direct patient care, ie. pump flow rates or patient determinants of success, labs and vital signs. The first LOE enters the discussion of a single measurement of patient success, HGB levels. Still left out of the discussion is actual scientifically derived recommendations on the entire process of patient management…Lancet Respir Med…
        An article by an international authorship neither a LOE or research article, rather a “how to” recommendation for the world to implement ECMO when needed. Discusses in depth the team, equipment and patient transfer, but does not list recommendations of patient management.

      April 21, 2020

      April 20, 2020

      April 16, 2020

      April 15, 2020

      April 14, 2020

      • 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.

      April 11, 2020

      April 10, 2020

      April 8, 2020

      • Extracorporeal membrane oxygenation (ECMO): does it have a role in the treatment of severe COVID-19? Apr 7. Hong. Int J Infect Dis.
        This article reviews success in decreasing mortality with ECMO in ARDS, SARS and MERS. However, data that ECMO reduces mortality in Covid-19 is lacking at this time. Also, ECMO will not be available at every location where it may be needed.
      • 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.

      April 6, 2020

      April 5, 2020

      April 4, 2020

      March 31, 2020

      March 20, 2020

      March 16, 2020

      March 2020

      February 12, 2020

    1. Cardiovascular / Hemodynamic Management
      Updated Frequently

      December 20, 2021

      • Bleeding Complications in Patients With Perioperative COVID-19 Infection Undergoing Cardiac Surgery: A Single-Center Matched Case-Control Study. 12/15/21. Chiariello GA. J Cardiothorac Vasc Anesth.
        The purpose of this study was to investigate a possible significant correlation between perioperative COVID-19 infection and hemorrhagic complications compared to non-COVID-19 patients who underwent on-pump, open-heart cardiac surgery from February 2020 to March 2021. Among them, 23 consecutive patients had perioperative diagnoses of COVID-19 infection (study group). These patients were compared with 46 corresponding matched controls (control group). The study group demonstrated markedly higher bleeding complications in the short and long term. In the study group, patients showed a significantly higher incidence of bleeding complications (48% v 2%, p = 0.0001) and cases of surgical reexploration for bleeding (35% v 2%, p = 0.0001), a higher incidence of severe postoperative thrombocytopenia (39% v 6%, p = 0.0007), and a higher need of blood components transfusions (74% v 30%, p = 0.0006). Chest tubes blood loss and surgical hemostasis time were markedly prolonged (p = 0.02 and p = 0.003, respectively).
        SAB Comment: These data have implications for CT surgeons, CT anesthesia and intensivists but may also possibly be worth noting for other surgical teams.
      • Incidence of venous thromboembolic events in COVID-19 patients after hospital discharge: A systematic review and meta-analysis. 12/13/2021. Zuin M. Thromb Res.
        This systematic review and meta-analysis reviews the incidence of venous thromboembolism (VTE) after hospital discharge with COVID-19 patients. The 11 papers meeting inclusion criteria included 18,949 patients. The mean length of follow-up was 61.7 days (range 21-180 days). The cumulative post-discharge rate of VTE in COVID-19 patients ranged between 0.2 and 14.8 with a pooled incidence of post COVID-19 VTE in 1.8% of cases. The incidence of VTE events was directly affected by age (p = 0.03) and male gender (p = 0.04) and inversely correlated with the length of follow-up period (p = 0.012). Conversely, no associations were identified with cancer (p = 0.14), VTE history (p = 0.82), ICU admission (p = 0.55) and mean length of hospitalization (p = 0.68).
        SAB Comment: These data are derived from multiple studies with varying periods of follow up and methods of detecting VTE with a wide heterogeneity in the incidence of VTE. Nevertheless, this systematic review does summarize the existing data well.
      • Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection. 12/15/2021. Patone M. Nat Med.
        An exhaustive review from the United Kingdom discussing cardiac complications of myocarditis, pericarditis and arrhythmias after COVID-19 SARS-CoV-2 mRNA immunizations. The data is evaluated by the cardiac cause of death, age, sex and numerous other contributing factors. Overall the statistics demonstrate the risk of death from vaccination related cardiac complications was rare, 1574 fatalities in 32,095,748 recipients who received two doses of immunization.

      December 6, 2021

      November 8, 2021

      October 18, 2021

      • Platelets Contribute to Disease Severity in COVID-19. 9/19/21. Barrett TJ. J Thromb Haemost.
        Platelet count and mean volume (MPV) were reviewed retrospectively in 3915 COVID-19 positive patients from March to June 2020. Immature platelet fraction (IPF) was followed in an additional 427 patients. Low platelet count, immaturity, and large size were associated with increased severity of disease and mortality. Additionally, autopsy specimens were obtained, and platelet RNA sequencing was carried out in 8 patients. Interestingly, there was evidence of replicating SARS-CoV-2 within a lung megakaryocyte. The authors found evidence that SARS-CoV-2 interacts with megakaryocytes to produce large immature hyperreactive platelets. The authors are investigating platelet-directed therapy.
        SAB Comment: This strength of paper lies in the availability of platelet immature fraction and platelet volume from routine lab testing. These data highlight the role of platelets in the immunothrombosis of COVID-19 and raise excellent further questions for therapeutics.

      September 13, 2021

      • COVID-19 Vaccination-Associated Myocarditis in Adolescents. 8/14/21. Jain SS. Pediatrics.
        This article reviews the clinical presentation and early prognosis of the rare complication of acute myocarditis following COVID-19 vaccination in adolescents. The authors pool data from 63 patients from 16 US institutions. Using cardiac MR imaging, the authors are able to characterize this entity with exquisite detail in the figures. The authors demonstrate the favorable short-term outcomes of this subset. This article represents some of the largest dataset examining this particular entity in this age group.
      • Early Convalescent Plasma for High-Risk Outpatients with Covid-19. 8/18/21. Korley FK. N Engl J Med.
        While prior studies using convalescent plasma have failed to demonstrate improved outcomes over placebo for inpatients, this randomized study examined its use in outpatients. Patients older than 50 years old were initially seen in the emergency room and diagnosed with COVID-19. Five hundred and eleven patients from 48 hospitals in 21 states in the US were included in this blinded study funded by the NIH, 257 received convalescent plasma and 254 received placebo. The primary outcome was disease progression defined by either hospital admission, seeking emergency or urgent care, or death. The study showed no significant difference between the two groups (i.e., those receiving convalescent plasma and those that did not).
      • Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting. 8/25/21. Barda N. N Engl J Med.
        This Israeli study compared the occurrence of adverse events in 884,828 recipients of the Pfizer/BioNTech COVID-19 vaccine to a like number of controls matched for risks on the day of vaccination. Vaccine recipients and controls were followed for 21 days after each injection. Vaccination was not associated with an elevated risk of most of the adverse events examined. Vaccination was associated with an elevated risk of myocarditis (risk ratio, 3.24 but absolute event rate only 2.23 per 100,000), lymphadenopathy (risk ratio, 2.43), appendicitis (risk ratio, 1.40), and herpes zoster infection (risk ratio, 1.43). From a second set of data, they showed that actual SARS-CoV-2 infection was associated with a substantially increased risk of myocarditis (risk ratio, 18.28) and with additional serious adverse events, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia.
        SAB Comment: To make meaning of a comparison of adverse events associated with vaccination to those associated with COVID-19 infection, one must assume a cumulative incidence level. The accompanying editorial adds context and assumes that, “given the current state of the global pandemic, however, the risk of exposure to SARS-CoV-2 appears to be inevitable.”

      August 30, 2021

      • SARS-CoV-2 infection and venous thromboembolism after surgery: an international prospective cohort study. 8/24/21. COVIDSurg Collaborative. Anaesthesia.
        This is a planned sub-study and analysis from a prospective, international, multicenter cohort study of patients undergoing all surgical procedures during October 2020 to determine incidence of postoperative venous thromboembolism (VTE) in patients without and with history of SARS-CoV-2 (before [more than 7 weeks]; recent [1-6 weeks]; peri-operative [7 days before to 30 days after]). Primary outcome measure VTE (PE or DVT) was within 30 days. No information on VTE prophylaxis pre- or post-operatively was available. VTE was independently associated with postoperative mortality (5.4%). In patients with SARS-CoV-2 mortality without VTE was 7.4%; with VTE was 40.8%. Recent and peri-operative SARS-CoV-2 infection may be an independent risk factor for postoperative VTE, and increased awareness and surveillance should be considered.

      August 16, 2021

      • Surviving Covid-19 with Heparin? 8/4/21. Ten Cate H. N Engl J Med.
        This editorial attempts to reconcile the differences in outcomes of the two studies below between critically ill and moderately ill COVID-19 patients who received heparin at therapeutic vs. thromboprophylactic doses. It is fairly clear that therapeutic anticoagulation does not provide increased benefit over thromboprophylaxis for critically ill patients; however, the degree of benefit of full anticoagulation over prophylaxis for patients with moderate disease remains an open question.
      • Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19. 8/5/21. REMAP-CAP Investigators. N Engl J Med.
        This randomized study of 1098 patients was stopped early because “In critically ill patients with COVID-19…therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis.” Major bleeding occurred in 3.8% of patients receiving therapeutic-dose anticoagulation vs. 2.3% receiving usual-care thromboprophylaxis. These data are the result of harmonized protocols of 3 international adaptive platform trials (REMAP-CAP, ACTIV-4A, and ATTACC). A limitation is that the majority of patients were in the UK where usual care changed from low-dose to intermediate dose prophylaxis during the study period, April-December 2020.
      • Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19. 8/5/21. ATTACC Investigators. N Engl J Med.
        This companion study reports outcomes following initial treatment with therapeutic vs. prophylactic heparin anticoagulation for 2,219 COVID-19 patients with moderate disease. Survival until hospital discharge without receipt of organ support during the first 21 days was 76.4% (801/1048) for those in usual-care thromboprophylaxis vs. 80.2% (939/1171) for those in the therapeutic anticoagulation group. Neither age, level of respiratory support at enrollment, nor thromboprophylaxis dose affected outcomes. The final posterior probability for superiority of therapeutic-dose anticoagulation vs. usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the cohort with an unknown d-dimer level. A table summarizes secondary outcomes, including major bleeding in 1.9% receiving therapeutic dose vs. 0.9% receiving thromboprophylaxis.

      July 26, 2021

      July 19, 2021

      June 14, 2021

      June 4, 2021

      May 7, 2021

      • SARS-CoV-2 vaccine and thrombosis: Expert opinions. 5/4/21. Elalamy I. Thromb Haemost.
        This article reviews the status of 4 COVID-19 vaccines (Pfizer, Moderna, Johnson & Johnson and AstraZeneca) with respect to thrombosis from an international viewpoint. Not only is it current and timely, but reviews:
        1. What is known about the pathophysiology;
        2. Goes over the risk/benefit ratio of vaccination;
        3. What to do if there is a concern for thrombosis after vaccination; and
        4. What not to do.

        Overall, this comprehensive article focuses on clinically relevant issues in a concrete fashion.

      April 23, 2021

      March 26, 2021

      March 24, 2021

      March 8, 2021

      • Altered pulmonary blood volume distribution as a biomarker for predicting outcomes in COVID-19 disease. 2/26/21. Morris MF. Eur Respir J.
        This group examined the CT scans of 313 COVID-19 patients and used an automated program to obtain the percentage of blood vessels with a cross-sectional area 1.25–5 mm2 (BV5%). If the (BV5%) was < 25 %, the data suggested odds ratio (OR) 5.58 for death, and OR 3.20 for intubation. Decreased BV5% has been noted in prior literature in patients with COPD and ARDS. While the decrease in BV5% may represent a change associated with ARDS, this novel marker is noteworthy and merits further investigation.
        SAB Comment: This is a tool we have not seen before, and if validated, may become clinically relevant due to the high-observed odds ratio for mortality and death.

      March 3, 2021

      • Acute Respiratory Distress Syndrome: Contemporary Management and Novel Approaches during COVID-19. 2/4/21. Williams GW. Anesthesiology.
        This is a concise yet comprehensive review of 25 years of ARDS intervention trials, primarily supported through the US ARDS and the Prevention and Early Treatment of Acute Lung Injury (PETAL) Networks and the RECOVERY trial in the UK. Although outcomes and understanding of ARDS has improved significantly, not all interventions studied resulted in clinical benefit and some were potentially harmful. In addition to the discussion, figures and a table nicely summarize findings from pre-COVID-19 and recent reports.
      • “Silent” Presentation of Hypoxemia and Cardiorespiratory Compensation in COVID-19. 2/4/21. Bickler PE. Anesthesiology.
        This well-written review discusses variability in the human response to hypoxemia from any cause, based upon longstanding research in both normal subjects and patients with pathologic conditions. The theory that COVID-19 is unique in its ability to cause hypoxemia without dyspnea (so-called “happy hypoxia”) is refuted, and the physiologic basis for this somewhat surprising condition is explained. When oxygen concentration falls, the most important compensatory mechanism to preserve oxygen delivery is augmentation of cardiac output. If cardiac reserve is compromised, patients experiencing profound hypoxemia are at increased risk for hypoxic organ damage and death.

      February 26, 2021

      February 24, 2021

      • D-dimer and Death in Critically Ill Patients With Coronavirus Disease 2019. 2/16/21. Short SAP. Crit Care Med.
        This is a study of 68 hospitals across America demonstrating that D-dimers, the result of cross-linked fibrin degradation, correlates to the prognosis of death. In a population of 3418 studied with an average age of 62 years, the majority males and significant numbers with hypertension and diabetes mellitus, the risk of death increased with level of D-dimer elevation as measured during the first 2 days of ICU admission. Patients were followed as close as possible to 90 days with an overall mortality of 39.6%. Most patients who died, 34.5% of all patients, did so in the first 28 days. The authors are careful to state this study is not intended to make recommendations for anticoagulation but only as a risk stratification for mortality.

      February 19, 2021

      February 12, 2021

      • Association of chronic anticoagulant and antiplatelet use on disease severity in SARS-COV-2 infected patients. 2/2/21. Ho G. J Thromb Thrombolysis.
        This article reviews data from Kaiser Permanente Northern California, which covers 4.4 million patients, and examined the records of the 28,076 patients with confirmed positive SARS-CoV-2 infection. 1% were prescribed anticoagulants within 3 months prior to diagnosis and 3% were taking antiplatelet agents. Neither was associated with a reduced risk of hospitalization, venous thromboembolism, emergency department visit, ICU stay, invasive ventilation or death. Based upon these data, authors do not recommend broad institution of anticoagulation or antiplatelet therapy for patients testing positive for SARS-CoV-2 infection.

      February 10, 2021

      • Autoantibodies May Drive COVID-19 Blood Clots. 2/2/2021. Hampton T. JAMA.
        This is a commentary and discussion of the potential role of autoantibodies in COVID-19 thrombosis. In a recent study of 172 hospitalized COVID-19 patients, 52% had at least 1 anti-phospholipid (aPL) antibody. Antibody levels were associated with severity of respiratory disease, kidney dysfunction, and immune hyperactivity. They promote thrombosis in animal models via release of neutrophil extracellular traps (NETs). Neutrophils from healthy people over-produced NETs when cultured with autoantibodies from COVID-19 patients, as seen with aPL antibodies from patients with antiphospholipid syndrome (associated with bacterial and viral infections). Strategies to reduce NET levels may prove beneficial in COVID-19.
      • Extracorporeal membrane oxygenation in patients with severe respiratory failure from COVID-19. 2/2/21. Shaefi S. Intensive Care Med.
        This article reports the results of a study on the use of V-V ECMO in selected COVID-19 patients treated in experienced centers with mortality reduction (66.8% survival at 60 days). The study represents ECMO patients admitted across all participating ICUs during the trial period (190/5122). The article includes detailed analysis and an interesting use of an emulation cohort to support conclusions, eliminate confounders and immortal time bias and provide comparator between ECMO and non-ECMO patients to provide a non-ECMO control group lacking in prior studies. The author emphasizes the importance of early initiation in carefully selected patients treated in experienced centers to maximize outcomes.

      February 1, 2021

      January 22, 2021

      • Thromboembolic complications in critically ill COVID-19 patients are associated with impaired fibrinolysis. 12/8/20. Kruse JM. Crit Care.
        While this review only has 40 ICU COVID-19 patients, the data suggest that a severe decrease in clot breakdown is a cause of the coagulopathy associated with COVID-19. Maximum lysis, especially following stimulation of the extrinsic coagulation system using rotational thromboelastometry (ROTEM), was inversely associated with an enhanced risk of thromboembolic complications. Combining values for maximum lysis with D-dimer concentrations revealed high sensitivity and specificity of thromboembolic risk prediction (area under curve of 0.92).
      • Venous thromboembolism and major bleeding in patients with COVID-19: A nationwide population-based cohort study. 1/5/21. Dalager-Pedersen M. Clin Infect Dis.
        This review from 6 Danish hospitals examines 30-day VTE and bleeding risks in 9,460 PCR+ patients for SARS-CoV-2, 226,510 SARS-CoV-2 negative patients and 16,281 patients with influenza. One thousand five hundred and forty of the COVID-19 patients were hospitalized. Overall 30-day risk for VTE was 0.4% (40/9,460) among COVID-19 positive patients compared with 0.3% (649/226,510) for COVID-19 negative patients and 1.0% (158/16,281) among influenza patients. Among hospitalized patients, risks for VTE were 1.5% (23/1,540) in COVID-19 positive patients compared with 1.8% (483/26,131) in COVID-19 negative patients and 1.5% (147/9,599) in hospitalized influenza patients. No differences were noted in major bleeding events. In this nationwide survey, the data demonstrate a low rate of VTE and bleeding for outpatients with SARS-CoV-2.

      January 13, 2021

      • Impact of cardiovascular disease and risk factors on fatal outcomes in patients with COVID-19 according to age: a systematic review and meta-analysis. 12/18/20. Bae S. Heart.
        This is a retrospective meta-analysis to investigate the impact of cardiovascular disease (CVD) and associated risk factors (hypertension, diabetes) on age-related mortality in COVID-19 patients. Fifty-one studies, including 48,171 patients were included, along with PRISMA diagrams and tables. Unsurprisingly, CVD, hypertension and diabetes increased mortality across all groups. However, when present in younger ages, the odds ratio of mortality compared with same age patients without the risk factors was disproportionately higher than the same age ratio in the elderly. While young patients had lower prevalence rates of cardiovascular comorbidities than elderly patients, relative risk of fatal outcome in young patients with hypertension, diabetes and CVD was higher than in elderly patients.

      January 8, 2021

      December 14, 2020

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

      December 11, 2020

      December 4, 2020

      November 23, 2020

      November 16, 2020

      • Neutrophil extracellular traps and thrombosis in COVID-19. 11/5/20. Zuo Y. J Thromb Thrombolysis.
        Forty-four patients with COVID-19 had blood collected for neutrophil extracellular traps (NETs) and neutrophil activation. Eleven of these patients developed thrombosis despite at least prophylactic heparin. Thrombosis in COVID-19 was associated with higher levels of circulating NETs and calprotectin (neutrophil activation). These data further add to the characterization of COVID-19 and the stepwise understanding of how to combat the epidemic.

      November 9, 2020

      November 4, 2020

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

      October 30, 2020

      • Venous Thromboembolism in COVID-19. 10/25/20. Schulman S. Thromb Haemost.
        This is an excellent review regarding the mechanisms and pathogenesis of the disease biomarkers and their clinical usefulness. Risk assessment models are discussed as well as the type and strength of prophylaxis based on available evidence. Recommendations or position statements from 10 sources are discussed along with treatment recommendations according to current guidelines. Thrombosis prophylaxis with low molecular weight heparin is recommended for most hospitalized patients along with a recommendation against escalating anticoagulant doses. Therapeutic anticoagulation is advised only in response to a very high suspicion or in the presence of documented venous thromboembolism. An excellent algorithm regarding VTE treatment is presented.

      October 23, 2020

      October 2, 2020

      • Biomarkers for the prediction of venous thromboembolism in critically ill COVID-19 patients. 9/14/20. Dujardin RWG. Thromb Res.
        These authors present a prediction model for venous thromboembolism (VTE) in critically ill COVID-19 patients. They studied 127 adult patients with confirmed infection admitted to the intensive care unit. Testing included daily liver and renal function, and C-reactive protein (CRP). Twice weekly D dimer, fibrinogen, and antithrombin levels were done. Weekly duplex scans in all, and chest CT done based on clinical suspicion. The probability of a VTE with a D dimer greater than 15,000 ng/ml and a CRP greater than 280 was 98%. Hypoxemia and other variables were not predictive. Study suggests inflammation is a driving force for the development of VTE.

      September 30, 2020

      • Cardiopulmonary exercise and the risk of aerosol generation while wearing a surgical mask. 9/11/20. Helgeson SA. Chest.
        The authors quantified the number of various-sized airborne particles 6 feet from exercising normal volunteers wearing type II procedural surgical masks. They found there was a minimal increase of particle number at low and moderate exercise but a doubling of the ambient baseline of small respirable particles (0.3–0.5 micrometer) with very hard exercise. Larger droplet sized particles were not significantly increased during any stage of exercise. These results may be applicable to gyms and health clubs if all participants wear surgical masks.

