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.

Retractions:

I. SARS COV-2 Pandemic

    1. Epidemiology
      August 30, 2021
      • SARS-CoV-2 variant prediction and antiviral drug design are enabled by RBD in vitro evolution. 8/16/2021. Zahradník J. Nature Microbiology.
        Following increasing rounds of in vitro binding to ever-decreasing amounts of ACE-2, the Receptor Binding Domain (RBD) sequence underwent mutation “evolution”. The progressive mutations mimicked the evolutionary path of amino acid substitutions that emerged with Alpha, Beta and Gamma variants! Also, the mutations correlated with the successive higher ACE-2 affinity of pandemic-emergent VOC. Additional evolving mutations had 1,000-fold increased binding and were more infectious. The high-affinity variant “RBD-62” administered before or after infection, inhibited hamster SARS-CoV-2 disease. The cryo-electron microscopy structure of RBD-62/ACE2 complex, provides a basis for future drug and vaccine development and in silico evaluation of antibodies.

      April 26, 2021

      March 29, 2021

      • The first 12 months of COVID-19: a timeline of immunological insights. 3/15/21. Carvalho T. Nature Reviews.
        Starting with a cluster in Wuhan, China in December 2019, this review summarizes in documentary style, month-to-month key clinical developments and laboratory discoveries over the first year of the COVID-19 pandemic. Many immunologists quickly pivoted from their existing research to study SARS-CoV-2. This brought about a remarkable convergence of knowledge focused on one viral infection. Clinical consortia were formed. In an unprecedented fashion, developments were announced in preprint servers and media to speed information dissemination. The authors prominently showcase the extraordinary leaps in understanding SARS-CoV-2 immune responses and highlight knowledge gaps and areas for future investigations.

      February 8, 2021

      • SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas. 2/4/21. Müller JA. Nat Metab.
        These investigators show that SARS-CoV-2 can cause diabetes in the absence of autoantibodies and other pancreatic disorders by directly infecting human exocrine (enzyme-producing) and endocrine (hormone-producing) pancreatic cells. Beta-cells (insulin-producing) express ACE-2, and TMPRSS2 allowing entry and then viral replication, inhibitable by remdesivir. The reduction in insulin-secretory granules in beta-cells results in reduced glucose-stimulated insulin secretion. The nucleocapsid protein was detected in four post-mortems in exocrine cells, beta-cells and in close proximity to the islets of Langerhans. These data suggest that SARS-CoV-2 targeting the pancreas leads to endocrine dysregulation (hyperglycemia, DKA, new onset Type-1 diabetes) and pancreatitis (up to 33%).

      January 25, 2021

      • Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia. 1/11/21. Grant RA. Nature.
        In this basic science article, using flow cytometry and transcriptomic profiling these investigators compared bronchoalveolar lavage (BAL) samples from 88 patients with SARS-CoV-2 respiratory failure to 211 patients with non-SARS-CoV-2 failure. In 10 SARS-CoV-2 BALs they analyzed single-cell RNA-seq. In SARS-CoV-2, the alveolar space was enriched in T cells (CD4+ and CD8+) and monocytes; only 31% had neutrophilia. Transcriptomes suggested that SARS-CoV-2 directly infects alveolar macrophages (AM), which produce T-cell chemo-attractants. T-cells then produce interferon-gamma. Feedback to AM promotes further T-cell activation. In contrast to non-SARS-CoV-2, SARS-CoV-2 causes a slowly unfolding, spatially limited alveolitis. Infected AM and T cells form a positive feedback circuit.

      January 11, 2021

      • Promising Therapy for Heart Failure in Patients with Severe COVID-19: Calming the Cytokine Storm. 1/6/2021. Peng X. Cardiovasc Drugs Ther.
        This detailed and well referenced review covers key mechanistic links between Covid-19 cytokine-storm, subsequent myocardial injury and progression to heart failure (HF). Heightened release of cytokines may result in myocardial damage through direct injury, general inflammation, thrombosis, hypoxemia and downregulation of ACE2 on cardiomyocytes and vascular endothelium. Key inflammatory cytokines include TNFa and IL-1b; both produce accumulation of interstitial collagen fibers and IL-6 which can induce cardiomyocyte hypertrophy and diastolic dysfunction. HF therapies may include cytokine inhibitors, corticosteroids, type-I and -III interferons, but their timing needs investigation. Current guidance suggests maintaining or starting ACEIs and ARBs; benefits may outweigh risks.
      • SARS-CoV-2 Variant – United Kingdom of Great Britain and Northern Ireland. 12/21/20. WHO.
        UK scientists sequenced a SARS-CoV-2 variant (VUI 202012/01) now representing >50% of isolates in South East England. The variant shows 14 mutations resulting in amino acid changes and three deletions. Significant mutations in the receptor binding domain are N501Y and P681H. A deletion at position 69/70 affects the Spike (S)-gene. The variant increases transmissibility between 40-70%, adding 0.4 to R0 bringing it to 1.5-1.7. Investigations are ongoing to determine if this variant will change symptom severity, antibody responses or vaccine efficacy. Most PCRs target multiple sequences and therefore the impact of the variant on diagnostics is not anticipated to be significant.
        SAB Comment: In order to understand the epidemiology of any variant, widespread and frequent genetic sequencing of viral testing samples is needed. Currently, the US lags far behind the UK in this regard, sequencing ~1% of samples vs. >10% in the UK. Therefore, relatively little is known about the spread of the “UK variant” in the US.

      January 4, 2021

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

      December 7, 2020

      • No evidence for increased transmissibility from recurrent mutations in SARS-CoV-2. 11/25/20. van Dorp L. Nat Commun.
        SARS-CoV-2 is not becoming more transmissible or virulent. In jumping from animal to human, SARS-CoV-2 might evolve or adapt toward higher transmissibility. This study examined whether viral changes have emerged repeatedly and independently (homoplasies) and if repeated mutations in human lineages made the virus more transmissible. Using a 99-country dataset of 46,723 SARS-CoV-2 genomes compared to the reference Wuhan-Hu-1, investigators did not identify a single recurrent mutation convincingly associated with increased viral transmission. So far, as an endemic human pathogen, recurrent mutations appear to be evolutionary neutral, single lineage and primarily induced via RNA editing, rather than being signatures of adaptive pressure and a new separate phenotype.

      November 30, 2020

      • Immunomodulation as Treatment for Severe COVID-19: a systematic review of current modalities and future directions. 11/20/2020. Meyerowitz EA. Clin Infect Dis.
        This current review of COVID-19 therapeutics stresses approaches to immune dysregulation and its evolving role in severe disease. Distinct early innate responses (first 5-7 days) and later adaptive immune responses must be recognized and treated accordingly. Antiviral treatment alone may be insufficient. To date, only dexamethasone shows a mortality benefit in randomized control trials when used later in the course. Late infectious and other steroid complications may be underreported. Various immunomodulatory strategies including early use of Janus kinase (JAK) inhibitors to rebalance the JAK-STAT pathways and Type I interferons are discussed. Promising early data are summarized for emerging therapies.

      November 23, 2020

      • SAB Comment: Interferon (IFN) gets its name because it “interferes” with viral replication. Suspecting that interferon is inadequately produced and/or its actions blocked, two important Science papers (below) examined possible mechanisms. Zhang et al, reports finding loss of function gene variants in 3.5% of severe COVID-19 patients that control induction and amplification of Type I IFNs. The effects of these lifelong inborn variants, not found in mild disease or healthy controls, are only exposed with development of severe viral pneumonia. In the other paper, Bastard, et al, found (presumed preexisting) high-titer IgG neutralizing autoantibodies against Type I IFNs-alpha and -omega only in severe COVID-19. The autoantibodies occur in at least 2.6% of women and 12.5% of men. The defects identified by Zhang, et al, if discovered early on, could be treated with Type I IFNs, and by Bastard et al, treated with Type I IFN-beta in particular, as autoantibodies against IFN-beta are rare.
        • Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. 10/23/20. Zhang Q. Science.
          These authors examined 659 severe COVID-19 patients for mutations in genes involved in the regulation of type I and III interferon (IFN) immunity. Following exome or genome sequencing examining rare variants at 13 candidate loci they found genetic defects in 3.5% of severe patients at eight of the 13 candidate loci involved in the TLR3- (double stranded RNA-responsive) and Interferon-regulatory factor-7 (IRF7)-dependent induction and amplification of type I IFNs. These variants resulted in enrichment of loss of function variants not found in mild COVID-19 patients or healthy individuals. Early type I IFN administration may benefit patients with these inborn variants.
        • Autoantibodies against type I IFNs in patients with life-threatening COVID-19. 10/23/20. Bastard P. Science.
          In COVID-19 pneumonia, at least 101/987 patients had low or undetectable serum IFN-α and high-titer neutralizing IgG autoantibodies (auto-Abs) against interferon-omega (IFN-ω) (13 patients), against the 13 types of IFN-α2 (n=36), or against both (n=52). In vitro, auto-Abs blocked IFNs inhibition of SARS-CoV-2. Auto-Abs were not present in asymptomatic or mild SARS-CoV-2 infection (n=663) and in only 4/1227 healthy individuals; 95/101 with auto-Abs were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity (seen in Zhang) accounts for life-threatening COVID-19 in at least 2.6% of women and 12.5% of men who could be treated with IFN-beta.

      October 26, 2020

      • Targeting complement cascade: an alternative strategy for COVID-19. 10/19/20. Ram Kumar Pandian S. 3 Biotech.
        The authors present well-referenced experimental support that complement cascade inhibition will counteract COVID-19 inflammation. Complement dysregulation can lead to cytokine storm and ARDS pathology. Activation and deposits of complement components are seen in animal models and at autopsy of COVID-19 patients. Pre-clinical and clinical studies using current and pipeline agents show pathway inhibition aids ARDS recovery. Viral infections including COVID activate complement via the lectin pathway via mannose-binding lectin associated serine protease 2 (MASP2). Complement inhibitors including monoclonal antibodies, proteins, peptides and small molecules exhibit promise blocking the complement components and their downstream effects in various pathological conditions including SARS-CoV.

      October 19, 2020

      • Evidence of a wide gap between COVID-19 in humans and animal models: a systematic review. 10/7/2020. Ehaideb SN. Crit Care.
        In this comprehensive literature review, replication-competent animal models were assessed for recapitulating full-spectrum human COVID-19, as well as prophylaxis, therapies, or vaccines. Animals included nonhuman primates (n = 13), mice (n = 7), ferrets (n = 4), hamsters (n = 4), and cats (n = 1). All animals supported high viral replication in the respiratory tract with mild clinical manifestations, lung pathology, IgG antibodies and full recovery. Older animals had more severe illness. None developed respiratory failure, multiple organ dysfunction or death. Transient systemic inflammation was observed occasionally in nonhuman primates, hamsters, and mice. No animals unveiled cytokine storms or coagulopathy supporting a wide gap between human and animal disease.

      October 12, 2020

      • Susceptibility of tree shrew to SARS-CoV-2 infection. 9/29/2020. Zhao Y. Sci Rep.
        SARS-Co-V-2 research has been hampered by poor susceptibility of animal models to SARS‑CoV‑2 infection, particularly the mouse. These investigators examined if a domesticated tree shrew, a species genetically close to primates and used in hepatitis, influenza and other research may be useful. SARS-CoV-2-infected tree shrews showed no clinical signs except mild fevers. Histologically, low levels of virus shedding and replication in tissues were observed. Mild pulmonary abnormalities were the main changes observed. The tree shrew may not be suitable for COVID‑19 research. However, tree shrew may be a potential asymptomatic intermediate host of SARS‑CoV‑2 besides bats and pangolins.

      October 7, 2020

      September 30, 2020

      • New Studies on COVID-19 Epidemiology
        The following four articles examine risk factors for developing COVID-19, for having severe disease and for death. Common findings include an increased risk of infection and hospitalization in Blacks but no increase in mortality. It should be noted that the mentioned hospitalization rates may depend on socio-economic factors and may not be a clear indicator of severity of disease.
        • Patterns of COVID-19 testing and mortality by race and ethnicity among United States veterans: A nationwide cohort study. 9/22/20. Rentsch CT. PLoS Med.
          This article presents a nationwide VA data set study (~6 million patients, February 8 to July 22) comparing positive COVID-19 test results with 30-day mortality. Healthcare disparities were explored by evaluating “associations between race/ethnicity and receipt of COVID-19 testing, a positive test result, and 30-day mortality, with multivariable adjustment for demographic and clinical characteristics including comorbid conditions, health behaviors, medication history, site of care, and urban versus rural residence.” The study confirms prior reports indicating that “Black and Hispanic individuals experience excess burden of SARS-CoV-2 infection” but not increased mortality and notes that these disparities “are not entirely explained by underlying medical conditions or where they live or receive care.” The article contains interesting distinctions and reinforces the importance of designing “strategies to contain and prevent further outbreaks in racial and ethnic minority communities.”
        • Risk Factors for Hospitalization, Mechanical Ventilation, or Death Among 10 131 US Veterans With SARS-CoV-2 Infection. 9/23/20. Ioannou GN. JAMA Netw Open.
          This large study showed no increase in mortality associated with Black or Hispanic race, obesity, COPD, hypertension or smoking (contrary to what has been found in smaller, prior studies). It did find the expected association of increased severity and mortality with older age (≥50) and multiple comorbidities.
        • Association of Race and Ethnicity With Comorbidities and Survival Among Patients With COVID-19 at an Urban Medical Center in New York. 9/25/20. Kabarriti R. JAMA Netw Open.
          Among 5902 patients with positive COVID-19 diagnosis treated at a single academic center in urban New York, non-Hispanic Black and Hispanic patients had a higher proportion of more than 2 medical comorbidities and were more likely to require inpatient hospitalization, but had outcomes including mortality that were at least as good as, and maybe even marginally superior to, their non-Hispanic White counterparts when controlling for age, sex, and comorbid conditions at presentation.
        • Racial Disparities in Incidence and Outcomes Among Patients With COVID-19. 9/25/20. Muñoz-Price LS. JAMA Netw Open.
          This article investigates the goal-described patterns and outcomes of COVID-19 by race, controlling for age, sex, socioeconomic status, and comorbid conditions among 2595 urban patients. COVID-19 positivity was associated with Black race. Among patients with COVID-19, both race and poverty were associated with higher risk of hospitalization, but only poverty was associated with higher risk of intensive care unit admission. The findings also imply that adverse outcomes and greater population mortality associated with Blacks early in the course of the US pandemic were primarily attributable to greater incidence of COVID-19 among African American residents rather than worse survival once hospitalized.

      September 21, 2020

      • The coronavirus is mutating – does it matter? 9/8/20. Callaway E. Nature.
        In an article from Nature, mutations in the SARS-CoV-2 are reviewed. Mutations in RNA viruses such as SARS-CoV-2 containing “proofreading” enzymes occur slowly. One distinct mutation in the spike protein gene occurs at the 614th amino-acid position: the aspartate (D, in biochemical shorthand) is replaced by glycine (G) in the virus’s 29,903-letter RNA code. The “D614G mutation” became the dominant SARS-CoV-2 lineage in Europe and the US. Despite early alarm, it does not enhance spread or affect antibody defense. More than 12,000 mutations in SARS-CoV-2 are catalogued. The author speculates that worrisome mutations could arise especially if antibody therapies producing selection pressure are not used wisely.

      September 4, 2020

      • Humoral Immune Response to SARS-CoV-2 in Iceland. 9/1/20. Gudbjartsson DF. N Engl J Med.
        Fifty-six percent of all SARS-CoV-2 infections in Iceland had been diagnosed with quantitative polymerase-chain-reaction (qPCR) assay, 14% had occurred in quarantined persons who had not been tested with qPCR (or who had not received a positive result, if tested), and 30% had occurred in persons outside quarantine and not tested with qPCR. Despite extensive screening by qPCR, a substantial fraction of infections were not detected, which indicates that many infected persons did not have substantial symptoms. But due to the low SARS-CoV-2 antibody seroprevalence, the Icelandic population is vulnerable to a second wave of infection.

      July 31, 2020

      • Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. 5/15/20. Grifoni A. Cell.
        To be effective, a COVID-19 vaccine has to elicit strong T cell immunity. Vaccines stimulate B cells to make antibodies against the virus. Helper T cells promote this. Those antibodies join with the virus, preventing it from entering a host cell and mark the virus for destruction. Once the virus infiltrates the host cell, antibodies are not effective. However, cytotoxic T cells can destroy infected host cells.
        T cell immunity does not prevent re-infection but reduces the severity of symptoms. Among patients recovered from COVID-19, CD4+ T cells were observed in all and CD8+ T cells were observed in about 70%. CD4+ responses to spike antigen correlated with IgG and IgA antibody titers. Each of M, spike, and N antigens accounted for 11%–27% of the total CD4+ response. The remaining responses were against other SARS-CoV-2 antigens. This suggests that vaccines that target multiple antigens may be more effective than the ones targeting only the spike antigen.
        T cell immunity is observed in persons infected and in about one-half of persons uninfected with SARS-CoV-2. The latter may have been previously infected with a virus such as one of the four human coronaviruses that cause colds. Thus, there is cross reactivity with other corona viruses. This may be a reason for variability in severity of clinical illness after infection.
        Many of the vaccine candidates lead to production of the spike protein and antibodies against it. If the vaccine does not produce the spike protein with correct confirmation, the generated antibodies may be binding but not neutralizing antibodies. This can promote viral replication or form complexes that trigger more inflammation. Memory B and T cells that recognize the virus can provide protective immunity for years although the antibody titers may decline within months. Efforts are being made to genetically modify certain immune cells to target the virus.

      July 22, 2020

      • Excess Deaths From COVID-19 and Other Causes, March-April 2020. 7/1/20. Woolf, SH. JAMA.
        The initial symptomatology, prodromal infective potential, anticipated course/severity, value of PPE and myriad additional variables were unknown when COVID-19 began its international journey. Early optimism in terms of containing and controlling the virus rapidly deteriorated as disease progression was recognized, the ability of asymptomatic carriers were known to be highly infectious and the initially unexpected benefit of universal face mask adoption created uncertainly about not only the viral spread but also the safety and reliability of the health system. Death is usually categorized accurately and reliable “death rate” statistics have been accumulated; the authors use seasonally adjusted U.S. death rates from December 29, 2013 to February 29, 2020 and compare historical to actual death rates reported between March 1, 2020 and April 2020 and include a secondary analysis in the five states most severely affected by the virus during the collection period. Careful data analysis was used to determine all-cause mortality and how COVID-19 influenced the total. The results attribute 65% of excess deaths to COVID-19-related causes and suggest that the total number is likely higher. Analysis was able to distinguish significant increases in other diseases during the period.
        Also included is an insightful discussion underscoring importance of accurate determination of COVID-19’s true impact on not only death but also on hidden morbidity (including COVID-19 delayed treatment and/or resource constraints) which is still being elaborated.
      • EDITORIAL: Mortality and Morbidity: The Measure of a Pandemic. 7/1/20. Zylke JW. JAMA.
        This editorial accompanying “Excess Deaths” further elaborates on the importance of, and difficulties associated with, estimating impact of COVID-19 on health systems and society. Peripheral effects are included and discussed. Together, the articles underscore the importance of classification and clarification in estimating disease impact, prevalence and spread in vulnerable populations and on society at large.
      • Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. 7/6/20. Pollan M. Lancet.
        Review by the SAB
        By Dr. Robert Coffey, on behalf of the SAB
        This article reports the results of antibody testing of 61,000 individuals across Spain, from April 27 to May 11, showing an overall national seropositive rate of only 5% (the majority of new diagnoses in Spain’s severe epidemic were made by May 1). Regions that experienced a more intense epidemic such as Madrid did have a seropositive rate of greater than 10%. Approximately one-third of the seropositive subjects reported having had no symptoms suggestive of COVID-19 infection. While specific locales such as Bergamo, Italy and some neighborhoods in Queens, NY may have seropositive rates high enough to confer local herd immunity, this does not seem to be occurring at a national level after severe epidemic episodes.

      July 20, 2020

      • SARS-CoV-2 infection protects against rechallenge in rhesus macaques. 5/20/20. Chandrashekar A. Science.
        Review by the SAB
        By Dr. Uday Jain, on behalf of the SAB
        Nine adult rhesus macaques infected with SARS-CoV-2 developed humoral and cellular immune responses leading to protective immunity. On re-challenge by SARS-CoV-2, there was a major attenuation of viral load in nasal mucosa and bronchoalveolar lavage in all of them. As the virus was still detectable, the protection was not sterilizing and the macaques could infect others. These results in primates suggest that patients who have COVID-19 may develop immunity to it. This is also essential for the development of a vaccine and determination of herd immunity.

      May 28, 2020

      • Duration of SARS-CoV-2 viral RNA in asymptomatic carriers. May 24. Yan X. Crit Care.
        Asymptomatic COVID-19 carriers are potentially a significant vector for the spread of SARS-CoV-2, but little is known about asymptomatic carriers. This research letter charts the RT-PCR positivity of 24 asymptomatic RT-PCR positive patients, showing persistent positivity can be lengthy (over 4 weeks). Viral cultures were not performed, so little can be said about infectivity of these asymptomatic carriers.

      May 27, 2020

      May 22, 2020

      May 21, 2020

      • Higher solar irradiance is associated with a lower incidence of COVID-19
        May 19. Guasp. Clinical Infectious Diseases.
        Opinion from SAB Member: Dr. Jay Przybylo
        This is an interesting study using statistical evaluation of population density and solar and weather influences on COVID-19 spread that correlates high urban population density and low UV radiation to increased COVID-19 infection rates. The graphs are difficult to interpret.
      • Simulated Sunlight Rapidly Inactivates SARS-CoV-2 on Surfaces
        May 20. Ratnesar-Shumate. The Journal of Infectious Diseases.
        Opinion from SAB Member: Dr. Jay Przybylo
        This is a biodefense research article proving that simulated sunlight inactivates SARS-CoV-2. 90% of the virus on different surfaces became inactivated in between 7-14 minutes. Lower intensity light containing UV spectra took longer to achieve effect. Different than the article describing the effect of UV light on large populations in geographic regions investigating natural effects of the sun and climate, this article is specific to the actual virucidal effect of the light.

      May 19, 2020

      • Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19). May 1. Diao. Front. Immunol.
        Lymphopenia is a feature in Covid-19, however the number of T cells marking progressive disease is not known. This retrospective analysis from Wuhan, China examined 522 cases from December 2019 to January 2020. The critical numbers of total T cells, CD4+ and CD8+ T cells indicating more critical illness or impending death were less than 800, 300, or 400/μL, respectively. Also, these T cells expressed enhanced surface PD-1 and Tim-3, so called “exhaustion markers”. T cell numbers are negatively correlated to the “cytokine storm” mediators TNF-α, IL-6, and IL-10. This study suggests low T lymphocyte counts mandates early intervention.

      May 16, 2020

      May 11, 2020

      May 1, 2020

      • A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Apr 30. Gordon. Nature.
        332 SARS-CoV-2 human protein interactions were identified by cloning virus proteins in human cells and then identifying associated human proteins. 40% are associated with endomembrane compartments or vesicle trafficking pathways. 66 interactions are targeted by 29 approved drugs, 12 in clinical trials, and 28 preclinical compounds. Viral assays at Mt Sinai in NY and the Institut Pasteur in Paris identified 2 sets of agents with antiviral activity — those affecting translation (e.g. hydroxychloroquine and the more effective PB28) and those modulating Sigma1 and 2 receptors (e.g. haloperidol and dextromethorphan). Intriguing methodology for identifying existing compounds for clinical trials.

      April 30, 2020

      April 29, 2020

      • Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study
        Apr 27. Bi. The Lancet Infectious Diseases.
        Opinion from SAB Member: Dr. Barry Perlman
        Retrospective epidemiologic analysis demonstrating the benefits of contact surveillance, adequate availability of testing, and quarantines. There were 391 confirmed cases of COVID-19 Jan 14-Feb 12 and 1286 close contacts confirmed before Feb 9 in Hubei province. Suspected cases and contacts were tested by RT-PCR nasal swabs. Asymptomatic close contacts who tested positive were quarantined at central facilities, while those who tested negative were quarantined at home or a central facility. Infection rate did not differ significantly by age, with on average 7% of close contacts becoming infected, 77% of these contacts having any symptoms, and 3% of infections having severe disease at initial assessment. Median time to recovery was 22 days with older patients and those with severe disease having a longer time to recovery. Contact-based surveillance reduced the duration an infected person could spread disease in the community by 2 days as compared with symptom-based surveillance.