      September 25, 2020

      • COVID-19 concerns aggregate around platelets. 9/10/20. Battinelli EM. Blood.
        This is a well-written, useful editorial which describes the essence of the following two papers, including its limitations and future steps.
      • Platelet gene expression and function in patients with COVID-19. 9/10/20. Manne B. Blood.
        Using platelet RNA sequencing, this group profiles gene expression in the platelets of COVID-19 patients (n= 41) and finds altered gene expression profiles in pathways associated with ubiquitination, antigen presentation, and mitochondrial dysfunction. Patients with COVID-19 have higher levels of platelet activation at rest and increased interactions with neutrophils, monocytes, and T cells compared with healthy donors. Platelet functionality studies demonstrate hyperactivity, as evidenced by increased aggregation, spreading on fibrinogen and collagen through upregulation of the MAPK pathway, and increased thromboxane generation. These new data help extend prior data into the basic science of the hypercoagulable state of COVID-19.
      • Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19. 9/10/20. Hottz E. Blood.
        This group demonstrates that COVID-19 is associated with increased platelet activation. They show that the platelets of critically ill COVID-19 patients exhibit increased platelet aggregation and platelet-monocyte aggregation. Further, these changes correlate with a worse outcome. Changes in platelet activation were associated with increased platelet expression of P-selectin and CD63. Platelets from patients with severe COVID-19 infection induce monocyte-derived tissue factor (TF) expression that is diminished by pretreating COVID-19 patient platelets with an anti–P-selectin neutralizing antibody or the clinically approved anti-αIIb/β3 monoclonal antibody, abciximab. These data are new and add to the understanding of the role that platelets play in the hypercoagulable state of COVID-19.

      September 21, 2020

      • Elevated D-dimers and lack of anticoagulation predict PE in severe COVID-19 patients. 9/9/20. Mouhat B. Eur Respir J.
        This article reviews 162 patients who had computed tomography pulmonary angiography (CTAP) with clinical pulmonary deterioration taken from 349 patients with COVID-19 in a French hospital. Twenty-seven percent had pulmonary embolism (PE). Review of their data with multivariate analysis demonstrates lack of anticoagulation and D-dimer > 2590 ng/ml to be predictive of PE. A D-dimer level >2590 ng/mL−1 was associated with a 17-fold increase (!), and lack of anticoagulation with a 4-fold increase in the risk of PE. Linearity was verified for D-dimers in the study population (test of linearity <0.001). This paper adds more details to the literature and helps guide the clinician.

      September 14, 2020

      • Association of Treatment Dose Anticoagulation With In-Hospital Survival Among Hospitalized Patients With COVID-19. 6/29/20. Paranjpe I. JACC.
        The authors studied 2,773 hospitalized patients with COVID-19. Therapeutic anticoagulation was administered to 28% of these patients and survival between those who received prophylactic versus therapeutic anticoagulation was similar. In patients who required mechanical ventilation who received treatment doses of anticoagulation, in-hospital mortality rates were lower. Bleeding was more common for intubated patients. Prospective randomized trials will be needed to confirm these findings but the results in this study are very encouraging. These preliminary results provide some guidance for selecting therapeutic heparin in critical situations.
      • Coagulation biomarkers are independent predictors of increased oxygen requirements in COVID-19. 8/17/20. Rauch A. J Thromb Haemost.
        This well-done study from Lille, France of 234 patients admitted with COVID-19 presents new data. von Willebrand factor (VWF) levels were associated with severity and oxygen need in COVID-19 at admission; low factor VIII (FVIII)/VWF ratio at admission is predictive of increased oxygen requirements; and coagulation biomarkers predict outcome independently of major comorbidities in COVID-19. Furthermore, FVIII is predictive of early thrombotic events irrespective of BMI in COVID-19.
      • Safety Update: COVID-19 Convalescent Plasma in 20,000 Hospitalized Patients. 7/19/20. Joyner MJ. Mayo Clin Proc.
        This was a study based on a collaborative effort of the FDA, Mayo Clinic and the national blood banking community. Over 20,000 patients received convalescent plasma in the US. In this report of 20,000 patients, the one week mortality was 13%; transfusion reactions were <1% (n=78). This is important data supporting the use of convalescent plasma. However, these data examined the safety of its use not the efficacy. While these data are important, we will be looking forward to further information in the future.

      September 9, 2020

      • Anticipating and managing coagulopathy and thrombotic manifestations of severe COVID-19. 8/16/20. Godoy LC. CMAJ.
        This is an interesting, informative, and well-written review. The explanation of the pathology beginning with the viral spike protein invading the cells facilitated by ACE2 followed by a cascade of reactions involving inflammatory and immunological pathways resulting in widespread endotheliitis is well stated. The clarity of the authors’ approach is refreshing. A summary of current recommendations is presented along with interesting individual studies that stimulate the reader and the researcher to pursue additional studies. It’s interesting to note that the reported bleeding rate using full anticoagulation is not much different than using lower doses.

      August 31, 2020

      August 5, 2020

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

      August 3, 2020

      July 31, 2020

      • COVID-19 and thrombotic or thromboembolic disease: Implications for prevention, antithrombotic therapy, and follow-up. 6/16/20. Bikdeli B. J Am Coll Cardiol.
        This article is an excellent clinically relevant review of thrombotic complications of COVID-19. Systemic and pulmonary venous and arterial thrombosis and thromboembolism are common in COVID-19. Thrombi are observed in virtually every organ. This is caused by inflammation, platelet activation, hypercoagulability, endothelial dysfunction, constriction of blood vessels, stasis, hypoxia, muscle immobilization, and disseminated intravascular coagulation (DIC).
        Fever and inflammation cause hypercoagulability and impair fibrinolysis. Cytokine interleukin-6 (IL-6) levels correlate with hypercoagulability and disease severity.
        Elevated antiphospholipid antibodies are associated with thrombosis. The liver increases production of procoagulant substances. Prothrombin time and activated partial thromboplastin time are moderately prolonged. Moderate thrombocytopenia is observed. C-reactive protein is elevated. Cytokine storm and excessive systemic inflammation are associated with lymphocytopenia, elevated D-dimer, elevated fibrin degradation products (FDP), and DIC. D-dimer levels and DIC are prognostic.
        Guidelines recommend thromboprophylaxis. Prophylaxis with low-molecular weight or regular heparin, fondaparinux, or a direct oral anticoagulant such as apixaban or rivaroxaban should be considered. Heparins bind tightly to COVID-19 spike proteins impeding the entry of the virus into cells. Heparins also downregulate IL-6 and reduce immune activation. A non-randomized study suggests that among patients requiring mechanical ventilation, systemic anticoagulation may be associated with reduced mortality without increasing major bleeding. However, systemic anticoagulation has not proven to be beneficial in ARDS due to other etiologies. After hospital discharge prolonged prophylaxis may be beneficial.

      July 27, 2020

      • A proposal for staging COVID-19 coagulopathy. 7/21/20. Thachil J. Res Pract Thromb Haemost.
        Authors from three continents propose a framework within which to stage COVID-19 associated hemostatic abnormalities, and potentially guide treatment. A theory that infected lung epithelium acts as the epicenter of coagulation with early stages that are difficult to diagnose is described, along with a 3-stage disease model. Currently there are no reliable markers to guide treatment; however patterns and questions for researchers are outlined. A table outlines 11 current international clinical trials on approaches to coagulopathy and are listed on clinicaltrials.gov.

      July 24, 2020

      • Blood type and outcomes in patients with COVID-19. 7/12/2020. Latz C. Ann Hematol.
        Retrospective study of 1289 SARS-CoV-2 + patients /7648 tested patients w/ known ABO blood type. No blood group had an increased or decreased risk of severe disease, inflammatory markers, intubation, or death.  Type A had the expected risk of +PCR, type A, type O had a lower risk and types B and AB and Rh+ patients had a higher risk.  These results contrast w/ previous reports, however data are not fully comparable.

      July 17, 2020

      • ABO Phenotype and Death in Critically Ill Patients with COVID-19. 7/1/20. Leaf RK. Br J Haematol.
        Review by the SAB
        By Lydia Cassorla, on behalf of the SAB
        In this Letter to the Editor, ABO blood type data from adults admitted to ICUs over 38 days in the 67-center Study of the Treatment and Outcomes in critically ill Patients from COVID-19 (STOP-COVID) study were analyzed. Patients were followed until hospital discharge, death, or May 8, 2020 – a date that included a minimum of 28 days follow-up for those still hospitalized. 2033/3239 (62.8%) had ABO data available. 799/2033 (39.3%) died within 28 days. Death rates were similar across ABO phenotypes in all race/ethnicity categories, as well as Rh status. Among White patients, the observed distribution of ABO phenotypes differed from expected, primarily due to blood type A being over-represented (45.1% observed vs. 39.8% expected) and blood type O being under-represented (37.8% observed versus 45.2% expected). Among Black and Hispanic patients the observed and expected distributions of ABO phenotypes were similar.

      July 10, 2020

      July 8, 2020

      June 3, 2020

      • The Spectrum of Cardiac Manifestations in Coronavirus Disease 2019 (COVID-19) – a Systematic Echocardiographic Study
        May 29. Szekely. Circulation.
        Opinion from SAB Member: Dr. Paul D. Scanlon
        This is a prospective survey of echocardiographic findings in 100 patients admitted with COVID-19–20% had repeat echo during clinical deterioration. At baseline, 61 had mild disease (no O2), 29 had moderate disease (non-inv O2), and 10 had severe disease (intubated). 32 had normal baseline echos, 39 had RV dilatation and dysfunction, 16 had LV diastolic dysfunction only, 10 had LV systolic dysfunction. Of the 20 who deteriorated, 12 (60%) had RV deterioration, of whom 5 (25%) had DVT (possible PE?). 5 (25%) had decrease in LVEF. Lung US was c/w ARDS, without evolution to cardiogenic pulmonary edema.

      May 21, 2020

      • 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.

      May 20, 2020

      May 6, 2020

      • Pediatric Multi-System Inflammatory Syndrome Potentially Associated with COVID-19. May 4. New York City Health Department.
        Based on 2020 Health Alert #13 from the New York City Health Department, multi-system inflammatory syndrome, recently reported by authorities in the United Kingdom, is also being observed among children and young adults in New York City and elsewhere in the United States and includes features of Kawasaki disease or features of shock. If a patient is less than 21 years old, with persistent fever (four or more days), and either incomplete Kawasaki disease, typical Kawasaki disease, and/or toxic shock syndrome-like presentation; and there is no alternative etiology identified that explains the clinical presentation, the patient should be presented to the New York City Health Department. The findings have been published: Jones VG, Mills M, Suarez D, et al. COVID-19 and Kawasaki disease: novel virus and novel case. Hosp Pediatr. 2020; doi: 10.1542/hpeds.2020-0123; and Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020 Mar 28;395(10229): 1033-1034. DOI: 10.1016/S0140-6736(20)30628-0.

      May 5, 2020

      May 2, 2020

      • 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.

      May 1, 2020

      • A Marker of Systemic Inflammation or Direct Cardiac Injury: Should Cardiac Troponin Levels be Monitored in COVID-19 Patients? 4/29/2020. Atallah. Eur Heart J Qual Care Clin Outcomes.
        Detailed discussion of potential evolution of cardiac injury during COVID-19 demonstrating increased mortality in patients developing cardiac dysfunction. Discusses enzymatic increases that aid in prognosis and risk classification. Troponin level increases associated with other markers of inflammation (IL-6). Also noted were increases in D-dimer and indications of a procoagulant state that could lead to ischemia, thrombosis and subsequent cardiac injury.
        “In summary, there are several mechanisms that could be at play to explain myocardial injury in relation to COVID-19 infection, that include but are not limited to: Myocarditis, sepsis and associated systemic inflammatory response, pro-coagulant condition, destabilization of coronary plaque, and hypoxia.”
        Manuscript concludes with 7 recommendations and is published on behalf of the European College of Cardiology.
      • 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.

      April 30, 2020

      • 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.
      • 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.

      April 28, 2020

      April 24, 2020

      • Lung Ultrasound in Children With COVID-19. Apr 23. Denina M. Pediatrics.
        Study involves a US application of 8 pediatric patients in Italy. The author concludes: practical, PoC application may be superior concurrent confirmation with radiological for hard evidence and superior for one patient who was recovering who had a clear X-ray but a presence of a Curly B line. None of them were ventilated, 2 patients were on oxygen. No pictures in the article, and a small number. US can replace X-ray in pediatrics.

      April 22, 2020

      • 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).

      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.

      April 20, 2020

      April 17, 2020

      • 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.
      • Suspected myocardial injury in patients with COVID-19: Evidence from front-line clinical observation in Wuhan, China. Apr 16. Deng Q. Int J Cardiol.
        This article from Wuhan n= 112 patients. ITS pre proof. Retrospective study. Comparison was 2 group of 4 patients with COVID 19 + VE: A: Those who survived and possibly d/c home to B: those who didn’t survive. Excluded 5 patient with pre existing cardiac conditions (CHF, MI 4 days ago ). Stastic believable: p, fitness test.…Lot of redundant numbers / lab….No biopsy or Nuclear study. Extensive data collection of these patients. Ongoing as patient (61) are still in hospital. Troponin & BNP not remarkable until 1 week before the death both of them rises, CPK & LDH late elevation. Covid-19 caused myocarditis – no solid evidence. Inflammatory process/hypoxia are likely cause of myocarditis. 5 Patients had pericardial effusion. TR Flow velocity.., PUM PR, CVP, stiffness of RT/ LT vent , wall motion ……. All Normal to high Normal. No other ECHO / EKG – All non specific. Hypoxia on vent support , ECMO (14), MOF, Cytokine Strom (no inflammatory markers – IL Panel), Met. Acidosis, renal/ liver failure, Abnormal coag. Profile …before Death. Pulm. Hypertension -> ARDS related? From the clinical standpoint and front-line data analysis in our study, though there was evidence of myocardial injury and 12.5% COVID-19 patients had cardiac abnormalities similar to myocarditis, the characteristic changes of cardiac troponin I over time and the absence of typical signs on echocardiography and ECG have suggested that myocardial injury is more likely related to systemic consequences rather than direct damage by the 2019 novel coronavirus. The elevation in cardiac markers was probably due to secondary and systemic causes and can be considered as the warning sign for recent adverse clinical outcomes of the patients.
      • The Science Underlying COVID-19: Implications for the Cardiovascular System. Apr 16 Liu PP. Circulation.
        This is a review article that is published ahead of print. It is well written and detailed and describes the relationship between COVID-19 and the cardiovascular system. Briefly, whereas COVID-19 is primarily a respiratory infection, it has important systemic effects including on the cardiovascular and immune systems. Between 8-28% of patients with COVID-19 infections will manifest troponin release early in the course of the disease, reflecting cardiac injury or stress. The presence of troponin elevation, or its dynamic increase during hospitalization, confers up to 5 times the risk of requiring ventilation, increases in arrhythmias such as VT/VF, and 5 times the risk for mortality. One feature of the virus is that it has enhanced ACE2 receptor binding affinity. Given that ACE2 receptors are located in the human oral pharynx and upper airway, this allows for person-to-person transfer. ACE2 has been confirmed recently as the SARS-CoV-2 internalization receptor that helps to facilitate cell entry. TMPRSS2 and ACE2 are co-expressed in lung, heart, gut smooth muscle, liver, kidney, neurons and immune cells35. Their distribution may help to explain patient symptoms or laboratory findings in COVID-19. And there is more described in the article.

      April 15, 2020

      April 11, 2020

      April 9, 2020

      April 8, 2020

      April 4, 2020

      April 3, 2020

      March 28, 2020

      March 27, 2020

      March 24, 2020

      March 20, 2020

    1. Multisystem Disease Management
      April 12, 2021

       

      • Secondary Bacterial Pneumonias and Bloodstream Infections in Patients Hospitalized with COVID-19. 4/6/21. Adelman MW. Ann Am Thorac Soc.
        These authors examined the secondary bacterial pneumonias and bloodstream infections (BSI) in 774 patients hospitalized with COVID-19 from February to May 2020. The most common bacteria grown was Staphylococcus aureus. Mortality did not differ between intubated patients with an identified bacterial respiratory pathogen and those without. Overall, mortality was 50% in patients with BSI versus 13.8% without (p<0.0001). These results suggest that hospitalization and central lines are more important than are COVID-19-specific effects in conferring susceptibility to specific pathogens. BSIs in their cohort were also largely related to risk factors, especially central lines, and pathogens associated with hospitalization and did not appear significantly different from the non-COVID data.

      March 26, 2021

      • Post-acute COVID-19 syndrome. 3/23/21. Nalbandian A. Nat Med.
        This comprehensive review of current literature divides post-acute COVID-19 into 2 categories: subacute, lasting 4-12 weeks, and chronic, lasting over 12 weeks. Concise discussions cover post-acute epidemiology, prevention and management of thromboemboli, pulmonary, cardiovascular, neurologic, renal, endocrine, and inflammatory complications as well as race/ethnicity factors, organ system involvement and potential interdisciplinary clinic management, findings from studies of post-acute COVID-19 prevalence, and active research. The need to include rehabilitation in multidisciplinary clinics is reinforced. Links to prominent patient advocacy groups are provided.

      March 17, 2021

      • Long-term survival of critically ill patients stratified by pandemic triage categories: a retrospective cohort study. 3/12/2021. Darvall JN. Chest.
        Australian study designed to evaluate accuracy/effectiveness of current triage (low, medium and high priority) criteria based on age, pre-existing co-morbidities and SOFA score with long-term survival at 5 and 10 years post discharge. Victoria hospital registry data (2007-2018; 23 ICU’s) linked with death registries to correlate predictive survival accuracy; 126,687 ICU admissions. Long-term survival for low and high priority admissions was similar. Triage score was unable to discriminate ICU utilization/cost when mortality factored with LOS and resource utilization. Survivor QALY’s/long term care not evaluated. “Future ICU triage research should focus on stratifying long-term survival outcomes for patients, accounting for a more detailed combination of premorbid functional status, comorbidities, and organ dysfunction severity scoring.”

      March 3, 2021

      • Acute covid-19 and multisystem inflammatory syndrome in children. 3/2/21. Rubens JH. BMJ.
        This is a clinical summary of children with acute COVID-19 and the associated multiple inflammatory syndrome in children (MIS-C). A small proportion of children go on to develop severe acute COVID-19 disease and require hospitalization because of respiratory compromise or complications of SARS-CoV-2 infection. Clinicians should consider MIS-C in children presenting with fever and abdominal symptoms, particularly if they develop conjunctivitis or rash, and refer to a pediatric emergency department for evaluation. MIS-C can have overlapping symptomatology with disease processes that require prompt treatment, such as sepsis, toxic shock syndrome, myocarditis, and meningitis.

      February 26, 2021

      February 24, 2021

      • Oral Complications of ICU Patients with COVID-19: Case-Series and Review of Two Hundred Ten Cases. 2/9/21. Hocková B. J Clin Med.
        Oral complications are common in long-term ICU COVID-19 patients requiring prolonged prone positioning and mechanical ventilation. This three patient case series and accompanying literature review of 210 cases suggests not only traumatic complications associated with positioning and mechanical ventilation (report re: intubation versus tracheostomy) but also use of antibiotics, antivirals and steroids plus difficulties associated with performing effective oral toilet as causative factors. Authors recommend a multidisciplinary approach in severe cases including dermatology, oral surgery and dentistry to study causation and routine monitoring and management of at-risk patients.

      February 22, 2021

      February 12, 2021

      • Mortality and renal outcomes of patients with severe COVID-19 treated in a provisional intensive care unit. 1/21/21. Hittesdorf E. J Crit Care.
        This study involves 116 COVID-19 patients who required mechanical ventilation and were cared for in an OR-ICU. The patients were followed for 90 days for mortality and renal outcomes. 30.2% died (n=35). Mortality among 45 patients receiving continuous replacement therapy (CRRT) was 40% (n=18) vs. 23.4% (n=17) in 71 patients who did not receive CRRT. The stage of AKI did not affect mortality compared with no AKI. However, those with stage 3 were more likely to require CRRT and to die during hospitalization. Only two survivors required dialysis at 90 days and outcomes did not differ from those cared for in a regular ICU.

      January 15, 2021

      • Facial Pressure Injuries from Prone Positioning in the COVID-19 Era. 1/3/21. Shearer SC. Laryngoscope.
        This study highlights the high frequency (48%) of facial pressure injuries associated with intubated COVID-19 patients placed in the prone position at a single US institution. Most of these patients were continuously in the prone position. Of 143 intubated ICU patients proned for an average of 123 hours, cheek and ear injuries accounted for the majority of damage, with the likelihood of injury increasing as proning times increased. A particular problem seemed to be pressure caused by commercial endotracheal tube fasteners. Suggestions for reducing these injuries are made. The study did not address injuries to the eye or elsewhere on the body.

      September 14, 2020

      September 4, 2020

      • SARS-CoV-2 another kind of liver aggressor, how does it do that?. 8/29/2020. Lozano-Sepulveda SA. Ann Hepatol.
        This is an overview of all the recent findings regarding the molecular biology of the virus and its several modes of assault on liver disease in COVID. Authors conclude the cross-talk cellular protein virus is pivotal for its harmful injury to the liver. Admits the pathogenesis is multifactorial, evolving understanding of pathogenesis. Its natural history of the disease is unestablished. It has an informative cartoon.
      • SARS-CoV-2 RNA in serum as predictor of severe outcome in COVID-19: a retrospective cohort study. 8/28/2020. Hagman K. Clin Infect Dis.
        These authors in this retrospective study have an observation for COVID-RNA in Serum (n= 61, + ve=high viral load e.g. unable to control viral replication) at admission (10th day symptoms) met with an outcome of critical disease or mortality with the hazard ratios of 7.2 and 8.6, respectively for critically ill patients compared to serum PCR negative (n= 106) group. Authors infer -Not detecting COVID-RNA in serum indicated a high chance of uncomplicated recovery. The disease severity was based on clinical profile (age, comorbidities) in this cohort. Noted with statistics age (& other comorbidity), decreases the ability to control viral replication. Detection of COVID in serum likely to be due to the inflammatory response or hematogenous spread of virus possibly more advanced stage of the infection/ inflammation. Other potential antiviral therapies (Remdesivir, convalescent plasma, steroid, IL 6 blockers) may have roles clearing the infection especially serum PCR positive patients to avoid the development of critical disease/death. Both groups had all the available (& variable) treatment (convalescent plasma, steroid, antiviral drugs). The PCR in serum was done 2 different methods in an overlap.

      August 25, 2020

      • What every intensivist should know about COVID-19 associated acute kidney injury. 8/11/20. Ostermann M. J Crit Care.
        Acute kidney injury (AKI) is a serious complication in the ICU (incidence < +/- 30%) with COVID-19 patients. The authors explore various etiologies: hypovolemia, hemodynamic instability, inflammation (direct viral invasion, microvascular thrombosis, and dysregulated renin-angiotensin-aldosterone system (RAAS) and of ACE II, iatrogenicity as well). There are no specific therapies for prevention or management of AKI guidelines. Detailed discussion of alternatives to renal replacement therapy (RRT) and other supportive measures are described. An overwhelming need for RRT practice is likely to be determined by the ground reality. A close collaboration between critical care medicine and renal services is essential when resources may be scarce.

      August 19, 2020

      • Association Between Anxiety and New Organ Failure, Independently of Critical Illness Severity and Respiratory Status: A Prospective Multicentric Cohort Study. 7/30/20. Mazeraud A. Crit Care Med.
        Interesting, multi-center prospective study evaluating patient’s admission anxiety level on new organ system failure within seven days following ICU admission. While not directly related to COVID-19 (or any specific admission diagnosis), patients identified with moderate to severe anxiety (State anxiety-assessed using state component of State-Trait Anxiety Inventory State) associated with disease severity (Simplified Acute Physiology Score II and Sequential Organ Failure Assessment) associated with increased risk for further deterioration when compared to lower stress comparators. Interesting with obvious implications for current pandemic given long prodrome with variable symptomatology and outcome increasing general anxiety in population with some estimates indicating a recent reported 25% incidence of suicidal ideation in younger age groups.

      July 27, 2020

      • Inflammation Profiling of Critically Ill Coronavirus Disease 2019 Patients. 7/23/2020. Fraser DD. Crit Care Explor.
        Report of a study comparing inflammatory profiling using multiple immunoassays between COVID-19 positive and negative ICU patients and a matched series of normal controls identifying a unique combination of six analytes distinguishing COVID-19 disease. Reported analytes were: tumor necrosis factor; granzyme B; heat shock protein 70; interleukin-18; interferon-gamma-inducible protein 10; and elastase 2.
        Discussion notes COVID-19 patients demonstrate findings consistent with systemic inflammation including increased circulating cytokine levels and lymphopenia potentially characterizing the “purported” cytokine storm frequently mentioned.
        Authors conclude: “In summary, we report sustained elevations in a unique combination of inflammatory analytes in COVID-19+ ICU patients. Our exploratory data are consistent with the slow, or absent improvement in COVID-19+ patients despite state-of-the-art ICU care, and could aid future hypothesis-driven research using larger ICU cohorts.”

      July 24, 2020

      • COVID-19 and the kidney: what we think we know so far and what we don’t. 7/22/20. Farouk SS. J Nephrol.
        Review by the SAB
        These authors are troubled by existing data related to true incidence, etiopathology, and its management with Covid-19. A heterogeneous report, with respect to population size, location, severity of illness, and definitions of acute kidney injury (AKI), show a wide range of rates of AKI occurrence in patients, from 1-46% and an equally wide percentage range of patients who were treated with kidney replacement therapy (KRT) (10-35%). Most patients with KRT were in the ICU (data was from the UK, Ireland, Italy, China, and the USA) and it has overwhelmed the nephrology services the world over. Potential explanations for these differences include the prevalence of co-morbid conditions and heterogeneity along racial and ethnic lines, local institutional policies about KRT timing, the use of extracorporeal KRT beyond classical “nephrological” indications. Using AKI as defined by “the 2019 Kidney Diseases: Improving Global Outcomes Consensus Conference” may standardize the whole process (a work in progress?). Mode of injury is also noted to be multifactorial. Though the link between AKI and poor outcomes is clear, prevalence and outcomes of COVID-19 in patients with chronic kidney disease and end-stage kidney disease has not yet been reported. In patients on immunosuppression like those with kidney transplants or glomerular disease, COVID-19 has presented a management dilemma.

      July 13, 2020

      • Thromboelastography Profiles of Critically Ill Patients With Coronavirus Disease 2019. 6/26/20. Yuriditsky E. Crit Care Med.
        Review by the SAB
        By Dr. Philip Lumb, on behalf of the SAB
        Interesting retrospective study of 64 critically ill COVID-19 patients with available/reported thromboelastograph studies within 72 hours of ICU admission; 50% showed hypercoagulable profile defined as a Clotting Index (CI) >3. It is noted that D-Dimer > 2,000 ng/ml associated with median CI 3.4 while D-Dimer <2,000 ng/ml median CI 2.1. Discussion indicates TEG profiles consistent with fibrinogen and platelet effect and authors suggest further studies evaluating platelet aggregation profiles. While value of TEG evaluation in COVID-19 patients has not been confirmed, nonetheless further investigation is warranted as results consistent with clinical severity markers, D-Dimer elevations and requirements for appropriate and timely anticoagulation.

      July 8, 2020

      May 14, 2020

      • Coronavirus Disease 2019, Prothrombotic Factors, and Venous Thromboembolism. May 12. Schulman. Semin Thromb Hemost.
        Nice short review of coagulation abnormalities in COVID-19 patients. States we need randomized clinical trials, before making recommendations advocating more aggressive anticoagulation to prevent VTE in COVID-19 patients.
      • Hyperinflammatory shock in children during COVID-19 pandemic. May 11. Riphagen. Lancet.
        A Correspondence to Lancet describing a hyperinflammatory shock syndrome in a cluster of children, 8 in a population of 2 million, however a 3-fold increase from normal over the 10-day inclusion period. 1 child died. Confusing, the article states that respiratory involvement did not occur, yet the included table shows 5 children suffered tachypnea. Only 2 of 8 children were proven COVID-19. Prior to publishing, another cohort of children has been admitted. Though not listed, the authors imply the COVID-19 diagnosis approached 50%. All children received immunoglobulin and aspirin.

      May 11, 2020

      • Pathogenesis and Treatment of Kawasaki’s Disease
        Sept. 17, 2005. Yeung. Opinion in Rheumatology.
        Opinion from SAB Member: Dr. Jay Przybylo
        This article defining Kawasaki Disease (“…an infectious trigger leads to massive activation of the immune system, resulting in a prolonged self-directed immune response at the coronary arteries”) equates COVID-19 as Kawasaki Disease in a small number of young children.

      May 8, 2020

      May 2, 2020

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

      May 1, 2020

      • 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.

      April 30, 2020

      April 29, 2020

      • Caution Needed on the Use of Chloroquine and Hydroxychloroquine for Coronavirus Disease 2019
        Apr 24. Fihn. JAMA.
        Opinion from SAB Member: Dr. Jay Przybylo
        Data from Brazilian researchers previously discussed now published. Study stopped when high dose chloroquine was found to result in more deaths in a group of patients with concurrent heart disease and associated other diseases. Of great interest is the accompanying editorial that addresses multiple issues associated with COVID-19 and chloroquine use.
      • COVID-19 and its implications for thrombosis and anticoagulation
        Apr 27. Connors. Blood.
        Opinion from C19SAB: Dr. Anil Hingorani, Dr. Louis McNabb
        AH: This article reviews the worldwide literature regarding the effects of COVID-19 on the hematologic system and proposes prophylaxis and treatment options for these patients that is clinically relevant and well organized. LM: Good overview on mechanisms of sepsis-induced coagulopathy. Concludes no data at this time for full anticoagulation of COVID-19 patients in the ICU setting unless proven or suspected VTE. The authors note that COVID-19 do not have propensity to bleed. Many centers are using moderate dosing of anticoagulation, i.e., BID LMWH in the ICU.
      • Patient blood management during the COVID-19 pandemic – a narrative review. Apr 27. Baron. Anaesthesia.
        Expert international consensus statement providing blood management recommendations during the COVID-19 Pandemic. Recommendations include management of the supply chain, donation precautions, elective surgery management and other important aspects of blood utilization. While designed to aid practitioners during the COVID-19 pandemic, nonetheless the recommendations may be considered more generally applicable for future use.

      April 28, 2020

      April 24, 2020

      April 23, 2020

      April 21, 2020

      April 17, 2020

      • Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Apr 16. Arachchillage DR. J Thromb Haemost.
        This is a pre-proof editorial. 11.5 % patients in Wuhan had consumptive coagulopathy -> DIC with PT, D Dimer, FSP high. Platelets – either N or low N. Caution with VV ECMO & ARDS Careful anti coagulation, ICH with Plt. Even if Platelet N be vigilant.
        DIC prognostic marker for COVID-19. A rise of D Dimer & Reduction of Platelet on VV ECMO = pump failure.
      • Gastrointestinal Symptoms and COVID-19: Case-Control Study from the United States
        Apr 8. Nobel. Gastroenterology.
        Opinion from SAB Member: Dr. Barry Perlman
        Retrospective, case-control study of COVID-19 associated gastrointestinal symptoms, including diarrhea and nausea/vomiting, in NYC patients and essential personnel who had nasopharyngeal swab testing for respiratory symptoms. 278 COVID-19 positive and 238 negative patients were included. Patients with GI symptoms at time of testing had a 70% increased risk of testing positive for COVID-19, while absence of GI symptoms did not impact the likelihood of a positive test result. Increasing BMI also correlated with increased risk of a positive test result. 35% of patients who tested positive had GI symptoms, and these patients were more likely to have illness lasting one week or greater. However, they had a significantly lower death rate and a non-significant lower rate of ICU admission. Of note, the paper does not discuss follow-up testing or the final diagnosis of the patients who had negative testing on presentation but went on to hospital admission (171), ICU admission (30) or death (3), so presumably a significant number of these patients had initial false negative tests and were actually COVID-19 positive.
      • Immune Thrombocytopenic Purpura in a Patient with Covid-19. Apr 16. Zulfiqar AA. N Engl J Med.
        Single case which responded to rxn with steroids, ivg, and eltromopag.

      April 10, 2020

      • 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.
      • ISTH interim guidance on recognition and management of coagulopathy in COVID-19 Mar 25. Thachil. Journal of Thrombosis and Haemostasis.
        Opinion from SAB Member: Dr. Barry Perlman
        Lymphopenia is common with COVID-19, and severely ill patients are likely to have coagulopathy. The following is an interim guidance statement on management of COVID-19 coagulopathy: 1) Upon presentation of COVID-19, the measurements advised, in order of importance, are of d-dimer, prothrombin time, and platelet counts. 2) Increased d-dimers are commonly reported in patients with severe illness and may predict mortality. Three- to four-fold increases in d-dimer may signal the need for admission in patients without other clear indicators of severity. 3) Prolongation in prothrombin times and degree of thrombocytopenia (100–150×109/L) have been modest. 4) In addition to the above parameters, fibrinogen should be monitored; nonsurvivors with severe illness have developed disseminated intravascular coagulation around day 4; significant worsening in these parameters at days 10 and 14 was also reported. 5) The panel advises use of prophylactic dose low-molecular-weight heparin unless there is active bleeding or a platelet count of <25×109/L; it is hoped that this strategy will impact septic-like coagulopathy and protect against venous thromboembolism. 6) Bleeding has been rare, but if present, panelists advise keeping platelet counts >50×109/L (and >20×109/L goal in nonbleeding patients), fibrinogen >2.0 g/L, and the prothrombin ratio <1.5.
      • Practice of novel method of bedside postpyloric tube placement in patients with coronavirus disease 2019. Apr 9. Yuan. Critical Care.
        Report of a Chinese version of Dobhoff tube: claims to insert in the second part of duodenum “easier” in Covid patient. No objective evidence.

      April 9, 2020

      April 8, 2020

      April 3, 2020

    1. Treatment / Prevention of COVID-19 (Current / Future)
      January 10, 2022

       

      • Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico. 12/15/2021. Dunkle LM. N Engl J Med.
        The results of this industry-funded, phase 3 trial of NVX-CoV2373 (Novavax) conducted from 12/27/2020-2/18/2021 in 29,582 volunteers in Mexico and the US are presented. Priority access was given to high risk and diverse persons in this randomized, placebo controlled trial, with a second dose after 21 days. The primary outcome was the incidence of a positive PCR 7 days after the second dose over 3 months (14 of 19714 vaccine and 63 of 9868 placebo recipients), representing a 90.4% efficacy. The vaccine was effective against variants of that period. After 3 months, a crossover procedure permitted vaccination for all, and the study continues for durability and safety.
      • Real-World Effectiveness Of Remdesivir In Adults Hospitalized With Covid-19: A Retrospective, Multicenter Comparative Effectiveness Study. 12/15/21. Garibaldi BT. Clin Infect Dis.
        This is a large population study (98,000 patients, 160 hospitals across 21 states), examining the still disputed clinical effectiveness of remdesivir. Compared to matched controls, remdesivir was associated with a statistically significant increase in the likelihood of clinical improvement and survival beyond 28 days in patients on no or low-flow oxygen. Of 36,656 matched individuals, 74.0% who received remdesivir and 68.3% of controls achieved clinical improvement before 28 days with a median time to clinical improvement of 7 days (IQR 5,19) in the remdesivir recipients and 9 days (IQR 5,28) for controls. Results are consistent with the outcome of the ACTT-1 trial and underscore the role of remdesivir in patients with mild respiratory symptoms and its failure to improve advanced disease.
      • Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial. 12/18/21. Ramacciotti E. Lancet.
        This trial from Brazil randomized 320 patients to receive post-hospital discharge prophylactic rivaroxaban or no anticoagulation (from Oct 8, 2020, to June 29, 2021). 165 patients (52%) had been in intensive care. Patients underwent bilateral lower-limb venous ultrasound and CT pulmonary angiogram at day 35. Rivaroxaban was associated with decreased rates of 1) symptomatic and fatal VTE 0.6% vs. 5% and 2) composite of symptomatic VTE, myocardial infarction, stroke, and cardiovascular death (0.6% vs. 5.6%). Furthermore, the magnitude of events was also decreased (more events were asymptomatic in the anticoagulant group than in the control group). This is the first trial demonstrating benefit of post-discharge prophylaxis.

      December 20, 2021

      • Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase 3, randomised, placebo-controlled trial. 12/5/2021. Temesgen Z. Lancet Respir Med.
        Hospitalised adult patients with COVID-19 pneumonia not requiring invasive mechanical ventilation were recruited during an 8 month period ending in January 2021 from 29 sites in the USA and Brazil and were randomly assigned (1:1) to receive three intravenous doses of lenzilumab (n=236) or placebo (n=243) delivered 8 h apart. The primary study endpoint – survival without invasive mechanical ventilation to day 28 – and was achieved in 198 (84%) patients who received lenzilumab and in 190 (78%) in the placebo group and the likelihood of survival was greater in the lenzilumab group (hazard ratio 1·54; 95% CI 1·02–2·32; p=0·040). Added value beyond primary outcome remains unknown, but side effects were comparable to placebo.

      December 13, 2021

      December 6, 2021

      • Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. 11/20/21. RECOVERY Collaborative Group. Lancet.
        A randomized platform trial (RECOVERY) evaluating aspirin 150 mg with usual care (7351 patients), versus usual care alone (7541 patients), was carried out between 11/01/2020 and 3/21/2021 in multiple hospitals worldwide. The primary outcome was 28 day mortality, which was 17% in both groups. Hospital discharge in 28 days was 75% in the aspirin group and 74% in the control group (p=0.0062). A 0.6% reduction of thrombotic events in the aspirin group was cancelled out by an identical increase in major bleeding events.
        SAB Comment: There is little information on the value of aspirin as a therapy for COVID-19. Although the authors support further study for patients who are not hospitalized, it is clearly stated this trial does not support the addition of 150 mg of aspirin to the usual treatment of hospitalized COVID-19 patients.
      • Dexamethasone in hospitalised coronavirus-19 patients not on intensive respiratory support. 11/26/21. Crothers K. Eur Respir J.
        This real-world observational study from US Veterans Administration hospitals found that, in patients not requiring high levels of oxygen support, dexamethasone treatment produced no mortality benefit, and in patients on room air, dexamethasone treatment appeared to cause harm. The authors compared the 90-day mortality of patients on room air treated with dexamethasone (n=3124) to those on room air not treated with dexamethasone (n=6006) and found that, after propensity score weighting, dexamethasone-treated patients had a 76% increase in 90-day mortality. The same comparison in patients supported with oxygen by nasal cannula showed that dexamethasone treated patients (n=4383) did not have a statistically significant improvement in 90-day mortality over nasal cannula supported patients not treated with dexamethasone (n=1437).
        SAB Comment: The higher mortality in patients not on oxygen treated with dexamethasone confirms guidelines issued by the NIH and others.
      • Do the Selective Serotonin Reuptake Inhibitor Antidepressants Fluoxetine and Fluvoxamine Reduce Mortality Among Patients With COVID-19?. 11/15/2021. Hoertel N. JAMA Netw Open.
        An invited commentary which analyzes the mechanisms of action of SSRI antidepressants’ effectiveness as anti-inflammatory agents and inhibitors of viral infection at the cellular level. SSRI’s are functional inhibitors of acid sphingomyelinase (FIASMA), along with hydroxycine, amitriptyline, some statins and mucolytics. The author considers the Acid Sphingo-Myelinase (ASM)-ceramide system of crucial importance as a treatment target in COVID-19 and thoroughly analyses research and evidence behind that statement.
        SAB Comment: This comment provides scientific pre-clinical background to a retrospective cohort study analyzing how patients on SSRI antidepressant may have better outcomes following SARS-CoV-2 infection.