      April 28, 2020

      • How Could This Happen? Narrowing Down the Contagion of COVID-19 and Preventing Acute Respiratory Distress Syndrome (ARDS)
        Apr 25. Alaerts. Acta Biotheor.
        Opinion from SAB Member: Dr. W. Heinrich Wurm
        A biologist’s deeply scientific but also philosophical review of the history, epidemiology and the viral genomics of the Corona virus family. The author provides a helpful template for understanding the present pandemic outbreak and focuses on the role of the renin-angiotensin system in acute lung injury and ARDS and SARS-CoV action during infection. His suggestions for future research list: 1) The correlation and interaction with previous medication, particularly ACE-inhibitors; 2) Creating immunologic profiles, particularly for patients at risk for ARDS; and 3) The influence of viral genomic differences on infectivity, virus reproduction and shedding and biochemical entry routes with host cells. In addition, the range of immunological reactions to the virus by the host deserves further scrutiny and will be of great importance in the vaccine development. A valuable contribution to both clinician scientists and investigators searching to contribute to solve the COVID-19 puzzle.

      April 24, 2020

      April 23, 2020

      • Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study. Apr 21. Chu. The Lancet Microbe.
        A science study with little clinical significance. A comparison of SARS-CoV-2 vs COVID-19 for entry and replication into numerous human and nonhuman cell lines. The authors state the article might be of pertinence to further cell studies on optimization of antiviral assays but not necessarily to human organs in the physiologic state — life.
      • Connecting clusters of COVID-19: an epidemiological and serological investigation
        Apr 21. Yong. The Lancet Infectious Disease.
        Opinion from SAB Member: Dr. Heinrich Wurm
        Fascinating account of a successful epidemiological disease tracking operation using RT-PCR and serologic testing to identify COVID-19 transmission among 3 clusters – 2 churches and a New Year’s gathering – in Singapore between mid-January and the end of February. While initial testing of all patients presenting with pneumonia using RT-PCR led to the diagnosis of overtly infected patients who were shedding virus, serologic testing played an important role in identifying convalescent cases or people with minimal symptoms, allowed assessment of disease penetration among the population and guidance towards containment efforts.
        • An accompanying editorial by Johns Hopkins epidemiologists, stresses the value of broad testing strategies to assess and contain the spread of COVID-19, particularly by measuring SARS-CoV-2-specific IgG antibody titers. It enumerates 4 distinct and valuable concepts gained from serological testing, including identifying potential candidates for donation of reconvalescent serum. It also points out several remaining challenges, among those sensitivity and specificity of the test, excluding cross reactivity to other viruses resulting in false positives, antibody kinetics determining the duration of immunity, as well as cost and portability of the test.
      • The important role of serology for COVID-19 control
        Apr 21. Winter. The Lancet Infectious Diseases.
        Opinion from SAB Member: Dr. W. Heinrich Wurm
        This accompanying editorial by Johns Hopkins epidemiologists stresses the value of broad testing strategies to assess and contain the spread of COVID-19, particularly by measuring SARS-CoV-2-specific IgG antibody titers. It enumerates 4 distinct and valuable concepts gained from serological testing, including identifying potential candidates for donation of reconvalescent serum. It also points out several remaining challenges, among those: sensitivity and specificity of the test, excluding cross reactivity to other viruses resulting in false positives, antibody kinetics determining the duration of immunity, and cost and portability of the test.

      April 21, 2020

      • Pulmonary and Cardiac Pathology in Covid-19: The First Autopsy Series from New Orleans. Apr 10. Fox. medRxiv.
        As of March 31, 2020, New Orleans has had the highest death rate per capita in the US. This is a non-peer reviewed report of the cardiopulmonary findings of the first 4 autopsies performed. The patients were African Americans with obesity and HTN. 3 had IDDM and 2 had chronic kidney disease. Lung parenchyma was edematous and firm, consistent with ARDS. 3 had areas of lung hemorrhage. Only the lung from the patient who had been on methotrexate showed focal consolidation. All cases showed evidence of diffuse alveolar damage with DC4+ aggregates around thrombosed small vessels. Heart tissue showed atypical myocyte degeneration but no myocarditis. The findings suggest that in addition to targeting the virus itself, therapy should also focus on the thrombotic and microangiopathic effects and the maladaptive immune response.

      April 20, 2020

      • Clinical Characteristics of Covid-19 in New York City. Apr 17. Goyal. NEJM.
        A prelude to what’s coming to us
        NEJM article about experience of 2 NYC Hospitals of first 393 patients with COVID 19.
        Comorbidity was noted to be higher in NYC as compared to China. NYC outcomes were noted different as well with regard to: Higher number of patients were ventilated, lower oxygen earlier, renal replacement, fluids, need for vaso active drugs to maintain hemodynamic stability. 33% required ventilators, 10.2% Mortality, 33% extubated, 66% were discharged – these numbers were higher than China data all across.
      • Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period
        Apr 14. Kissler. Science.
        Opinion from SAB Member: Dr. Barry Perlman
        Viral, environmental, and immunologic data from other corona viruses were used to project SARS-CoV-2 transmission and determine social distancing measures that may be needed through 2025. Models suggest that SARS-CoV-2 could cause outbreaks in any season, exhibiting annual, biennial, or sporadic patterns depending on duration of immunity after infection. If similar to other coronaviruses, recurrent SARS-CoV-2 winter outbreaks are likely. Incidence through 2025 will depend on duration of immunity and cross immunity with other coronaviruses. In all models, infection resurgence occurred when social distancing measures were lifted, but restrictive social distancing could also decrease development of population immunity. In the absence of increased critical care capacity and effective new treatments or vaccines, intermittent social distancing will be needed through 2022. Increased critical care capacity, testing, and surveillance are needed to better determine what intermittent social distancing policies may maintain critical care availability while building population immunity.
      • Spread of SARS-CoV-2 in the Icelandic Population
        Apr 14. Gudbjartsson. The New England Journal of Medicine.
        Opinion from SAB Member: Dr. J. Lance Lichtor
        In this study of corona virus spread in Iceland, using targeted testing of persons at high risk for infection and population screening, the frequency of coronavirus infection in the overall Icelandic population was stable from March 13 to April 1, which showed that containment measures in Iceland were working. Testing was a critical component and is a model for other countries.

      April 17, 2020

      • Assessing Viral Shedding and Infectivity of Tears in Coronavirus Disease 2019 (COVID-19) Patients. Apr 16. Seah IYJ. Ophthalmology.
        The nasolacrimal system can act as a conduit for viruses to travel from the upper respiratory tract to the eye. The authors measured the presence of SARSCoV-2 with viral isolation and quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis. As the 17 patients in the study were being monitored clinically via routine nasopharyngeal swabs, these results were compared with those of tears to understand further patterns of viral shedding. Of the 17 patients recruited, none demonstrated ocular symptoms. However, 1 patient developed conjunctival injection and chemosis during the stay in the hospital. Fourteen patients showed upper respiratory tract symptoms at presentation, including cough, rhinorrhea, and sore throat. No evidence was found of SARS-CoV-2 shedding in tears through the course of the disease even for the one patient with conjunctival injection.
      • Visualizing speech-generated oral fluid droplets with laser light scattering. Apr 15. Anfinrud, P. NEJM.
        NEJM letter to the editor, from the NIH, explaining and demonstrating sprays of secretions from speaking. The included graphic video illustrates the degree of droplet/aerosol formation from speech alone.

      April 15, 2020

      • Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. Mar 17. van Doremalen N. NEJM.
        This widely published letter to the editor addresses the viability of SARS-CoV-2 in aerosols and on various surfaces and compares it to SARS-CoV-1, the original severe acute respiratory syndrome coronavirus that is most closely related to the coronavirus responsible for the Covid-19 pandemic. Scientists from the National Institute of Allergy and Infectious Diseases, CDC, UCLA and Princeton participate in this work. It showed that under experimental conditions both viruses are detectable in aerosols for several hours and up to 24 hours on cardboard and stainless steel. The fact that the stability of the two SARS viruses were similar indicates that other factors, like high viral load in the upper respiratory tract and the possibility that people infected with the virus may shed and transmit the virus while asymptomatic, account for the difference in epidemiological characteristics.
      • Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Feb 14. Liang, W. Lancet Oncology.
        Cases with COVID-19 acute respiratory disease from 575 hospitals in China were monitored prospectively to determine whether cancer patients are at increased risk of COVID-19 and have a poorer prognosis. 18/1590 cases had a history of cancer, which is 3-4 times higher than the overall incidence of cancer in China. Cancer patients had an almost 5x higher risk of severe events — ventilation or death. Chemotherapy or surgery within the past month as associated with the highest risk. Lung cancer patients did not have a higher risk of severe events compared with other cancer patients. The authors suggest that during infectious disease events such as COVID-19, chemotherapy or elective cancer surgery should be postponed in endemic areas, and the increased risk to cancer patients should be taken into account regarding infection prevention and treatment.
      • Stability and Viability of SARS-CoV-2. Apr 14. Petti S. N Engl J Med.
        In follow-up to the experimental aerosol publication by van Doremalen et al., a number of letters to the editor address the fact that the message derived from the experiment created the impression in the lay press that there is proof of airborne transmission under non-aerosolizing conditions. In response, the authors reiterate their statement that the stability of aerosolized CoV-2 is similar to that of CoV-1. What follows from this finding is the fact that aerosols created by procedures (i.e. drilling) or patients (i.e.coughing) have been associated with nosocomial transmission of emerging viruses (SARS-Co-V-1 and MERS-CoV) and that there is no reason to believe COVID-19 will act differently under similar conditions.

      April 14, 2020

      April 13, 2020

      April 11, 2020

      • Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19 Apr 9. Chu. Clinical Infectious Diseases.
        Opinion from SAB Member: Dr. Philip Lumb
        Ex-vivo investigation (excised donor lung segments from surgical patients with lung tumors) inoculated with either SARS-CoV-2 or SARS-CoV preparations. Infection and replication capacity of the two preparations were compared. Excellent methodology section detailing specimen and culture preparation, biohazard security and virology challenge and critical analysis. Results demonstrated that SARS-CoV-2 was more capable of infecting and replicating in lung tissue than SARS-CoV. The discussion includes the statement, “These findings may explain the high viral load in the respiratory secretions of COVID-19 patients during the early days on presentation or even during incubation, and thus the its person-to-person transmissibility.” This is a meticulously conducted experiment with well described methodology and important conclusions that provides insight into why COVID-19 propagates rapidly, has variable penetrance and clinical outcomes, and gives a theoretical rationale for early use of antiviral medication. An important study that could help define future therapeutic intervention and further ongoing research.
      • Coronavirus Disease 2019 in Children – United States, February 12-April 2, 2020. Apr 10. CDC COVID-19 Response Team. MMWR Morb Mortal Wkly Rep.
        22% of US population is < age 18. As of 4/2/20 1.7% of reported US COVID-19 patients were < age 18. Clinical data were only available for a small proportion —11%. Of those, 73% had symptoms of fever, cough, or shortness of breath compared with 93% of adults aged 18–64 years during the same period; 5.7% of all pediatric patients, or 20% of those for whom hospitalization status was known, were hospitalized, lower than the percentages hospitalized among all adults aged 18–64 years (10%) or those with known hospitalization status (33%). Three pediatric deaths were reported. These data support previous findings that children with COVID-19 might not have reported fever or cough as often as do adults, but due to the low percentage of cases with available clinical data, this conclusion should be considered preliminary.
      • Effect of throat washings on detection of 2019 novel coronavirus. Apr 10. Guo. Clin Infect Dis.
        11 COVID-19 positive patients were studied with 24 paired PCR testing from both nasal swabs and self-administered throat washings using 20 ml. saline. In 18 pairs of tests the results agreed (1 pair positive and 17 pairs negative) however in 6 pairs of tests the nasal swab was negative while the throat washing was positive. While this is a very small study conducted patients who were 48-57 days after symptom onset, it raises the question of whether throat washings may prove to be superior in sensitivity and simplicity for identification of PCR positive COVID-19 patients.
      • Presymptomatic Transmission of SARS-CoV-2 – Singapore, January 23-March 16, 2020. Apr 10. Wei. MMWR Morb Mortal Wkly Rep.
        As of March 17, Singapore had reported 243 cases of COVID-19 disease of which 157 were locally acquired. Of those 157, 10 patients from 7 clusters, (6.4%), were felt to have been transmitted 1-3 days before the source patient experienced onset of symptoms. The mechanism of transmission was not certain. Public policy implications are discussed.

      April 10, 2020

      April 9, 2020

      April 8, 2020

      April 5, 2020

      • Aerosol and Surface Stability of SARS-CoV-2 as Compared With SARS-CoV-1 Van Doremalen. Mar 17. NEJM.
        COVID-19 SAB Opinion from: Dr. W. Heinrich Wurmn
        This widely published letter to the editor of the NEJM addresses the viability of SARS-CoV-2 in aerosols and on various surfaces and compares it to SARS-CoV-1, the original severe acute respiratory syndrome coronavirus that is most closely related to the coronavirus responsible for the COVID-19 pandemic. Scientists from the National Institute of Allergy and Infectious Diseases, CDC, UCLA and Princeton participate in this work. It showed that the SARS-CoV-2 virus survives and is detectable in aerosols for several hours and up to 24 hours on cardboard and stainless steel. This indicates that the virus spreads through the air and by touching contaminated surfaces. The fact that the stability of the two SARS viruses were similar indicates that other factors, like high viral load in the upper respiratory tract and the potential that people infected with the virus may shed and transmit the virus while asymptomatic, account for the difference in epidemiological characteristics.

      April 4, 2020

      • Ten Weeks to Crush the Curve. Apr 1. Fineberg. NEJM.
        Editorial advocating 6 steps to “defeat” Covid-19 by early June: Establish united command, increase diagnostic test availability for everyone with symptoms, supply health workers with PPE and equip hospitals to care for surge, differentiate population based on presence or absence of current infection and treat accordingly, inspire and mobilize public, research.

      April 3, 2020

      March 31, 2020

      March 27, 2020

      March 26, 2020

      March 25, 2020

      November 13, 2006

    1. Diagnosis of Infection or Immunity (Including Organization / Reliability)
      September 13, 2021

      August 30, 2021

      • COVID-19 Vaccine Safety in Adolescents Aged 12-17 Years – United States, December 14, 2020-July 16, 2021. 8/5/21. Hause AM. MMWR Morb Mortal Wkly Rep.
        A statistical analysis of the Pfizer COVID-19 vaccine in children 12 years or older in the US demonstrated its safety. Reactions to the vaccine are uncommon and mostly mild. Myocarditis is one rare but severe reaction more common in boys after the second vaccination and that resulted in no deaths.
      • Durability of mRNA-1273 vaccine–induced antibodies against SARS-CoV-2 variants. 8/12/21. Pegu A. Science.
        The authors assess the impact of SARS-CoV-2 variants B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.429 (Epsilon), B.1.526 (Iota), and B.1.617.2 (Delta) on binding, neutralizing, and ACE2-competing antibodies elicited by the Moderna mRNA-1273 vaccine over seven months. Cross-reactive neutralizing responses were rare after a single dose. At the peak of response to the second vaccine dose, all individuals had responses to all variants. Binding and functional antibodies against variants persisted in most subjects, albeit at low levels, for 6 months after the primary series of the mRNA-1273 vaccine. Across all assays, B.1.351 had the lowest antibody recognition. The authors believe that these data complement ongoing studies to inform the potential need for additional boost vaccinations.

      August 9, 2021

      • Covid-19 Breakthrough Infections in Vaccinated Health Care Workers. 7/28/21. Bergwerk M. N Engl J Med.
        At the largest Israeli medical center, healthcare workers with COVID-19 exposure or symptoms underwent extensive evaluations from 1/20/21 – 4/28/21 to investigate infectivity and breakthrough infections. Breakthrough cases with neutralizing antibody (nAb) titers within a week before documented infection were matched with 4-5 uninfected controls. Among 1,497 healthcare workers fully vaccinated with BNT162b2 for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented (0.4%). Eighty-five percent were B.1.1.7. (Alpha). Most were asymptomatic or mild, yet 19 had persistent symptoms at 6 weeks. nAb titers during the peri-infection period were lower in patients than in controls (ratio, 0.36). Higher nAb levels were associated with lower viral load. No secondary infections were documented. In all 37 patients for whom the suspected source of infection was identified, it was an unvaccinated person, mostly household members.
      • Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. 7/21/21. Bernal JL. N Engl J Med.
        British investigators used a test-negative case-control design to estimate the effectiveness of vaccination against symptomatic disease caused by the delta variant or the predominant alpha variant (B.1.1.7) over the period that the delta variant began circulating. With the Pfizer vaccine, the effectiveness of two doses was 93.7% among persons with the alpha variant (N=14,837) and 88.0% among those with the delta variant (N=4,272). Data ran up to 5/16/21. With the AstraZeneca vaccine, the effectiveness of two doses was 74.5% among persons with the alpha variant and 67.0% among those with the delta variant. Effectiveness was only 31% for alpha and 49% for delta after just one dose of either vaccine.
      • Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination. 7/26/21. Schmidt T. Nature Med.
        Heterologous priming with a single dose of the AstraZeneca ChAdOx1 nCoV-19 adeno vector vaccine followed by boosting with either the Pfizer or the Moderna mRNA vaccine is currently recommended in Germany. This study compares multiple aspects of immune response (spike-specific IgG, neutralizing antibodies, spike-specific CD4 T cells, and spike-specific CD8 T cell levels) in subjects receiving this heterologous regimen to the responses in subjects receiving two-dose homologous regimens with AstraZeneca vaccine or with an mRNA vaccine. All regimens were similarly well tolerated. Immune response levels were significantly higher with the heterologous regimens than after a two-dose AstraZeneca regimen and higher or comparable in magnitude to homologous mRNA vaccine regimens.
        SAB Comment: Heterologous vaccine strategies were initially pioneered in HIV and Ebola. Currently, at least 5 EU countries have recommended it as a means of producing fewer side effects than a two-dose AstraZeneca regimen.

      June 28, 2021

      • Mild SARS-CoV-2 Infections and Neutralizing Antibody Titers. 6/23/2021. Bonfante F. Pediatrics.
        In this prospective Italian study of 70 children and 82 parents in 57 family clusters with asymptomatic or mild COVID-19, anti-nucleocapsid-spike protein IgG/IgM was confirmed and neutralizing antibody levels (nAbs) were quantified by the Plaque Reduction Neutralizing Test for 7-8 months post-infection. nAbs declined less and levels were higher in children and than in parents. Children <3 developed the highest, longest lasting nAb levels, 4.5 times higher than in parents 1-2 months post infection and 7.9 times higher at 3-6 months. In this cohort, nAb levels correlated with viral loads but not with disease severity. Findings and implications for vaccination policy are discussed in an accompanying editorial.
      • Mortality after surgery with SARS-CoV-2 infection in England: a population-wide epidemiological study. 6/21/21. Abbott TEF. IBr J Anaesth.
        This retrospective British NHS database study addresses surgical mortality associated with SARS-CoV-2 from 1/1/2020 to 2/28/2021. Of 2.5 million surgeries, 1.0% of patients died and 1.1% of patients were infected. The mortality was 21% in patients with SARS-CoV-2 and 0.8% in those uninfected (OR 5.7). With elective surgery, 1% were infected, and mortality was 7.1%, compared to 0.1% (OR 25.8). Emergency procedure mortalities were 25.1% compared to 3.4% (OR 5.5). Statistics include data for procedure types and disease severity, and demonstrate the safety of elective procedures, with precautions, in healthy patients with no SARS-CoV-2 history. The authors estimate about one-half of 4.5 million expected surgical procedures were postponed.
      • The SARS-CoV-2 mRNA vaccine breakthrough infection phenotype includes significant symptoms, live virus shedding, and viral genetic diversity. 6/12/21. Pollett SD. Clin Infect Dis.
        This pilot report from the US Military Health System examined 24 PCR confirmed infections more than 14 days after full Pfizer (92%) and Moderna (8%) vaccination. Sixty-seven percent had no co-morbidities, 63% were health care workers, and 71% were White. Five were asymptomatic, and none required hospitalization; however, symptoms lasted up to 2 weeks and were reported as severe in 3. Viral cultures and complete genomic sequencing were performed in many cases. Strains included wild type as well as variants of concern. Some were shedding live virus 7 days after symptom onset. Authors recommend larger, prospective studies of vaccine breakthrough infections.
        SAB Comment: The CDC recently reported 4,115 cases from 47 states of breakthrough infections in fully vaccinated individuals who were hospitalized or died (mortality 18%) as of 6/21/21. Seventy-six percent were older than 65 years. Twenty-six percent of hospital admissions were not initiated for COVID-19. One hundred forty-two in 750 fatalities (19%) were not attributed to COVID-19. “The number of COVID-19 vaccine breakthrough infections reported to CDC likely are an undercount of all SARS-CoV-2 infections among fully vaccinated persons. National surveillance relies on passive and voluntary reporting, and data might not be complete or representative.”
      • Three Doses of an mRNA Covid-19 Vaccine in Solid-Organ Transplant Recipients. 6/23/21. Kamar N. N Engl J Med.
        This letter documents the humoral antibody response to 3 doses of the Pfizer-BioNTec vaccine in 101 solid organ transplant recipients 97 months post transplant, none of whom have become infected. The second dose was given 30 days after the first, and the third, 60 days after the second. Titers for spike protein antibodies were obtained before the first, second and third doses and one month after the third dose. Before the second dose, only 4 patients had antibodies, increasing to 40% before the third dose. After the third dose, 68% had antibodies. 33 patients (who were older, with a higher degree of immunosuppressive and a lower GFR) presumably remained at risk for infection.
        SAB Comment: Besides antibodies, the immune system has redundant lines of defense including T-cells (e.g., cellular immunity) that may be protective though not easily assessed. We await further “real world” studies on actual numbers and severity of infections in solid organ transplant patients, regardless of antibody levels.
      • Variants of concern are overrepresented among post-vaccination breakthrough infections of SARS-CoV-2 in Washington State. 6/24/21. McEwen AE. Clin Infect Dis.
        In an effort to determine mRNA vaccine efficacy against SARS-CoV-2 variants of concern (VOC), the University of Washington performed genetic sequencing of the SARS-CoV-2 virus on all positive PCR samples between February 23 and April 27, 2021. Of the 5,174 unvaccinated cases, 68% were VOC compared to 100% of the 20 breakthrough cases in vaccinated patients. Most breakthrough cases were symptomatic (~80%) but none were hospitalized. No single VOC was significantly more common in the breakthrough cases compared with unvaccinated cases. This is consistent with previous reports that mRNA vaccines provide excellent protection to all current strains of the virus, though there is a rare VOC breakthrough.
        SAB Comment: As the pandemic continues, more VOC that could be a problem even for vaccinated people may evolve. This emphasizes the importance of the current vaccination effort and world-wide control of the pandemic.

      June 4, 2021

      • COVID-19 Vaccine Breakthrough Infections Reported to CDC – United States, January 1-April 30, 2021. 5/27/21. CDC COVID-19 Vaccine Breakthrough Case Investigations Team. MMWR Morb Mortal Wkly Rep.
        In this brief weekly report, the CDC provides an important glimpse into the post-vaccination scenario in the US. During the 4 months ending April 30, 2021, a total of 10,262 breakthrough infections have been reported. Of those, 63% were female, median age 58 years, of which 27% were asymptomatic, 10% hospitalized and 2% died. By the end of the study, although 100 million individuals had been vaccinated in the US, SARS-CoV-2 transmission was still in full swing with 355,000 new cases daily. Variants were detected at a similar rate among vaccinated and non-vaccinated patients. Underreporting of asymptomatic cases and limited RNA sequencing represent current and future limitations to these statistics. Notably, beginning May 1, 2021, the CDC transitioned from monitoring all reported COVID-19 vaccine breakthrough infections to investigating only those among patients who are hospitalized. Monthly reports and additional information on vaccination breakthrough initiatives by the CDC can be found here.
      • Immune response to SARS-CoV-2 variants of concern in vaccinated individuals. 5/26/2021. Becker M. Nat Commun.
        Authors examined the antibody (Ab) response to the Pfizer vaccine in serum and saliva as well as neutralizing Abs to the UK, S. Africa, Mink, and LA SARS-CoV-2 variants. Subjects were either post-vaccine (n=22), post infection + vaccine (n=26), or neither previously infected or vaccinated (n=45). IgG response is strongest in previously infected individuals post-vaccine. For the UK, Mink, and LA variants, antibody response to vaccine was nearly identical for vaccinated and previously infected individuals compared with wild-type variant. However IgG response to the S. African variant was varied and reduced immunity in both groups. The second dose of the vaccine was an important contributor to evidence of protection.
      • Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents. 5/27/21. Frenck RW Jr. N Engl J Med.
        The BNT162b2 COVID-19 RNA vaccine (Manufacturer: Pfizer, Inc., and BioNTech) was proven effective with few side effects in 12-15 year old recipients (n=1131) who received 2 injections 21 days apart versus controls (n=1129). Among participants without evidence of previous SARS-CoV-2 infection, no COVID-19 cases with an onset of 7 or more days after dose 2 were noted among BNT162b2 recipients, and 16 cases occurred among placebo recipients. The observed vaccine efficacy was 100% (95% CI, 75.3 to 100).

      May 24, 2021

      • Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women. 5/13/21. Collier AY. JAMA.
        This excellent cohort report of the immunologic response to mRNA vaccination in pregnant (30), lactating (16), nonpregnant (57), and post SARS-CoV-2 pregnant (22) and nonpregnant women (6) demonstrates its effectiveness in pregnancy and potential for newborn protection. At 2 to 8 weeks post second dose, both neutralizing antibodies and cellular responses were measured in maternal serum, cord blood, and breast milk. Vaccination-produced neutralizing antibody titers higher than those from infection. Antibodies were detected in both cord blood and breast milk. Neutralizing antibody titers to variants were reduced, but cellular responses were preserved. A very useful glossary of immunological assays is included.

      May 10, 2021

      May 7, 2021

      • Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants. 5/5/21. Abu-Raddad LJ. New Engl J.
        This letter to the editor reports effectiveness of the Pfizer-BioNTech vaccine against UK and S. African variants that represented 50% and 44.5% of infections, respectively, in the Qatari research cohort community at the time of study. Estimated vaccine effectiveness against any documented B.1.1.7 variant infection was 89.5% (95% CI 85.9-92.3) and 75% against B.1.351 (CI (70.5–78.9) at 14 or more days after second doses in nearly 400,000 people. Effectiveness against severe, or fatal disease due to any SARS-CoV-2 variant was 97.4% (95% CI, 92.2-99.5). Although effectiveness against the B.1.351 variant was ~20% below previous reports from the clinical trial or real-world conditions in Israel and the US, protection from hospitalization or death was >90%. Effectiveness was found to be significantly improved after second dose.

      May 3, 2021

      • Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. 4/21/21. Shimabukuro TT. N Engl J Med.
        Early results of mRNA COVID-19 vaccination of pregnant women between 12/14/2020 and 2/28/2021 were obtained from v-safe after-vaccination health checker, v-safe pregnancy registry (patients enrolled by identification through v-safe participation), and VAERS, the vaccine adverse event reporting system. Comparison was to nonpregnant v-safe participants and historical pregnancy outcome statistics. The 35,691 pregnant v-safe participants (94% healthcare workers) reported reactions to vaccination similar to those who were not pregnant. In the registry, 827 pregnancies were completed, 86% with a live birth, and 9% with preterm births. There were 104 spontaneous abortions among the 92 preconception and 1132 first trimester participants. These frequencies are comparable to historical rates. The most common VAERS pregnancy report was spontaneous abortion, reported in 46 patients out of at least 35,691 (0.16%), a rate far lower than published, probably because of underreporting. Although more longitudinal follow-up is necessary, no problems regarding the administration of mRNA COVID-19 vaccine during pregnancy were revealed.
      • Vaccine Breakthrough Infections with SARS-CoV-2 Variants. 4/21/2021. Hacisuleyman E. N Engl J Med.
        In this brief scientific report, authors describe 2 cases of women fully vaccinated with the mRNA vaccines (1 Pfizer, 1 Moderna) who nonetheless developed SARS-CoV-2 infection within a few weeks of vaccination. Both had evidence of vaccine efficacy (neutralizing Abs to the wild type spike protein). Complete genomic sequencing revealed somewhat unique variants. In one, the variant was related to, but not identical to, the B.1.1.7 (UK) variant along with elements of the B.156 (NY) variant. Both patients had mild disease.

      April 23, 2021

      April 21, 2021

      April 19, 2021

      • Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies. 3/27/2021. Planas D. Nat Med.
        These investigators examined SARS-CoV-2 antibodies present in noses and sera from infected individuals or vaccinees, for potency vs. authentic mutants B.1.1.7 (UK) and B.1.351 (S-Africa) and the common D614G (US). They utilized a new “S-Fuse” neutralization assay: reporter cells become fluorescence positive overnight. Vaccinee nasal antibodies were rarely detected. Sera from 54/58 individuals at 9 months, neutralized UK and US. However, against S-Africa, sera had a 6-fold reduction; 40% lacked activity. Only 6-weeks post full Pfizer mRNA vaccination (n=19), sera already showed 14-fold reductions against S-Africa compared to US. Thus, the S-Africa strain may pose ongoing risks even in immunized individuals.

      April 16, 2021

      April 12, 2021

      • Antibody responses to the BNT162b2 mRNA vaccine in individuals previously infected with SARS-CoV-2. 4/1/2021. Ebinger J. Nature Medicine.
        The response to the Pfizer vaccine in individuals previously infected with SARS-CoV-2 was compared to that in individuals not previously infected. Spike-specific IgG antibody (Ab) levels and an assay for ACE2 binding inhibition as a surrogate for Ab neutralization were measured. Previously infected individuals (n=35) had a more robust neutralization response to vaccine dose #1 than naïve individuals (n=228), however after the second dose of vaccine the IgG levels and neutralization responses were similar between groups. Symptoms after dose #1 for those with prior infection more resembled those after dose #2 for naïve individuals (more severe). Authors question whether previously infected individuals need 2 vaccine doses. The question of whether previously infected individuals require 2 Pfizer vaccine doses to achieve equivalent protection from re-infection is raised, and will require further real-world study.

      April 2, 2021

      • Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma. 3/29/21. Cele S. Nature.
        Using a live virus-neutralizing assay, investigators tested the effectiveness of convalescent plasma collected from donors during the first (original) and second (S. African variant) waves of COVID-19 against both types of virus. First-wave plasma was effective against first-wave virus, however showed a 15-fold decrease in effectiveness against S. African variant virus. Second-wave plasma was effective against the then-predominant variant strain and, although it demonstrated a 2.3 fold decrease in activity against the original strain, it was still effective. This provides preliminary evidence that vaccines based on variant-of-concern sequences could retain effective activity against other SARS-CoV-2 lineages.

      March 24, 2021

      • Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study. 3/17/21. Hansen CH. Lancet.
        To define the degree to which infection with SARS-CoV-2 confers protection towards subsequent reinfection, the authors analyzed Denmark’s extensive PCR-test data from 2020. Before June, 11,727 people tested positive, and 72 (0.65%) of these again tested positive during the last three months of the year. Protection against repeat infection was 80.5%. Individuals older than 65 years had less protection (47%), and protection for males and females was equal. There was no evidence of waning protection over time (3-6 months vs over 7 months of follow-up). The lower natural immunity in people aged 65 and older underlines the need to vaccinate previously infected individuals in the age group.
        SAB Comment: Though similar to a study from the Cleveland Clinic, highlighted in issue 69 of the COVID-19 Resource Newsletter, this is a much larger study with different details.
      • Association of Age With SARS-CoV-2 Antibody Response. 3/22/2021. Yang HS. JAMA Netw Open.
        In this retrospective study, 31,426 (hospital + outpatient, age 1 – 80+) patients with COVID-19 were evaluated for both quantitative and qualitative antibody/AB tests for functional neutralizing capacity. Authors note that despite similar seroprevalence in various age groups, COVID-IgG, total receptor binding domain/ (RBD= Avidity), total antibodies (TAb), and surrogate neutralizing antibody SNAb activities displayed an inverse/ variable relation with age. These findings are likely to be applied for screening, management in selecting CP prescription and vaccine strategies. The children and their AB response explains symptomatology and represent a reservoir of virus. The included graphs are illustrative and complimentary to the article conclusions.

      March 17, 2021

      • Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7. 3/8/21. Wang P. Nature.
        These investigators report that the “UK variant” (B.1.1.7) remains sensitive to both convalescent plasma and serum collected from vaccinated individuals during Moderna phase I trials (both collected Spring 2020), but refractory to neutralization by most monoclonal antibodies (mAbs) to the spike N-terminal domain (NTD), and relatively resistant to a few mAbs to the receptor-binding domain (RBD). The “South African variant” (B.1.351), containing the E484K mutation is more resistant to neutralization by convalescent plasma (9.4x) and serum from vaccinated individuals (10.3-12.4x). The virus is refractory to most NTD mAbs and multiple individual mAbs to the RBD. This study reinforces concerns about emergent variants and the need for vaccines and mAbs that target them.
      • Reinfection Rates among Patients who Previously Tested Positive for COVID-19: a Retrospective Cohort Study. 3/15/21. Sheehan MM. Clin Infect Dis.
        In a retrospective cohort study, PCR testing in the Cleveland Clinic Health System from March 2020 to February 2021 was analyzed to detect repeat SARS-CoV-2 infection. Of 8,845 individuals with initially positive PCR tests, 62 had reinfections, defined as a positive PCR test at least 90 days following the first positive PCR. Half were asymptomatic, few were hospitalized, and none required intensive care. Protection offered against reinfection was 82%. Risk of reinfection declined with time after initial infection. The authors suggest that the protection afforded by infection with SARS-CoV-2 is adequate to delay vaccination of these people, if vaccine is in short supply.
        SAB Comment: A negative PCR test after the first infection was not part of their definition of reinfection therefore, the authors acknowledge that persistent shedding of virus could account for some reinfections.

      March 8, 2021

      February 22, 2021

      • mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. 2/3/21. Wang Z. Nature.
        This basic science article in Nature showed similar antibody and memory B cell responses in volunteers who received mRNA vaccinations vs those naturally infected. Of note, against emerging variants, whole plasma (containing many diverse antibodies) remained active, neutralizing, and protective, though reduced in both groups. Monoclonal antibodies (mAbs) from laboratory-derived single B cells remain active in neutralizing current virus. However, against emerging mutants, neutralization by the most potent single mAbs was reduced/abolished. Further, when single mAbs were placed in extended virus co-culture, virus mutations resulted. This suggests that clinically, caution is warranted in treating with single mAb infusions rather than mAb combinations as single mAbs may drive virus mutations.

      February 12, 2021

      • Rapid decline of neutralizing antibodies against SARS-CoV-2 among infected healthcare workers. 2/8/21. Marot S. Nature Communications.
        Serological testing is used to identify individuals who are immunized and potentially “protected” against re-infection. From 28 January to 21 March 2020, 26 healthcare workers from Pitié-Salpêtrière University Hospital in France were enrolled in this study. Healthcare workers with mild COVID-19 were tested three weeks (D21), two months (M2) and three months (M3) after the onset of symptoms. All healthcare workers displayed seroconversion at D21 after symptom onset, and elicited a neutralizing antibodies response to SARS-CoV-2 correlated with the anti-receptor binding domain antibody levels. However, this neutralizing activity declines, and may even be completely lost, in association with a decrease in systemic IgA antibody levels from 2 months after disease onset.

      February 10, 2021

      • Global absence and targeting of protective immune states in severe COVID-19. 1/25/21. Combes A. Nature.
        This fascinating study shows that immune response to COVID-19 is complex and differs between severe systemic effects in some patients and milder symptoms in others. Authors exposed the differences by studying whole blood analysis identifying individual cellular elements and expression in samples of severe and mild disease. Examination of serum in mild disease shows production of interferon-stimulated genes which blunt overproduction of anti-SARS-CoV-2 antibodies which in severe disease are higher and associated with lower viral titers than seen in mild disease. The authors make research suggestions to study modification of this response.
      • Occurrence and Timing of Subsequent Severe Acute Respiratory Syndrome Coronavirus 2 Reverse-transcription Polymerase Chain Reaction Positivity Among Initially Negative Patients. 2/5/21. Long DR. Clin Infect Dis.
        The authors compared the occurrence of a discordant result of RT- PCR in two health systems. They assessed the conversion rate to a new positive in less than 7 days. They noted the conversion rate was at 3.5% (4.1% at the University of Washington, 2.8% at Stanford). Retesting was done based on clinical symptoms of patients. These observations suggest that false-negative RT-PCR results do occur, but at a low frequency. Neither team was able to calculate a true clinical sensitivity or false-negative proportion due to the lack of a gold-standard.
      • Transmission of COVID-19 in 282 clusters in Catalonia, Spain: a cohort study. 2/2/21. Marks M. Lancet Infect Dis.
        In an attempt to identify variables that affect the transmission dynamics of SARS-CoV-2, these investigators from Spain analyzed contact tracing data associated with a randomized control trial. Quantitative RT-PCR and clinical data was analyzed on 282 adult, non-hospitalized index cases with a total of 753 contacts. The viral load of the index case was the leading determinant of the risk of PCR positivity among contacts and viral load significantly influenced the risk of developing the symptomatic disease in a dose-dependent manner. No association of risk of transmission was found with reported mask usage by contacts, with the age or sex of the index case, or with the presence of respiratory symptoms in the index case.

      February 8, 2021

      • Evolution of antibody immunity to SARS-CoV-2. 1/18/21. Gaebler C. Nature.
        SARS-CoV-2 neutralizing antibody levels eventually decrease post-illness or vaccination. It is unknown how well memory B cells produce antibodies many months later. Eighty-seven individuals were assessed at 1.3- and 6.2-months post-infection. As expected, IgM, and IgG anti-SARS-CoV-2 spike protein receptor binding domain (RBD) antibody titers decreased significantly. Functionally, plasma viral killing activity decreased fivefold. However, at 6.2 months, memory B-cells remained unchanged and continued evolving antibodies showing antibody sequence changes with increased potency and resistance to RBD mutation. Following up on known stool SARS-CoV-2 persistence, the authors related ongoing memory B-cell evolution to lingering antigen immunoreactivity shown in intestinal biopsies 4 months post-infection.
      • SARS-CoV-2 viral load is associated with increased disease severity and mortality. 10/30/20. Fajnzylber J. Nature Communications.
        The authors quantified SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. Amongst participants hospitalized with COVID-19, the authors report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation. Forty-four percent of those on a ventilator had detectable viremia compared to 19% of those receiving supplemental oxygen by nasal cannula and 0% of individuals not requiring supplemental oxygen. Compared to individuals who were discharged from the hospital, those who eventually died had significantly higher levels of plasma viremia at the time of initial sampling.

      January 19, 2021

      • Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19). 1/12/21. van Kampen JJA. Nat Commun.
        The CDC currently uses a minimum disease duration of 10 days in their symptom-based strategy as the statistically estimated likelihood of recovering a replication-competent virus approaches zero after ten days of symptoms. In a study of 129 hospitalized patients, duration and key determinants of infectious SARS-CoV-2 shedding in patients with severe and critical COVID-19 was assessed. Median time for infectious virus shedding was 8 days post-symptom onset; ≤5% probability for isolating infectious SARS-CoV-2 when duration of symptoms was ≥ 15.2 days. Median viral load was significantly higher in culture + samples than culture – samples. Probability of isolating infectious virus was < 5% when neutralizing antibody titer was 1:80 or higher. Detection of subgenomic RNAs outlasted detection of infectious virus. Based on their findings, a longer disease duration could be considered for severely-ill patients.

      January 13, 2021

      • SARS-CoV-2 Transmission From People Without COVID-19 Symptoms. 1/7/21. Johansson MA. JAMA Netw Open.
        A decision analytical model was used including multiple scenarios for the infectious period and the proportion of transmission from individuals who never have COVID-19 symptoms. Baseline assumptions were taken from meta-analyses and included an incubation period of a median of 5 days. In the various analyses peak infectiousness was varied between 3 and 7 days. Under a broad range of values for each of these assumptions, at least 50% of new SARS-CoV-2 infections were estimated to have originated from exposure to individuals who were asymptomatic at the time of transmission (combining those who never develop symptoms with those who are pre-symptomatic).
        SAB Comment: This highlights the importance of mask-wearing and social distancing even as vaccines are rolled out.

      January 11, 2021

      • Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers. 12/28/20. Lumley SF. N Engl J Med.
        This is an original article from 4 Oxford University Hospitals that followed its employees for SARS-CoV-2 infection. Testing was performed every 2 weeks or if symptomatic. 10% of 12,541 staff tested positive from March through November 2020. Polymerase chain reaction assays of both anti-spike IgG and anti-nucleocapsid IgG demonstrated that healthcare workers who tested positive suffered mild disease and were afforded immunity for the length of the study, 31 weeks.

      January 8, 2021

      December 4, 2020

      December 2, 2020

      November 23, 2020

      • Preexisting and de novo humoral immunity to SARS-CoV-2 in humans. 11/6/20. Ng K. Science.
        Using diverse assays for antibodies recognizing SARS-CoV-2 proteins, these investigators examined preexisting humoral immunity to the novel and older coronaviruses in humans. Using flow cytometry, predominately IgG class cross-reacting antibodies particularly targeting the S2 subunit of the spike glycoprotein were detectable in the SARS-CoV-2-uninfected, especially children and adolescents. SARS-CoV-2 infection induced higher titers of SARS-CoV-2 S-reactive IgG antibodies, targeting both proteolytically-cleaved S1 (attachment) and S2 (entry) subunits, along with contemporaneous IgM and IgA. Notably, SARS-CoV-2-uninfected donor sera exhibited specific neutralizing activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes. Cross-reacting immunological memory may be critical to understand susceptibility to SARS-CoV-2 infection.

      November 9, 2020

      October 23, 2020

      • Pasteurization Inactivates SARS-CoV-2 Spiked Breast Milk. 10/22/20. Conzelmann C. Pediatrics.
        Bench Research, Human Milk, and SARS-CoV-2. 10/22/20. Furman L. Pediatrics.
        A team of German virologists determined that the SARS-CoV-2 virus can be shed and is detectable in human breast milk but does not replicate in that environment. Inoculation of breast milk with various strains of the virus resulted in a 40-90% decrease in viral titer due to antiviral properties of breast milk alone. Heating to 63°C (145°F) for 30 minutes (Holder pasteurization) completely inactivated the virus.
        Welcoming these findings, an accompanying editorial by two US pediatricians is strongly in favor of allowing infected mothers to breastfeed their babies whenever possible as the milk duct epithelium’s lack of proteases required to allow virus entry prevents vertical transmission of COVID-19 from an infected mother.

      October 21, 2020

      • The duration of infectiousness of individuals infected with SARS-CoV-2. 10/13/20. Walsh KA. J Infect.
        The potential duration of patient infectiousness, as derived from virus culture and contact tracing studies, for those individuals in whom SARS-CoV-2 RNA is detected is summarized. Thirteen various quality studies and 2 large contact tracing studies were included. The data suggests that COVID-19 patients with mild-to-moderate illness are highly unlikely to be infectious beyond 10 days from symptom onset. Evidence from a limited number of studies indicates that patients with severe-to-critical illness, and/or those who are immunocompromised, may be infectious for a prolonged period, possibly for 20 days or more. Research is needed to confirm these findings and to provide information on the duration of infectiousness in subgroups such as children, and asymptomatic and immunosuppressed patients.
      • Transmission Dynamics by Age Group in COVID-19 Hotspot Counties – United States, April-September 2020. 10/15/20. Oster AM. MMWR Morb Mortal Wkly Rep.
        CDC analyzed temporal trends in percent test positivity by age group in COVID-19 hotspot counties before and after their identification as hotspots. Among 767 U.S. hotspot counties identified during June and July 2020 (24% of counties, 63% of population) early increases in the percent positivity among persons 24 years old and younger were followed by several weeks of increasing percent positivity in persons 25 years old and older, particularly those in the South and West. Addressing transmission among young adults is an urgent public health priority.

      October 5, 2020

      • Detection of SARS-CoV-2 with SHERLOCK One-Pot Testing. 9/16/2020. Joung J. N Engl J Med.
        Both CRISPR (clustered regularly interspaced short palindromic repeats)- based diagnostic tests and SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) can detect viruses, but are not practical for Point of Care testing. The newly described “STOPCovid.v2” (SHERLOCK Testing in One Pot version-2) uses a novel magnetic bead RNA extraction with loop-mediated isothermal amplification and CRISPR-mediated detection, all in 15-45 minutes using minimal equipment and available reagents. Nasal swab testing showed a sensitivity of 93.1% and a specificity of 98.5%. STOPCovid.v2 false negative samples had RT-qPCR Ct values greater than 37. STOPCovid.v2 detected a viral load 1/30th detected by RT-qPCR.

      October 2, 2020

      • Patterns of COVID-19 testing and mortality by race and ethnicity among United States veterans: A nationwide cohort study. 9/22/2020. Rentsch CT. PLoS Med.
        This article presents a nationwide VA data set study (~6 million patients, February 8 to July 22) comparing positive COVID-19 test results with 30-day mortality. Healthcare disparities were explored by evaluating “associations between race/ethnicity and receipt of COVID-19 testing, a positive test result, and 30-day mortality, with multivariable adjustment for demographic and clinical characteristics including comorbid conditions, health behaviors, medication history, site of care, and urban versus rural residence.” The study confirms prior reports indicating that “Black and Hispanic individuals experience excess burden of SARS-CoV-2 infection” but not increased mortality and notes that these disparities “are not entirely explained by underlying medical conditions or where they live or receive care.” The article contains interesting distinctions and reinforces the importance of designing “strategies to contain and prevent further outbreaks in racial and ethnic minority communities.”
      • Sensitive Detection of SARS-CoV-2-Specific Antibodies in Dried Blood Spot Samples. 9/24/20. Morley GL. Emerg Infect Dis.
        Dried blood spot (DBS) samples can be obtained directly from patients without venipuncture and stored and shipped without refrigeration. DBS samples were compared to matched serum samples in 80 patients to detect coronavirus 2 spike antibodies with a relative 98.1% sensitivity and 100% specificity. The authors propose that DBS sampling offers an alternative for population-wide serologic testing in the coronavirus pandemic.

      September 30, 2020

      September 14, 2020

      September 9, 2020

      August 26, 2020

      August 17, 2020

      August 12, 2020

      • Case Rates, Treatment Approaches, and Outcomes in Acute Myocardial Infarction During the Coronavirus Disease 2019 Pandemic. 8/7/20. JAMA Cardiol.
        Using discharge coding of >15,000 acute MI hospitalizations over 17 months from a multi-state US health system, a significant decrease in observed vs. expected numbers during the early COVID-19 period, March-May 2020, was observed in all regions. NSTEMI patients disproportionately decreased and hospital cardiac death rates increased, particularly in STEMI patients. Trends largely normalized by study end, May 10, 2020. These data suggest that patients avoided presenting to hospital with possible AMI during the early COVID-19 period, potentially forfeiting the benefit of early reperfusion in some cases.

      August 10, 2020

      • Characterization of the Inflammatory Response to Severe COVID-19 Illness. 6/25/2020. McElvaney OJ. ATS.
        This article offers a detailed measurement of inflammatory mediators in 20 severely ill patients compared with a group of moderately ill patients and a group of normal controls. It’s proposed that similar characterisations and treatment trials might someday allow for a tailor made treatment regimen of immune modulators to be given to each patient optimizing their recovery. The accompanying editorial highlights the finding in the original study that alpha-1-antitrypsin (AAF), which has an anti-inflammatory effect, is reduced in patients with severe Covid-19 pneumonia, and a trial of AAF supplementation may be warranted.