      November 22, 2021

      November 8, 2021

      • A randomized, placebo-controlled clinical trial of bamlanivimab and etesevimab together in high-risk ambulatory patients with COVID-19 and validation of the prognostic value of persistently high viral load. 10/31/21. Dougan M. Clin Infect Dis.
        This Phase 3 portion of the industry-funded BLAZE-1 trial characterized the effect of bamlanivimab (700mg) with etesevimab (1400mg) infusion at this lower dose on overall patient clinical status and virologic outcomes in ambulatory patients 12 years or older, with mild-to-moderate COVID-19, and 1 or more risk factors for progressing to severe COVID-19 and/or hospitalization. Of 769 patients, the difference in hospitalization and/or death within 29 days for those receiving these monoclonal antibodies vs. placebo was 0.8% vs. 5.8% respectively. All 4 recorded deaths were in the placebo group. Persistently high viral load at Day 7, previously observed and considered a predictor of progression to a more serious form of COVID-19, was corroborated in this phase of the trial.
        SAB Comment: In February, 2021, the FDA issued an Emergency Use Authorization (EUA) for the doses used in this study, in mild to moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg). In September this EUA was extended to include post-exposure prophylaxis. This EUA excludes states with resistance to these drugs over 5% (see FDA release for the most recent authorized areas).
      • Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab. 10/27/21. Gupta A. N Engl J Med.
        This is an interim analysis of COMET-ICE, a multicenter, double-blinded, randomized, phase 3 trial for COVID-19 outpatients with symptoms less than or equal to 5 days with an additional comorbidity, which were treated with Sotrovimab 500 mg IV (n = 291) or placebo (n = 292). An interim analysis revealed that 1% of the treated group as compared to 7% in the placebo group had disease progression leading to hospitalization or death (relative risk reduction 85%). The authors noted low adverse events and retained activity against variants of concern, including the alpha, beta, gamma, delta, and lambda variants. The drug can address the unmet needs of patients who have vaccine breakthrough, are unvaccinated, or are immunocompromised and may not respond to a vaccine.
        SAB Comment: The drug is promising for COVID-19. It acts against the non-receptor-binding motif, unlike current authorized COVID-19 monoclonal antibodies, which act on the receptor-binding motif.
      • Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia: The COVID STEROID 2 Randomized Trial. 10/21/2021. COVID STEROID 2 Trial Group. JAMA.
        In this international, blinded, randomized clinical trial including 1000 adults with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in significantly more days alive without life support at 28 days. Treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. None of the analyzed secondary outcomes (including mortality) were statistically significant. The number of patients with serious adverse reactions (ie, septic shock, invasive fungal infection, and clinically important gastrointestinal bleeding) appeared similar between the groups. This trial took place between August 2020 and May 2021 in Europe and India. The trial may have been underpowered to identify a significant difference.
      • Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial. 10/22/2021. Reis G. Lancet Global Hlth.
        The TOGETHER study, a placebo-controlled, randomized, adaptive platform study, aimed to assess the efficacy of fluvoxamine (SSRI) vs. placebo (N = 741 vs. N = 756) in preventing hospitalization or transfers for COVID-19 patients. The authors stated that patients were transferred to a hospital at a lower rate with early prescription of fluvoxamine compare with the placebo (11% vs. 16%, RR 0.68 and probability of superiority). The authors claimed there was a role for this repurposed drub with patients with symptoms greater than 7 days with an additional comorbidity and the unvaccinated as well as low resource centers.
        SAB Comment: Since the study was conducted in different circumstances there is a need to reproduce to prove the validity of the drug.
      • Investigating Lipid-Modulating Agents for Prevention or Treatment of COVID-19: JACC State-of-the-Art Review. 10/15/2021. Talasaz AH. J Am Coll Cardiol.
        Following up on several successful retrospective cohort studies suggesting a benefit of statins in COVID-19, this systematic summary of 40 ongoing US and WHO registered randomized controlled trials focuses on evolving trends, underlying mechanism of action, value and side effects of statins (17 trials), omega-3 fatty acids (14 trials), fibrates (3 trials), niacin (3 trials) and the cholesteryl ester transfer protein inhibitor dalcetrapib (1 trial). Despite its lack of definitive results, this review contributes substantially to our understanding and appreciation of the potential role lipid modulating agents in COVID-19 may play and opens new horizons for research and clinical practice.
      • Pre-admission anticoagulant therapy and mortality in hospitalized COVID-19 patients: A retrospective cohort study. 10/23/2021. van Haaps TF. Thromb Res.
        This Dutch retrospective cohort study of over 3000 patients included 1072 who were on anticoagulant or antiplatelet therapy before admission to hospital for COVID-19, and their matched controls. They, like most previous investigators, found no difference in all-cause 21-day mortality or ICU admission between the groups.

      October 25, 2021

      October 18, 2021

      • Administration of Monoclonal Antibody for COVID-19 in Patient Homes. 10/14/21. Malani AN. JAMA Netw Open.
        In this research letter, during the spring 2021 COVID-19 surge with peak counts of 1,300 cases per day, a Michigan healthcare system introduced successful in-home IV administration of monoclonal antibodies by paramedics to 144 high-risk COVID-19 patients with mild symptoms. This resulted in decompression of hospital facilities with only 8 patients requiring hospital admissions and no intubations or mortalities. Triage was accomplished by 3 nurses and prime risk factors were obesity, cardiovascular disease, and diabetes.
      • REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19. 9/29/21. Weinrich D. NEJM.
        This report represents the phase 3 portion of Regeneron’s adaptive trial to demonstrate the efficacy of a combination of two monoclonal antibodies (imdevimab and casirivimab) in outpatients with COVID-19 and risk factors for severe disease in comparison to placebo. The phase 1-2 portion of this trial published one year ago showed a reduction of viral load and medical visits in 275 symptomatic patients. This phase compared 3 larger groups of patients, each receiving the antibody combination in two different doses or placebo. A highly significant relative risk reduction of 71% for hospitalization or death over placebo and a 4-day reduction in resolution of symptoms underlined the value of this treatment modality. In addition, the authors conclude that effectiveness does not depend on baseline serum antibody status.
      • Tocilizumab administration for the treatment of hospitalized patients with COVID-19: A systematic review and meta-analysis. 10/4/21. Kyriakopoulos C. Respirology.
        This well-written review includes 52 studies (nine randomized controlled trials [RCTs] and 43 observational) with a total of 27,004 patients. In both RCTs and observational studies, the use of tocilizumab was associated with a reduction in mortality; 11% in RCTs and 31% in observational studies. The need for mechanical ventilation was reduced by 19% in RCTs. Both RCTs and observational studies showed a benefit from tocilizumab on the composite endpoint of mortality or need for mechanical ventilation. Tocilizumab improved mortality both in ICU and non-ICU patients.
      • Tocilizumab and remdesivir in hospitalized patients with severe COVID-19 pneumonia: a randomized clinical trial. 10/5/21. Rosas IO. Intensive Care Med.
        In this randomized controlled trial of patients with severe COVID-19 pneumonia, 434 were randomly assigned to tocilizumab plus remdesivir and 215 to placebo plus remdesivir. Of the 649 patients, 88.2% received corticosteroids. The median time from randomization to hospital discharge or “ready for discharge” was 14 days with tocilizumab plus remdesivir and 14 days with placebo plus remdesivir. Although large platform trials showed a survival benefit of tocilizumab in patients with severe COVID-19 and declining respiratory status, this trial did not confirm treatment benefit of tocilizumab in combination with remdesivir.
        SAB Comment: Although the use of tocilizumab along with steroids is recommended in a number of major guidelines (WHO, NIH, IDSA), this industry-sponsored RCT fails to confirm its effectiveness when used with steroids and the antiviral, remdesivir.

      October 4, 2021

      • Antibody and cellular therapies for treatment of covid-19: a living systematic review and network meta-analysis. 9/24/21. Siemieniuk RA. BMJ.
        This updatable meta-analysis from the World Health Organization and British Medical Journal collaboration reviews the results of 47 randomized trials (selected for quality from 1050) dating to July 2021. It evaluates research on monoclonal antibodies, polyclonal antibodies, convalescent plasma, intravenous immunoglobulin (IVIg), umbilical cord mesenchymal stem cells, peripheral blood nonhematopoietic enriched stem cells, anti-SARS-CoV-2 IVIg, and therapeutic plasma exchange. The authors’ current conclusions are that in patients with nonsevere COVID-19, the antiviral monoclonal antibodies casirivimab-imdevimab (Regeneron) probably reduce risk of hospitalization, and that bamlanivimab, bamlanivimab-etesevimab (Lilly), and sotrovimab (GlaxoSmithKline) may reduce risk of hospitalization. None of the other interventions reviewed appear to have any impact when given to patients with nonsevere COVID-19, and none of the monoclonal antibodies or other therapies appear to have any impact when given to patients with severe covid-19 with the exception that casirivimab-imdevimab may reduce the risk of mortality in patients with severe COVID-19 who do not have detectable antibodies to the SARS-CoV-2 spike protein.
        SAB Comment: Our policy has been to refrain from including nonpeer reviewed preprints in our newsletter. While this review article includes 10 such preprints among the 47 studies considered, we believe that those studies have essentially undergone peer review by the authors of this systematic review.
      • Convalescent plasma for COVID-19: a meta-analysis, trial sequential analysis, and meta-regression. 9/28/2021. Snow TAC. Br J Anaesth.
        Authors identified 17 randomized controlled trials that recruited 15,587 patients with 8,027 (51.5%) allocated to receive convalescent plasma (CP). “In patients with COVID-19, there was no clear mortality benefit associated with CP treatment. In patients with mild disease, CP did not prevent either the need for mechanical ventilation or ICU admission.” Meta-regression did not reveal association with titre of CP, timing of administration, or risk of death and treatment effect (P>0.05). Risk of bias was high in most studies. Authors state that it is unknown whether early high-titre CP could benefit high-risk patients, or those with worsening illness who lack endogenous anti-SARS-CoV-2 antibodies.
      • Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial. 9/17/21. Ader F. Lancet Infect Dis.
        DisCoVeRy is a phase 3, open-label, adaptive, multicenter, randomized, controlled trial conducted in 48 sites in Europe, studying 857 COVID-19 patients. Four hundred twenty-nine patients were admitted with mild to moderate symptoms (WHO scale of more than 3 and less than 6), had symptoms for more than 7 days, and who were on oxygen prescription were treated with remdesivir, while 428 patients were treated with standard care. Outcome were measured at days 3 through 29. No clinical benefit regarding viral clearance, mortality, morbidity or recovery was noted with remdesivir.

      September 27, 2021

      • Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. 9/4/21. Marconi VC. Lancet Respir Med.
        This oral Janus kinase inhibitor with anti-cytokine properties and potential antiviral effectiveness has been studied extensively in hospitalized patients with COVID-19. Sponsored by Pfizer, the COV-BARRIER trial enrolled 1525 participants from 101 centers in 12 countries between June 2020 and January 2021. While its ability to reduce disease progression was not significant, 28-day all-cause mortality was reduced by 5% (from 13% to 8%) in the baricitinib group compared to the placebo population (HR 0.57) which translates in one additional death prevented per 20 baricitinib-treated patients. An accompanying editorial highlights the effectiveness and safety of JAK inhibitors in combination with steroids and remdesivir. It also provides plausible explanations for the observed differences in the results of this trial (COV-BARRIER) and the ACCT-2 trial of baricitinib.
      • Fostamatinib for the treatment of hospitalized adults with COVID-19: A randomized trial. 9/1/21. Strich JR. Clin Infect Dis.
        Fostamatinib is an oral tyrosine kinase inhibitor that is FDA-approved for the treatment of chronic idiopathic thrombocytopenic purpura. Its active metabolite inhibits both the release of proinflammatory cytokines and platelet mediated thrombus formation provoked by anti-spike immune complexes. In this NIH-led pilot study, fostamatinib was given to 30 patients with advanced COVID-19 requiring oxygen and receiving remdesivir and corticosteroids. Compared to the placebo group, lung injury appeared to resolve more quickly, serious side effects were significantly reduced, and several biomarkers improved significantly. Larger confirmatory trials are needed to establish the drug’s role in advanced SARS-CoV-2 infections.

      September 20, 2021

      • Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial. 9/4/21. Kyriazopoulou E. Nat Med.
        From December 2020 to March 2021, 594 COVID-19 positive patients at 30 study sites underwent a phase 3 double-blinded randomized controlled trial evaluating the efficacy and safety of early initiation of anakinra treatment on the WHO clinical progression scale (WHO-CPS) at day 28. The study patients (405 anakinra and 189 placebo) all had a soluble urokinase plasminogen activator receptor (suPAR) titer >6ng/ml, which is an early predictor of severe respiratory failure. At 28 days, the odds ratio of having a worse clinical status on the WHO-CPS was 0.36 in the anakinra group. The study includes consideration of CRP, neutrophil to lymphocyte ratio, ferritin, AST and IL-6 levels as well as SOFA scores.
      • Results of the CAPSID randomized trial for high-dose convalescent plasma in severe COVID-19 patients. 8/31/2021. Körper S. J Clin Invest.
        This RCT from Germany, randomized 105 COVID-19 hospitalized adults with COVID-19 requiring respiratory support or intensive care treatment to standard care with or without convalescent plasma from August 2020 to December 2020. Demographic profiles and other COVID-19 treatments were similar for the two groups. The transfusion of 3 U of convalescent plasma over 5 days did not change mortality, respiratory recovery or discharge from the ICU or hospital. However, the authors note that those patients who received transfusions with higher levels of neutralizing antibodies had improved outcomes.
      • The effect of immunosuppressants on the prognosis of SARS-CoV-2 infection. 9/3/21. Ward D. Eur Respir J.
        This retrospective Danish study found that pre-COVID-19 exposure to corticosteroids increased the risk of ICU admission and death in patients who developed PCR-positive COVID-19. The authors analyzed 36,737 cases of COVID-19, of which 527 were exposed to immunosuppressants within the 120 days preceding a positive PCR. For patients exposed to systemic glucocorticoids (at least 7.5mg prednisone equivalent per day), compared to unexposed patients, the adjusted risk ratio for ICU admission was 1.76 and of death was 2.38. Exposure to other immunosuppressants, including selective immunosuppressants, interleukin inhibitors, tumor necrosis factor inhibitors, calcineurin inhibitors, hydroxychloroquine and chloroquine, was not associated with an increased risk of hospitalization, ICU admission nor death.
        SAB Comment: This information may be useful to providers prescribing immunosuppressive drugs during the pandemic. Though the use of steroids is associated with worse COVID-19 disease, this study is not designed to determine if reducing steroid dose is helpful.

      August 30, 2021

      • Association of in-hospital use of ACE-I/ARB and COVID-19 outcomes in African American population. 8/19/2021. Li S. J Clin Invest.
        A retrospective analysis of over 6200 COVID-19-positive patients admitted to one NY hospital system 2/24/20-5/31/20 was analyzed to determine whether use of ACE-I/ARB (N=1,138) was associated with COVID-19 in-hospital mortality in African Americans (AA) compared with non-AA population. In a multivariate logistic regression model ACE-I/ARB use was independently associated with reduced risk of in-hospital mortality in the entire population (OR, 0.66) however the benefit was greater in the AA population (OR 0.44) (N=1,621), than in the non-AA population (OR 0.75). When analyzing each medication class separately, ARB in-hospital use was significantly associated with reduced in-hospital mortality in the AA population (OR, 0.196), while ACE-I use was not associated with impact on mortality in any population. Authors hypothesize that this is due to a higher ACE D-allele prevalence in the AA population. The benefit of ACE-I/ARB and difference in AA population was only seen with adjustment for confounding risk factors. However a major shortcoming is that all patients were not followed out – data included all COVID patients admitted within the study period yet nearly 9% of patients were still hospitalized at the end of the study.
      • Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis. 8/16/2021. Kyriazopoulou E. Lancet Rheumatol.
        Aggregate data on 1,185 patients from 9 international studies (8 observational, 1 randomized controlled study) were analyzed. In the individual patient-level meta-analysis (N=895 from 6 studies), after adjusting for age, comorbidities, baseline PaO2/FiO2 ratio, CRP concentrations, and lymphopenia, 28-day mortality was significantly lower in patients treated with anakinra (38 [11%] of 342) than standard of care with or without placebo (137 [25%] of 553; adjusted OR 0.32), and lowest if CRP >100 mg/L (OR 0.28). However the survival benefit of anakinra was significant when given without dexamethasone (OR 0.23), but not with dexamethasone co-administration; in those breathing spontaneously (OR 0.3) but not those invasively ventilated. Anakinra may be useful in spontaneously ventilating patients with a contraindication to steroids or for those with CRP >100. Larger randomized trials are needed to clarify the role of anakinra in COVID-19.

      August 9, 2021

      • Dexamethasone and tocilizumab treatment considerably reduces the value of C-reactive protein and procalcitonin to detect secondary bacterial infections in COVID-19 patients. 8/6/21. Kooistra EJ. Crit Care.
        This prospective observational study from a single Dutch medical center compares the established predictive value of inflammatory biomarkers C-reactive protein (CRP) and procalcitonin (PCT) in identifying secondary bacterial infections in severe COVID-19 patients admitted between March and April 2020. A second patient cohort was treated in their ICU after August 2020 which received dexamethasone with or without a single dose of tocilizumab 8mg/kg IV. Results showed marked blunting of the CRP and PCT response during and a rebound after cessation of immunosuppression which could be falsely interpreted as a signal of secondary infection, while the blunted response may mask ongoing secondary infection.
      • Drug-induced phospholipidosis confounds drug repurposing for SARS-CoV-2. 7/30/21. Tummino TA. Science.
        Many drugs are reported to have in vitro activity against SARS-Co-V-2. Some of these “repurposed” drugs including hydroxychloroquine, azithromycin and amiodarone are already in trials. This investigation discovered a shared mechanism of many “repurposed” drugs: phospholipidosis, which is a phospholipid storage disorder induced by cationic amphiphilic drugs. For all 23 drugs tested, development of intracellular phospholipidosis correlated with antiviral “efficacy.” Conversely, drugs active against the same targets that did not induce phospholipidosis were not antiviral. Phospholipidosis does not reflect specific target-based activities, but is a toxic confound. Early detection of phospholipidosis could eliminate screening artifacts, steering focus on molecules with real potential. The accompanying editorial points out that that “mechanism-informed” strategy for drug repurposing can work (e.g., remdesivir) and may result in clinically useful results. Conversely, repurposing drugs based on hypothesis-free cellular screens “has not yet yielded any effective treatments for COVID-19, nor for any disease.” These latter mass screenings are not shortcuts, but rather costly, scientific “dead-ends.”
      • Efficacy and safety of remdesivir in hospitalised COVID-19 patients: a systematic review and meta-analysis. 7/31/21. Angamo MT. Infection.
        This is a meticulous review of pooled data taken from 4 RCTs and 3 controlled observational trials covering a 12-month span starting December 2019 comparing remdesivir treatment to placebo or standard care. Remdesivir significantly accelerated recovery at day 7 (21%) and day 14 (29%), lowered the incidence of high oxygen flow therapy by 27% and mechanical ventilation by 47%, and decreased mortality on day 14 by 39% but not on day 28. Serious adverse effects were less common in the remdesivir group and the authors conclude that remdesivir treatment is effective and safe early in SARS-CoV-2 infections.

      July 26, 2021

      • Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2. 7/21/21. Drayman N. Science.
        Out of 1,900 clinically tested drugs tested in vitro, eight drugs inhibited the activity of one of two SARS-CoV-2’s major proteases, 3CLpro. The most potent inhibitor was masitinib, an orally bioavailable tyrosine kinase inhibitor (TKI) previously tested in human cancers, neurologic and mast cell disorders. In SARS-CoV-2, masitinib acts as a competitive inhibitor of 3CLpro, not as a TKI. SARS-CoV-2-infected mice treated with masitinib showed >200-fold viral titer reductions in nose and lung with reduced lung inflammation. Masitinib was effective in vitro against alpha, beta, and gamma variants. Clinical trials are recommended with use of masitinib early in infection.
        SAB Comment: Clinical studies of masitinib are currently on temporary hold due to the potential for adverse cardiac effects.

      July 19, 2021

      July 9, 2021

      • Efficacy and safety of remdesivir in COVID-19 caused by SARS-CoV-2: a systematic review and meta-analysis. 6/25/21. Singh S. BMJ Open.
        Investigators reviewed and analyzed 4/52 RCTs with a total of 7324 patients to evaluate the efficacy of remdesivir for COVID-19 patients. The results indicated that there is no benefit with mortality rate. A benefit favoring remdesivir over control does exist in terms of rates of clinical improvement and faster time to clinical improvement. No difference was shown in respiratory failure in two (flawed) studies. All outcomes except mortality were influenced by two studies which were riddled with high risk of bias and low quality evidence. In a cost to benefit analysis, remdesivir has a limited role in poor countries.

      June 28, 2021

      • Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia. 6/16/21. Guimarães PO. N Engl J Med.
        This randomized, double-blind, placebo-controlled and industry-sponsored trial (“STOP COVID”) involving 289 hospitalized patients with Covid-19 pneumonia in Brazil showed tofacitinib superior to placebo in reducing the incidence of death or respiratory failure (18 vs 29% – HR 0.63). Overall mortality was 2.8% in the tofacitinib group vs. 5.5% for placebo. Standard therapy (antivirals, glucocorticoids, anticoagulation) was comparable between groups, as were adverse events. This study corroborates the findings of the NIH funded ACTT-2 trial and the value of JAK inhibition for the treatment of Covid-19 pneumonia in patients who are not yet receiving invasive mechanical ventilation.
        SAB Comment: NIH COVID-19 treatment guidelines recommend against the use of JAK inhibitors other than baricitinib for the treatment of COVID-19, except in a clinical trial.

      May 24, 2021

      • A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes. 5/11/21. Guo Y. Nature.
        The current monoclonal antibodies (mAb) from Regeneron and Lilly are based on the Hunan strain Spike sequence present prior to the emergence of mutants. Chinese scientists now report the development of a mAb called P4A1 that inhibits the Spike Receptor Binding Motif of the Spike Receptor-Binding Domain and acts against wild type and mutant Spike proteins. Also, P4A1 was engineered for safety, to extend its half-life and to reduce risk for Antibody-Dependent Enhancement of infection. In a rhesus monkey COVID model, a single infusion resulted in complete viral clearance. These data suggest P4A1’s potential against SARS-CoV-2 related diseases.
      • Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial. 5/17/21. RECOVERY Collaborative Group. Lancet.
        In this randomized open-label study, 5795 hospitalized patients received high-titer convalescent plasma (CP) plus usual care and 5763 received usual care alone in 177 UK National Health Service hospitals. Ninety-two percent received corticosteroids. The study was halted prematurely, as there were no significant differences between groups in all-cause 28-day mortality (24%), progression to invasive ventilation (12-13%), renal replacement therapy (4%) or the proportion discharged from hospital within 28 days (66%). Mean age was 63, nearly 2/3 were male, and 77% were white. Median number of days since symptom onset was 9. Only 5% required mechanical ventilation at randomization. A well-written editorial reviewing this study and findings of other studies of CP can be found here.
        SAB Comment: The RECOVERY trial includes the largest randomized study thus far of CP therapy for COVID-19. Although some retrospective observational studies of CP were encouraging, randomized controlled studies have not confirmed benefit. Questions remain about whether the average timing of CP therapy in this study was beyond the window of potential efficacy and whether selected patients may benefit from CP, particularly those with immune deficiencies.
      • Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study. 5/17/21. Drake TM. Lancet Rheumatol.
        This prospective, multicenter cohort study shows convincingly that patients who take NSAIDs before and in the early stages of a SARS-CoV-2 infection are not at a higher risk of dying or experiencing more severe disease. Using a proven data mining protocol, 72,179 hospitalized patients in 255 hospitals in the UK, with confirmed COVID-19, were enrolled and analyzed. Of those patients, 4,211 or 5.8% used NSAIDS (but not aspirin) before their illness. Propensity score matching resulted in balanced, well matched treatment groups and matched odds ratios for mortality, ICU admission, invasive ventilation, acute kidney injury, among others, showed no statistical difference. The authors urge policy makers to review advice issued early in the course of the pandemic regarding the use of NSAIDs and disease severity.