      August 5, 2020

      July 31, 2020

      July 27, 2020

      July 22, 2020

      • Impact of delays on effectiveness of contact tracing strategies for COVID-19: a modelling study. 7/16/20. Kretzschmar ME. Lancet Public Health.
        Review by the SAB
        By Dr. Lance Lichtor, on behalf of the SAB
        The authors used a mathematical model that describes the different steps of a symptomatic contact tracing strategy for COVID-19. They found reducing the testing delay (i.e., shortening the time between symptom onset and a positive test result, assuming immediate isolation) is the most important factor for improving contact tracing effectiveness. Reducing the tracing delay (i.e., shortening the time to trace contacts, assuming immediate testing and isolation if found positive) might further enhance contact tracing effectiveness, though this additional effect rapidly declines with increasing testing delay.
      • Redefining cardiac biomarkers in predicting mortality of inpatients with COVID-19. 7/17/2020. Qin JJ. Hypertension.
        Detailed, retrospective analysis of available cardiac biomarkers of 3219 patients admitted to 9 hospitals in Hubei province between December 31st, 2019 and March 4th, 2020. Entry criteria included patients from 18 to 75 years old with documented COVID-19 on admission (RT-PCR and/or Chest CT) and high sensitivity cardiac troponin (hs-cTnI) or CKMB on admission with primary endpoint 28-day mortality. Statistical processing includes additional biomarker profiles, primary and secondary cardiac effects and analysis suggesting that in COVID-19 need to redefine reference range for Upper Limit of Normal to understand impact of cardiac effects.
        The authors conclude “the abnormal cardiac biomarker pattern in COVID-19 patients was significantly associated with increased mortality risk, and the newly established COVID-19 prognostic cutoff values of hs-cTnI, CK-MB, (NT-pro)BNP, CK, and MYO were found to be much lower (~50%) than reference upper normal limits for the general population.” Valuable information that needs to be confirmed in different populations.

      July 10, 2020

      July 1, 2020

      June 29, 2020

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

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

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

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

      • The Laboratory Diagnosis of COVID-19 – Frequently Asked Questions. 6/8/20. Fang FC. Clin Infect Dis.
        Review by the SAB
        By Dr. Lydia Cassorla, on behalf of the SAB
        This review from the clinical laboratories of the University of Washington breaks down information about testing for COVID-19 in a useful question-and-answer format. Subjects include PCR, serology, point-of-care testing, correlation with clinical disease, and biomarkers.

      June 5, 2020

      • Prevalence of Asymptomatic SARS-CoV-2 Infection: A Narrative Review
        June 3. Oran DP. Annals of Internal Medicine.
        Opinion from SAB Member: Dr. David M. Clement
        A well-written, concise review of 16 studies describing the prevalence and significance of asymptomatic persons infected with SARS-CoV-19. Four of five of the studies that included longitudinal serial testing to distinguish asymptomatic vs. presymptomatic persons showed otherwise healthy asymptomatic persons rarely (0-10%) became symptomatic. On the other hand, 89% of RT-PCR + nursing home patients were presymptomatic. Their conclusion is that asymptomatic infection is a significant factor in the rapid progression of the SARS-CoV-2 pandemic, and that current medical practice and public health measures should be modified to address this challenge.

      June 3, 2020

      • The role of SARS-CoV-2 antibodies in COVID-19: Healing in most, harm at times
        May 20. French MA. Respirology.
        Opinion from SAB Member: Dr. Edward S. Schulman
        This is an excellent commentary that all should read. Though some antibodies to the spike glycoprotein promote virus neutralization and other protective antibody functions, particular IgG antibodies might enhance the infection of immune cells and/or disease progression. One example is antibody‐dependent enhancement of virus uptake by macrophages by enhancing antibodies as described in dengue virus infection that has also been demonstrated for SARS‐CoV‐1. Therefore, current development of antibody-dependent strategies, whether human monoclonal antibodies, convalescent plasma or choosing the right target for vaccine is complex. Depending on the peptide targeted on the spike glycoprotein by the human immune system or the vaccine lab, neutralizing or enhancing activity may result. Simply having a “positive SARS-CoV-2 antibody” on a serological test may not be a license for a “passport.”
      • SARS-CoV-2 Antibody Testing – Questions to be asked
        May 25. Ozcurumez MK. Journal of Allergy and Clinical Immunology.
        Opinion from SAB Member: Dr. Barry Perlman
        Informative article by the COVID-19 Task Force of the German Society for Clinical Chemistry and Laboratory Medicine addressing the interpretation of antibody testing. Topics discussed include:
        • Possible indications for COVID-19 serology
        • Value of antibody testing in diagnosis
        • Does presence of antibodies indicate end of infectivity?
        • Does presence of antibodies indicate immunity?
        • Comparison of different assay technologies
        • Ensuring assay quality
        • Baseline samples from asymptomatic or healthy individuals
        • Estimating demand for antibody testing

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

      May 28, 2020

      May 27, 2020

      • Chronological Changes of Viral Shedding in Adult Inpatients with COVID-19 in Wuhan, China
        May 23. Huang. Clinical Infectious Diseases.
        Opinion from SAB Member: Dr. Barry Perlman
        This is a retrospective study of 308 COVID-19 inpatients at one hospital in Wuhan between 1/11/20 and 2/21/20 who received > 5 ORF1ab gene RT-PCR tests. Viral loads (based upon cycle threshold) peaked 2-4 days after admission and then decreased with treatment. A rebound seen around 7, 16, and 22 days after admission was more common in non-severely ill patients. 43% of patients had positive tests after 2 negative tests. On day 30 of treatment most patients had undetectable virus by RT-PCR tests. High viral loads (cycle threshold < 30) correlated with critical illness, mortality, decreased serum albumin, decreased Th and Ts cells, lower lymphocyte, eosinophil, and basophil counts, and increased neutrophil counts, serum glucose, corrected calcium, LDH, CKMB, myoglobin, ultra TnI, and NT-proBNP. Sputum viral loads were higher than in nasopharyngeal samples, and respiratory loads were higher than in GI samples. The authors suggest that positive RT-PCR test rebound reflects surviving coronavirus particles.
      • Olfactory and gustatory function impairment in COVID-19 patients: Italian objective multicenter-study. May 21. Angelo Vaira. Head Neck.
        A 25 author study from Italy that was based on 345 patients who were either home-quarantined health care workers (161) or hospitalized patients (184), and all patients were swab positive for COVID-19. About 75% reported combined olfactory and taste disorders. Interestingly, of those who did not report any taste or smell disturbance, 30% had objective signs of odor dysfunction and those who had isolated odor or taste dysfunction had 20-30% more taste or odor dysfunction, that is the opposite dysfunction. Also, for 30%, the first sign of COVID-19 infection was chemo-sensitive dysfunction.
      • Predicting infectious SARS-CoV-2 from diagnostic samples
        May 22. Bullard. Clinical Infectious Diseases.
        Opinion from SAB Member: Dr. Barry Perlman
        Many studies have assumed that “viral shedding” based on positive RT-PCR testing suggests presence of infectious virus. This is a retrospective cross-sectional Canadian study to determine whether presence of SARS-CoV-2 RNA by RT-PCR predicts infectivity. 26/90 (29%) samples positive by RT-PCR targeting the 122nt portion of the envelope gene incubated on Vero cells demonstrated viral growth. Only samples with RT-PCR cycle threshold (Ct) < 24 and symptom to test time (STT) < 8 days showed growth. Specificities for the thresholds of Ct > 24 and STT > 8 days were 97% and 96%, respectively. If confirmed by larger studies utilizing additional RT-PCR targets, these results suggest that Ct and STT can predict duration of infectivity with high specificity and would avoid the unnecessary isolation resulting from policies based upon 2 negative RT-PCR results.

      May 22, 2020

      • Olfactory Dysfunction and Sinonasal Symptomatology in COVID-19: Prevalence, Severity, Timing, and Associated Characteristics. May 19. Speth. Otolaryngol Head Neck Surg.
        The lead author was from the United States, though the patients were from Sweden. 103 patients were studied. The prevalence of hyposmia or anosmia was 61.2%, the mean onset was 3.4 days after symptoms of COVID-19 first appeared and was severe in nature and was strongly correlated with a concomitant loss of taste. 30% to 50% of participants experienced nasal obstruction or rhinorrhea, which they attributed to COVID-19. However, there was no correlation between these symptoms and OD. Only older age was negatively associated with having OD and female sex was possibly positively associated with having OD.
      • Olfactory Dysfunction in COVID-19: Diagnosis and Management
        May 20. Whitcroft. JAMA.
        Opinion from SAB Member: Dr. J. Lance Lichtor
        This is a study that examines olfactory dysfunction both with and without COVID-19. The basis of olfactory dysfunction, as the authors explain, may be due to disruption of cells in the olfactory neuroepithelium, and that the virus may actually penetrate the brain and then have downstream effects on brain regions that may adversely affect olfactory function. The authors explain also how olfactory dysfunction should be assessed and how it might be treated.

      May 20, 2020

      • Clinically Applicable AI System for Accurate Diagnosis, Quantitative Measurements, and Prognosis of COVID-19 Pneumonia Using Computed Tomography
        May 17. Zhang. Cell.
        Opinion from SAB Member: Dr. Barry Perlman
        A variety of projects are investigating how artificial intelligence (AI) tools can be utilized during the COVID-19 pandemic. In this report, CT results from 4154 patients and clinical information from 843 patients in China were used to develop an AI system to diagnose COVID-19 pneumonia and differentiate it from other common (viral, bacterial, and mycoplasma) pneumonias. Data from retrospective and pilot prospective studies were used to validate the system, with sensitivities of 87-95% and specificities of 82-89%. System performance was superior to that of junior radiologists and comparable to mid-senior radiologists. It was found that lung CT findings correlated with clinical and biochemical evidence of disease severity in other organs systems. This AI system may assist in early diagnosis, prognosis prediction, management, evaluation of drug treatment efficacy, and follow up of COVID-19 patients.

      May 19, 2020

      • Antibody Testing For Covid-19
        May 15. Mathur. American Journal of Clinical Pathology.
        Opinion from SAB Member: Dr. Barry Perlman
        Accurate antibody tests can help with diagnosis, identify those with asymptomatic infections, determine prevalence in a population, aid in contact tracking, and measure progression to herd immunity. The 10 antibody tests that are currently FDA-approved have, on average, a sensitivity of 84.9% and a specificity of 98.6%. Sensitivities of these tests range from 58% to 94%. 90 additional tests are available for use, but are not yet FDA approved and don’t have sensitivity and specificity established. Table 2 demonstrates that positive predictive value varies widely depending on both the accuracy of the tests and local disease prevalence. When prevalence is high, such as in the greater NY area, antibody tests with specificity and sensitivity of 98% or better can be used as reliable screening tools. In areas of low prevalence, a test would need 100% specificity to avoid false positive results that could incorrectly indicate that someone is immune to COVID-19. The authors warn against using serologic tests not yet FDA approved with unknown accuracy to guide decision making.
      • Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction–Based SARS-CoV-2 Tests by Time Since Exposure
        May 13. Kucirka. Annals of Internal Medicine.
        Opinion from SAB Member: Dr. Barry Perlman
        This analysis illustrates that the predictive value of a negative SARS-CoV-2 RT-PCR test result depends on both pre test probability and test timing relative to exposure or symptom onset. Therefore, it applies more to “ruling out” infection in exposed patients and health care workers, rather than “clearing” asymptomatic patients for elective surgery. Using results from 7 previous studies reporting SARS-CoV-2 RT-PCR results, a Bayesian hierarchical model was created to estimate the false-negative rate by day since symptom onset or virus exposure. The model assumed a typical 5-day incubation period to symptom onset. The probability of RT-PCR false negative decreased from 100% on day 1 of exposure to 20% on day 8 (3 days after typical symptom onset), and then increased again to 66% on day 21. Therefore, the lowest post test probability from 1 negative RT-PCR test is achieved when the test is done on day 8, 3 days after symptoms onset. However, the post test probability from a negative day 8 sample varied from 1.2% to 14% depending on the pretest probability. The model suggests that negative RT-PCR tests early or late in infection should not be used to rule out COVID-19 if suspicion is high based on clinical and epidemiologic information.

      May 16, 2020

      • A serological assay to detect SARS-CoV-2 seroconversion in humans
        May 12. Amanat. Nature Medicine.
        Opinion from SAB Member: Dr. Jay Przybylo
        A dense, technical Brief Communication stating in the first sentence that the authors developed “a serological enzyme-linked immunosorbent assay” that then proceeds to describe the purpose and method culminating in the assay to assess the presence of SARS-CoV-2 spike protein antibody.
      • Asymptomatic Seroconversion of Immunoglobulins to SARS-CoV-2 in a Pediatric Dialysis Unit
        May 14. Hains. JAMA.
        Opinion from SAB Member: Dr. Jay Przybylo
        This is a Research Letter describing the futility of limiting the spread of SARS-CoV-2 using a pediatric dialysis unit as an example. A single patient presented to the unit and was isolated for therapy. This initiated testing on everyone, patients and staff, in the unit. 38% of patients and healthcare workers who presented repeatedly to this unit seroconverted positive to the virus by serum evaluation over a two-week period, proof that this virus is rapidly spreading in unrecognized ways.
      • Corona Viruses and the Chemical Senses: Past, Present, and Future
        May 14. Pellegrino. Chemical Senses.
        Opinion from SAB Member: Dr. J. Lance Lichtor
        In this review of chemosensory ability in patients with COVID-19, the authors sought to determine whether chemosensory dysfunction is the same with COVID-19 as it is with other pandemics including SARS and MERS and whether COVID-19 represents a special case of viral infection attacking the olfactory system. They also discussed whether the taste disturbances with COVID-19 are a misrepresentation of olfactory disturbances rather than the direct impact of SARS-CoV-2 on taste and chemical sensitivity of skin and mucous membrane pathways. First, whether taste disturbance is olfactory-dependent or instead reflects true taste loss in COVID-19 is currently unclear. Second, olfactory disturbances may not be as prominent in SARS and MERS as with COVID-19. Third, the reduction in sensitivity being associated with reduced ability to promote the clearing of pathogenic agents from the nasal cavities can only be speculated. Certainly, distinguishing each aspect of chemo-sensation in patients with confirmed and suspected COVID-19 diagnosis as well as with other respiratory illnesses is needed to determine whether the chemical senses are uniquely affected by COVID-19 infection.
      • Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population-based cohort study. May 12. Banerjee. The Lancet.
        Opinion from SAB Members: Drs. Barry Perlman and Heinrich Wurm
        BP: To better assess the impact of COVID-19 on mortality, EMR data from 3 862 012 individuals in the United Kingdom > 30 yrs old were used to model 1 yr mortality in excess of baseline and deaths due to underlying conditions. Based on reported prevalence, 1 yr mortality from underlying conditions were estimated. The excess COVID-19 related deaths were then modeled at varying relative COVID-19 mortality risks and suppression related prevalence scenarios. 20% of the study population had at least one high-risk condition and 10% had multiple conditions. Excess deaths from COVID-19 decreased with increasing suppression measures. At a relative risk of 2, full suppression would result in minimal excess mortality. These models could help determine appropriate social distancing and isolation measures, particularly for individuals at highest risk. However, the models don’t take into account non-linear increase in mortality rates if health systems become overwhelmed, the impact of poor compliance with social isolation policies, impact of specific morbidities or multiple co-morbidities on risk of COVID-19 mortality, or impact of social distancing on underlying conditions.
        HW: In this population-based cohort study, a team of authors from the Institute of Health Informatics at the University College of London, used 3.8 million electronic health records as the basis for their modeling. They estimated the excess number of deaths over 1 year under different COVID-19 incidence scenarios based on 4 different levels of transmission suppression and differing mortality impacts based on 3 different relative risk scenarios for the disease. The result is a model and an online tool for understanding mortality – in excess of the expected – due to the COVID-19 pandemic. It signals an urgent need for sustained, stringent suppression measures.

      May 15, 2020

      • Currently available intravenous immunoglobulin contains antibodies reacting against severe acute respiratory syndrome coronavirus 2 antigens. May 12. Díez. Immunotherapy.
        Antibodies against common human coronaviruses are present in the normal population. 2 IVIG products Gamunex-C and Flebogamma DIF were tested with ELISA assays from different manufacturers for crossreactive antibodies to SARS-CoV-2 and other coronaviruses including SARS-CoV and MERS-CoV. While cross reactivity was demonstrated, further research is needed to determine clinical efficacy and safety for COVID-19 treatment.
      • Real-time tracking of self-reported symptoms to predict potential COVID-19
        May 11. Menni. Nature Medicine.
        Opinion from SAB Member: Dr. Lydia Cassorla
        This interesting report may represent a sign of the future of disease prediction models. 2.6M users reported symptoms on a smartphone-based app during a 4 week period beginning 24 March 2020. 93.6% in GB (balance in US). 15,638 UK and 2,763 US app users reported having had an RT-PCR SARS-CoV-2 test, and having received the result. Of the UK cohort with a (+) COVID PCR test, 65% reported a loss of smell and taste, compared with 23% of those with a (-) test result. “We re-ran logistic regressions adjusting for age, sex and BMI to identify other symptoms besides anosmia that might be associated with being infected by SARS-CoV-2. All ten symptoms queried (fever, persistent cough, fatigue, shortness of breath, diarrhea, delirium, skipped meals, abdominal pain, chest pain and hoarse voice) were associated with testing positive for COVID-19 in the UK cohort…In the US cohort, only loss of smell and taste, fatigue and skipped meals were associated with a positive test result.” A prediction model was created including factors of age, sex, loss of smell/taste, cough, fatigue, and skipped meals. “In the UK test set, the prediction model had a sensitivity of 0.65 (0.62–0.67), a specificity of 0.78 (0.76–0.80), an area under the curve (AUC) of the receiver operating characteristic curve (ROC) (that is, ROC-AUC) of 0.76 (0.74–0.78), a positive predictive value of 0.69 (0.66–0.71) and a negative predictive value of 0.75 (0.73–0.77).” Application of the model to the US cohort showed similar sensitivity and increased specificity of 0.83. Limitations include self-selection of cohorts, self-reporting, testing selection bias, and in GB the influence of media reports. The authors recommend adding loss of smell/taste to WHO symptom list for COVID-19.
      • Risk Factors for Viral RNA Shedding in COVID-19 Patients. May 12. Fu. Eur Respir J.
        Retrospective study of 410 confirmed COVID-19 patients in China who received follow-up RT-PCR testing after symptoms started to improve. 14% had 1 negative test followed by 1 positive test. Median time to 2 consecutive negative tests was 19 days after symptom onset (range 3-44 days) and 7 days after fever resolution. 96% tested negative within 30 days of symptom onset. 40 patients had fever resolution after testing negative. Coronary heart disease, serum albumin < 35 g/L, and initiation of antiviral treatment > 7 days after symptom onset were independent risk factors for prolonged positive tests.

      May 14, 2020

      • Dynamic profile for the detection of anti-SARS-CoV-2 antibodies using four immunochromatographic assays. May 12. Demey. J Infect.
        4 immunochromatographic lateral flow assay tests (LFA) from Asian manufacturers for Sars-CoV-2 IgM and IgG were evaluated and the kinetics of antibody detection in 22 RT-PCR positive patients were determined. Median antibody detection time from onset of symptoms ranged from 8-10 days depending on the manufacturer. Sensitivity range for detecting either IgM or IgG was 60-80% on day 10 but all assays were 100% sensitive on day 15. IgM was not detected in 3 patients with two of the assays and was not reliably detected prior to IgG. 1 cross reaction was seen with other human coronaviruses (other than SARS-CoV).
      • Gastrointestinal, hepatobiliary, and pancreatic manifestations of COVID-19
        Apr 29. Patel. Journal of Clinical Virology.
        Opinion from SAB Member: Dr. David M. Clement
        This paper is a good overview of the current literature on GI disease with COVID-19. A well written, concise review of the GI symptoms, laboratory abnormalities, outcomes, possible mechanisms of GI disease, and outcomes in COVID-19 patients with GI disease are included. The prolonged Rt-PCR positivity of fecal samples is discussed, concluding that this could be a significant mode of viral transmission, and should be taken into account.
      • Taste Changes (Dysgeusia) in COVID-19: A systematic review and metaanalysis
        May 1. Aziz. Gastroenterology.
        Opinion from SAB Member: Dr. J. Lance Lichtor
        The authors performed a retrospective analysis of published articles that reported on ageusia/dysgeusia as a symptom in laboratory-confirmed COVID-19 patients and found that almost half of the patients (49.8%) with COVID-19 have altered taste sensation. Though it is not certain that taste or smell changes can predict COVID-19, certainly the clinical feature can raise the suspicion of COVID-19 and lead to early testing and diagnosis.

      May 13, 2020

      • Prolonged Persistence of SARS-CoV-2 RNA in Body Fluids. May 9. Sun. Emerg Infect Dis.
        This prospective study from China reports on the results of serial PCR tests for hospitalized SARS-CoV-2 RNA from 49 patients, beginning with onset of symptoms. 43 mild and 6 considered severe cases. They sampled throat, sputum, NP, and feces every 3d. 95% of severe patients had clearance of RNA in all samples 7-8 days later than for mild cases, on average. Throat swab cleared first in mild but not severe cases. It is difficult to comment on their statistical findings as they collected only 32.75% of their desired samples for a variety of reasons. No asymptomatic patients included.
      • SARS-CoV-2 in pregnancy: symptomatic pregnant women are only the tip of the iceberg. May 11. Khalil. Am J Obstet Gynecol.
        A dramatically titled UK article testing all pregnant women presenting for delivery for COVID-19. During a 3-week period ending early in April, of the 129 pregnant women tested, only 1 presented with symptomatic infection. However, 7% tested asymptomatic positive. None of these women developed symptoms and all were discharged with healthy infants at ~2 days.

      May 12, 2020

      • COVID-19 Convalescent Plasma; Phase 2
        May 6. Knudson. Transfusion.
        Opinion from SAB Member: Dr. Louis McNabb
        This article discusses methodological issues in using convalescent plasma for COVID-19 patients, such as: donor selection, the fact that some donors have over ten times the antibody level of other donors, the existence of many different antibody tests, factoring in the weights of recipients, and pre- and post-antibody measurements in recipients.

      May 11, 2020

      • Considerations for Assessing Risk of Provider Exposure to SARS-CoV-2 after a Negative Test
        May 8. Long. Anesthesiology.
        Opinion from SAB Member: Dr. Barry Perlman
        The SARS-CoV-2 RT-PCR test is not 100% sensitive and, therefore, can result in a false negative. It has been questioned whether 1 negative test preop can be used to guide the level of PPE needed to adequately protect an anesthesiologist during an intubation or other aerosol generating procedure. Negative predictive value (NPV) and post test probability of SARS-CoV-2 infection were calculated based upon estimated prevalence in the population and test sensitivity and specificity. Using a “most likely” prevalence estimate of 1.0%, post test probabilities ranged from 1 in 89 to 1 in 1,636 with a median of 1 in 338. Based on the results: 1) If prevalence is uncommon, 1 negative test should provide “reassurance” regarding risk of exposure from an asymptomatic patient; 2) If surgical volume is high, exposure to aerosolized SARS-CoV-2 from asymptomatic, 1 test negative patients might occur on a regular basis; 3) If prevalence is high, full PPE should be used for test negative patients; 4) Due to estimate uncertainty in prevalence and testing sensitivity, there is a wide range in the calculated negative predictive value. The authors recommend that a lower threshold of NPV to justify use of universal airborne precautions regardless of preop test results be determined but be re-evaluated if prevalence estimates change.
      • Convalescent Plasma To Treat Coronavirus Disease 2019 (Covid-19): Considerations For Clinical Trial Design
        May 6. Barone. Transfusion.
        Opinion from SAB Member: Dr. Louis McNabb
        This article discusses many of the issues in collecting and administering convalescent plasma, and outlines the clinical trials in the USA currently in progress.
      • Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in severe patients with COVID-19. May 1. Sciascia. Clin Exp Rheumatol.
        Pilot, prospective, open, single arm, multi center study of off-label tociliuzamab, a humanized anti Il-6 receptor antibody, with 63 patients hospitalized with severe COVID-19 in Italy. Patients also received either lopinavir/ritonavir or darunavir/cobicistat. There was no significant survival difference with oral versus IV tociluzamab. D-dimer and CRP significantly decreased by day 1 of treatment. Administration within 6 days of hospital admission was associated with a 2x increased likelihood of survival. There were no severe-to-moderate adverse events from tociluzamab infusion.
      • Sample Pooling as a Strategy to Detect Community Transmission of SARS-CoV-2. Apr 6. Hogan. JAMA.
        In this research letter, a group of Stanford pathologists replicated a study done to determine the prevalence of trachoma in a population using RT-PCR in pooled samples to determine whether community transmission was in fact active during the early phases of SARS-CoV-2 arrival in the US when routine testing was done only on travelers and their contacts. There were two positives among 2888 nasal and lower respiratory samples tested both late in February when COVID-19 prevalence increased sharply. The pooled screening method is a lower cost method to test large populations quickly, using less reagents, and increase overall testing efficiency at an expected slight loss of sensitivity. The result is early detection of community transmission and timely implementation of appropriate infection control measures to reduce spread.
      • The Role of Antibody Testing for SARS-CoV-2: Is There One?
        Apr 29. Theel. Journal of Clinical Microbiology.
        Opinion from SAB Member: Dr. W. Heinrich Wurm, Dr. Barry Perlman
        WHW: This well-written correspondence presents a deep dive into the state-of-the-art SARS-CoV-2 serology as of mid-April 2020. While outlining the usefulness and applicability of serologic testing, the authors shed light on the absence of FDA oversight of a burgeoning industry of 91 manufacturers. This is a must read for anyone looking for: 1) A tutorial on the optimal use and interpretation of currently available serological testing; 2) verification studies used by laboratories; or 3) the role serologic testing plays in: a) Developing population immunity; b) Development of vaccine; c) Identifying convalescent plasma donors; d) Monitoring the response of vaccines. BP: Richly detailed commentary regarding the current state of SARS-CoV-2 serology testing. It points out the current lack of FDA oversight for serologic testing, which has resulted in a variety of approaches that differ in assay format, antibody detected, target antigen, and specimen type. In addition, it is not yet known whether antibody detection indicates clinical immunity. While some may decide not to read the entire article, the abstract provides a nice summary and useful information.
      • Tocilizumab for the Treatment of Severe COVID-19. May 5. Alattar. J Med Virol.
        Retrospective review of 25 ICU patients in Doha, Qatar with confirmed severe COVID-19 who received tociluzamab and were followed for 14 days. Patients received a median of 5 other antiviral medications. 92% had at least 1 adverse event, including anemia, increased ALT, or QT prolongation. Tociluzamab was associated with a rapid decrease in oral temperature and serum CRP. Significant radiologic improvement and decreased invasive ventilation were seen on days 7 and 14.