      May 7, 2021

      • Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. 5/2/21. RECOVERY Collaborative Group. Lancet.
        This long-awaited trial assessing the effectiveness of tocilizumab differentiated itself from several earlier attempts in two important aspects:

         

        1. It enrolled 4,116 of 21,550 adults at 131 sites in the UK as part of the RECOVERY trial between April 23, 2020 and January 24, 2021 and is therefore adequately powered and statistically sound.
        2. It demonstrated a small but significant benefit across a spectrum of disease severity and various degrees of respiratory support. Results included an improvement in mortality from 35% to 31% (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028) and an impressive drop in median time to being discharged from more than 28 days to 19 days.

        In addition, patients who were not receiving invasive mechanical ventilation at randomization were less likely to progress to invasive mechanical ventilation or death. An accompanying editorial that addresses the still unacceptably high mortality figures and the urgent need for additional therapies can be found here.

      April 19, 2021

      • Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial. 4/12/21. Ramakrishnan S. Lancet Respir Med.
        This is a prospective, randomized, open-label, phase-2, parallel-group, age-stratified, 146-patient UK study from July 16 to December 2, 2020 testing inhaled budesonide within 7 days of early symptom development versus standard care. Participants were self-monitored (temperature, pulse oximetry), contacted daily to record symptoms (O2 saturation and temperature), and intermittently self-collected nasopharyngeal swab specimens for analysis. Primary endpoints compared urgent care and emergency room visits and hospitalizations for worsening symptoms, which occurred in 1% of budesonide treated participants, and 14% of the usual care treated group. The study was terminated early with positive results for budesonide inhalant use. Authors concluded that budesonide was effective in treating early COVID-19 infection, could be applicable to global healthcare systems, and that further validation was required.
      • Editorial: Early treatment with inhaled budesonide to prevent clinical deterioration in patients with COVID-19. 4/12/21. Agusti A. Lancet Respir Med.
        This editorial, accompanying the article above, gives perspective to the study and discusses the implications of terminating the study early. The rationale for and use of budesonide (and potentially other inhaled corticosteroids) encourages further trials to confirm the value of this readily available therapy, with significant implications for a cost-effective and easily accessible disease mitigation strategy that could be used globally.

      April 16, 2021

      • Use of low-molecular weight heparin, transfusion and mortality in COVID-19 patients not requiring ventilation. 4/12/21. Grandone E. J Thromb Thrombolysis.
        Prior data has been conflicting with the utility of prophylactic low-molecular weight heparin (LMWH) with COVID-19. This group from Padua retrospectively examined the mortality of 264 non-ventilated inpatients with COVID-19 with respect to the prophylactic use of LMWH enoxaparin. One hundred fifty-six patients (87.7%) received standard LMWH prophylaxis during hospitalization. LMWH was significantly and independently associated with a reduction in mortality in these patients, (OR 0.31, 95% CI 0.13–0.85), as compared to patients who did not receive anticoagulation. Although transfusion or bleeding complications were not higher in these patients, the number of transfusions were significantly and independently associated with mortality. The median fatalities age was 80.5 years. These data suggest that COVID-19 patients who do not require ventilation benefit from prophylactic doses of LMWH.

      April 12, 2021

      April 7, 2021

      • New Decade, Old Debate: Blocking the Cytokine Pathways in Infection-Induced Cytokine Cascade. 3/31/21. Rizvi MS. Crit Care Explor.
        Providing deep perspective, this narrative review summarizes literature beginning in 1994 evaluating the efficacy and safety of anticytokine therapy for dysregulated immune responses to infectious pathogens. The longstanding idea of neutralizing “cytokine storm” induced by bacterial sepsis and/or ARDS, using cytokine pathway inhibitors or nonpharmacologic cytokine removal has a “grim history.” Severe COVID-19 causes less cytokine release than either condition; however, anticytokine therapy is being used. Discussions include potential reasons for failure, such as the complexity and variation of cytokine cascades, and future directions.
      • The role of antirheumatics in patients with COVID-19. 4/5/21. Nissen CB. Lancet Rheumatol.
        This review, written by an international panel of rheumatologists, nicely summarizes current knowledge of COVID-19 therapy targeting the immune system. Topics include evidence for potentially useful immune modulators (steroids and baricitinib), those under active investigation (tocilizumab, colchicine and anakinra), undergoing early trials (TNF blockade, anti-complement therapy and intravenous immunoglobin) and disproven treatments (hydroxychloroquine). Authors stress that the timing, dosing and interaction of these therapies is incompletely understood, and the hope that studies now underway will provide more clarity.
      • Toxicity of herbal medications suggested as treatment for COVID-19: A narrative review. 4/5/21. DiPietro MA. J Am Coll Emerg Physicians Open.
        The lack of a proven COVID-19 remedy has led to a host of recommendations promoting the use of various plant-based therapeutics, particularly traditional Chinese medicines. Authored by two emergency medicine physicians, this well-researched review of the major characteristics and toxicities of herbal preparations currently in use and sometimes recommended as treatments for COVID-19 provides valuable information on the symptomatology of “toxidromes” caused by mismanagement or overdoses of potentially toxic extracts including oleander and Datura species.

      March 17, 2021

      • α1-Antitrypsin: Key Player or Bystander in Acute Respiratory Distress Syndrome? 3/15/2021. Hogan G. Anesthesiology.
        This is a detailed review of α1-Antitrypsin (AAT), a serine protease inhibitor with a half-life of 4-5 days. AAT plays a vital role in conserving the balance between levels of pulmonary proteases and antiproteases, reduces inflammation, and modulates innate immune function and bacterial clearance. Investigators have demonstrated a therapeutic effect for sepsis, and potential benefit in models of endotoxin-induced acute lung injury, ventilator-induced lung injury, and lung transplantation. Authors discuss its potential as a novel treatment for ARDS and COVID ARDS.

      March 8, 2021

      March 1, 2021

      • Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. 2/25/21. The REMAP-CAP Investigators. New Engl J.
        Focusing on therapeutic success for COVID-19 patients requiring organ support measures, 895 patients were randomly assigned to receive one of two IL-6 receptor antagonists and were compared to a 402-patient control group receiving standard care, including glucocorticoids and antivirals. Tocilizumab was given to 366 patients starting in April, and sarilumab, available only since June, to 49 patients. Statistical criteria for efficacy were met in October 2020 and demonstrated significant therapeutic benefit for the primary outcome, expressed in more organ-support free days and lower in-hospital mortality. Both drugs also improved secondary outcomes, including 90-day survival, time to ICU and hospital discharge, among others. Authors link the success of IL-6 antagonists in this series to their use in the sickest patients while organ dysfunction is still reversible.

      February 22, 2021

      February 19, 2021

      February 12, 2021

      • SAB Comment: The SAB policy is to only review articles that have undergone peer review for inclusion on this website. We are making an exception for the following two studies due to their therapeutic implications for COVID-19 patients. Final versions of these studies will be presented as they become available.
        • ATTACC, ACTIV-4a & REMAP-CAP multiplatform RCT: Results of interim analysis. 1/28/21. NHLBI.
          This is new, exciting RCT data for decreasing morbidity and mortality for COVID-19 with therapeutic anticoagulation. This interim data from NHLBI examines 3 international trials, suggesting decreased morbidity and mortality for COVID-19 patients with therapeutic anticoagulation for patients not in the ICU.
        • Inhaled budesonide in the treatment of early COVID-19 illness: a randomised controlled trial. 2/8/21. Ramakrishnan S. medRxiv.
          This open label trial from Oxford, UK, convincingly showed that a steroid inhaler used twice daily within 7 days of onset of mild COVID-19 significantly improves outcome measured primarily in hospitalization and secondarily in days to recovery from symptoms, fever and low oxygen saturation. Statistically, the difference in proportions was 0.131, 95% CI (0.043, 0.218), p=0.004, indicating a relative risk reduction of 90% for patients using the budesonide inhaler compared to usual care.
          SAB Comment: This study has not yet been peer reviewed, was partially funded by Astra Zeneca and was halted early due to the December surge in COVID-19 cases in the study area. However, the authors plead convincingly that this ubiquitous treatment modality can influence the course of illness and possibly avoid prolonged recovery from SARS-CoV-2.

      February 10, 2021

      • Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. 2/5/21. RECOVERY Collaborative Group. Lancet.
        As part of the British RECOVERY trial which includes 176 hospitals, 2582 hospitalized patients with COVID-19 were randomized to receive azithromycin 500 mg daily for 10 days and compared to 5181 patients receiving standard care. The 28-day all-cause mortality for both patient groups was 22% indicating that azithromycin has no benefit for COVID-19 and should be used for antimicrobial indications only.
        SAB Comment: The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial is an investigator-initiated, individually randomized, controlled, open-label, adaptive platform trial to evaluate the effects of potential treatments in patients admitted to hospital with COVID-19. After completing work on azithromycin, dexamethasone, hydroxychloroquine, lopinavir–ritonavir, convalescent plasma, and tocilizumab, study into the effects of REGN-COV2 (a combination of two monoclonal antibodies directed against SARS-CoV-2 spike glycoprotein), aspirin, and colchicine are still underway.

      February 8, 2021

      February 3, 2021

      • Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. 12/31/20. Baden LR. NEJM.
        This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the US. Persons at high risk for SARS-CoV-2 infection or its complications (with locations or circumstances that put them at an appreciable risk of SARS-CoV-2 infection, a high risk of severe COVID-19, or both) were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (Moderna) (100 μg) or placebo 28 days apart. Site-selection and enrollment processes were adjusted to increase the number of persons from racial and ethnic minorities in the trial. The mRNA-1273 vaccine showed 94.1% efficacy at preventing COVID-19 illness, including severe disease. All the severe COVID-19 cases were in the placebo group. Aside from transient local and systemic reactions, no safety concerns were identified.
      • Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. 12/31/20. Polack FP. NEJM.
        In this ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, the authors randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 (BioNTech-Pfizer) vaccine candidate. Forty-three thousand four hundred forty-eight (43,448) individuals received injections. Eight patients who received the vaccine developed COVID-19 compared to 162 patients who received placebo, i.e., the vaccine was 95% effective. None of the eight vaccinated patients who developed COVID-19 required hospitalization. The safety profile included short-term, mild-to-moderate pain at the injection site, fatigue, and headache. Although the vaccine can be stored for up to 5 days at standard refrigerator temperatures once ready for use, very cold temperatures are required for shipping and longer storage.

      February 1, 2021

      January 22, 2021

      • Renin-angiotensin system inhibitors in hospitalised patients with COVID-19. 1/10/21. Williams B. Lancet Respir Med.
        This editorial provides a commentary on the ACEI/ARB controversy. While highlighting the REPLACE COVID trial which examined the impact of continuing or withdrawing chronic ACEIs or ARB treatment in 152 patients hospitalized with COVID-19 across 20 international centers which resulted in no difference in outcome, it stresses the global collaboration, scale and speed with which investigators conducted observational cohort studies with similar results which made this small RCT’s results convincing. In addition, the authors refer to the larger BRACE CORONA RCT with identical yet unpublished results and refer to recent literature showing that there is no increase in ACE2 expression caused by ACEIs and ARBs in pulmonary or renal tissue.
      • The Association of Low Molecular Weight Heparin Use and In-hospital Mortality Among Patients Hospitalized with COVID-19. 1/4/21. Shen L. Cardiovasc Drugs Ther.
        This paper examines 525 COVID-19 hospitalized patients from Wuhan. Twenty-three percent were treated with low molecular weight heparin (LMWH). These patients were likely to be older, have more co-morbidities and had more severe COVID-19 parameters. Compared with non-LMWH group, LMWH group had a higher unadjusted in-hospital mortality rate (21.70% vs. 11.10%; p = 0.004), but a lower adjusted mortality risk (adjusted odds ratio [OR], 0.20; 95% CI, 0.09–0.46). These retrospective data suggest that LMWH use was associated with lower all-cause in-hospital mortality. The survival benefit was particularly significant among more severely ill patients.
        SAB Comment: This retrospective study suggests benefits of LMWH on mortality and contributes to the ongoing debates about the use of anticoagulants in these patients. This further highlights the need for the upcoming RCTs.

      January 19, 2021

      • Persistent Post-COVID-19 Inflammatory Interstitial Lung Disease: An Observational Study of Corticosteroid Treatment. 1/12/21. Myall KJ. Ann Am Thorac Soc.
        This is a well-written narrative following 837 COVID-19 patients seen between February and May 2020 in metropolitan London, UK hospitals. Four weeks after discharge, 39% had not returned to baseline and underwent further study. Thirty patients with persistent respiratory symptoms and interstitial lung disease received an initial maximal dose of prednisolone 0.5mg/kg with rapid weaning over a 3-week period which improved diffusion capacity by 31.6% and FVC by 9.6% which resulted in symptomatic and radiological improvement. This preliminary data requires further study into the natural history and potential treatment for patients with persistent inflammatory interstitial lung disease following SARS-CoV2 infection.

      January 15, 2021

      • Early corticosteroids are associated with lower mortality in critically ill patients with COVID-19: a cohort study. 1/5/21. Monedero P. Crit Care.
        This is a prospective, multicenter, observational, cohort study in 882 critically ill adult patients with COVID-19 admitted to 36 critical care units in Spain. Beginning in early March to the end of June 2020, patients receiving corticosteroids within 48 hours of ICU admission had a lower mortality compared to those receiving steroids later (30 vs. 40% – HR 0.71) or not at all. Patients treated early did better overall with shorter ICU stays, fewer ventilator days and a lower incidence of organ dysfunction. Higher dosages were found to be more effective. Corticosteroid administration occurred on average 12 days after symptom onset. The authors recommend corticosteroids as early as day 7 provided inflammatory markers are elevated.

      January 13, 2021

      • Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults. 1/6/21. Libster R. N Engl J Med.
        This article describes an Argentine randomized, double-blind, placebo-controlled trial of convalescent plasma (CP) with IgG titers >1:1000 against SARS-CoV-2 within 72 hours following the onset of mild COVID-19. CP reduced disease progression in adult patients older than 75 years or 65-74 years old with co-morbidities. Severe respiratory disease developed in 13/80 patients (16%) who received 250 ml of CP and 25/80 (31%) who received 250 ml normal saline (relative risk, 0.52). Benefit was more frequent following units with higher IgG titers, indicating a dose-dependent effect. Deaths were 2/80 in the CP group vs. 4/80 in the placebo group.

      January 8, 2021

      • A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19. 12/28/20. ACTIV-3/TICO LY-CoV555 Study Group. N Engl J Med.
        The antiviral drug remdesivir has been shown to decrease the time to recovery in hospitalized patients with COVID-19. However, the preliminary results of a study involving a single infusion of the neutralizing monoclonal antibody LY-CoV555 when co-administered with remdesivir, did not demonstrate efficacy, among hospitalized patients (sample size 300) who had COVID-19 without end-organ failure, measured at day 5 vs those who received placebo. LY-CoV555 met the pre-specified criteria for futility and further enrollment was stopped.
      • Update to living systematic review on drug treatments for covid-19. 12/18/20. Siemieniuk RAC. BMJ.
        First 6-month follow-up and therefore “living” review of randomized trials examining COVID-19 treatment options were discussed, specifically their comparative effectiveness that have not been tested head-to-head. Leading off with a uniquely designed interactive infographic diagram (available on the web but not featured on the PDF download) that links therapeutics to 11 different outcomes, the review tabulates and discusses results and allows for a quick search as well as in-depth sourcing using extensive tables and bibliographic links sorted by outcome modality. This encyclopedic review originated from 20 institutions in 13 countries, including 3 in China, and in its conclusions highlights the beneficial effect of glucocorticoids on mortality and mechanical ventilation, while questioning other drugs, including tocilizumab and remdesivir.

      January 6, 2021

      • Corticosteroid use in COVID-19 patients: a systematic review and meta-analysis on clinical outcomes. 12/15/20. van Paassen J. Crit Care.
        This well-conducted systematic review and meta-analysis to evaluate safety and effectiveness of corticosteroids in COVID-19 included 44 studies and 20,197 patients collected between December 1, 2019 and October 1, 2020. Primary outcomes were short-term mortality and viral clearance (based on RT-PCR in respiratory specimens). Secondary outcomes were need for mechanical ventilation, other oxygen therapy, length of hospital stay and secondary infections. Non-peer reviewed and pre-published manuscripts were excluded from analysis. Findings from observational studies and RCTs confirm beneficial effect of corticosteroids on short-term mortality and reduction in mechanical ventilation. A possible signal of delayed viral clearance and an increase in secondary infections was noted. Optimal timing, dose and duration of corticosteroids, in relation to safety, remain subjects for further investigation.
      • Corticosteroids for Patients With Coronavirus Disease 2019 (COVID-19) With Different Disease Severity: A Meta-Analysis of Randomized Clinical Trials. 12/10/20. Pasin L. J Cardiothorac Vasc Anesth.
        In this meta-analysis of 5 studies involving treatment with steroids of 7,692 COVID patients, the authors note that the effect of corticosteroids therapy on survival with COVID patient varies with different respiratory support. The use of corticosteroids may be detrimental to patients who do not require oxygen support (NNH/number needed to harm=29) and increases mortality. Its effectiveness for mechanically ventilated patients was (NNT/number needed to treat=19). The majority of COVID-19 patients not requiring oxygen/mechanical ventilation will have a better survival benefit without steroids.
      • COVID-19 Convalescent Plasma Treatment of Moderate and Severe Cases of SARS-CoV-2 Infection: A Multicenter Interventional Study. 12/7/20. Alsharidah S. Int J Infect Dis.
        SAB Comment: This is a non-randomized observational study from Kuwait. Research is needed to determine patient groups that benefit.
        One hundred and thirty-five patients with moderate-severe COVID-19 disease who received 2 units of convalescent plasma (CP) within 3 days of hospital admission had an earlier and higher rate of clinical improvement compared with 233 control patients. Moderate disease was found in 86.5% of CP group (n=89) who had a time to clinical improvement of 7 days versus 68% of controls with time to clinical improvement of 8 days (p=0·006). Severe disease was found in 61% of CP group (n=46) with time to clinical improvement of 7 days vs. 35% of controls with time to clinical improvement of 15.5 days (p=0·003). Overall 30-day mortality was 18% CP group vs. 39% controls. Moderate disease patients had a significantly lower mortality following CP (11% vs. 30%, p= 0.001).

      December 18, 2020

      • Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. 12/11/20. Kalil AC. N Engl J Med.
        This article provides the encouraging outcome of a randomized trial enrolling 1033 patients in 8 countries, led by the team that conducted ACTT-1, the remdesivir randomized control trial. The oral anti-inflammatory drug baricitinib, a selective inhibitor of Janus kinase (JAK) 1 and 2, in combination with remdesivir, proved safe and superior to remdesivir alone for the treatment of hospitalized patients with COVID-19. While the primary outcome, time to recovery, improved by one day only, patients with impending respiratory failure benefitted most with progression to death or invasive ventilation being 31% lower in the combination group. The discussion includes a detailed review of the drugs’ potential dual action as an anti-inflammatory and antiviral and makes a pertinent comparison with dexamethasone and the RECOVERY trial.
        The incidence of side effects of JAK inhibitors (immunosuppression, secondary infections, and thrombosis) were not significantly higher when baricitinib was added.

      December 14, 2020

      December 11, 2020

      December 7, 2020

      • Repurposed Antiviral Drugs for Covid-19 – Interim WHO Solidarity Trial Results. 12/2/20. WHO Solidarity Trial Consortium. N Engl J Med.
        Beginning in March 2020, the WHO Solidarity trials enrolled 11,330 patients in 405 hospitals in 30 countries representing all six WHO regions and randomly assigned them to receive either remdesivir, lopinavir, hydroxychloroquine or interferon beta-1a regimens or to receive hospital-specific standard care. None of these drugs achieved the desired goal of a reduction in 28-day mortality. Except for remdesivir, all trials have since been discontinued.
        SAB Comment: Despite a negative outcome, this work is encouraging as it shows WHO’s capability to direct a rigorous global study protocol and a complex data collection and report it in a timely manner.