      May 8, 2020

      • Interpreting Diagnostic Tests for SARS-CoV-2
        May 6. Sethuraman. JAMA.
        Opinion from SAB Member: Dr. Barry Perlman
        Viewpoint from authors in India and Japan discusses interpretation of RT-PCR and ELISA serology testing. There are a variety of RT-PCR tests. Most target envelope, nucleocapsid, spike, RNA-dependent RNA polymerase (RdRp), or ORF1. Most have comparable sensitivities with the RdRp test showing lower sensitivity. RT-PCR nasal swab testing becomes positive as early as day one of symptom onset, peaks within the first week, and starts to decline by week 3. Sputum and fecal sample positivity persists longer than for nasopharyngeal samples. Of note, a positive result reflects presence of viral RNA and does not necessarily mean viable virus. IgM and IgG ELISA testing may be positive as early as day 4 of symptom onset, and rises in weeks 2 and 3. IgM declines by week 5 and disappears by week 7, while IgG persists beyond week 7. Antibody detection to NC protein is most sensitive, while antibody testing to the S receptor-binding domain is more specific and might indicate neutralizing antibodies. Paired testing with initial RT-PCR and then 2 weeks later can increase diagnostic accuracy. It is not known how long neutralizing antibodies will persist and provide protection.

      May 7, 2020

      • Molecular testing for acute respiratory tract infections: clinical and diagnostic recommendations from the IDSA’s Diagnostics Committee. May 6. Hanson KE. Clin Infect Dis.
        Diagnostics Committee of the Infectious Diseases Society of America recommendations for respiratory molecular testing based on comprehensive literature review. Highly sensitive and specific nucleic acid amplification tests (NAAT) are the diagnostic gold-standard in clinical virology and also has utility for bacterial pneumonia testing. Rapid testing may decrease unnecessary antibiotic use, improve antiviral prescribing, limit additional testing, shorten hospital and ED lengths of stay, and optimize infection control, but factors such as study design, sample sizes, and test accuracy, performance and resulting negatively impact ability to combine study results to demonstrate benefits. May be most useful clinically with intermediate pre-test probability and intermediate disease severity. Questions posed by the IDSA:
        • To test or not to test. Whether test result will impact therapy depends upon illness severity, symptom duration, comorbidities, possible immunosuppression, choices of testing and their availability, result turn-around time, and disease prevalence. Multiplex bacterial pneumonia panels are too new to evaluate test performance and clinical impact.
        • Which test. For influenza, CDC and IDSA recommend testing. For SARS-CoV-2, there are more than 24 NAATs authorized for emergency use, and results can be impacted by sampling site (nasal, oral, or lower airway) and when in the illness the sample is obtained. Optimal approach for COVID-19 testing has not been defined. Use of multiplex NAAT with or without bacterial testing needs further study.
        • Interpretation of bacterial DNA in lower resp. tract sample. Issues include colonization versus pathogen, false positive due to dead or impaired organisms, significance of organism quantitation.
        • Improved antibiotic stewardship due to NAAT testing. Rapid test results may allow antibiotics to be stopped, but false positives may increase antibiotic use.
        • Recommendations for future studies shown in Table 2.
      • What’s new in lung ultrasound during the COVID-19 pandemic. May 6. Volpicelli G. Intensive Care Med.
        A highly technical description from Europe of the differential diagnosis and possibly unique lung ultrasound findings in patients with COVID-19. Good videos and excellent table. This would be helpful for a provider in the ICU or ED already trained in lung ultrasound.

      May 5, 2020

      • Antibody Detection and Dynamic Characteristics in Patients with COVID-19
        Apr 19. Xiang. Clinical Infectious Diseases.
        Opinion from SAB Member: Dr. Barry Perlman
        Serologic study of 85 SARS-CoV-2 RT-PCR test confirmed COVID-19 patients, 24 patients with symptoms but negative RT-PCR testing, and 60 controls. Serologic test was an ELISA for IgM and IgG against the SARS-CoV-2 nucleocapsid N protein. COVID-19 patients showed IgM by 4 days after symptom onset with peak by day 9. IgG increased sharply 12 days after symptom onset, with all COVID-19 patients positive for both IgG and IgM by day 30. For symptom positive but test negative patients, 88% had IgM and 71% had IgG, demonstrating false negative RT-PCR results. 3 controls had IgG but not IgM, which represent either false positives or asymptomatic infection. For RT-PCR confirmed patients: IgM sensitivity 77%, specificity 100%, PPV 100%, NPV 80%. IgG sensitivity 83%, specificity 95%, PPV 95%, NPV 84%. The authors suggest that IgG can be used to diagnose COVID-19 in pneumonia patients, and if negative, serology testing should be repeated 10 days after onset.
      • Role of serology in the COVID-19 pandemic
        May 1. Stowell. Clinical Infectious Diseases.
        Opinion from SAB Member: Dr. Barry Perlman
        Editorial of serologic study by Xiang et al. which demonstrated ability to measure IgG and IgM in COVID-19 patients with good sensitivity and specificity. The editorial points out that variability in kinetics and magnitude of the serologic response, especially early in infection, can result in false negative results, and IgM results may be false positive. In addition, it is not known if positive serology correlates with disease immunity. Suggested uses for serologic testing: 1) COVID-19 symptoms but RT-PCR negative; 2) Populations to determine degree of community exposure; 3) Frontline healthcare workers; 4) Convalescent plasma donation.

      April 30, 2020

      • Covid-19 may present with acute abdominal pain. Apr 29. Saeed. Br J Surg.
        This is a report of evolving understanding of the range of presenting symptoms of Covid-19 patients. Of 76 patients presenting to the ER in Oslo, Norway, during a 15-day period with a chief complaint of abdominal pain, 9 were found to be positive for coronavirus. All 9 had other GI symptoms – 3 nausea, 5 nausea+vomiting and 1 diarrhea. 5 had fever. None complained of respiratory problems. When coronavirus infection was diagnosed, pulmonary evaluation revealed 6 had ground glass opacities on CT. The diagnoses included cholecystitis in 1 and appendicitis in 1 however the report indicates that all were discharged home for self-quarantine and none required ICU care. This led to modifications in their institutional protocols. “Droplet isolation and testing for COVID-19 are now performed on all patients with abdominal pain.”

      April 28, 2020

      • Updated diagnosis, treatment and prevention of COVID-19 in children: experts’ consensus statement (condensed version of the second edition)
        Apr 24. Shen. World Journal of Pediatrics.
        Opinion from SAB Member: Dr. Lydia Cassorla
        This review provides guidance in the form of an updated consensus statement regarding COVID-19 in children. In early February 2020, an expert committee with more than 30 Chinese experts from 11 academic medical organizations formulated the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children. According to the 28 February 2020 WHO COVID-19 situation report, pediatric cases in China accounted for 2.4% of 55,924 confirmed cases. Close contact with infected persons with or without symptoms is the main transmission route of SARS-CoV-2 to children, resulting in mostly clustered cases. “There is no direct evidence of vertical mother-to-child transmission, but newborns can be infected through close contact.”
        Risk factors, diagnosis, severity classifications, early warning indicators, differential diagnosis, and treatment are discussed. Risk factors for severe disease include underlying diseases, immunosuppressant Rx and age<3 months. Most manifestations and laboratory findings are similar to adults, with atypical symptoms such as GI manifestations and listlessness noted. The group recommends antipyretics such as ibuprofen and acetaminophen if T>38.5 degrees C, and nebulizer treatments to manage mucus plugs. “Antiviral drugs without clear evidences of safety and efficiency are not recommended to be used in pediatric patients. The revised antiviral drug therapy remains interferon-alpha (IFN-alpha) sprays and aerosol inhalation. We do not recommend using lopinavir/ritonavir, ribavirin or chloroquine phosphate in pediatric patients.” Intubation and controlled ventilation is recommended if non-invasive mechanical ventilation does not result in clinical improvement after 2 hours. Plasma exchange to treat cytokine storm, immunoglobulin and anticoagulation are mentioned. 27 references provided, including the group’s initial statement.

      April 24, 2020

      • Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection. Apr 23. Spinato G. JAMA.
        Retrospective phone assessment of alteration in taste and smell among 202 consecutive patients who presented to an Italian outpatient facility. Using a symptom-based rhino-sinusitis outcome measure called Sino-Nasal Outcome Test-22 (SNOT-22), degree of impairment was assessed. 50% of patients had moderate to complete loss of taste and smell but only 12% found this to be an early symptom. There is strong evidence that the density of ACE2 receptors in the nasal mucosa is linked to this symptomatology and that it is specific to COVID-19 infection, but neither loss of taste or smell was assessed objectively in this study.
      • Sonographic signs and patterns of COVID-19 pneumonia
        Apr 21. Volpicelli. The Ultrasound Journal.
        Opinion from SAB Member: Dr. Barry Perlman
        This paper describes the use of lung ultrasound (LUS) for diagnosis of COVID-19 pneumonia, and discusses signs that distinguish it from classic ARDS. Sonographic signs with COVID-19 are similar to those seen with ARDS–clusters of B lines and small peripheral consolidations. More particular to early COVID-19 pneumonia is “a shining band-form artifact spreading down from a large portion of a regular pleural line, often appearing and disappearing with an on–off effect in the context of a normal A-lines lung pattern visible on the background.” It is important to also consider clinical presentation, symptom timing, laboratory findings and co-morbid diseases when using LUS for diagnosis or following progression of COVID-19. The use of LUS in the pediatric COVID-19 population is not discussed, but at the time of this review one small preliminary study of 8 pediatric patients showed LUS utility for both diagnosing and following the resolution of disease.

      April 23, 2020

      April 21, 2020

      • Profile of RT-PCR for SARS-CoV-2: a preliminary study from 56 COVID-19 patients. Apr 20. Xiao. Clin Infect Dis.
        Preliminary RT-PCR study on 56 recovering COVID-19 patients in Wuhan, China showed that virus shedding continued up to 6 weeks after symptom onset, with a mean time to negative RT-PCR conversion of 24 days. Patients with positive RT-PCR tests more than 24 days after symptom onset tended to be older and more likely to have HTN or DM. Of note, all patients had mild-moderate illness, none required ICU admission, and all recovered. Also, a second negative test was used for confirmation, although 4 patients tested RT-PCR positive after 2 consecutive presumably false negative results.
      • Response to COVID-19 in Taiwan: Big Data Analytics, New Technology, and Proactive Testing. Mar 3. Wang. JAMA Network.
        The rapid, coordinated and aggressive Taiwanese response to the pandemic threat that was quite successful through Feb 24. Dated article, not useful to front-line providers.
      • SARS-CoV-2 shedding and infectivity. Apr 19 Atkinson. Lancet.
        The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
      • Smell and taste dysfunction in patients with COVID-19. Apr 19. Xydakis. Lancet Infect Dis.
        As the authors note in their first sentence of this letter to the editor: “The plural of an anecdote is not evidence,” and indeed, they provide little more evidence concerning taste and smell dysfunction than what’s already been described.
      • Category: Diagnosis of Infection or Immunity
        Testing for SARS-CoV-2: Can We Stop at Two?
        Apr 19. Lee. Clinical Infectious Diseases.
        Opinion from SAB Member: Dr. Lydia Cassorla
        This report from Singapore highlights data as of Feb. 29, 2020 from a set of patients hospitalized with typical symptoms and a history of travel or contacts suggestive of COVID-19 illness. 72/80 (88.6%) tested negative on their first upper respiratory PCR, 5 were positive on the second day, and 3 turned positive on the third daily test. The authors stress that single or even two consecutive daily negative tests may not detect all infected patients. Their PCR test was developed and commercialized in Singapore, targeting N and ORF1ab genes. This report highlights an important point that repeated testing is often required to confirm infection. Readers should keep in mind that PCR tests are not all alike, and implementation such as swabbing location and technique vary. Therefore, sensitivity data can be expected to vary as well.
      • Well-aerated Lung on Admitting Chest CT to Predict Adverse Outcome in COVID-19 Pneumonia. Apr 18. Colombi. Radiology.
        Retrospective study of 236 ED patients in Italy admitted with positive RT-PCR tests and chest CT findings consistent with COVID-19 pneumonia. Lower zone predominance of ground-glass opacities and consolidations were most common findings. > 27% of lung with decreased aeration on admit CT was associated with 5x greater risk of ICU admission or death. Concomitant emphysema was about 2x more common in patients who were admitted to ICU or died.

      April 20, 2020

      April 14, 2020

      • A role for CT in COVID-19? What data really tell us so far Apr 11. Hope. The Lancet
        Opinion from SAB Member: Dr. Barry Perlman
        Opinion piece from academic radiologists that CT should not be used to diagnose COVID-19, as the described ground-glass opacities and consolidation are not specific. The positive predictive value of CT is low unless pre-test probability is high, and in one study of confirmed COVID-19 patients from the Diamond Princess cruise ship, 1/3 did not have CT lung opacities and 20% of symptomatic patients had negative CT findings. Further, use of CT during the pandemic is “logistically challenging” in terms of resource allocation, cleaning, and potential exposure of COVID-19 to caregivers and other patients.
      • Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications. Apr 6. Wu. medRxiv.
        Study from China on 179 recovered patients hospitalized with “mild” COVID. Neutralizing antibody development peaked at day 10-15, thereafter remained stable, but 30% of patients had very low antibody titers. This information could help inform vaccine trials and selection of donors for immune globulin therapy.
      • The Role of Chest Imaging in Patient Management during the COVID-19 Pandemic: A Multinational Consensus Statement from the Fleischner Society Apr 3. Rubin. CHEST.
        Opinion from SAB Member: Dr. Barry Perlman
        Recommendations from a multidisciplinary panel of radiologists, pulmonologists, and other disciplines from 10 countries on the use of chest X-ray (CXR) and CT for managing COVID-19 patients. Ultrasound was not considered due to the panel member’s limited experience with ultrasound in COVID-19 patients at the time of the meeting. They recommend that chest imaging should not be used for patients with suspected COVID-19 and mild clinical features. Rather, it is useful when patients are at risk for disease progression, develop worsening respiratory status, or have moderate-severe disease and high pre-test probability of COVID-19 infection. CT is more sensitive than CXR in mild or early COVID-19 infection, and for alternative diagnoses such as acute heart failure or pulmonary thromboembolism. However, local resources, expertise, infection control issues, and clinical judgment impact the decision as to which modality should be used. Table 2 provides a nice summary of the recommendations.

      April 13, 2020

      • Developing antibody tests for SARS-CoV-2. Apr 4. Petherick. The Lancet.
        Outlines the race to develop and approve a test with a different purpose—to assess not current viral infection, but immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). LC: A summary of achievements to date, test types, and challenges of widespread testing for immunity to SARS CoV-2.

      April 11, 2020

      April 10, 2020

      • PCR Assays Turned Positive in 25 Discharged COVID-19 Patients Apr 8. Yuan. Clinical Infectious Diseases.
        COVID-19 SAB Opinion from: Dr. Lydia Cassorla
        172 patients discharged from a Shenzhen hospital following clinical improvement and 2 consecutive day negative PCR tests for COVID-19 virus. They were then followed at home with nasal and cloacal swab PCR testing every 3 days during a planned 14-day quarantine. 25 patients (14.5%) re-tested positive and were returned to hospital. Some had new symptoms. The authors suggest that the pre-discharge testing may be more reliable in detecting persistent virus carriers if separated by 48 hours.

      April 9, 2020

      April 8, 2020

      April 4, 2020

      April 3, 2020

      • Developing antibody tests for SARS-CoV-2 Mar 3. Petherick. The Lancet.
        COVID-19 SAB Opinion from: Dr. Lydia Cassorla
        Outlines the race to develop and approve a test with a different purpose-to assess not current viral infection, but immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A summary of achievements to date, test types, and challenges of widespread testing for immunity to SARS CoV-2.

      April 2, 2020

      April 1, 2020

      March 31, 2020

      March 30, 2020

      March 27, 2020

      March 22, 2020

      March 16, 2020

    1. Risk Factors / Demographics / Resource Requirements / Outcomes
      September 13, 2021
      • 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study. 8/28/21. Huang L. Lancet.
        This extensive study reports the condition at 12 months of a cohort of 1,307 COVID-19 patients discharged January-May 2020 from a single hospital in China. Patients in nursing or care homes, immobile or with osteoarthritis, and with psychiatric disorders or dementia were excluded from the study. A review of the report of their condition at 6 months appears in Newsletter 51. Intensive evaluations included multiple standardized questionnaires, physical exam, blood tests, pulmonary evaluation, use of healthcare resources and work status. Patients with at least one persistent symptom decreased from 68% at 6 months to 49% at 12 months. The most common problem, fatigue and muscle weakness decreased from 52% to 20%. The proportion with dyspnea and anxiety or depression worsened slightly. Of those who were employed prior to hospitalization, 88% had returned to work. Outcome with regard to severity of initial disease, males vs. females and patients vs. matched community controls is characterized.

      August 9, 2021

      July 26, 2021

      June 4, 2021

      May 10, 2021

      • 3-month, 6-month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: a prospective study. 5/8/21. Wu X. Lancet Respir Med.
        This is a prospective, longitudinal cohort study from China of 83 severe COVID-19 patients (admitted February and March 2020, so none received glucocorticoids) who did not require IMV, yet still had 29-day hospital stays. Patients with HTN, DM, CVD, cancer, any pulmonary disease or tobacco use had been excluded. At 3-, 6-, 9- and 12-months post admission, they underwent pulmonary function testing, documenting abnormalities with gradual improvement even after 9 months. Radiological abnormalities (24%) and DLCO less than 80% of predicted (33%) persisted at 12 months despite near normal lung volumes, 6M walk and dyspnea assessment.
        SAB Comment: These results indicate that even previously healthy patients who have recovered from COVID-19 may warrant pulmonary evaluation and consideration of timing regarding elective surgery.
      • Mortality after In-Hospital Cardiac Arrest in Patients with COVID-19: A Systematic Review and Meta-Analysis. 5/8/21. Ippolito M. Resuscitation.
        This is a well-performed meta-analysis of resuscitation (CPR) following in-hospital cardiac arrest, confirming bleak survival statistics. The article includes an interesting debate regarding universal do not resuscitate orders for COVID-19 arrest resuscitation and comparison with ICU resuscitation of comparably ill patients without COVID-19. The authors suggest further discussion and data analysis is necessary following improved results for in-hospital cardiac arrest (IHCA) over time. Conclusion: Although one of three COVID-19 patients undergoing IHCA may achieve return of spontaneous circulation, 90% are not expected to survive 30 days or to hospital discharge.

      May 7, 2021

      • Trends in Patient Characteristics and COVID-19 In-Hospital Mortality in the United States During the COVID-19 Pandemic. 5/3/21. Roth GA. JAMA Netw Open.
        This analysis of mortality trends in the US among 20,736 patients in 107 hospitals in 31 states comes from the American Heart Association COVID-19 cardiovascular disease registry. In comparison with March/April patients, the odds ratio of mortality decreased approximately one-third later in the year, after adjusting for age, sex, medical history, and COVID-19 severity. ICU length of stay, use of mechanical ventilation, and mortality in age groups over 50 decreased, although mortality remained highly associated with age. Use of corticosteroids and remdesivir increased. Reasons and other independent risk factors are discussed.

      May 3, 2021

      • Hospital-Level Variation in Death for Critically Ill Patients with COVID-19. 4/23/21. Churpek MM. Am J Respir Crit Care Med.
        This multicenter cohort study utilized the STOP-COVID database to explore the wide variation in published mortality rates for critically ill COVID-19 patients. Data were evaluated on 4019 adult ICU patients admitted to 70 US hospitals between March-June 2020. Thirty-eight percent of patients died within 28 days, with an unadjusted interhospital mortality range of 12-91% (OR 2.06). After mixed-effect regression adjustment for patient- and hospital-level domains, the interhospital range attenuated to 32-44% (OR 1.22). In individual patients, acute physiology contributed 49%, demographics, comorbidities and socioeconomic status 32%, hospital strain and quality 17%, and treatments 3% to mortality risk. The authors emphasized that lower socioeconomic status of the community served by the hospital (characterized by a high percentage of patients who traveled more than 45 min to get to work) is an important contributor to interhospital variability, suggesting that COVID-19 exacerbates disparities in US healthcare. Individual mortality is also impacted by hospital ICU-bed capacity and strain, but treatments had the least impact on outcome variability. [Readers should note that the study reflects an early stage of the pandemic, prior to the positive evidence of steroid therapy on outcome in ventilated patients.]

      April 16, 2021

      April 12, 2021

      • 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records. 4/6/21. Taquet M. Lancet Psychiatry.
        This study provides a rich source of data covering a multitude of neurological and psychiatric symptoms in the wake of COVID-19. Using anonymized records from 62, mostly US healthcare organizations, from 3 patient cohorts, one with COVID-19 and two with other contemporaneous illnesses, the authors identify a COVID-specific incidence of neurologic and psychiatric diagnoses of 34% overall, with 13% receiving their first such diagnosis. They convincingly show a link to severity of illness with an incidence of 46% among all patients admitted to ICUs and to a diagnosis of delirium and encephalopathy where the overall incidence rose to 62%. The long-term impact of prolonged recovery due to neurological or psychiatric sequelae of COVID-19 represents a global public health challenge.

      April 7, 2021

      • Mortality and Readmission Rates Among Patients With COVID-19 After Discharge From Acute Care Setting With Supplemental Oxygen. 4/1/21. Banerjee J. JAMA Netw Open.
        A retrospective study of 621 adult COVID-19 pneumonia patients (65% male) who were discharged from inpatient care (76%) or ED (24%) from 2 large urban public hospitals with a carefully executed, patient-focused discharge and follow-up plan showed excellent outcomes. 76% were insured by Medicaid and 84% were Spanish-speaking. Interventions included pre-discharge patient education, non-automated daily telephone contact 7 days/week until not needed, facility-dispensed equipment (pulse oximeter, O2 tank, concentrator), and vendor support. All-cause mortality was low – 1.3% (95% CI, 0.6%-2.5%) with none outside hospital, and 30-day hospital readmission rate was 8.5% (95% CI, 6.2%-10.7%). Median follow-up time was 26 days. Readmission rates were lower than the overall post-acute care 30-day readmission rate (15.2%) for California Dept. of Health Care Services patients in 2020, and compare favorably to privately insured pre-COVID patients in an earlier, referenced report.