      December 4, 2020

      • A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia. 11/24/20. Simonovich VA. N Engl J Med.
        Convalescent plasma with a median titer of 1:3200 of total SARS-CoV-2 antibodies was administered a median of 8 days after the onset of symptoms to 228 hospitalized patients with severe COVID-19 pneumonia. Placebo was administered to 105 patients. Other therapy was not standardized. After 30 days there was no significant difference in outcome. Adverse effects of plasma transfusion could not be evaluated. This also suggests that passive immune therapy with monoclonal antibodies may not be beneficial to such a population.
        SAB Comment: Other studies indicate that antibodies administered early after onset of symptoms to patients with mild disease are beneficial.

      December 2, 2020

      November 2, 2020

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

      October 30, 2020

      • Aspirin Use is Associated with Decreased Mechanical Ventilation, ICU Admission, and In-Hospital Mortality in Hospitalized Patients with COVID-19. 10/23/20. Chow JH. Anesth Analg.
        This multi-center cohort study of 412 COVID-19 patients explored the theory that aspirin’s anti-platelet and anti-inflammatory properties might be beneficial in lowering the risk of serious outcomes. Ninety-four patients who had taken aspirin within 7 days of admission were compared with 314 patients who had not. Aspirin use was independently associated with decreased hazard ratio (HR) of mechanical ventilation (HR 0.56), ICU admission (HR 0.57), and in-hospital mortality (HR 0.53). There were no differences in major bleeding (p=0.69) or overt thrombosis (p=0.82) between aspirin users and non-aspirin users and confounding variables were carefully controlled. Potential mechanisms are discussed including aspirin’s ability to lower interleukin-6, C-reactive protein, and macrophage stimulation. Randomized controlled trials are necessary to confirm these results.
      • Awake prone positioning for COVID-19 hypoxemic respiratory failure: A rapid review. 10/23/20. Weatherald J. J Crit Care.
        Using a “rapid review” technique, these authors from Calgary synthesize 35 studies (none randomized) evaluating the effect of awake proning in 414 COVID-19 patients with respiratory failure. All but one study showed improvement in oxygenation while prone, but generally not sustained when returned to the supine position. 29% of patients went on to require intubation. The authors conclude that “many questions remain unanswered when considering the use of awake prone positioning.”
      • Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomized controlled trial (PLACID Trial). 10/22/20. Argwal A. BMJ.
        A randomized, controlled trial of convalescent plasma (CP) in 227 treated and 224 control hospitalized patients with moderate COVID-19 from 39 hospitals in India. Patients who received 200 ml of CP x 2 had less dyspnea and fatigue and a 24% higher rate of negative PCR on day 7 (P<0.05). No difference in the levels of inflammatory markers such as ferritin, C-reactive protein, D-dimer, or LDH was observed. However, there was no difference in progression to severe disease or mortality at 28 days between groups, including a subgroup of patients who received plasma with neutralizing antibody titers >1:80.
      • Convalescent plasma is ineffective for covid-19. Lessons from the Placid Trial. 10/22/20. Pathak EB. BMJ.
        In light of the prevalence of micro-thrombosis and the large number of thrombotic complications in COVID-19 patients, authors of this accompanying editorial highlight the pro-thrombotic properties of plasma and recommend that future blinded convalescent plasma (CP) trials exclude plasma without detectable neutralizing antibodies or treatment of control groups with other plasma. They point out that coagulation-related events in previous CP trials were not rigorously screened for their potential relationship to the treatment.

      October 26, 2020

      • Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. 10/21/20. Stone JH. N Engl J Med.
        This is a prospective, randomized, placebo-controlled study where treated patients received a single dose of 8mg/kg of tocilizumab (161 of 243 enrolled patients). The results showed that tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with COVID-19.
      • Time to Reassess Tocilizumab’s Role in COVID-19 Pneumonia. 10/20/20. Parr JB. JAMA Intern Med.
        The author’s conclusions in this excellent editorial are informed by three studies (two are randomized prospective) reported in this issue of JAMA Internal Medicine and by two additional randomized prospective studies. Although observational studies by the STOP-COVID investigators and others report mortality benefit and other positive outcomes, findings from the randomized prospective trials described herein (total of 542 patients treated) do not support routine tocilizumab use in COVID-19. A well-constructed summary table of the five studies is provided.

      October 21, 2020

      • Famotidine Use Is Not Associated With 30-day Mortality: A Coarsened Exact Match Study in 7158 Hospitalized COVID-19 Patients from a Large Healthcare System. 10/15/20. Yeramaneni S. Gastroenterology.
        This large retrospective study from HCA Healthcare repudiates 2 smaller studies from Columbia and Hartford which reported a two-fold reduction in risk of death or intubation for COVID-19 inpatients. One thousand one hundred twenty-seven patients (15.7%) received famotidine and 6031 (84.3%) did not. Applying multivariable logistic regression within a carefully matched cohort showed no association between in-hospital famotidine use and 30-day mortality after adjustment for WHO severity, smoking status, and listed medications.
        SAB Comment: Due to famotidine’s ability to inhibit a protease essential for SARS-CoV-2 virus replication in vitro, it is under intense study in many centers. A clinical trial administering high-dose IV treatment (120 mg IV q8h) is currently under way at Columbia.

      October 19, 2020

      • Acute Respiratory Distress Syndrome: Contemporary Management and Novel Approaches during COVID-19. 10/5/20. Williams GW. Anesthesiology.
        This is a succinct, well-written review of best practice treatment strategies for non-COVID-19 ARDS with research-based updates on appropriate strategies for COVID-19 associated-ARDS treatments. Figures and brief descriptions are provided on the research supporting low tidal volumes, PEEP levels, prone positioning, PaO2 targets, steroid treatment, fluid management, ECMO and early neuromuscular blockade.
      • Blood purification therapy with a hemodiafilter featuring enhanced adsorptive properties for cytokine removal in patients presenting COVID-19: a pilot study. 10/12/2020. Villa G. Crit Care.
        Italian preliminarily prospective observational study of 37 patients receiving immunomodulatin or support of renal function using Baxter’s oXiris heparin-coated extracorporeal hemodiafilter Feb-April 2020. Compared to the expected (65%!) mortality rates, as calculated by APACHE IV, the mean observed rates were 8.3% lower after treatment. Reduction in serum IL-6 concentrations correlated with improved organ function, measured as decreased SOFA score. The best improvement in mortality rate was observed in patients receiving early treatment during in ICU. Anticoagulation regimens were inconsistent. 7 treatments (19%) resulted in clotting.
      • Convalescent plasma for patients with severe COVID-19: a matched cohort study. 10/10/20. Rogers R. Clin Infect Dis.
        This small study from 3 hospitals compared 64 recipients of 1-2 units of CP (median 7 days after symptom onset) with 177 matched controls. Neither in-hospital mortality (~15%) nor overall rate of hospital discharge differed significantly, although the rate of hospital discharge among patients older than 65 years who received convalescent plasma (CP) was significantly higher (RR 1.86, 95% CI 1.03 – 3.36). There was a greater than expected frequency of transfusion reactions in the CP group (2.8% per unit transfused). Authors suggest adequately powered randomized studies should target patients older than 65 years when assessing CP treatment efficacy.
      • The impact of protocol-based high-intensity pharmacological thromboprophylaxis on thrombotic events in critically ill COVID-19 patients. 10/12/20. Atallah B. Anaesthesia.
        This study was conducted to discover if high-intensity thromboprophylaxis would lead to fewer thrombotic events in COVID-19 positive patients. These patients were selected for high-intensity thromboprophylaxis when the D-dimer level was > 2ug/ml, and for therapeutic anticoagulation when the level was >3ug/ml. High-intensity thromboprophylaxis (enoxaparin 40 milligrams bid), but not therapeutic anticoagulation was associated with fewer thromboembolic events. Low D-dimer levels were independently associated with fewer venous thromboembolism events. Bleeding events in the high intensity thromboprophylaxis group were 2.7% compared to 16.5% using therapeutic anticoagulation. The authors conclude that high intensity thromboprophylaxis may reduce the incidence of thrombotic events without a significant increase in bleeding.
      • Treatments Considered for COVID-19. 10/15/20. The Medical Letter.
        This latest edition of The Medical Letter’s “Treatments Considered for COVID-19” was released on October 15, 2020 and included comprehensive (over 100 pages) up-to-date tables of drug, vaccine and other treatment classes. The columns include “Drug and Dosage,” “Efficacy,” “Adverse Effects/Interactions” and “Comments,” all with thorough referencing.
        Updates added to this edition include:

         

        • remdesivir – new guidelines from NIH and IDSA,
        • convalescent plasma – new guidelines from IDSA,
        • monoclonal antibodies, mesenchymal stem cell therapy, corticosteroids – new guidelines from NIH and IDSA,
        • IL-6 Inhibitors – new guidelines from IDSA; JAK inhibitors – data from NIH’s ACTT-2 trial on baricitinib, and
        • antimalarials – results from the RECOVERY trial, PPIs, vaccines and SSRIs.

      October 14, 2020

      October 12, 2020

      • Compassionate Use of Remdesivir in Pregnant Women with Severe Covid-19. 10/8/20. Burwick RM. Clin Infect Dis.
        This is a multicenter review of the outcomes for 67 pregnant and 19 immediate post-partum patients with moderate to severe COVID-19 treated with remdesivir. Outcomes were generally good, but there was no comparison to a control group. Remdesivir was well tolerated, with a low incidence of serious adverse events (16%). Most adverse events were related to pregnancy and underlying disease; most laboratory abnormalities were Grades 1 or 2. There was one maternal death attributed to COVID-19 and no neonatal deaths.
      • Remdesivir for Adults With COVID-19: A Living Systematic Review for an American College of Physicians Practice Points. 10/5/20. Wilt TJ. Ann Intern Med.
        Of the 89 pertinent articles that these authors reviewed, only 4 fit their strict criteria and were chosen for this review. They concluded that from the best evidence available so far, remdesivir probably improves recovery, reduces serious adverse events and may reduce mortality and time to clinical improvement in hospitalized adults with COVID-19. For patients not on a ventilator, a 5-day course may provide similar benefits to, and fewer harmful effects, than a 10-day course. The review is titled “Living” because these authors, from the VA system, plan to update their literature search every 2 months through December 2021.
      • Remdesivir for the Treatment of Covid-19 — Final Report. 10/8/20. Beigel JH. N Engl J Med.
        This article is a follow-up to the initial “preliminary report” that was published May 22, 2020 and was included as 47% of the patients in the review above. This “final report” of the ACTT-1 study provides later outcomes and analysis of the same 1062 patients in the “preliminary” report, randomized between February 21 and April 19 to receive 10 days of remdesivir or placebo. Similar to the analysis in the first report, those who received remdesivir had a median recovery time of 10 days compared with 15 days among those who received placebo. Kaplan–Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and estimates of mortality by day 29 (new in this report) were 11.4% with remdesivir and 15.2% with placebo.
      • Updated guidance on the management of COVID-19: from an American Thoracic Society/European Respiratory Society coordinated International Task Force (29 July 2020). 10/6/20. Bai C. Eur Respir Rev.
        In this article, the Task Force (American Thoracic Society/European Respiratory Society coordinated International Task Force 29 July 2020) make consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but not with hydroxychloroquine except in the context of a clinical trial. COVID-19 patients with a venous thromboembolic event can be treated with therapeutic anticoagulant therapy for 3 months. Routine screening of patients for depression, anxiety and post-traumatic stress disorder was also suggested by the task force.

      October 9, 2020

      • Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial (HESACOVID). 9/20/2020. Lemos ACB. Thromb Res.
        This paper randomized 20 COVID-19 patients requiring mechanical ventilation. Ten patients were assigned to either therapeutic enoxaparin (enoxaparin) or to prophylactic anticoagulation (SQ heparin). There was an increase in the PaO2/FiO2 ratio in the therapeutic group, p=0.0004 which was not seen in the prophylactic group, p=0.487. Patients in the therapeutic group had a rate of successful liberation from mechanical ventilation (hazard ratio: 4.0, p=0.031) and more ventilator-free days (15 days versus 0 days, p = 0.028). There was no difference in mortality.  While the dataset is small, it does show promise and is an introduction for larger upcoming trials.

      October 7, 2020

      October 5, 2020

      • Convalescent Plasma for the Treatment of COVID-19: Perspectives of the National Institutes of Health COVID-19 Treatment Guidelines Panel. 9/25/20. Pau AK. Ann Intern Med.
        Data are currently insufficient for the NIH to recommend for or against convalescent plasma (CP) for COVID-19. Enrollment in adequately powered US RCTs is slow.FDA analysis (4330 patients):

         

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

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

        • 30-day mortality 29.1% in low-titer group vs. 24.7% in the high-titer group (not statistically significant).
        • Suggestion that high-titer plasma beneficial when administered within 72 hours of Dx.
      • COVACTA trial raises questions about tocilizumab’s benefit in COVID-19. 9/9/20. Furlow B. Lancet Rheumatol.
        IL-6 has both pro-inflammatory (e.g. “cytokine storm”) and anti-inflammatory effects. Retrospective studies suggested that the IL-6 antagonist tocilizumab reduced mortality. On July 29, 2020, Hoffmann-La Roche announced results of COVACTA, a Phase 3 tocilizumab randomized controlled trial in severe COVID-19 pneumonia. Tocilizumab failed to meet the primary endpoint of improved clinical status or mortality. However, treated patients spent a week less in the hospital. The full results await publication. Proper timing of administration assessing clinical signs of hyperinflammation may prove crucial. The results of the much larger tocilizumab RECOVERY trial are pending.
      • High Potency of a Bivalent Human VH Domain in SARS-CoV-2 Animal Models. 9/4/2020. Li W. Cell.
        Using a phage-generated library, these investigators found spike glycoprotein (S) -receptor binding domain-avid high-affinity VH binder ab8. Bivalent VH, VH-Fc ab8, bound with high avidity to S and to patient-derived S-mutants. VH-Fc ab8 was markedly effective as a prophylactic and a therapeutic, interfering in ACE-2 binding in a mouse-adapted SARS-CoV-2 and in a hamster model. The potency was enhanced by its relatively small size vs. a complete antibody (80 vs. 150 kDa). S-specificity was shown; VH-Fc ab8 did not aggregate and did not bind to 5,300 human membrane-associated proteins. These data provide a strong rationale for its therapeutic evaluation.

      September 25, 2020

      • Glucocorticoid therapy does not delay viral clearance in COVID-19 patients. 9/22/2020. Ji J. Crit Care.
        This is a (LtE) retrospective observational study regarding glucocorticoids and Covid viral clearance. Out of 684 patients noted 29.5% had viral RNA clearance within 14 days after illness onset and 30.7% cases had viral RNA clearance between 14 and 28 days, and 39.8% cases had viral RNA clearance over 28 days. There were no differences on the age, gender, and underlying diseases between different groups. The degree of decrease in CD4 T cell and B cell counts on admission was related with the prolonged viral RNA clearance. The results show that GC therapy shortened hospital stay days but had no effect on the virus clearance time. This is true for the severe and critical patients as well. The GC treatment had no effect on the peripheral lymphocyte counts, including CD4 T cells, CD8 T cells, NK cells, and B cells.

      September 23, 2020

      • Bridging the Gap at Warp Speed – Delivering Options for Preventing and Treating Covid-19. 9/15/20. Slaoui M. N Engl J Med.
        This article summarizes ongoing initiatives by industry and the Departments of Defense and HHS to develop and distribute novel therapeutics safely and effectively by the end of 2020. Under the code name Operation Warp Speed (OWS), teams are focused on:

         

        • Creating passive immunity using convalescent plasma, hyperimmune globulin and monoclonal antibodies (mAbs);
        • Inhibiting viral replication using new and repurposed antivirals like remdesivir;
        • Prevention of disease in high-risk cohorts applying neutralizing mAbs; and
        • Developing novel immunomodulators and anticoagulants.

        OWS plans to attack COVID-19 using some of these options before an anticipated vaccine release in early 2021. The article does not address the progress of ongoing vaccine development efforts by OWS.

      September 21, 2020

      • Favorable outcomes of COVID-19 in recipients of hematopoietic cell transplantation. 9/8/20. Shah GL. J Clin Invest.
        From Sloan Kettering, a retrospective study of 77 COVID-19 PCR+ recipients of allogeneic and autologous hematopoietic cell transplant and chimeric antigen receptor T cell therapy (44% admitted). Of the 77 cellular therapy recipients, the results were: Allo = 35, Auto = 37, CAR-T = 5. The median time from cellular therapy was 782 days. Overall survival at 30 days was 78%. Clinical variables significantly associated with more severe disease (greater than non-rebreathing mask oxygen) or death were number of comorbidities, infiltrates and neutropenia. Worsening graft-versus-host-disease was not identified. The authors observed rapid recovery in lymphocyte populations across lymphocyte subsets which are critical to anti-viral responses and immune reconstitution.

      September 16, 2020

      September 14, 2020

      • COVID-19: more than a cytokine storm. 9/5/20. Riva G. Crit Care.
        This commentary from Modena, Italy cites the current overemphasis on therapies combating the cytokine storm of the innate COVID-19 immune response and “neglect” of fighting the adaptive immune response. Lymphocyte dysregulations in COVID-19 include lymphopenia (CD4+ and CD8+), T cell exhaustion and a skewing toward a low IFN-Ɣ CD4+ tolerogenic balance. Some of these adaptive deficiencies also are evident in cancer and with aging. The authors advocate trials with immunotherapeutic drugs that may reverse T cell impairment. Trials to determine appropriate immunomodulatory drugs, antibodies, biomarkers and their optimal timing are beginning.
      • Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19. 8/21/20. Spinner C. JAMA.
        In this international study (United States, Europe, and Asia) of COVID-19 patients with pulmonary infiltrates but oxygen saturation above 94% (moderate COVID-19 pneumonia), patients who received a 5-day course of remdesivir did better on day 11 than a comparable group of patients who received standard care only. However, a 10-day course of remdesivir failed to show clinical improvement compared to standard care. The results suggest that remdesivir works when given early and may not have additional benefit once patients progress to more severe illness.
      • Subcutaneous Enoxaparin Safely Facilitates Bedside Sustained Low-Efficiency Hemodialysis in Hypercoagulopathic Coronavirus Disease 2019 Patients-A Proof-of-Principle Trial. 7/23/2020. Neumann-Haefelin E. Crit Care Explor.
        Faced with recurrent filter clotting and incomplete dialysis in hypercoagulable COVID-19 patients needing renal replacement therapy, these authors changed therapeutic anticoagulation from unfractionated heparin to low molecular weight heparin. In their retrospective study of 3 patients, LMWH markedly increased successful completion of RRT. Their protocol reduces the risk of discarding important resources, filter and blood and at the same time provides adequate dialysis quality.

      September 4, 2020

      September 2, 2020

      • Anakinra in COVID-19: important considerations for clinical trials. 5/21/20. King A. Lancet Rheumatol.
        This comment is of interest for clinicians and researchers working with the Interleukin IL-1α and IL-1β inhibitory agent anakinra in COVID-19 patients with evidence of hyperinflammation. The authors review and critique 10 ongoing trials with anakinra and suggest using worsening lymphopenia as a marker of disease progression and severity and increasing C-reactive protein as evidence of worsening inflammation. They also favor subcutaneous administration due to the drug’s short half-life and implore the trial gate keepers to ensure collection of core outcome measures, like ferritin levels for current and future trials.

      August 31, 2020

      August 25, 2020

      August 19, 2020

      • Convalescent plasma for COVID-19. 8/8/20. Mucha SR. Cleve Clin J Med.
        While convalescent plasma has yet to be proven effective, it has generated great interest as a possible COVID-19 therapy and clinical trials are underway. For those interested in a well-written review of the questions and potential risks that must be taken into consideration, this report is a worthwhile read. Potential downsides include TACO, TRALI, antibody dependent enhancement of infection and attenuated immune response. Current limitations include obstacles to effective testing of donor neutralizing antibody levels. This topic is at the center of the current controversy surrounding a potential FDA emergency use authorization for convalescent plasma, (now on hold).
      • Late Onset Infectious Complications and Safety of Tocilizumab in the Management of COVID-19. 8/14/20. Pettit NN. J Med Virol.
        Tocilizumab while previously showing some positive results in treating COVID-19, in this controlled study demonstrated higher complication rates, especially infectious, and death.

      August 17, 2020

      • COVID-19: pharmacology and kinetics of viral clearance. 8/8/20. Farina N. Pharmacol Res.
        In addition to critically reviewing the results of currently available therapeutic options, investigators examined viral clearance dynamics in a cohort of 1000+ patients enrolled in a COVID-19 hydroxy-chloroquine and lopinavir/ritonavir research protocol at a single center in Milan. Viral clearance was assessed as time to negative RT-PCR as well as determining the proportion of patients with a negative test within 14 and 28 days. Significantly, persistence of the virus did not identify patients with higher mortality risk.

      August 14, 2020

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

      August 12, 2020

      August 10, 2020

      • Therapeutic plasma exchange in adult critically ill patients with life-threatening SARS-CoV-2 disease: A pilot study. 7/31/20. Faqihi F. J Crit Care.
        This article reports preliminary data on total plasma exchange as rescue therapy for 10 consecutive eligible adult COVID-19 ICU patients. (Technique using Spectra Optia™ Apheresis System w/ Depuro D200 Adsorption Cartridge and volume replacement w/ 5% albumin or fresh frozen plasma if PT>37 sec.) All patients were mechanically ventilated and had life-threatening illness and cytokine release syndrome (average PaO2/FiO2 ratio 110, SOFA 11, APACHE II 22.5). After 5-7 treatments P/F >250 in all and vasopressors weaned. One on ECMO, 2 had PE, and there was 1 sudden death during ventilator weaning. Nine patients were discharged from hospital. No reported adverse effects. Confounding factors include steroid and other concurrent treatments.
        (Note: this is not convalescent plasma treatment.)
      • Editorial: Attenuating hyperinflammation in COVID-19: A change in paradigm? 7/23/20. Molnar Z. J Crit Care.
        This editorial accompanying Faqihi’s report of total plasma exchange as rescue therapy for life-threatening COVID-19 presents an interesting discussion of the history of our understanding of host-based detrimental “dysregulated immune responses” including “cytokine storm,” along with potential blood purification therapies. The good news is that multiple trials in this domain are registered on ClinicalTrials.gov.

      August 7, 2020

      August 3, 2020

      • Emerging pharmacological therapies for ARDS: COVID‑19 and beyond. 7/11/2020. Horie S. Intensive Care Med.
        Members of the Regenerative Medicine Institute of the National University of Ireland authored this exhaustive overview of the current state of promising emerging pharmacological therapies of ARDS in patients with and without COVID-19. The review focuses on ongoing clinical and preclinical trials and uses well-designed tables and diagrams to enhance a complex array of pathophysiological mechanism and therapeutic interventions ranging from immune response modulation, to epithelial and endothelial integrity repair, anticoagulation and COVID-19 specific antiviral and anti-inflammatory therapies.
        A valuable source, aimed at the research community, the authors express hope for identification of subtypes of ARDS and application to allow better targeting of specific therapeutic interventions in the future.

      July 31, 2020

      • Prevalence of Gastrointestinal Symptoms and Fecal Viral Shedding in Patients With Coronavirus Disease 2019: A Systematic Review and Meta-analysis. 6/11/20. Parasa S. JAMA.
        Gastrointestinal (GI) symptoms of COVID-19 include loss of appetite, nausea, vomiting, diarrhea, and abdominal discomfort. These symptoms might start before or occur with or without other symptoms such as fever, myalgias, and cough. Lower gastrointestinal tract is rich in ACE2 receptors.
        About 40% of the patients’ stool tests positive for SARS-CoV-2 RNA. This is primarily due to RNA fragments of the virus. One study showed live virus on electron microscopy in a small percentage of patients. These patients’ stools are infectious. Patients who have virus in the stool take longer to clear it. Although a small percentage of patients have GI symptoms, up to one-half shed virus in the stool. Virus protein shell is also found in gastric, duodenal, and rectal cells.
        More than one-half of COVID-19 hospitalized patients have elevated lactate dehydrogenase and other liver enzymes indicating injury to the liver or bile ducts. This is likely to be due to an overactive immune system or due to drugs causing liver damage.

      July 29, 2020

      • Considering the potential for an increase in chronic pain after the COVID-19 pandemic. 7/24/20. Clauw DJ. Pain.
        An International panel reviews the underlying factors likely to lead to or exacerbate chronic pain in individuals during a pandemic whether or not an infection actually takes place. Addressing both chronic pain management professionals and acute care providers, this synopsis reminds us of post-SARS syndrome and urges us to prepare for post-COVID-symptomatology which includes chronic debilitating illnesses, like chronic fatigue, irritable bowel syndrome and interstitial cystitis and other conditions marked by a chronic pain experience. Registries, awareness and multidisciplinary teams will be required to deal with this likely scenario.
      • Remdesivir for Severe COVID-19 versus a Cohort Receiving Standard of Care. 7/25/20. Olender SA. Clin Infect Dis.
        Pharma-sponsored proof of benefit of remdesivir in patients with severe COVID-19 is demonstrated by comparing patients’ clinical status on day 14 during two parallel studies. One is an international, 16-site retrospective cohort study of clinical outcomes in 800+ patients receiving standard-of-care treatment for severe COVID-19 infection; the other is an international, 45-center, phase 3, randomized, open-label trial comparing two courses of remdesivir in 312 patients. Remdesivir was associated with significantly greater recovery (74 vs 59%) and 62% reduced odds of death versus standard-of-care treatment.

      July 24, 2020

      • Nutrition of the COVID-19 patient in the intensive care unit (ICU): a practical guidance. 7/19/20. Thibault R. Crit Care.
        Review by the SAB
        By Dr. Heinrich Wurm, on behalf of the SAB
        French authors propose a flow chart and identify ten key issues for optimizing the nutrition management of COVID-19 patients in the ICU. Prominent among those is a preference for enteral nutrition whenever possible, attention to avoid the refeeding syndrome and awareness of the propofol infusion syndrome. Existing guidelines like GLIM* are valuable and their application encouraged. The use and limitations of indirect calorimetry during Covid-19 is discussed.
        * Global Leadership Initiative on Malnutrition

      July 17, 2020

      July 15, 2020

      July 14, 2020

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

      July 10, 2020

      • Improved Clinical Symptoms and Mortality on Severe/Critical COVID-19 Patients Utilizing Convalescent Plasma Transfusion. 6/23/20. Xia X. Blood.
        Review by the SAB
        By Dr. Lydia Cassorla, on behalf of the SAB
        This article may be of interest to those looking to learn from the Chinese experience with convalescent plasma (CP). 138/1568 COVID-19 patients from this retrospective single-center Chinese cohort study received CP. Death (2.1% vs. 4.1%) and requirement for ICU care (2.4% vs. 5.1%) in the CP group were close to half of that in the untreated patients. Patients with higher initial lymphocyte counts and those who received CP treatment within 7 wks. from onset of clinical disease were more likely to respond.
      • Rate of venous thromboembolism in a prospective all-comers cohort with COVID-19. 7/2/20. Rieder M. J Thromb Thrombolysis.
        Review by the SAB
        By Dr. Lydia Cassorla, on behalf of the SAB
        This German prospective single-center study analyzed 190 ED patients with suspected COVID-19 March-April 2020. 49 SARS-CoV-2 positive (25.8%). 141 SARS-CoV-2-negative patients served as a control group. After 30-day follow-up, VTE was diagnosed in 3 SARS-CoV-2-positive patients (6.1%, including 2 ICU patients) vs. 5 SARS-CoV-2-negative (3.5%), however the difference was not statistically significant (p = 0.427). 30-day mortality was similar (6.1% vs. 5%, p = 0.720). COVID-19 disease severity correlated with the maximum D-dimer level during follow-up, but not D-dimer at admission.
        Dyspnea was more common in the SARS-CoV2 negative group (41.7% vs. 52.4%, p = 0.002), whereas cough (58.3% vs. 37.6%, p < 0.0001) and fever (75% vs. 48.2%, p < 0.0001) were more frequent in COVID-19 patients. The rate of hospital admission was higher in the SARS-CoV-2 positive group (81.6% vs. 66.7%, p = 0.068) D-Dimers at admission did not differ between both groups (1.1 ± 1.4 mg/l vs. 0.8 ± 1.7 mg/l, p = 0.3).

      July 8, 2020

      • Cardiopulmonary Resuscitation in Intensive Care Unit Patients With Coronavirus Disease 2019. 7/1/20. Cheruku S. J Cardiothorac Vasc Anesth.
        Review by the SAB
        By Dr. Philip Lumb, on behalf of the SAB
        Interesting discussion involving practical, ethical and medical (physicians, ICU staff and ancillary personnel) decisions and preparations to perform cardiac resuscitation in terminally ill COVID-19 patients. Focuses on planning and preparing appropriate patients for potential resuscitation by informed discussion with patient/family, insertion of central venous access lines with long IV connections for access and infusion outside patient care area. CPR performed with automated chest compressor. Other safety elements described to protect staff and value of simulation in preparation emphasized. Novel approach to preparing for and performing CPR in COVID-19 patients.
      • Revisiting the Protein C Pathway: An Opportunity for Adjunctive Intervention in COVID-19? 6/10/20. Mazzeffi M. Anesth Analg.
        Review by the SAB
        By Dr. Barry Perlman, on behalf of the SAB
        Discussion of hypercoagulability in COVID-19 with a focus on the anticoagulant and anti-inflammatory properties of Protein C. The authors suggest that two modulators of the Protein C pathway — recombinant thrombomodulin and 3K3A-APC — may be beneficial in the treatment of severe COVID-19 as they are not associated with an increased risk of bleeding.

      July 6, 2020

      • Drug-Induced Liver Injury and COVID-19 Infection: The Rules Remain the Same. 6/8/20. Olry A. Drug Saf.
        Review by the SAB
        By Dr. Philip Lumb, on behalf of the SAB
        Editorial noting that patients have been discontinued/withdrawn from studies because of suspected drug-induced liver damage that does not meet international guidelines for association. A summary of currently used drugs in COVID-19 and possible interactions that may cause liver damage is listed. However, the authors state that since many drugs used in therapeutic interventions may be related to liver damage, it is important to discuss acute liver injury on internationally defined biologic criteria “on the Upper Limit of Normal of serum alanine aminotransferase activity (ALT), serum alkaline phosphatase activity (ALP) and serum concentration of total bilirubin,” which are provided in the editorial as well as a severity grading score to include in association. Internationally recognized criteria for DILI should be satisfied to confirm the diagnosis prior to premature removal of patients from potentially important clinical trials.
      • Inhalational volatile-based sedation for COVID-19 pneumonia and ARDS. 6/25/20. Jerath A. Intensive Care Med.
        Review by the SAB
        By Dr. Heinrich Wurm, on behalf of the SAB
        In light of a growing shortage of sedatives and intravenous anesthetics, this narrative review from Toronto highlights the benefits and technical details of volatile anesthetics for sedation in the critical care unit during the COVID-19 pandemic.
        Spearheaded in Europe – volatile anesthetics using in-line vaporizers may provide added benefits, like bronchodilatation and an anti-inflammatory effect, but safe use requires trained teams familiar with volatile anesthetics administration in the ICU. The authors provide a comprehensive and realistic review of available options and alternatives.

      July 1, 2020

      May 29, 2020

      • High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients
        Apr 22. Llitjos JF. Journal of Thrombosis and Haemostasis.
        Opinion from SAB Member: Dr. Anil Hingorani, Dr. Lydia Cassorla
        AH: This French paper is a short communication where the authors describe venous duplex exams in 26 patients in the ICU with COVID-19. 8 patients were on prophylactic heparin doses and 18 were on therapeutic doses. All patients were intubated. The rate of VTE was 100% for the patients on prophylactic doses and 56% for those on therapeutic doses. 8 patients had PE. The authors do not mention the location of lower extremity DVT. This paper is novel and raises questions. It confirms data from a 48 patient series with 84% VTE incidence from China (Extremely High Incidence of Lower Extremity Deep Venous Thrombosis in 48 Patients with Severe COVID-19 in Wuhan).
        LC: This is a French retrospective study from March 19 to April 11, 2020 of 26 consecutive ICU patients from 2 units with severe COVID‐19 who were screened for VTE on ICU admission and at least every 7 days. 8 (31%) were treated with prophylactic anticoagulation, and 18 (69%) were treated with therapeutic anticoagulation. The overall rate of VTE in patients was 69%. The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with therapeutic anticoagulation (100% vs 56%, respectively, P = .03) 6 (23%) had PE. This documents a high incidence of VTE despite prophylaxis and supports trends towards more aggressive anticoagulation.
      • Understanding the COVID-19 coagulopathy spectrum
        May 21. Thachil J. Anaesthesia.
        Opinion from SAB Member: Dr. Anil Hingorani, Dr. Lydia Cassorla
        AH: This editorial is a summary article covering the link of the immune system to thrombosis. The paper asks clinical questions concerning the use of additional anticoagulants (beyond heparin) for certain patients and raises the use of thromboelastography for clinical guidance.
        LC: This is a useful editorial that summarizes current trends in management and proposes an algorithm for management of COVID-19 related hypercoagulability. If no contraindications, inpatients should receive prophylaxis with LMWH, or unfractionated heparin if indicated. They propose a low bar for imaging (but not a screening regimen) and ramping up anticoagulation according to findings and potentially thrombolysis if the situation continues to worsen. The potential role of point-of-care TEG or ROTEM viscoelastic testing and questions for the future are addressed. While consideration of antiplatelet therapy and the results of more clinical trials are pending, perhaps the most important message is that each center should have a plan.

      May 28, 2020

      • Chloroquine or hydroxychloroquine for COVID-19: why might they be hazardous? May 22. Funck-Brentano C. Lancet.
        A commentary on a Lancet article that retrospectively reviewed the occurrence of significant ventricular arrythmias in 96,032 hospitalized Covid-19 patients from 671 hospitals in six continents. Groups of 1,868 to 6,221 patients each that were given chloroquine or hydroxychloroquine with or without a macrolide were compared to 81,144 control Covid-19 patients who received none of these drugs. While the occurrence of repetitive ventricular arrythmias was much higher in the treated groups (4.3-8.1% versus 0.3%), several lines of reasoning in this commentary suggest that the increase in these arrhythmias was not a major contributor to the increased death rate among these (presumably sicker) patients.
      • Lack of viral clearance by the combination of hydroxychloroquine and azithromycin or lopinavir and ritonavir in SARS-CoV-2-related acute respiratory distress syndrome. May 24. Hraiech S. Ann Intensive Care.
        Letter to the editor that showed a little more than a month after treatment with either hydroxychloroquine and azithromycin or lopinavir and ritonavir or control, that mortality was not different between groups. A retrospective analysis from France.
      • Remdesivir for the Treatment of Covid-19 – Preliminary Report
        May 22. Beigel JH. The New England Journal of Medicine.
        Opinion from SAB Member: Dr. Philip Lumb
        Results from the Adaptive COVID-19 Treatment Trial (ACTT-1), an international, double-blind, placebo-controlled trial of IV remdesivir in adults with documented COVID-19 disease hospitalized with evidence of lower respiratory tract involvement sponsored by the National Institutes of Allergy and Infectious Diseases (NIAID). Patients were randomly assigned to remdesivir or placebo for up to 10 days. It is important to note that “the initial primary outcome measure was the time to recovery, defined as the first day, during the 28 days after enrollment, on which a patient satisfied categories 1, 2, or 3 on the eight-category ordinal scale.”
        Patients were enrolled from February 21 until April 19 at 60 trial sites in the US, Denmark, UK, Greece, Germany, Korea, Mexico, Spain, Japan, and Singapore. Eligible patients were randomized to either study drug or placebo in a 1:1 ratio stratified by study site and disease severity at enrollment; routine therapy in place at the institution was continued. On March 22, the primary outcome was amended by trial statisticians (unaware of the treatment assignments or outcome data) and approved on April 2 prior to any outcome data being available. This change led to the early observation that is now widely recognized as the statement presented by the NIAID sponsors that “remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with COVID-19 and evidence of lower respiratory tract infection.” It is important to read the trial details to understand the reasons for the change and the validity of the results as reported.
        This is an example of a well conducted, adaptive platform clinical trial conducted under difficult circumstances across multiple institutions with appropriate Data Safety Monitoring Board (DSMB) oversight and interim analyses. On April 27, the DSMB reviewed results and because patient enrollment had been completed (patient follow up continuing) at the time of what had been intended to be an interim review, and it was noted that the remdesivir group had a shortened time to recovery when compared to placebo, these results were reported to the NIAID and subsequently made public.
        Hidden in the press coverage but of clinical concern is the now secondary outcome indicating the “odds of improvement were higher in the remdesivir group…than in the placebo group.” The discussion is particularly illuminating regarding the complexities of the study, the enrollment supervision complexity given travel restrictions (lack of study monitors), local and environmental controls and the nature of the study itself; the addition of an experimental therapy supported by routine care across all institutions involved. The authors conclude: “The full statistical analysis of the entire trial population must occur in order to fully understand the efficacy of remdesivir in this trial. These preliminary findings support the use of remdesivir for patients who are hospitalized with COVID-19 and require supplemental oxygen therapy. However, given high mortality despite the use of remdesivir, it is clear that treatment with an antiviral drug alone is not likely to be sufficient.”
        I found this manuscript a fascinating description of an adaptive trial undertaken in difficult circumstances that produced interesting, clinically relevant results that await further analysis for final determination of the remdesivir’s efficacy. However, it stimulated the inclusion of the drug into routine management of COVID-19 patients and suggests that early administration is likely to be of greater benefit.

      May 27, 2020

      May 22, 2020

      May 21, 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.

      May 20, 2020

      • 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.
      • 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.

      May 16, 2020

      • 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.
      • 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.
      • Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. May 8. Hung. Lancet.
        Multicenter, prospective, open-label, randomized phase 2 trial with adult confirmed COVID-19 patients in 6 Hong Kong hospitals. 52 combination medication patients received lopinavir, ritonavir, ribavirin, and Interferon beta-1b. For 34 combination medication patients who started treatment after 7 days of symptom onset, interferon beta-1b was omitted due to concerns of pro inflammatory side effects. 41 controls received just lopinavir and ritonavir. Stress steroids were also given to patients requiring oxygen support, and approximately half the patients in each group received antibiotics. The time to negative nasopharyngeal swab RT-PCR (primary endpoint) was 7 days for the combination medication group and 12 days for the control group. The combination group also had earlier time to negative RT-PCR from other specimen locations, quicker alleviation of symptoms, earlier hospital discharge, and decreased IL-6 levels. One control patient withdrew due to 6x increased alanine transaminase, but there were no differences in mild, self limiting adverse effects between the 2 groups. Of note, for patients who started treatment > 7 days after symptom onset, there were no significant differences in outcome between the combination medication group (minus interferon beta-1b) and the control group, suggesting the beneficial effects of interferon beta-1b. However, it is not known if patients who start treatment after 7 days of symptoms onset would benefit from interferon beta-1B. Further, since severe COVID-19 patients were not included, further studies are needed to determine if these patients would benefit from the combination therapy.

      May 15, 2020

      • 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.
      • 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.

      May 14, 2020

      • COVID and the Renin-Angiotensin System: Are Hypertension or Its Treatments Deleterious? May 12. Zores. Front Cardiovasc Med.
        Review of the RAAS with implications for COVID-19. A decrease in cell surface ACE2 may reduce binding of SARS CoV-2 but result in greater activation of angiotensin type 1 receptor (AT1R) by angiotensin II, causing more severe tissue damage. Decreased ACE2 may also increase thrombosis development via metabolism to angiotensin IV and activation of the angiotensin type 4 receptor. In contrast, increased ACE2 on the cell membrane due to up regulation by ACEI or ARBs may increase viral binding but result in less the damage due to less AT1R activation by angiotensin II. Studies are needed to determine whether ACEI or ARBs are beneficial or harmful in COVID-19 patients, but current recommendations are to continue these medications if the patient had been taking them for hypertensive management prior to infection.
      • The tug-of-war between coagulopathy and anticoagulant agents in patients with COVID-19
        May 8. Canonico. European Heart Journal – Cardiovascular Pharmacotherapy.
        Opinion from SAB Member: Dr. Lydia Cassorla, Dr. Anil Hingorani
        LC: This brief report from the pharmacology literature outlines possible drug-drug interactions between anticoagulants and experimental drugs for COVID-19 patients including antivirals and anti-cytokine Rx. Most are due to hepatic metabolism. The interaction with cytochrome P450s and P-glycoprotein are the principal mechanism involved in DDIs. It includes a summary table that pretty much says it all. AH: Useful for listing drug to drug interactions of anticoagulants and other agents used for COVID-19, though I am not sure why they are using the older term NOAC rather than the safer term DOAC.
      • Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients
        May 6. Klopfenstein. Medecine et Maladies Infectieuses.
        Opinion from SAB Member: Dr. Philip Lumb
        Retrospective case-control study demonstrating possible benefit of Tocilizumab prescription (TCZ: recombinant humanized anti-interleukin-6 receptor [IL-6R] monoclonal antibody used in the treatment of rheumatoid arthritis) when combined with standard care. The article describes a small number of cases, but contains a well-referenced discussion that considers the theoretical basis for use; the methodology and results are clearly presented.

      May 13, 2020

      • 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.
      • Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19? May 10. Panigrahy. Cancer Metastasis Rev.
        Discusses inflammatory process and potential development of stimulation of inflammatory resolution as an adjunctive, novel, host-centric mechanism to clear inflammatory debris and aid recovery. Mechanisms of inflammation and dysregulated host response in disease states described and theoretical basis for therapeutic development advanced.
      • Our recommendations for acute management of COVID-19. May 10. Mojoli. Crit Care.
        A 16 step narrative on “how we do it” from an Italian critical care team. Listing of current practice ranging from “do not trust a negative nasal swab” to “we prefer lung ultrasound over other imaging techniques”.
        While much is familiar, there are surprises: “we introduce hydroxychloroquine 200 mg TID and azithromycin 500mg daily”, but no mention of anticoagulation, or proning.
        A quick and interesting read for anyone interested to explore how other units operate.