      April 2, 2021

      March 26, 2021

      • Racial and Ethnic Disparities in COVID-19 Incidence by Age, Sex, and Period Among Persons Aged <25 Years – 16 U.S. Jurisdictions, January 1-December 31, 2020. 3/18/21. Van Dyke ME. MMWR Morb Mortal Wkly Rep.
        This is a data-rich CDC report on nearly 700,000 COVID-19 cases in young people from jurisdictions representing 23% of the US population. (Included cases represent 77% of total cases due to absent ethnicity data in the remainder.) Incidences among multiple minorities ranged from 0.77 to 4.57 relative to non-Hispanic Whites and disparities evolved during 2020. Large disparities January–April generally decreased May–December, primarily due to higher incidence among Whites. Children <10 rarely tested positive, however incidence increased stepwise from ages 10-24. The largest persistent disparities involved Native Hawaiian and Pacific Islanders, Native Americans, and Hispanics. Ethnic minorities often live in multigenerational homes and include essential workers unable to shelter at home. Equitable and timely access to testing, prevention, and vaccination is urged.

      March 17, 2021

      • Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7. 3/8/21. Davies NG. Nature.
        The B.1.1.7 “UK” variant is known to be more infectious. This British study shows it is more lethal. B.1.1.7 is identified with PCR, as the S gene is not amplified: S gene target failure = SGTF. Based on 4,945 deaths within 28 days of community testing of 1,146,534 patients with known SGTF status, authors estimate that the associated adjusted hazard of death is significantly increased across age groups. For example, in 55-69 year old subjects, estimated absolute risk of death within 28 days after a positive test in the community for males increased from 0.6% to 0.9% (95% CI 0.8–1.0%); for females it increased from 0.18% to 0.28% (0.25–0.31%).
        SAB Comment: In a separate retrospective British study with similar results ~55,000 adults >30 years old with the B.1.1.7 variant were matched with an equivalent number of controls. It was highlighted in our Newsletter Issue 68, and can be found here.

      February 12, 2021

      February 8, 2021

      • A rapid review of the pathoetiology, presentation, and management of delirium in adults with COVID-19. 12/25/20. Hawkins M. J Psychosomatic Res.
        In this in-depth literature review of delirium in COVID-19, the authors initially identified 10,000 publications and after removing duplicates and screening abstracts, 229 studies were included in the review. This review serves as a source of reference for intensivists dealing with various aspects of diagnosing and treating delirium. After reviewing current information on prevalence, symptoms and etiology, prevention and management are highlighted in a summarizing table. In the absence of randomized clinical trials on this topic, the discussion is limited to reporting diverse empirical management with and without pharmacological intervention, stressing the fact that delirium can be a core symptom at presentation and may be under-recognized and under-diagnosed.

      January 13, 2021

      • 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. 1/8/21. Huang C. Lancet.
        175-199 days after symptom onset, 1733 of 2469 discharged Wuhan COVID-19 patients (median age 57) completed questionnaires to evaluate symptoms and quality of life along with physical examinations, a 6-min walking test, and blood tests. Reduced 6-min walk, fatigue, pulmonary abnormalities, and anxiety or depression were prevalent. 73% of men and 81% of women reported at least one symptom (76% overall). Most common were fatigue or muscle weakness (63%), sleep difficulties (26%), and anxiety or depression (23%). Symptoms were positively correlated with previous COVID-19 illness severity.
        SAB Comment: Many with mobility or neurologic issues were excluded, therefore accurate percentages may be higher.

      January 6, 2021

      • Factors Associated With Severe SARS-CoV-2 Infection. 12/16/20. Ouldali N. Pediatrics.
        This 60-hospital French national study used an established meningitis surveillance network to study demographics of COVID-19 pediatric patients. Data collection was from February 15-June 1, with 397 children and included an estimated 38.5% of the total cases in France. The primary outcome was the proportion of patients with disease progression, and secondary outcomes were defined by age groups. The median age was 16 months. Three percent of children (4/135) <90 days old developed severe disease. MIS-C increased with age. There was severe disease overall in 11% (23/306). Of the 6 mortalities only one was entirely due to COVID-19. Findings suggested that the rate of severe forms was the lowest in very young children and was the highest for children ≥ 10 years.

      December 16, 2020

      December 11, 2020

      • Tobacco use as a well-recognized cause of severe COVID-19 manifestations. 11/30/20. Gupta AK. Respir Med.
        Though we have reviewed articles, some saying that COVID-19 is worse in smokers and others that it is not, the authors reviewed 23 articles that met their criteria. The authors noted that pre-existing comorbidities in tobacco users such as cardiovascular diseases, diabetes, respiratory diseases, and hypertension are found to further aggravate the disease manifestations. More generally, smoking is a potential risk factor for, not only contracting the viral infection, but also making the treatment of such COVID-19 patients more challenging.

      December 4, 2020

      November 30, 2020

      November 9, 2020

      October 28, 2020

      October 26, 2020

      • Prediction models for covid-19 outcomes. 10/21/2020. Sperrin M. BMJ.
        A risk prediction algorithm to estimate hospital admission (n=10,776) and mortality (n=4,384) from covid-19 was created and validated using a UK dataset derived from 6.08 million 19-100 year old patients and validated with data from an additional 2.17 million. Study period was Jan 24-April 30 for the initial cohort and May 1-June 30, 2020 for the validation cohort. The model, including age, ethnicity, deprivation, BMI, and a range of comorbidities, predicted ¾ of deaths with excellent discrimination (Harrell’s C statistics >0.9). People in the top 20% of predicted risk of death accounted for 94% of deaths.
      • Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality from coronavirus 19 in adults: national derivation and validation cohort study. 10/21/2020. Clift AK. BMJ.
        Editorial discussing the potential utility of prediction models referencing article 1528 and a second BMJ report published in September on the 4C mortality score (calculated at hospital admission to predict in-hospital mortality for patients with confirmed or likely covid-19). Models have serious shortcomings and require constant updating however may also inform public health policies, vaccine allocation, and provide decision support for treatment.

      October 2, 2020

      September 21, 2020

      • Racial/Ethnic Variation in Nasal Gene Expression of Transmembrane Serine Protease 2 (TMPRSS2). 9/10/20. Bunyavanich S. JAMA.
        Nasal epithelium contains a protease (transmembrane serine protease 2 – TMPRSS2) which facilitates SARS-CoV-2 virus entry into the body. In a racially diverse cohort participating in an asthma study between 2015 – 2018, Black individuals exhibited a significantly higher expression of TMPRSS2 in nasal epithelium compared with other self-identified races/ethnicities. This finding may shed further light on the observed higher burden of COVID-19 among Black individuals. Protease inhibitors, like camostat mesylate, are undergoing clinical trials to test their utility for COVID-19 treatment via TMPRSS2 inhibition.

      September 16, 2020

      September 2, 2020

      • Viral dynamics and immune correlates of COVID-19 disease severity. 8/28/20. Young BE. Clin Infect Dis.
        One hundred COVID-19 patients from Singapore underwent prospective study of infectivity and immune response on days 1, 3, 7,14, 21 and 28 after enrollment. No positive viral cultures were found in respiratory samples (n=21) obtained more than 14 days after symptom onset and all positive viral cultures occurred in patients with PCR cycle threshold values <30. Disease severity was associated with earlier seroconversion, higher peak IgM and IgG levels, and higher levels of inflammatory markers, but not duration of viral shedding by PCR. Results have implications for duration of isolation/quarantine and from whom to potentially obtain convalescent plasma.

      August 31, 2020

      August 17, 2020

      August 14, 2020

      August 7, 2020

      • Post-discharge venous thromboembolism following hospital admission with COVID-19. 8/3/20. Roberts LN. Blood.
        These authors identified 1,877 patients with COVID-19 discharged from the hospital, and noted that there were nine episodes of Hospital Associated Venous Thromboembolism (HA-VTE) diagnosed within 42 days compared with 2019 hospital discharge data. The authors calculated an odds ratio of 1.6 compared to historically “similar” groups of patients. They concluded that hospitalization of patients with COVID-19 does not appear to increase the risk of post-discharge HA-VTE compared to hospitalization with other acute medical illnesses. Their data suggests empiric post-discharge thromboprophylaxis is not necessary, thereby supporting the ACCP recommendations to not offer post-discharge thromboprophylaxis.
      • SARS-CoV-2 Infection and COVID-19 During Pregnancy: A Multidisciplinary Review. 5/30/2020. Narang K. Mayo Clin Proc.
        A long summary: 15 pages. There’s obviously different physiology concerning gestation and pregnancy. Earlier reports suggest higher rates of preeclampsia and other pregnancy-related complications. Angiotensin-converting enzyme 2 receptor is upregulated in normal pregnancy. So, with higher ACE2 expression, pregnant women may be at elevated risk for complications from SARS-CoV-2 infection. Upon binding to ACE2, SARS-CoV-2 causes its downregulation, thus lowering angiotensin-(1-7) levels, which can mimic/worsen the vasoconstriction, inflammation, and pro-coagulopathic effects that occur in preeclampsia. Indeed, early reports suggest that, among other adverse outcomes, preeclampsia may be more common in pregnant women with COVID-19.

      August 3, 2020

      July 22, 2020

      • Outcomes from intensive care in patients with COVID‐19: a systematic review and meta‐analysis of observational studies. 6/30/20. Armstrong B. Anaesthesia.
        Fascinating meta-analysis of 10,150 adult patients in 24 studies (enrollment was December 16, 2019 until May 28, 2020) from 11 countries with ICNARC (UK) database (national, rapidly updated registry) accounted for most cases in the study (results were unchanged when removed) with ICU death as primary endpoint. Mortality trended down from ~50% to 41.6% over time with confirmed by meta regression analysis by publication date indicating decreasing mortality. Discussion includes possibility of increasing sophistication of care outside ICU and despite likely increasing severity of ICU patients, therapeutic sophistication improvement was likely responsible for better outcome.
        Excellent analysis with interesting discussion and conclusions emphasizing need for better national data reporting in real time to better follow disease progression and resource utilization.

      July 20, 2020

      • Individualizing Risk Prediction for Positive COVID-19 Testing: Results from 11,672 Patients. 6/20/20. Jehi L. Chest.
        Review by the SAB
        By Dr. Lance Lichtor, on behalf of the SAB
        The authors of this article developed an online risk calculator that can identify individualized risk of a positive COVID-19 test. All patients from Cleveland Clinic in Ohio and Florida were tested, not just those who had the disease. Findings included: lower risk for Asians vs whites; lower risk for those who had pneumococcal polysaccharide vaccine and flu vaccine; higher risk with poor socioeconomic status; and reduced risk of testing positive in patients who were on melatonin, carvedilol, and paroxetine.
      • The Impact of Coronavirus Disease 2019 Pandemic on U.S. and Canadian PICUs. 7/8/20. Sachdeva R. Pediatr Crit Care Med.
        Review by the SAB
        By Dr. Philip Lumb, on behalf of the SAB
        This report is from a large pediatric ICU registry (Virtual Pediatric Systems, Los Angeles, CA), with data from over 200 hospital units and >1.5 million patient admissions. In order to determine the manner in which COVID-19 was affecting PICU’s, VPS expanded data collection related to COVID-19 to all Canadian and US PICU’s regardless of prior VPS membership to provide a near real-time dashboard including admissions, patient demographics and comorbidities, therapeutic interventions, deaths and length of stay. Data collection, from March 4 to May 20, represented 3,228 bed capacity comprising most US and Canadian resources from major teaching institutions to smaller hospitals with multifunctional PICU’s. At the peak of the admissions in late April, ~40% of admissions >18yo and ~12% >30yo indicating unusual age disparity than normally seen and providing insight into future PICU adjustments. Detailed description of analysis and future research directions are provided, demonstrating the value of high reliability registry with capability to provide rapid resource allocation and patient demographic, therapeutic and outcome information.

      May 28, 2020

      • A simple algorithm helps early identification of SARS-CoV-2 infection patients with severe progression tendency. May 21. Li Q. Infection.
        This study based on over 300 Chinese patients, creates a simple algorithm, named age-LDH-CD4 model, to identify COVID-19 patients with increased likelihood of disease progression.
      • COVID-19 and NSAIDS: A Narrative Review of Knowns and Unknowns
        May 24. Pergolizzi Jr. JV. Pain and Therapy.
        Opinion from SAB Member: Dr. Robert L. Coffey
        A brief commentary article reviewing the possible mechanisms for an increase in susceptibility to COVID-19 or for a worsened prognosis in patients taking NSAIDs. The possibility that the anti-inflammatory effects might in fact be helpful is noted. The previously reported association of NSAID use and poor outcome is described, but this may be due to the association of higher NSAID use with increasing age. The review of the literature presented here indicates that “to date there is no strong evidence in favor or disputing the use of NSAIDs in patients diagnosed with COVID-19.”
      • RAAS inhibitors do not increase the risk of COVID-19
        May 22. Fernández-Ruiz I. Nature Reviews Cardiology.
        Opinion from SAB Member: Dr. David M. Clement, Dr. Jay Przybylo
        DC: This editorial briefly reviews 5 recent retrospective studies that all confirm prior speculation that pre-COVID-19 use of ACE2 inhibitors and ARBs is not associated with increased susceptibility to COVID-19 and does not have harmful effects in patients with COVID-19. These results justify prior guideline advice to continue ACE2is and ARBs in the COVID-19 era.
        JP: An editor for Nature combined the results of multiple papers investigating the effect of ACEi and ARB therapy on the susceptibility to COVID-19, concluding that despite the lack of controlled studies, the aggregate of the cited studies provides proof that these drugs do not provide an entry portal for the infection and are safe to continue. This easily understood paper serves as a valuable resource for physicians of any specialty caring for patients on RAAS therapy who are infected with COVID-19.

      May 27, 2020

      • Association of renin-angiotensin-aldosterone system inhibitors with COVID-19-related outcomes in Korea: a nationwide population-based cohort study
        May 22. Jung. Clinical Infectious Diseases.
        Opinion from SAB Member: Dr. Jay Przybylo
        In a Korean population of patients taking Renin-angiotensin-aldosterone system (RAAS) inhibitors, the risk of death was higher compared with non-users. However, after adjustment for age, sex, Charlson Comorbidity Index, immunosuppression, and hospital type, the use of RAAS inhibitors was not associated with higher mortality.
      • Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. May 22. Petrilli. BMJ.
        An extensive prospective outcome study from NYC from 4 Ac Care Hospitals with 394 ICU beds and 1357 non-ICU beds. Out of about 12,000 patients for that period, 5,279 patients were positive for COVID-19: 48.1% were treated as outpatients, and 51.9% required admission to hospital. Out of those who got admitted: 63.4% were discharged, 36.1% experienced critical illness, 24.3% who were discharged to a hospice or among the 990 patients with critical illness, 63.4% required mechanical ventilation, 10.3% required non-ICU care.
        The study involved those admitted without critical illness, and those admitted to ICU, mechanical ventilation, discharge to hospice, or death. Then fitted multivariable logistic regression models with admission and with critical illness as the outcomes to identify factors associated with those outcomes. Authors also looked at admission values objectively for prediction of outcome as well. They found mortality to be 57% among all ICU or ventilated patients slightly higher than ARDS mortality. Some of the markers (either admission or admission to hospital) were common for worse outcome: Admission from March 16 to April 5, age > 55 years, unknown for smoking history, BMI > 40, CHF, O2 Sat % < 92, low Lymphocyte, high normal for C reactive, D Dimers, Procalcitonin, Troponin.
        Overall, they found that age and comorbidities are powerful predictors of requirement for admission to hospital rather than outpatient care; however, the degree of oxygen impairment and markers of inflammation are most strongly associated with poor outcomes during hospital admission. The study has very elaborate, descriptive analysis backed by statistics. It has a self-explanatory graph of several categories of clinical values to outcome.
      • Incidence, clinical outcomes, and transmission dynamics of severe coronavirus disease 2019 in California and Washington: prospective cohort study
        May 12. Lewnard JA. BMJ.
        Opinion from SAB Member: Dr. W. Heinrich Wurm
        For the practicing clinician, this study represents an epidemiological deep dive using the Kaiser Permanente database of 1840 patients (as of April 22, 2020) in a prospective cohort study aimed to:
        1. Assess population-based rates of COVID-19 disease over time in three distinct geographic areas (Southern CA: 15.6, Northern CA 23.3, WA 14.7)
        2. Model
          • estimated hospital length of stay for survivors (9.3 days) and non-survivors (12.7 days)
          • ICU admission rates and median length of stay for males (48.5% and 10.6 days) and females (32% and 14.9 days)
          • Fatality risk by age group (median 18.9%; >80yrs: 37.3)
        3. Study transmission dynamics by following the effective reproduction number over the study period within each region.

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

      • Proposed Modifications in the 6-minute Walk Test for Potential Application in Patients with mild Coronavirus Disease 2019 (COVID-19): A Step to Optimize Triage Guidelines. May 19. Mantha. Anesthesia & Analgesia.
        The authors propose to have patients perform the 6 minute walk test (while wearing a mask) to better discriminate between Covid-19 patients with mild pneumonia and those with severe pneumonia. They recommend adding this test to the established WHO criteria for severe pneumonia that includes 1) severe respiratory distress, 2) a respiratory rate of >30 breaths/min, or 3) an SpO2 ≤93% on room air. They propose a 1400 foot distance covered as the point of discrimination (approx 3 METS), but do not provide any patient data.

      May 19, 2020

      • Age and sex differences in soluble ACE2 may give insights for COVID-19. May 14. Edsfeldt. Crit Care.
        Research letter detailing longitudinal study of soluble ACE2 (sACE2) levels by gender and age to determine potential differences and possible determinants of COVID-19 susceptibility for elderly male patients based on observation that disease more prevalent in adults>children and men>women. sACE2 levels analyzed from individuals registered in the pediatric osteoporosis prevention (POP) study; from age 7.7 years to 23.5 years at 2 to 3 year intervals. Results indicated that sACE2 levels increase more as boys age than girls. Authors suggest results support for observations re: age and sex prevalence for COVID-19 susceptibility.

      May 16, 2020

      May 14, 2020

      • COVID-19 and Racial/Ethnic Disparities
        May 11. Hooper. JAMA.
        Opinion from SAB Member: Dr. J. Lance Lichtor
        In this viewpoint article, the authors highlight the health disparities among African Americans and Latinos. The incidence of COVID-19 disease is higher, and the number of patients who die from the disease is greater in these groups of patients. It’s hard to know why, but social and structural determinants of health, racism and discrimination, economic and educational disadvantages, health care access and quality, individual behavior, and biology may be determinants. This is not the first time, in that pulmonary tuberculosis, for example, disproportionately affects persons of lower socioeconomic status. As the authors note, the “pandemic presents a window of opportunity for achieving greater equity in the health care of all vulnerable populations.”

      May 13, 2020

      • Prognostic Value of Leukocytosis and Lymphopenia for Coronavirus Disease Severity. May 8. Huang. Emerg Infect Dis.
        In this meta-analysis report from Los Angeles CA and Winston-Salem NC investigators analyzed data from 8 English-language studies representing 1280 unique adult cases of COVID-19 from China and Singapore, of which 46% were classified severe. “Pooled data across early studies validate a significant correlation between elevated leukocyte count and decreased lymphocyte count among patients with severe cases of COVID-19 compared with those with mild cases. Why lymphopenia is associated with severe illness remains unclear.”

      May 11, 2020

      • Association between ABO blood groups and risk of SARS-CoV-2 pneumonia. May 7. Li. Br J Haematol.
        In this brief study report of 265 COVID-19 patients from Wuhan, China, “The ABO blood group … showed a distribution of 39.3 %, 25.3 %, 9.8 % and 25.7 % for A, B, AB and O, respectively. The proportion of blood group A in patients infected with SARS-CoV-2 was significantly higher than that in healthy controls (39.3 % versus 32.3 %, P= 0.017), while the proportion of blood group O in patients infected with SARS-CoV-2 was significantly lower than that in healthy controls (25.7 % versus 33.8 %, P< 0.01).” The theory that adhesion of SARS-CoV-2 to ACE-2 receptor is inhibited by human natural anti-A antibodies is discussed.
      • Association Between Hypoxemia and Mortality in Patients With COVID-19. Apr 6. Xie. Mayo Clin Proc.
        Single center retrospective study of 140 patients with moderate to critical suspected or confirmed COVID-19 pneumonia in Wuhan, China. Those with SpO2 90% or less were more likely to be older, male, have HTN, and present with dyspnea. 26% died. Cutoff SpO2 of 90.5% showed a 85% sensitivity and 97% specificity for survival. Hypoxemia (SpO2 < 90%) despite O2 or dyspnea were independently associated with increased risk of death.

      May 8, 2020

      • Acute Physiology and Chronic Health Evaluation II Score as a Predictor of Hospital Mortality in Patients of Coronavirus Disease 2019
        May 7. Zou. Crit Care Med.
        Opinion from SAB Member: Dr. David M. Clement, Dr. Jagdip Shah
        DC: Especially in healthcare settings with overextended resources, accurately predicting mortality may or may not be useful for frontline providers. In this retrospective, single referral hospital study from China of 154 ICU patients with COVID-19, an admitting Acute Physiology and Chronic Health Evaluation (APACHE) II score of equal to or greater than 17 predicted mortality with a sensitivity of 96% and a specificity of 86%, better than other predictive indices.
        JS: This single, tertiary center, retrospective, small study (N= 154) in China compared three ICU scoring systems on day one of ICU admission to decide which one is a better predictive tool for survival (e.g. a futility index) with COVID-19 patients with MOF. The three scoring systems compared were APACHE II (age, Glasgow Coma Scale, vital signs, oxygenation, chemistry values, hematology values & organ insufficiency [0 to 71]; used for general critical illness), Sequential Organ Failure Assessments (PaO2:fiO2 ratio, mean arterial pressure, creatine, GCS, platelet count, bilirubin [0 – 24]; used for general critical illness), and Confusion, Urea, Respiratory rate, Blood pressure, Age 65 (CURB65; used for pneumonia). Their aim was to describe the difference of epidemiologic and clinical characteristics between survivors and deaths in an attempt to provide an effective clinical tool to predict the probability of death among patients with COVID-19 based on data about admission and the first day in the ICU. The APACHE II score performed better to predict hospital mortality in patients with COVID-19 compared with SOFA and CURB65 scores. APACHE II scores greater than or equal to 17, serve as an early warning indicator of death, which may help to provide guidance for making further clinical decisions. The authors’ conclusion is useful and applicable when you have a tremendous surge of ICU admissions in a short time, shortage of equipment, manpower (DRs & RNs), and patients with comorbidities. The authors capture a few hallmark comorbidities: hypoxic encephalopathy, abnormal Na & K, abnormal hepatic panel, a higher platelet:lymphocyte ratio, (an index of inflammatory process?). ROC & AUC is a tool for sensitivity/specificity index: AUC FOR APACHE II = 0.966, SOFA = 0.867, CURB65 = 0.844.

      May 7, 2020

      • An Italian programme for COVID-19 infection in multiple sclerosis
        Apr 30. Sormani. The Lancet Neurology.
        Opinion from SAB Member: Dr. Barry Perlman
        This article describes a program developed by the Italian MS Society, Italian MS Foundation, and MS Study Group of the Italian Neurological Society to help guide management of patients with multiple sclerosis during the COVID-19 pandemic. Case report forms were sent to >200 neurologists in Italy and data was collected on 232 patients with known or suspected COVID-19. 96% had mild infection. Of the 3% with critical infection, 1 recovered and 5 died. Further data collection is needed to determine if MS disease or treatment impacts COVID-19 infection.

      May 6, 2020

      May 5, 2020

      May 1, 2020

      • Correlation between Heart fatty acid binding protein and severe COVID-19: A case-control study. Apr 30. Yin. PLoS One.
        In patients who had measurements of heart fatty acid binding protein (HFABP), a serum cardiac specific biomarker for myocardial injury, the authors found a correlation between elevated HFABP and progression to severe COVID-19 illness. However only 46 of 245 patients had the test and the study had no control group. During hospitalization, severe illness was observed in 87.5% of HFABP positive patients vs. 40% in those who were HFABP negative (P = 0.002). We do not know why some patients had HFABP measured, making the results difficult to interpret.
      • COVID-19 Related Genes in Sputum Cells in Asthma: Relationship to Demographic Features and Corticosteroids
        Mar 27. Peters. American Journal of Respiratory and Critical Care Medicine.
        Opinion from C19SAB: Dr. Louis McNabb, Dr. Jay Przybylo
        LM: African Americans, males, and diabetics have increased expression of ACE2 and TMPRSS2 which might theoretically explain why these groups are at increased risk for COVID-19. Inhaled corticosteroids decreased expression of ACE2 and TMPRSS2 and theoretically might favorably modify the risk from COVID-19. JP: Thorough study demonstrating asthmatics taking inhaled corticosteroids might be at lower risk of significant COVID-19 infection via activity on the ACE2 receptor.
      • Obesity could shift severe COVID-19 disease to younger ages. Apr 30. Kass. The Lancet.
        A Lancet “Correspondence” from Johns Hopkins describing a negative correlation between age and BMI in 265 COVID-19 patients.
      • Patients with cancer appear more vulnerable to SARS-COV-2: a multi-center study during the COVID-19 outbreak
        Apr 29. Dai. Cancer Discovery.
        Opinion from C19SAB: Dr. J. Lance Lichtor
        Based on a retrospective analysis of patient information collected from 14 hospitals in Hubei Province, China, patients affected by the SARS-CoV-2 coronavirus for 105 hospitalized patients with cancer and 536 patients without cancer were compared. Patients with hematological cancer (1st), lung cancer (2nd), and cancers in metastatic stages demonstrated higher rates of severe events compared to patients without cancer. In addition, patients who underwent cancer surgery showed higher death rates and higher chances of having critical symptoms. In addition, patients on immunotherapy had the highest death rate and the most severe illness. It is expected that people with systemic disease should do less well. Unfortunately, the authors did not compare the two groups to hospitalized patients with cancer but without COVID-19.
      • Variation in COVID-19 Hospitalizations and Deaths Across New York City Boroughs. Apr 29. Wadhera. JAMA.
        New York City has emerged as the epicenter of the COVID-19 outbreak. New York City is composed of 5 boroughs (the Bronx, Brooklyn, Manhattan, Queens, and Staten Island), each with unique demographic, socioeconomic, and community characteristics. Prior analyses have shown health inequities across these boroughs. The author relied on available public records from the recent past (census, age, M: F, race / ethnicity, education level, annual average income, available hospital bed, etc.) & current death rate from Covid-19 for each borough. Graphs & table suggests – Bronx: highest hospitalization & death rate, black population, lowest education, poverty & lowest income population of all the boroughs of NYC.
        The author provides raw data for comparison. Author provided table numbers but failed to make any conclusion for important health policy answers. Assumption people did not travel to another borough? Surge capacity for each hospital was not taken in account. The study is ongoing?

      April 30, 2020

      April 29, 2020

      April 28, 2020

      April 24, 2020

      April 23, 2020

      • COVID-19 and African Americans. Apr 15. Ingraham. JAMA.
        A very important social/cultural aspect of the pandemic, with preliminary data clearly laid out by author. But this will not help front-line workers, and as the author states, what to make of the disparities is not clear: “Data fully adjusted for comorbidities have not been reported but it is likely that some, if not most, of these differences in disease rates and outcomes will be explained by concomitant comorbidities.”
        Blacks have disproportionately been victims of COVID-19. Evidence of potentially egregious health care disparities is now apparent. Persons who are African American or black are contracting SARS-CoV-2 at higher rates and are more likely to die. COVID-19 has become the herald event that now fully exposes the deep and chronic social wounds in US communities. The Johns Hopkins University and American Community Survey indicate that to date, of 131 predominantly black counties in the US, the infection rate is 137.5/100,000 and the death rate is 6.3/100,000.5. This infection rate is more than 3-fold higher than that in predominantly white counties. Moreover, this death rate for predominantly black counties is 6-fold higher than in predominantly white counties. Comorbidities (HBP, DM, Obesity……) and preventive measures may not be able to be practiced, health care access…author claims many unstated factors are playing out. Public health is complicated and social reengineering is complex, but change of this magnitude does not happen without a new resolve.
      • Is Adipose Tissue a Reservoir for Viral Spread, Immune Activation and Cytokine Amplification in COVID-19. Apr 22. Ryan. Obesity (Silver Spring).
        Obesity has been recognized as a risk factor for poor outcome with COVID-19 infection. The paper theorizes that adipose tissue may act as a reservoir for increased viral spread, immune activation, and cytokine amplification. Nice review of adipose tissue cytokine pathways. Areas of research are suggested.
      • Symptom Screening at Illness Onset of Health Care Personnel with SARS-CoV-2 Infection in King County, Washington. Apr 17. Chow. JAMA.
        Typical symptom screening for Covid-19 will miss 20 percent of health care workers with the virus. Perhaps more alarming is that health care personnel worked a median of two days with symptoms.

      April 21, 2020

      • Binding of SARS-CoV-2 and angiotensin-converting enzyme 2: clinical implications. Apr 18. Murray. Cardiovasc Res.
        Literature review, mostly on a molecular cell-biology level, of the RAAS system as it may interact with SARS-CoV-2. Nothing new, and the conclusion is to follow the guidelines of many organizations to continue ACEI and ARBs in patients already on such drugs.
      • Diabetic patients with COVID-19 infection are at higher risk of ICU admission and poor short-term outcome
        Apr 9. Roncona. Journal of Clinical Virology.
        Opinion from SAB Member: Dr. Jagdip Shah
        A detailed, retrospective meta-analysis from 3 centers in northern Italy. 9 articles were included, which notably included data from China. This meta-analysis demonstrated that diabetic patients with COVID-19 infection have a higher risk to be admitted to the ICU during the infection. Moreover, diabetes increased the risk of mortality during the infection. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in abstracting data and assessing validity. Quality assessment was performed using the Newcastle-Ottawa quality assessment scale. The main outcome was the risk of ICU admission in diabetic patients with COVID-19 infection while the second was the overall mortality risk in COVID-19 patients with diabetes. Data was pooled using the Mantel-Haenszel random effects models reporting odds ratio (OR) and 95% confidence interval (CI). Statistical heterogeneity between groups was measured using the Higgins I-squared statistic. Results: Among 1382 patients (mean age 51.5 years, 798 males), diabetes was the second most frequent comorbidity. Diabetic patients had a significantly increased risk of ICU admission (OR: 2.79, 95% CI 1.85–4.22, p < 0.0001, I-squared=46%). In 471 patients (mean age 56.6 years, 294 males) analyzed for the secondary outcome, diabetic subjects had higher mortality (OR 3.21, 95% CI 1.82–5.64, p < 0.0001, I-squared=16%).
      • Inflammatory bowel diseases and COVID-19: the invisible enemy. Apr 20. D’Amico. Gastroenterology.
        More of an opinion paper than anything, reviewing past literature on infections in IBD patients on immunosuppresives and biologics. Will not help those treating COVID-19 much.

      April 20, 2020

      April 17, 2020

      • Does COVID-19 Disprove the Obesity Paradox in ARDS? Apr 16. Jose RJ. Obesity (Silver Spring).
        A disporportionate number of non-survivors of COVID-19 patients are obese. The authors postulate that factors may include a chronic pro-inflammatory status, difficult airway, pulmonary elastance, compliance, potential pulmonary hypertansion and RV function may be contributing factors.
      • Prediction models for diagnosis and prognosis of covid-19 infection: systematic review and critical appraisal. Apr 7. Wynants, L. BMJ.
        A review and appraisal of 27 prediction model studies for diagnosis, prognosis, and risk of hospital admission due to COVID-19. Age, temperature, and signs/symptoms were the most reported predictors of suspected disease. Age, sex, CT, CRP, LDH, and lymphocyte count predicted severe prognosis. However, all studies had high risk of bias due to reporting and methodology flaws, such as small sample sizes, non-representative control patients, exclusion of those who had not reached the clinical event of interest by the conclusion of the study, and model overfitting. The authors warn against using prediction models based on questionable data, and recommend that better and more standardized data collection and reporting methodologies are needed to determine the predictors that could be used to guide clinical decisions during the COVID-19 pandemic.

      April 14, 2020

      April 13, 2020

      • Covid-19: death rate is 0.66% and increases with age, study estimates. Apr 4. Mahase. BMJ.
        Based on aggregate data on cases and deaths in mainland China, the overall death rate from covid-19 was estimated at 0.66%, rising sharply to 7.8% in people aged over 80 and declining to 0.0016% in children aged 9 and under. They estimated that nearly one in five people over 80 infected with covid-19 would probably require hospital admission, compared with around 1% of people under 30. They also estimated that the average time between a person displaying symptoms and dying was 17.8 days, while recovering from the disease was estimated to take slightly longer, with patients being discharged from hospital after an average of 22.6 days. Estimated case fatality ratio for symptomatic patients in China was 1.38% (1.23% to 1.53%). For all infected patients, the ratio was. 0.66% (0.39% to 1.33%). Data on underlying health conditions was not available.

      April 11, 2020

      • Covid-19: death rate is 0.66% and increases with age, study estimates. Apr 1. Mahase. BMJ.
        Based on aggregate data on cases and deaths in mainland China, the overall death rate from covid-19 was estimated at 0.66%, rising sharply to 7.8% in people aged over 80 and declining to 0.0016% in children aged 9 and under. They estimated that nearly one in five people over 80 infected with covid-19 would probably require hospital admission, compared with around 1% of people under 30. They also estimated that the average time between a person displaying symptoms and dying was 17.8 days, while recovering from the disease was estimated to take slightly longer, with patients being discharged from hospital after an average of 22.6 days. Estimated case fatality ratio for symptomatic patients in China was 1.38% (1.23% to 1.53%). For all infected patients, the ratio was. 0.66% (0.39% to 1.33%). Data on underlying health conditions was not available.
      • Factors associated with prolonged viral RNA shedding in patients with COVID-19. Apr 10. Xu. Clin Infect Dis.
        Prolonged viral RNA shedding associated with male sex, treatment with steroids, and worse illness. Two-thirds of patients had prolonged viral RNA shedding (>15 days). RT-PCR testing, and not viral cultures were the tests used. This is a paper that could be combined with other PCR/culture papers in the future, to help clinicians.
      • Prediction for Progression Risk in Patients with COVID-19 Pneumonia: the CALL Score Apr 9. Ji. Clinical Infectious Diseases.
        Opinion from SAB Member: Dr. Jack Lance Lichtor
        The authors, based on a retrospective analysis of 208 COVID-19 patients who were admitted to 1 of 2 hospitals in the Fuyang province in China, developed a score based on multivariate COX analysis. There was a stable group and the progressive group. These factors were found to be significant: age, comorbidity, lymphocyte count, D-dimer, and LDH. The nomogram demonstrated good accuracy in estimating the risk of progression of illness. The diagnosis of COVID-19 was based on real-time reverse-transcriptase polymerase chain reaction. The score may help to decide where to put patients with the disease: either at a district hospital or a tertiary center. A prospective study is needed to confirm.

      April 9, 2020

      April 8, 2020

      April 7, 2020

      April 2, 2020

      March 31, 2020

      March 30, 2020

      February 13, 2020

    1. Emerging Clinical Data and Guidelines (USA / International)
      August 30, 2021
      • An outbreak caused by the SARS-CoV-2 Delta variant (B.1.617.2) in a secondary care hospital in Finland, May 2021. 7/29/21. Hetemäki I. Eurosurveillance.
        Authors describe a Delta variant outbreak that originated from one inpatient. It spread within the hospital and to three primary care facilities. Fifty-eight patients and 45 healthcare workers became infected; 18 elderly patients admitted with other conditions died following infection. Among infected individuals, 19% were fully vaccinated, 47% had 1 dose and 34% were unvaccinated. Over 90% of vaccinations were with BioNTech-Pfizer vaccine. Both symptomatic and asymptomatic infections were found among vaccinated healthcare workers, and secondary transmission occurred from patients with symptomatic infections despite use of PPE. Presymptomatic and asymptomatic individuals also infected others. Authors recommend FFP2/3 respirators (~N95 or higher grade) while treating COVID-19 patients.
        SAB Comment: The above report, based upon careful contact tracing, highlights the value of universal masking with respirators of FFP2 of N95-level or greater when caring for COVID-19 patients.

      August 16, 2021

      • SAB Comment: The following two studies on vaccine-induced immune thrombocytopenia (VITT) provide two different views of a complex therapeutic question that remains unresolved. What is the appropriate dose (therapeutic versus prophylactic) and timing of anticoagulant therapy in the treatment of COVID-19 and what is the incidence of VITT in the general population stratified by age and sex following vaccination?
        • Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis. 8/11/21. Pavord S. N Engl J Med.
          A study of 294 patients presenting to UK hospitals (03/22-06/06 2021) found incidence of vaccine-induced immune thrombocytopenia and thrombosis (VITT) following ChAdOx1 nCoV-19 (AstraZeneca) vaccination among individuals younger than 50 years at least 1:50,000 which is consistent with previous reports. The study details diagnosis, patient demographics and common timeline for vaccination to symptomatology. Useful tables detail definition criteria (definite, probable, possible, unlikely) and clinicopathological findings. Age stratification notes incidence in older than 60 years at least 1/100,000. The authors conclude “The high mortality associated with VITT was highest among patients with a low platelet count and intracranial hemorrhage. Treatment remains uncertain, but identification of prognostic markers may help guide effective management.”
        • Cerebral venous thrombosis after vaccination against COVID-19 in the UK: a multicentre cohort study. 8/9/21. Perry RJ. Lancet.
          Investigators studied 95 patients from 43 UK hospitals with image-confirmed cerebral venous thrombosis following vaccination for COVID-19 looking for vaccine-induced immune thrombotic thrombocytopenia (VITT), which was defined as acute thrombosis accompanied by D-dimer greater than 2,000 along with a minimum platelet count less than 150,000. Seventy-six (80%) of 95 patients were investigated for anti-PF4 antibodies, a reliable marker for VITT. Seventy in 96 had VITT, all following AstraZeneca vaccine. Of 26 without VITT, 21 had received AstraZeneca vaccines, and four had received Pfizer vaccines. VITT patients were younger (mean 47 vs. 57), more likely to have multiple venous thromboses (14% vs. 0) or hemorrhages (33% vs. 14%), and more disabled at discharge compared with non-VITT patients. Mortality was 29% in the VITT cohort vs. 4% in the non-VITT cohort. One non-VITT patient had serious extra-cerebral thrombosis. Non-heparin anticoagulant and intravenous immunoglobulin treatments were associated with an improved outcome. Diagnosis criteria are proposed.
      • Persistent Endotheliopathy in the Pathogenesis of Long COVID Syndrome. 8/10/21. Fogarty H. J Thromb Haemost.
        Findings of pulmonary endotheliopathy and microvascular immunothrombosis have been highlighted in autopsies in acute COVID, but their contributions to Long-COVID are unknown. Long-COVID patients (n=50, age 50 + 17 years, medium post-COVID =68 days) showed that prothrombic markers (endogenous thrombin potential, peak thrombin, etc.) and endothelial activation markers (VWF:Ag, Factor VIII, etc.) and plasma soluble thrombomodulin were significantly elevated vs. controls (nonhospitalized asymptomatic, n=17, mean age 47 ± 12 years), especially in elderly, hospitalized and patients with co-morbidities. Typical acute phase markers (e.g., CRP, neutrophil counts, IL-6) were normal. Endotheliopathy assays (e.g., VWF) correlated inversely with the 6-Minute Walk Test.

      August 9, 2021

      July 9, 2021

      • Age and Acute Ischemic Stroke Outcome in North American Patients With COVID-19. 7/5/2021. Dmytriw AA. J Am Heart Assoc.
        This is a detailed prospective database analysis of 126 patients with COVID-19 who suffered acute ischemic strokes (AIS) and were treated at 19 stroke centers in the US and Canada between March and September 2020. The study looked at 3 separate age groups and corroborates earlier observations of better outcomes and lower rates of mortality among patients under 55 years of age with AIS and COVID-19 and adds the observation of a higher incidence of large vessel occlusion in this cohort. In addition, using multivariable binary logistic regression models, the study finds that the risk of poor outcomes, including death, increases with every year of age.
      • Risk factors for long covid in previously hospitalised children using the ISARIC Global follow-up protocol: A prospective cohort study. 7/2/21. Osmanov IM. Eur Respir J.
        This is a study of 518 COVID-19 infected children admitted to a pediatric hospital in Moscow and followed for 5-12 months — the largest follow-up pediatric study to date. Parents were interviewed using an internationally designed and accepted protocol. Average age was 10.4 years (<1-18 years range) and near equal distribution between sexes. Long COVID was found in 24.3% of children. Fatigue and sleep disturbance were the most common complaints followed by loss of smell. Symptoms declined over time. Risk factors for persistent symptoms were patients older than 6 years old and a history of allergic disease. Psycho-social issues were uncommon and no deaths were reported.

      June 28, 2021

      • Underlying Medical Conditions Associated With Severe COVID-19 Illness Among Children. 6/7/21. Kompaniyets L. JAMA Netw Open.
        A data rich CDC review studying 43,465 children 18 years old and younger hospitalized with COVID-19 infection through January 2021. After a complete description on data retrieval and analysis, results revealed children with diabetes, obesity and those with cardiac anomalies were more commonly hospitalized than previously healthy children. Overall children with any chronic disease were hospitalized 3 times more frequently. Asthma was a risk for severe infection. Children younger than 2 years old and born prematurely were prone to hospitalization. Finally, Hispanic and Black children suffered severe infection more frequently than Whites.

      June 14, 2021

      • Hospitalization of Adolescents Aged 12-17 Years with Laboratory-Confirmed COVID-19 – COVID-NET, 14 States, March 1, 2020-April 24, 2021. 6/10/21. Havers FP. MMWR Morb Mortal Wkly Rep.
        In the US, “Most COVID-19-associated hospitalizations occur in adults, but severe disease occurs in all age groups, including adolescents aged 12–17 years. COVID-19 adolescent hospitalization rates from COVID-NET peaked at 2.1 per 100,000 in early January 2021, declined to 0.6 in mid-March, and rose to 1.3 in April. Among hospitalized adolescents, nearly one third required intensive care unit admission, and 5% required invasive mechanical ventilation; no associated deaths occurred. Recent increased hospitalization rates in spring 2021 and potential for severe disease reinforce the importance of continued COVID-19 prevention measures, including vaccination and correct and consistent mask wearing among persons not fully vaccinated or when required.” –MMWR Summary
      • Rehabilitation post-COVID-19: cross-sectional observations using the Stanford Hall remote assessment tool. 5/27/21. O’Sullivan O. BMJ Mil Health.
        These authors report the development and use (April to Nov 2020) of a video teleconferencing tool to evaluate rehabilitation needs for patients with ongoing post-COVID-19 symptoms and included patients with COVID syndromes who never had a confirmatory COVID-19 viral test. They found that the initial severity of symptoms did not predict the level of ongoing disability. They conclude that post-COVID-19 symptoms should be considered in all patients, regardless of the acute illness severity and whether they have had laboratory confirmation. They find that a significant proportion of patients require assessment and management, with symptoms such as shortness of breath, fatigue, and mood disorders impacting activities of daily living and return to work.

      May 24, 2021

      May 7, 2021

      • Association of Maternal SARS-CoV-2 Infection in Pregnancy With Neonatal Outcomes. 4/29/21. Norman M. JAMA.
        To determine the outcome in newborn infants of mothers testing positive for SARS-CoV-2 in pregnancy, this prospective cohort study looked at the outcomes of 88,159 infants born in Sweden during the first 10 months of the pandemic. After matching infants by maternal characteristics, the 2,323 infants of SARS-CoV-2-positive mothers were found to have more respiratory problems (2.8% vs 2.0%, OR 1.42), mostly explained by a more preterm birth. Mortality, breastfeeding rates at discharge, length of stay in neonatal care, hypoxic-ischemic encephalopathy, meconium aspiration, pneumonia, sepsis, and hypoglycemia did not differ significantly between the two groups. Twenty-one (0.9%) of the 2,323 infants of SARS-CoV-2-positive mothers had positive PCR tests, most with no morbidity and none with pneumonia. View a pertinent accompanying editorial here.

      April 2, 2021

      • ABCDEF Bundle and Supportive ICU Practices for Patients With Coronavirus Disease 2019 Infection: An International Point Prevalence Study. 3/31/21. Liu K. Crit Care Explor.
        This is an international, 2-day (June 3 and July 1) survey on the compliance of nutrition, sleep hours and ABCDEF Bundles for 262 COVID-19 patients in 212 ICUs. The authors reported that 47.3% of patients were on mechanical ventilation and 4.6% were on ECMO. Each element of the ABCDEF Bundle was implemented at alarmingly low percentages (16% to 52% compliance), while nutritionally recommended protein was provided to only 50% of ICU patients. Because these supportive measures are known to prevent ICU patients from developing the physical, cognitive and mental disabilities of post-intensive care syndrome, authors strongly suggest that efforts be made to adhere to all evidence-based gold standards of the ABCDEF Bundles including protein supplements and avoiding sleep deprivation in ICU patients.
      • Post-covid syndrome in individuals admitted to hospital with covid-19: retrospective cohort study. 4/1/21. Ayoubkhani D. BMJ.
        This is a study of post-COVID syndrome in 47,000+ hospitalized COVID-19 patients individually matched to United Kingdom NHS controls. Patients were discharged by 8/31/2020 and followed for a mean of 140 days, with the study ending on 9/30/2020. The readmission rate was 29% (3.5 times that of controls), and mortality was 12% (7.7 times that of controls). New respiratory disease was 27% more frequent than controls. The risk of diabetes increased 1.5 times, and that of a major cardiovascular event by three times. Younger and ethnic minority patients had greater relative risk than those over age 70. There is an accompanying editorial expressing a need for adjustment of the NHS patient follow-up practices.

      March 26, 2021

      • Predictors of clinical deterioration in patients with suspected COVID-19 managed in a ‘virtual hospital’ setting: a cohort study. 3/24/21. Francis NA. BMJ Open.
        The authors actively followed up on 900 UK COVID-19 patients to determine rates of overnight hospitalization or death over a median period of 21 days from outpatient diagnosis (n=455) or hospital discharge (n=445). 76 patients (8.4%) experienced clinical deterioration. 15 previously hospitalized patients and 3 never-hospitalized patients died, and 58 others required COVID-related hospitalization. Of 35 clinical and laboratory features examined, including O2 saturation, the only predictors of clinical deterioration were increased age (OR 1.04 per year of age), severe renal insufficiency (OR 9.1 for eGFR <30), a history of cancer (OR 2.9), or mental health problems (OR 1.76).

      March 15, 2021

      • Attributes and predictors of long COVID. 3/11/21. Sudre CH. Nat Med.
        This letter addresses cases of so-called “long COVID” that are rising. These authors examine prevalence and early predictive risk factors. Starting when they were pre-symptomatic, individuals prospectively self-reported symptoms between 3/2020-9/2020 using the COVID Symptom Study app. In 558/4,182 (13.3%) incident cases, symptoms lasted ≥4 weeks; 189 (4.5%) for ≥8 weeks and 95 (2.3%) for ≥12 weeks. Symptoms of fatigue, headache, dyspnea and anosmia increased with age, BMI and female sex. Experiencing >5 symptoms in week 1 predicted long COVID (odds ratio = 3.53 (2.76–4.50)). A simple model identifies at-risk individuals with early symptom patterns for trials of prevention or treatment and plan education and rehabilitation.
      • Body Mass Index and Risk for COVID-19-Related Hospitalization, Intensive Care Unit Admission, Invasive Mechanical Ventilation, and Death – United States, March-December 2020. 3/11/2021. Kompaniyets L. MMWR Morb Mortal Wkly Rep.
        From March-December 2020, the authors evaluated the association between body mass index (BMI) and risk for severe COVID-19 outcomes in 148,494 adults who were diagnosed with COVID-19 during an emergency department or inpatient visit at 238 US hospitals. Of those patients, 28.3% were overweight and 50.8% were obese. Authors conclude that being overweight and obesity are risk factors for hospitalization, ICU admission, and death among patients aged ≥65 years. There was a downslope for death in patients with BMIs of  23.7 to 25.9; an upswing was similar for patients with a median age of 55 years at the dynamic point. The authors discuss the clinical and public health implications of higher BMI, the need for COVID-19 illness management, vaccine prioritization and policies to increase access to nutrition and physical activities to help address the increases in obesity severity.