      May 12, 2020

      May 11, 2020

      • Evidence for and against vertical transmission for SARS-CoV-2 (COVID-19). May 3. A A. Am J Obstet Gynecol.
        Maternal-neonatal transmission of COVID-19 is discussed through evaluating previous published articles. The data presented is biased in two ways. In China, the bulk of deliveries is through C-section, 94%. Conclusions are drawn between delivery method of which there are too few vaginal deliveries. The data is also skewed by the authors evaluating neonatal results from 12 papers, but one paper supplies 50% of the data. Still, the paper provides an excellent description of IgG and IgM involvement post-delivery.
      • Rapid development of an inactivated vaccine candidate for SARS-CoV-2. May 6. Gao. Science.
        Chinese equivalents of the CDC are sharing their latest efforts to prophylactic treatment of COVID 19 in absence of clear therapeutic modalities. The authors claim to have developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies neutralized 10 representative SARS-CoV-2 strains (may address other Corona / RNA SARS & MERS +/-), suggesting a possible broader neutralizing ability against SARS-CoV-2 strains. Three immunizations using two different doses (3 μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support clinical development of SARS-CoV-2 vaccines for humans. The authors, in development of the vaccine, isolated SARS-CoV-2 strains from the bronchoalveolar lavage fluid (BALF) samples of 11 hospitalized patients (including 5 patients in intensive care), among which 5 are from China, 3 from Italy, 1 from Switzerland, 1 from UK and 1 from Spain. The vaccine noted to elicit attenuated clinical, histopathologic, and bio chemical response. A smaller controlled double arm animal study to evaluate “Cytokine storm” response was encouraging as well. Phase I, II, and III will occur later this year!!
      • Severe acute respiratory syndrome coronavirus 2 detection in the female lower genital tract. Apr 29. Cui. Am J Obstet Gynecol.
        Case series from China of 35 COVID-19 + female patients, 37-88 yo, who had careful PCR testing of anal and vaginal sites, all negative.

      May 6, 2020

      • Randomized Clinical Trials and COVID-19: Managing Expectations
        May 4. Bauchner. JAMA.
        Opinion from SAB Member: Dr. Jagdip Shah
        Today there are more than 1,000 studies addressing various aspects of COVID-19 registered on ClinicalTrials.gov, including more than 600 interventional studies and randomized clinical trials (RCTs). It has become common practice to report the glimpses of preliminary results in social media and the popular press. The authors question how we (clinicians, press, public, politicians) should understand the results. The authors appeal to investigators to be strict on control groups, statistical power, proper selection of clinical endpoints, and blinding methods, and strongly advocates merging smaller trials for better robust outcomes. This article was open for comments and an excellent comment from Bhatt A. from Oxford points out that the International Committee of Medical Journal Editors (ICMJE) should be firmer in its proactive stance and guidance to ethics committee verdicts than simply relying on ethics approvals, which all small and uncontrolled studies will have, but which may not have meaning or purpose.
      • Severe ARDS in COVID-19-infected pregnancy: obstetric and intensive care considerations. Apr 14. Schnettler. Am J Obstet Gynecol MFM.
        Single case report in a high-risk pregnancy (age 39, mild myotonic dystrophy, and hx of prior cva on BCP). Patient did require ventilator and proning. Although patient had improved, still on vent at time of writing the article. Suggested algorithms for management at different gestational ages. Some outdated recommendations for treatment. Main interesting point is proning in pregnancy.

      May 5, 2020

      • Use of drugs with potential cardiac effect in the setting of SARS-CoV-2 infection. May 2. Sacher. Arch Cardiovasc Dis.
        French editorial for mitigating risk of arrhythmias due to COVID-19 treatment. Preliminary studies do not document QT prolongation related deaths from hydroxychloroquine/azithromycin, although in one study acute renal failure was a strong predictor of extreme QTc prolongation. Risk factors for QT prolongation and Torsades de pointes:
        1. Modifiable. Hypokalemia, hypocalcemia, hypomagnesemia, bradycardia.
        2. Non-modifiable. Congenital long QT syndrome, female, age > 65, baseline QTc>460 ms, cardiac disease, history of kidney or liver disease, sepsis.
        3. Related to COVID-19 infection. Myocarditis, arrhythmias, hypokalemia, ARF Cardiac workup and optimization prior to initiation of COVID-19 medication treatment should be guided by risk factors (Figure 1). ECG is required before starting drug combinations that can both cause QT prolongation. QTc < 460ms is considered low risk, while if > 500 ms QT prolonging drugs should be avoided or stopped.
        The importance of determining QTc accurately and methods for correctly calculating it are discussed.

      May 2, 2020

      • Testing an Old Therapy Against a New Disease: Convalescent Plasma for COVID-19. Apr 30. Rubin. JAMA.
        A Medical News article written more for general consumption than presenting scientific and clinical results. I first thought to go to the referenced articles that contained only a handful of patients with encouraging results. Then, I noticed a well-developed article summarizing all that has been done so far with transfused plasma including references into the 1890s. Puts the use of transfused plasma into a rational perspective.

      May 1, 2020

      • 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.
      • Inhaled Nitric Oxide and COVID-19. Apr 28. Ignarro. Br J Pharmacol.
        In this letter to the editor, the authors note that NO may have an antiviral effect and in patients with SARS-CoV, reversed pulmonary hypertension, improved severe hypoxia and shortened the length of ventilatory support. Whether the same will improve hypoxia in patients with COVID-19 infection with moderate to severe COVID-19 with pneumonia and under assisted ventilatory support is being studied.
      • Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Apr 29. Wang. The Lancet.
        2:1 randomized, placebo controlled double blind controlled study on 237 patients in Hubei province China on patients with confirmed COVID-19 disease of 10 days duration or less. No statistically significant results reported although trend to shorter time to clinical improvement requires confirmation in larger studies.

      April 30, 2020

      • The Role of the Renin-Angiotensin System in Severe Acute Respiratory Syndrome-CoV-2 Infection. Apr 29. Alfano. Blood Purif.
        Interesting discussion of ACE and ACE 2 receptors and related interactions and detailed explanation of logic to continue ACE inhibitors in patients with COVID-19. This is despite early concerns that ACE inhibitors and angiotensin II receptor blockers could affect ACE2 actions and exacerbate disease. While this recommendation is well-publicized, the explanation provides a good summary of the interactions and logic behind the recommendation.
      • 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.
      • Use of tocilizumab for COVID-19 infection-induced cytokine release syndrome: A cautionary case report
        Apr 20. Radbel. CHEST.
        Opinion from SAB Member: Dr. Philip Lumb
        The article reviews experimental rationale for use of tocilizumab (IL-6 receptor antagonist) as COVID-19 therapy based on cytokine release syndrome (CRS) and subsequent secondary hemophagocytic lymphohistiocytosis which may add/cause to lung pathologies. Syndromes characterized by production of inflammatory cytokines including IL-6, IL-10 and TNF alpha providing therapeutic rationale for tocilizumab which is commonly used to treat CRS secondary to CAR T-cell therapy. 2 case reports detailing patient deterioration and death following tocilizumab therapy despite a decrease in CRP (IL-6 surrogate) following therapy. While no direct correlation to tocilizumab and mortality is suggested, authors caution against use.

      April 29, 2020

      April 25, 2020

      • 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.

      April 24, 2020

      April 23, 2020

      April 22, 2020

      • COVID-19: consider cytokine storm syndromes and immunosuppression. Mar 16. Mehta. The Lancet.
        Jay: Letter to Editor. Authors from a medical society (HLH Across Specialty Collaboration) use data from China to redefine Cytokine Storm as Haemophagocytic LymphoHistiocytosis (sHLH). No advance in therapy is advocated.
        Cassorla: “Secondary haemophagocytic lymphohistiocytosis (sHLH) is an under-recognised, hyperinflammatory syndrome characterised by a fulminant and fatal hypercytokinaemia with multiorgan failure. Cardinal features of sHLH include unremitting fever, cytopenias, and hyperferritinaemia; pulmonary involvement (including ARDS) occurs in approximately 50% of patients.” The authors raise the question of whether mortality from COVID-19 could be reduced by identifying the subset of patients with severe disease who have sHLH (using a scoring calculator), and treating with immunosuppression therapy.
      • 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.”

      April 21, 2020

      • Clinical characteristics and risk assessment of newborns born to mothers with COVID-19. Apr 18. Yang. J Clin Virol.
        Small prospective study of 7 newborns delivered by cesarean section at 36 weeks or greater from COVID-19 infected women in Wuhan, China. 6 mothers had symptoms prior to delivery, and the 7th developed fever post delivery. 2 of 5 neonates admitted to NICU received nCPAP for mild respiratory distress. Their CXRs showed bilateral ground-glass opacities and granular high density shadows. All 7 were isolated from their mothers post delivery and after discharge from the hospital were isolated at home. Of the 6 newborns tested, no throat swabs, amniotic fluid, or umbilical cord blood were RT-PCR positive.
      • 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.

      April 20, 2020

      April 17, 2020

      • Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19) A review. Apr 13. Sanders. JAMA.
        JAMA review detailing currently reported COVID-19 therapeutic strategies; cautions there is no cure and no specific therapies can be recommended. Reinforces basic medical care, treatment of infection and associated complications, etc. Therapeutic options well defined and described across categories. Recognition that future controlled trials necessary to define more appropriate management options.

      April 16, 2020

      • Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. Apr 13. Gordan C. Journal of Biological Chemistry.
        No antiviral agents are currently approved to treat COVID-19. This study shows a probable mechanism of antiviral action for remdesivir and supports continued evaluation of its clinical effectiveness and safety.
        SARS-CoV-2 replication depends on viral RNA-dependent RNA polymerase (RdRp). Remdesivir (RDV) is a prodrug that when triphosporylated resembles ATP. It has been shown to have broad in vitro and animal model antiviral activity including SARS-CoV and MERS-CoV. The presumed mechanism of action is competition of remdesivir triphosphate for ATP, causing delayed chain-termination (termination after 3-5 more nucleotide incorporations). Human mitochondrial RNA polymerase has high selectivity for ATP over RDV-TP, consistent with low cytotoxicity of remdesivir. In this in vitro study of purified SARS-CoV, MERS-CoV, and SARS-Cov-2 RdRp, remdesivir triphosphate was efficiently incorporated into RNA, causing delayed termination of RNA synthesis after 3 additional nucleotides were incorporated (i+3). In comparison, chain termination did not occur with Lassa virus RdRp, which is consistent with its higher binding affinity for ATP over RDV-TP. The other antivirals sofosbuvir and ribavairin, and several nucleostide analogs, showed less competition with ATP in this model.

      April 15, 2020

      April 14, 2020

      April 13, 2020

      April 11, 2020

      April 10, 2020

      • Compassionate Use of Remdesivir for Patients with Severe Covid-19 Apr 10. Grein. NEJM.
        Opinion from SAB Member: Dr. Louis McNabb
        An uncontrolled, observational study showing the potential benefit of remdesivir (68% of patients had improvement in oxygenation). Larger, controlled studies are necessary to confirm efficacy.
      • 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.
      • Is There an Association Between COVID-19 Mortality and the Renin-Angiotensin System—a Call for Epidemiologic Investigations. Mar 30. Hanff. Clin Infect Dis.
        Is there a relationship between the renin-angiotensin system and mortality due to Covid-19? Indeed, people with cardiovascular disease have a higher incidence of mortality due to the disease. Activation of the renin–angiotensin system (RAS) is significant in the pathogenesis of cardiovascular disease and specifically coronary atherosclerosis. But also, angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2. More study is needed.
      • 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.
      • 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.

      April 9, 2020

      April 8, 2020

      April 7, 2020

      April 6, 2020

      April 4, 2020

      • Race to find COVID-19 treatments accelerates Mar 27. Kupferschmidt. Science. 
        COVID-19 SAB Opinion from: Dr. Jay Przybylo
        Remdesivir, developed by Gilead Sciences to combat Ebola and related viruses, shuts down viral replication by inhibiting a key viral enzyme, the RNA polymerase. It didn’t help patients with Ebola in a test during the 2019 outbreak in the Democratic Republic of the Congo. But in 2017, researchers showed in test tube and animal studies that the drug can inhibit the SARS and MERS viruses. As compassionate use, which required Gilead to review patient records; some doctors have reported anecdotal evidence of benefit, but no hard data. Remdesivir may be much more potent if given early. Chloroquine and hydroxychloroquine decrease acidity in endosomes, compartments that cells use to ingest outside material and that some viruses co-opt during infection. But SARS-CoV- 2’s main entryway is different: It uses its so-called spike protein to attach to a receptor on the surface of human cells. Studies in cell culture have suggested chloroquine can cripple the virus, but the doses needed are usually high and could cause severe toxicity. “Researchers have tried this drug on virus after virus, and it never works out in humans.” Hydroxychloroquine might actually do more harm than good. It has many side effects and can, in rare cases, harm the heart-and people with heart conditions are at higher risk of severe COVID-19. Lopinavir-ritonavir combination. Abbott Laboratories developed the drugs to inhibit the protease of HIV, an enzyme that cleaves a long protein chain during assembly of new viruses. The combination has worked in marmosets infected with the MERS virus, and has also been tested in patients with SARS and MERS, though those results are ambiguous. But the first trial with COVID-19 was not encouraging. SOLIDARITY combines these two antivirals with interferon-beta, a molecule involved in regulating inflammation that has lessened disease severity in marmosets infected with MERS. But interferon-beta might be risky for patients with severe COVID-19, Herold says. “If it is given late in the disease it could easily lead to worse tissue damage, instead of helping patients,” she cautions. Other approved and experimental treatments are in testing against coronavirus or likely soon to be. They include drugs that can reduce inflammation, such as corticosteroids and baricitinib, a treatment for rheumatoid arthritis. Some researchers have high hopes for camostat mesylate, a drug licensed in Japan for pancreatitis, which inhibits a human protein involved with infection. Other antivirals will also get a chance, including the influenza drug favipiravir and additional HIV antiretrovirals. Researchers also plan to try to boost immunity with “convalescent” plasma from recovered COVID-19 patients or monoclonal antibodies directed at SARS-CoV-2.

      April 3, 2020

      April 1, 2020

      March 31, 2020

      • Antihypertensive drugs and risk of COVID-19? Mar 26. Tignanelli. The Lancet.
        Suggestion that clinicians should consider withholding angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) because of a potential increased risk of worse clinical outcomes in patients with coronavirus disease 2019 (COVID-19) as well as calcium channel blockers as an alternative.

      March 30, 2020

      March 27, 2020

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      March 17, 2020

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      March 12, 2020

      February 25, 2020

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

    1. Anesthesia Care (All patients in COVID-19 era)
      January 15, 2021

       

      • COVID-19, Personal Protective Equipment, and Human Performance. 1/6/21. Ruskin KJ. Anesthesiology.
        This article addresses the issue of the varieties of PPE worn by healthcare workers. The authors discuss how various varieties of PPE may cause increased work of breathing, reduced field of vision, communication mishaps, thermoregulation derangements, limitations of physical dexterity and mental, physical, and psychological fatigue and stress which lead to decreased human performance. These effects are not individual weaknesses. Here the authors suggest some helpful remedies to address the physiologic and psychologic challenges imposed by non-standardized PPE. There is a need for a new, standardized, integrated design for PPE to improve the safety of patients and healthcare workers.

      October 19, 2020

      • Aerosolisation during tracheal intubation and extubation in an operating theatre setting. 10/12/20. Dhillon RS. Anaesthesia.
        This study reports measurements and size characterization of aerosols generated and spread throughout a standard positive pressure operating room (with 26 room volume air exchanges per hour) during intubation and extubation of 3 study patients. Face-mask ventilation, tracheal tube insertion and cuff inflation generated small particles 30–300 times above background noise that remained suspended in airflows and spread from the patient’s facial region throughout the confines of the operating room. The authors believe that these findings support careful use of PPE throughout standard ventilation operating rooms.

      October 14, 2020

      • A quantitative evaluation of aerosol generation during tracheal intubation and extubation. 10/6/20. Brown J. Anaesthesia.
        This is a pertinent report on measurement of 0.3-10 nm aerosolized particles using real-time, high-resolution environmental monitoring in ultraclean ORs with laminar flow ventilation and 500–650 air changes / hour. Tracheal intubation sequences including face-mask ventilation produced very low particle quantities (average concentration, 1.4 particles/L, n = 14, p < 0·0001 vs. cough). Tracheal extubation, particularly when the patient coughed, produced a detectable aerosol (21 particles/L, n = 10), 15-fold greater than intubation (p = 0.0004) but 35-fold less than a volitional cough (p < 0.0001). The study does not support the designation of elective tracheal intubation as an aerosol-generating procedure.

      August 19, 2020

      • Infection Prevention Precautions for Routine Anesthesia Care During the SARS-CoV-2 Pandemic. 8/3/20. Bowdle A. Anesth & Analg.
        Authors promote precautions that are practical, affordable, and efficient to adjust routine anesthesia care to the current and near-future environment. Consideration for asymptomatic and pre-symptomatic SARS-CoV-2 infection, and the potential for false-negative tests inform recommendations to reduce the risk of transmission via anesthesia care behaviors. Universal N95 or higher respiratory protection is proposed for anesthesia providers with consideration given to whether the entire surgical team should use equivalent respiratory protection. Tables provide a useful summary of PPE, hand hygiene and other recommendations.

      July 15, 2020

      July 8, 2020

      May 29, 2020

      • Coagulation changes and thromboembolic risk in COVID-19 pregnant patients
        May 11. Benhamou D. Anaesthesia Critical Care & Pain Medicine.
        Opinion from SAB Member: Dr. Anil Hingorani, Dr. Joseph Anthony Caprini
        AH: A good review of the literature for prophylaxis for pregnant COVID-19 patients.
        JC: This article contains important information for the anesthesiologist including hematologic changes that reflect thrombosis more than an increased incidence of bleeding. I don’t agree with the authors opinion that only selective patients admitted to the hospital should receive prophylactic anticoagulation. Pregnancy is associated with a mild hypercoagulable state, and combining the effects of the virus one would logically conclude that prophylaxis is indicated unless there is an increased risk of bleeding. In my opinion the number one priority is to prevent the patient from developing a thrombotic complication. I would place less emphasis on neuraxial anesthesia. The incidence of thrombosis post discharge in these patients is significant particularly if they have comorbidities. Many of these patients may benefit from prophylaxis for a period of time during the convalescence. A careful detailed thrombosis risk assessment on admission, during hospitalization and updated upon discharge in my opinion should be a standard part of the workup of these patients. The choice of assessment can be whatever is a commonly used in the hospital and may vary widely according to countries.

      May 20, 2020

      • 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.

      May 8, 2020

      May 7, 2020

      • Anesthesia Considerations and Infection Precautions for Trauma and Acute Care Cases During the COVID-19 Pandemic. Apr 24. Gong Y. Anesthesia & Analgesia.
        Recommendations from The Task Force of the Chinese Society of Anesthesiology for Trauma and Acute Care about surgery in a hospital during the Covid-19 pandemic. The article looks like it is from high-powered anesthesiologists in Beijing. Somewhat repetitive information in this long review article. It’s complete information regarding the subject.
      • 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.
      • 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.

      May 5, 2020

      May 1, 2020

      April 25, 2020

      • How to Rapidly Deploy Intubation Practice Changes in a Pediatric Hospital During the COVID-19 Pandemic. Apr 22. Brown. Anesthesia & Analgesia.
        Authors from Seattle Children are sharing the protocol for intubation for Covid-19 and unknown patients, anywhere in the hospital irrespective of age/HT/WT or comorbidity of these patients. It has good illustrations. Since Seattle is where Covid-19 started its journey in this country, they had to think fast, act, create something “out of box which will fit across the facility. They practiced on simulation to” perfect it “in the era of intubation and age of social distancing, aerosol, inline HEPPA filters, inline suctioning, video laryngoscope, covers for it, drugs, dirty / clean tray… the list looks complete. It’s worth following for those still trying to address the issue.

      April 21, 2020

      • COVID-19 pandemic: Greater protection for healthcare providers in the hospital hot zones? Apr 18. Ip. A&A.
        In this letter to the editor, the authors recommend that even in the OB suite, health care workers should be protected.
      • Interim considerations for obstetric anesthesia care related to COVID-19. Apr 5. SOAP. 
        This is interim guidance based on expert opinion of a group of SOAP representatives and differs from SOAP’s more formal consensus statements based on systematic reviews and delphi processes. This content will be updated regularly and integrates information and links to recommendations from the WHO and CDC. Has guidelines for L&D, pre-hospital screening, OB suite training, neonatal, staff, training, and simulation.
      • 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.
      • 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.

      April 20, 2020

      April 17, 2020

      April 15, 2020

      April 14, 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.

      April 11, 2020

      April 10, 2020

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      March 2020

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

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The IARS would like to recognize the COVID-19 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 SAB meet regularly 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!

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