      March 12, 2021

      • Association between ABO blood types and coronavirus disease 2019 (COVID-19), genetic associations, and underlying molecular mechanisms: a literature review of 23 studies. 3/9/21. Zhang Y. Ann Hematol.
        International reports generally agree that blood type O is a protective factor. Most, but not all, report that the blood type conferring greatest risk for infection is A. One of the largest retrospective cohort studies indicated risk ratios for infection of 0.87, 1.09, 1.06, and 1.15 for O, A, B, and AB individuals, respectively. Although some report no correlation between blood type and COVID-19 severity or mortality, most studies found that types A and AB had higher risk of severe illness or death, while type O was protective against severe outcomes or death. Potential molecular mechanisms are discussed.
      • Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort study. 3/10/21. Challen R. BMJ.
        The authors gauged the mortality and future healthcare needs resulting from the new COVID-19 infection variant, B.1.1.7 (VOC-202012/1, from southeast UK in late 2020). The absence of the S gene was found to be a proxy for the B.1.1.7 variant. Patients with this variant were matched for age, sex, ethnicity, and region, with patients with the prior common variants to produce 54,906 pairs. The mortality hazard ratio associated with infection with VOC-202012/1 compared with infection with previously circulating variants was 1.64 in patients who tested positive for COVID-19 in the community. In this comparatively low-risk group, this represents an increase in deaths from 2.5 to 4.1 per 1,000 detected cases.
      • Timing of surgery following SARS-CoV-2 infection: an international prospective cohort study. 3/10/21. COVIDSurg Collaborative. Anaesthesia.
        This prospective cohort study included 140,000 patients undergoing surgery in 1647 hospitals in 116 countries during October 2020. Thirty-one hundred twenty-seven patients with SARS-CoV-2 diagnosed, 0-2, 3-4, 5-6, and >7 weeks prior to surgery were compared with those without SARS-CoV-2. Mortality was increased in all SARS-CoV-2 groups except the >7-week group, as were pulmonary complications. Patients with symptoms lasting >7 weeks also had increased mortality. Mortality in all patients from 0-6 weeks was increased from 1.5% up to 4%. Even asymptomatic patients in the 0-6 week group had increased mortality. Deferring elective surgery for seven weeks, and even longer in the presence of ongoing symptoms is recommended. The report explains statistical methods and includes many graphs.

      March 10, 2021

      • Neurological outcome and quality of life three months after COVID-19: a prospective observational cohort study. 3/8/21. Rass V. Eur J Neurol.
        This prospective, multicenter, observational study (n=135) includes patients from 3 categories of disease: severe (n=32 in ICU), moderate (n=72 in COVID-19 ward) and mild (n=31 outpatient). The authors conducted a detailed and systemic evaluation for neurological, psychological, and functional outcomes with a battery of tests at 3 months post COVID-19 infection. The article notes an alarming frequency of central and peripheral nervous systems and functional long-term issues. New onset of neurological disease was found in 20 patients while 82 patients showed neurological signs and symptoms on follow-up. There were disturbing numbers of quality of life, cognitive and functional outcome as well. The majority of those numbers came from ICU patients.

      March 3, 2021

      February 26, 2021

      February 8, 2021

      February 1, 2021

      January 27, 2021

      • Development and validation of the ISARIC 4C Deterioration model for adults hospitalised with COVID-19: a prospective cohort study. 1/11/21. Gupta R. Lancet Resp Med.
        ISARIC4C is a global initiative with the purpose of preventing illness and death from infectious disease outbreaks. This article presents information on development and validation of a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or death) among consecutively hospitalized adults with suspected or confirmed COVID-19 prospectively recruited to ISARIC4C study across 260 hospitals in England, Scotland, and Wales. The authors contend that the 4C Deterioration model, designed to be used on admission, has strong potential for clinical utility and generalizability to predict clinical deterioration and inform decision-making among adults hospitalized with COVID-19. The Mortality and Deterioration calculator can be accessed with the following link: isaric4c.net/risk/.
        SAB Comment: While the SAB does not endorse management strategies or interventions, its members believe this manuscript and accompanying calculator to evaluate risk of disease progression or death MAY be useful in supplementing case management decisions.
      • Improving clinical management of COVID-19: the role of prediction models. 1/11/21. Wynants L. Lancet Resp Med.
        This is an editorial indicating that the main clinical advantage of the ISARIC4C predictive model is that required patient specific data is available from daily routine care and may help inform stratification of patients on the basis of clinical severity. In combination, the 4C Deterioration and Mortality models could be utilized in creating an evidence-based clinical pathway for patients with COVID-19. Validated predictive models may improve clinical management and resource utilization.

      January 25, 2021

      • Neutralizing antibody titres in SARS-CoV-2 infections. 1/4/21. Lau E. Nature Communications.
        SARS-CoV-2 infection elicits effective neutralizing antibody titers in most individuals. Using plaque reduction neutralization (PRNT) assays, a “gold-standard,” kinetics of virus neutralizing antibody responses were examined from a cohort of 195 infections collected days 0 to 209 after symptom onset. Of 115 sera collected ≥61 days after onset of illness tested, 99.1% remained seropositive for both 90% (PRNT90) and 50% (PRNT50) neutralization endpoints. Investigators estimated it takes at least 372, 416 and 133 days for PRNT50 titers to drop to the detection limit for severe, mild, and asymptomatic patients, respectively. Results were uninfluenced by age or corticosteroid use.

      January 6, 2021

      • Variation in US Hospital Mortality Rates for Patients Admitted With COVID-19 During the First 6 Months of the Pandemic. 12/22/20. Asch DA. JAMA Intern Med.
        This cohort study from a US-managed health company evaluated outcomes for 38,517 adults with COVID-19 admitted to 955 US hospitals during two time periods (January to April and May to June). The primary outcome was the hospitals’ risk-standardized event rate (RSER) of 30-day in-hospital mortality or referral to hospice, adjusted for patient-level characteristics. RSERs declined from 16.6% to 9.3%. Individual hospitals did better when the prevalence of COVID-19 in their surrounding communities was lower. The article speculates on possible causes for this improvement, including fewer overwhelmed hospitals, improved knowledge and medical care, and possibly smaller infective inoculums as mask-wearing became more common.

      December 18, 2020

      • Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations. 12/8/20. Diorio C. Blood Adv.
        This study, designed for researchers, examined 50 COVID-19 pediatric hospitalized patients for soluble C5b9 and thrombotic microangiopathy. C5b9 were found to correlate with the severity of disease and serum creatinine. Thrombotic microangiopathy was found in 17 of the 19 patients examined. These data help characterize COVID-19 disease in the pediatric population and help form the building blocks for further study.
      • On the whereabouts of SARS-CoV-2 in the human body: A systematic review. 10/30/20. Trypsteen W. PLOS Pathogens.
        This article is a well-presented review of available literature through June 2020. The strength of this paper resides in its focus on viral presence and evidence of replication and infectivity in different organ systems. It acknowledges the fact that the presence of an ACE2 receptor does not control viral cell entry per se. It concludes that while we have a good understanding of the presence and replication mechanisms in the respiratory system, a full understanding of the underlying mechanism of organ toxicity – direct viral, micro-vascular or inflammatory – in other systems (heart, kidney, CNS) remains inconclusive.

      December 11, 2020

      • Characteristics of Adults aged 18-49 Years without Underlying Conditions Hospitalized with Laboratory-Confirmed COVID-19 in the United States, COVID-NET – March-August 2020. 12/3/20. Owusu D. Clin Infect Dis.
        This article describes a Center for Disease Control-funded, cross-country study of non-pregnant adults younger than 50 years old providing the causes of hospital admissions due to COVID-19. While fever was a common presenting symptom, the illness primarily affected the pulmonary system. 22% were admitted to ICU although death occurred in <1%. 74% of patients were male and authors discuss the possibility of genetics linked to ACE2 receptor as a cause of infection severity.
        Of note, 42% of patients were Hispanic/Latino; treatment was not controlled; obesity and the use of steroids were not reported; 20% of patients were healthy prior to infection; 12% received remdesivir.
      • Pulmonary embolism in COVID-19 patients: Prevalence, predictors and clinical outcome. 12/3/20. Scudiero F. Thromb Res.
        This retrospective database study from 7 Italian hospitals looked over the echocardiogram results of 224 patients with COVID-19 of whom 14% had PE confirmed by CTA. The purpose was to identify which echocardiographic findings best predict pulmonary embolism. PE patients were hospitalized a longer time after symptom onset, showed higher D-dimer level and a higher prevalence of myocardial injury. At multivariable analysis, tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary arterial pressure were the only parameters independently associated with PE. Mortality rates (50% vs 27%; p = 0.010) and cardiogenic shock (37% vs 14%; p = 0.001) were significantly higher in PE patients.
      • The ADAMTS13-von Willebrand factor axis in COVID-19 patients. 11/23/20. Mancini I. J Thromb Haemost.
        This study examines the VWF antigen to ADAMTS13 activity ratio in 50 COVID-19 hospitalized patients and demonstrates that this ratio was strongly associated with COVID-19 severity. Three groups of patients were studied, namely those receiving nasal oxygen, CPAP treatment, or intubation with ventilatory support. The authors suggest that these data represent potential new markers of disease severity and further support the concept of micro thrombogenesis in patients with severe COVID-19.
        SAB Comment: This is new scientific information to help understand pathophysiology of micro thrombosis but routine ADAMTS13 testing isn’t recommended.

      December 7, 2020

      • Loneliness, Mental Health, and Substance Use among US Young Adults during COVID-19. 10/28/20. Horigian VE. J Psychoactive Drugs.
        Frequently discussed in mass media, this paper presents the psychologic issues associated with the COVID-19 pandemic. In addition, intensivists and anesthesiologists should be aware of possible alcohol and drug use intended by the patient to relieve depression associated with this illness and its treatment.
      • Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. 11/30/20. Meinhardt J. Nature Neurosci.
        Viral penetrance of the CNS is likely through diverse routes. These investigators demonstrate in 33 autopsies morphological changes associated with SARS-CoV-2 neurotropism, such as thromboembolic ischemic infarction of the CNS and the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. By exploiting the proximity of olfactory mucosal, endothelial and nervous tissue, including olfactory and sensory nerve endings, virus can cross into the olfactory CNS. Subsequently, SARS-CoV-2 appears to penetrate other areas of the CNS, including the primary respiratory and cardiovascular control centers in the medulla oblongata.
      • Tissue-specific Immunopathology in Fatal COVID-19. 11/20/20. Dorward DA. Am J Respir Crit Care Med.
        In eleven post-mortems these authors investigated whether inflammation is primarily a direct reaction to SARS-CoV-2 or an independent organ-specific immunopathologic reaction. Using multiplex PCR and in situ viral spike protein detection, SARS-CoV-2 organotropism was mapped. Multiple virus-independent aberrant immune responses mostly in lungs and reticuloendothelial system were found. These viral-independent immunopathologic features included monocyte/myeloid-rich pulmonary artery vasculitis, pulmonary parenchymal expansion of monocytes/macrophage-lineages and in the reticuloendothelial system, iron-laden macrophages and plasma cell responses. They concluded that a disconnect between viral presence and inflammation implicates immunopathology as a primary mechanism of organ injury in severe COVID-19.

      December 4, 2020

      • Assessment of 135,794 Pediatric Patients Tested for Severe Acute Respiratory Syndrome Coronavirus 2 Across the United States. 11/23/20. Bailey LC. JAMA Pediatr.
        This is an epidemiologic, retrospective study of 135,794 patients younger than 25 years old tested for SARS-CoV-2 during the first 9 months of 2020 — 3% of the nation’s 2.5 million children — in a country-wide study of a consortium of children’s hospitals admissions. An overall low positive COVID-19 rate of 4% was found. Black, Hispanic and Asian youth were underrepresented yet produced higher positive results. Of the 5374 children testing positive, only 359 were hospitalized and 8 died. Six of the deaths had complex preexisting comorbidities.
        Preexisting respiratory and cardiac morbidity was not a significant issue in those hospitalized. Endocrine, metabolic and malignancy-associated illnesses were linked to hospitalizations from COVID-19. Obesity was not defined.
      • Dosing of thromboprophylaxis and mortality in critically ill COVID-19 patients. 11/23/20. Jonmarker S. Crit Care.
        This is a retrospective analysis for 2 ICUs in Stockholm. In March, patients received low-dose LMWH and in April, all got medium- or high-doses. The baseline characteristics for these 152 COVID-19 patients were similar. For patients who received high-dose prophylaxis, 28-day mortality was lower (13.5%) compared to those who received medium dose (25.0%) or low-dose (38.8%), p = 0.02. Hazard ratio was 0.33 among those who received high-dose prophylaxis. There were fewer thromboembolic events in the high- (2.7%) vs medium- (18.8%) and low-dose thromboprophylaxis (17.9%) groups, p = 0.04. Bleeding rates were similar.

      December 2, 2020

      • Comprehensive health assessment three months after recovery from acute COVID-19. 11/21/20. van den Borst B. Clin Infect Dis.
        This is a well-performed and conducted study on 124 mild (not admitted), moderate and severe (ICU survivors) COVID-19-positive patients at 3-month follow-up. The comprehensive (anthropometric, psycho-social, exercise tolerance, frailty, social coping, PTSD, etc.) study indicates that significant abnormalities persisted in majority of patients irrespective of initial illness severity. Improvement in lung radiography was present in severe cases, but pulmonary function remained mildly depressed including decreasing pulse oximetry on 6-minute walk test. The conclusion is that COVID-19, as previously noted, presents long-term health care challenges including physical, psychological, neurologic and quality of life which could lead to significant future personal and societal health care burden.

      November 30, 2020

      • Delirium in Older Patients With COVID-19 Presenting to the Emergency Department. 11/19/20. Kennedy M. JAMA Netw Open.
        Delirium at presentation occurred in 28% of patients older than 65 years presenting to 7 US Emergency Departments. In this retrospective chart review, a total of 817 patients (mean age 78) with COVID-19 were analyzed and 16% presented with delirium as a primary symptom. Associated conditions and multivariant risk factors were identified, and impaired consciousness was listed as the predominant symptom occurring in 54% of patients with a delirium diagnosis. Delirium as a leading symptom is frequently underreported but associated with adverse outcomes and hence an important marker for poor patient outcomes (ICU stay, intubation and hospital death).

      November 23, 2020

      • Immune suppression in the early stage of COVID-19 disease. 11/18/20. Tian W. Nat Commun.
        Using elegant quantitative advanced mass spectrometry proteomics and integrated data analysis with hierarchical clustering and functional correlational network strategies, these authors analyzed urine samples from COVID-19 (n=14), non-COVID-19 pneumonia cases (n=13) and healthy donors (n=10). A total of 5991 proteins were identified; 1986 proteins were significantly changed in the COVID-19 vs the other groups. More than 10 pathways significantly changed and 10x were more down-regulated than up-regulated. Showing heatmaps and protein interaction diagrams, the molecular signatures suggested a two-stage pathogenesis: immunosuppression and tight junction/cell-cell adhesion impairments early on and an activated immune response in late stages of severe COVID-19 pneumonia.
      • Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial. 11/15/20. Monk PD. Lancet Respir Med.
        A small company-sponsored pilot study comparing the clinical course of 48 patients treated for 14 days with a daily dose of nebulized interferon beta-1a to the clinical course of 50 placebo-treated patients as assessed by 9-point WHO Ordinal Scale for Clinical Improvement [OSCI]. Patients receiving the medication had greater odds of improvement on the OSCI scale (odds ratio 2.32) and a higher percentage of recovered patients (58% vs 35%) at the end of the observation period (day 28). The medication was well tolerated compared with placebo. Larger studies are planned. These results contrast with the absence of effect noted in a prior trial of interferon beta-1a given subcutaneously.

      November 18, 2020

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

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

      November 16, 2020

      • Association between red blood cell distribution width and mortality of COVID-19 patients. 11/7/2020. Lorente L. Anaesth Crit Care Pain Med.
        Red blood cell distribution width (RDW), a parameter of RBC form and size variability, is associated with increased mortality in a number of disease states. This prospective observational study from 8 Canary Islands ICUs analyzed data from 118 survivors and 25 deaths with COVID-19. RDW performed comparably to APACHE II and SOFA scores in predicting mortality and is easier to measure. Levels were higher on admission to ICU and when >13% predicted mortality. RBC transfusion, hemoglobin disorders, and myelodysplastic syndromes increase RDW values.
      • Frequency of venous thromboembolism in 6513 patients with COVID-19: a retrospective study. 11/2/20. Hill JB. Blood Adv.
        This single health-system venous thromboembolism (VTE) study described the use of standard heparin or LMWH prophylaxis in most of the 6513 COVID-19 patients. Dose was increased if BMI >40 and decreased if creatinine clearance < 30. Ninety-day VTE rate was 2.2% (n=86) when receiving prophylaxis vs. 11% without. Eighty-four of 86 VTE patients had received prophylaxis. PADUA Score was high in 89%. Including arterial thrombosis in 7 patients, the overall incidence of VTE was 3.1% and 7.2% if mechanically ventilated. Fifty percent inpatient VTEs met the definition of prophylaxis failure. Only three of 2075 hospitalized patients (0.14%) without VTE surviving to discharge had VTE after discharge. The authors conclude these data support a traditional approach to VTE prophylaxis both during and following hospitalization.
        SAB Comment: We note a surprisingly low rate of VTE in this large, retrospective study, equally divided between DVT and PE. It did not include thrombosis in the microcirculation or ECMO circuit. Most were failures or breakthroughs on VTE prophylaxis. One may question the use of so few risk factors for modification of standard dosing and the conclusion that the data support a traditional approach.

      November 11, 2020

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

      November 9, 2020

      • Decision-making around admission to intensive care in the UK pre-COVID-19: a multicentre ethnographic study. 11/3/2020. Griffiths F. Anaesthesia.
        As triage of ICU beds during COVID-19 becomes a topic of concern, this multicenter ethnographic study conducted between June 2015 and May 2016 in six UK NHS hospitals attempts to explore the decision-making process applied to ICU admissions through observations, interviews and retrospective analysis outside the pandemic. Fifty-five decision events were observed and analyzed and 44 physicians, varying in training and specialty, were interviewed. Results are reported in multiple vignettes and the heuristic nature of the decision-making process is reviewed. Suggestions for improving transparency, consistency and equity of decision‐making around ICU admission are offered.

      October 30, 2020

      October 28, 2020

      • Aspergillosis Complicating Severe Coronavirus Disease. 10/21/20. Marr KA. Emerg Infect Dis.
        Mounting evidence suggests that severe respiratory virus infections, especially influenza and coronavirus 2 infections, can be complicated by Aspergillus airway overgrowth with pulmonary infection characterized by mixed airway inflammation and bronchial invasion. This article reviews these issues succinctly and adds data on 20 COVID-19 patients to the growing world literature. The authors note that the syndromes of pulmonary aspergillosis complicating severe viral infections are distinct from classic invasive aspergillosis. They state that combined with severe viral infection, aspergillosis in COVID-19 pneumonia comprises a constellation of airway-invasive and angio-invasive disease and see an urgent need for strategies to improve diagnosis, prevention, and therapy.
        SAB comment: An article previously highlighted in the Newsletter clarifies some of the important issues specific to diagnosing and treating pulmonary aspergillosis in COVID-19 patients.

      October 19, 2020

      October 14, 2020

      • In-hospital cardiac arrest in critically ill patients with covid-19: multicenter cohort study. 9/30/20. Hayek S. BMJ.
        This article discusses a multicenter (68 sites) US study which followed 5019 admitted COVID-19 patients, 701 (14%) of whom had in-hospital cardiac arrest. The influence of patient demographics, co-morbidities and critical care facilities on outcome are also described. Patients younger than 45 years were more likely to receive CPR with 21.2% (11/52) surviving to hospital discharge with normal or mild neurocognitive deficit compared to 2.9% in patients 80 years or older. The article confirms generally poor results of CPR in COVID-19 but provides interesting discrimination between age, ICU size and co-morbidities. It raises key questions regarding triage and informed assent discussions.

      October 12, 2020

      October 7, 2020

      • Clinical Outcomes of In-Hospital Cardiac Arrest in COVID-19. 9/28/20. Thapa S. JAMA Int Med.
        This research letter reports single-center results of CPR in 60 COVID-19 patients out of 1309 admitted between March 15 and April 3 who developed cardiac arrest (4.6%). Non-shockable rhythms presented in 52 (96.3%) with no patients surviving to discharge. The discussion notes results of CPR with those previously reported for in-hospital cardiac arrest (25% with 86% presenting non-shockable) and provides potential consequences of COVID-19. The authors suggest the importance of further research and consideration of guidelines for CPR in COVID-19.
      • Outcomes of Cardiopulmonary Resuscitation in Patients With COVID-19—Limited Data but Further Reason for Action. 9/28/20. Modes M. JAMA Int Med.
        Important discussion based on dismal post-CPR outcomes in accompanying research letter. While recognizing the difficulties of performing CPR in COVID-19 patients, the importance of developing a clearly defined care plan following a detailed, continuing discussion on outcome prognosis between the healthcare team and patient-family unit is emphasized. The concept of initiating an informed assent with the family in which the care team makes real-time decisions on DNAR (do not attempt resuscitation) is raised. Additionally, healthcare disparities and associated availability of advanced care directives highlight need for healthcare systems to adopt clearly defined protocols and emphasizes “goals of care” discussion between patients and families. Resource links provided.

      October 5, 2020

      • High Frequency of SARS-CoV-2 RNAemia and Association With Severe Disease. 9/23/20. Hogan CA. Clin Infect Dis.
        Paired nasopharyngeal and plasma samples from 85 COVID-19 patients, median age 55, revealed plasma RNAemia in 28/85 (32.9%), including 22/28 (78.6%) who required hospitalization, and older age (63 vs. 50 years; P = .04). In models adjusted for age, RNAemia was more frequent in individuals who developed severe disease including ICU admission (32.1% vs 14.0%; P = .04), invasive mechanical ventilation (21.4% vs. 3.5%; P = .02), and all 4 deaths. Plasma RNA persisted for a maximum of 10 days. Authors suggest potential utility as a prognostic indicator.
      • Reduced Monocytic Human Leukocyte Antigen-DR Expression Indicates Immunosuppression in Critically Ill COVID-19 Patients. 9/14/20. Spinetti T. Anesth Analg.
        Major histocompatibility complex (MHC) Class II molecules present processed extracellular proteins and are only expressed on the surface of “professional” antigen presenting cells such as dendritic cell and macrophages/monocytes. As such, there are clear implications for SARS-CoV-2. This small monocentric prospective study examined CD14+ monocytic HLA-DR (mHLA-DR) expression in 9 ICU vs. 7 non-ICU hospitalized COVID-19 patients. The investigators found on flow cytometry significant downregulation of surface expression of this marker indicating immunosuppression. The decrease found on ICU admission persisted on days 3 and 5. The authors suggest that immune monitoring in the ICU could indicate who might benefit from immunological intervention (e.g. GM-CSF, IFNγ).

      October 2, 2020

      September 30, 2020

      September 25, 2020

      • Probative Value of the D-Dimer Assay for Diagnosis of Deep Venous Thrombosis in the Coronavirus Disease 2019 Syndrome. 9/15/20. Gibson CJ. Crit Care Med.
        The authors tested the utility of the D-dimer assay for the diagnosis of deep vein thrombosis. Despite the excellent correlation between the D-dimer and the presence of DVT, the positive predictive value was 21.8%. DVT is only one aspect of the thrombotic problems in these patients. Many do not recommend leg duplex scanning using the sole criteria of D-dimer. One interesting aspect of this study was that all ICU patients received therapeutic anticoagulation. That may have been reflected in the low incidence of DVT discovered in these patients. Unfortunately, there are no data presented regarding the incidence of bleeding in these patients.
      • Stroke Risk, phenotypes, and death in COVID-19: Systematic review and newly reported cases. 9/15/20. Fridman S. Neurology.
        This is a complex study of stroke characteristics in COVID-19 patients by an international team of neurologists who pooled results from 10 studies with their own case series for a total of 160 patients. Their goal is to estimate overall incidence of stroke (1.8%) and mortality (34.4%), determine risk factors, particularly in patients under age 50, and identify clinical phenotypes and associated mortality separating all strokes from ischemic etiology. Large vessel occlusion contributed to a high percentage of strokes in younger patients and occurred before the onset of COVID-19 symptoms in 49% of those cases, while pulmonary involvement correlated with strokes in older patients and poor outcomes.

      September 23, 2020

      September 21, 2020

      September 16, 2020

      September 9, 2020

      September 4, 2020

      • COVID-19-associated hyperinflammation and escalation of patient care: a retrospective longitudinal cohort study. 8/21/20. Manson JJ. Lancet Rheumatol.
        A retrospective observational cohort study of 269 consecutive adult inpatients from the UK during March 2020 identified a “hyperinflammatory” subgroup predictive of a considerably higher risk of severe disease or death based upon C-reactive protein >150 mg/ml or a doubling from >50 mg/L w/in 24 hours, or Ferritin levels >1500 μg/L. These simple biomarkers had a predictive hazard ratio of 2.2 (1.6-2.9) for next-day escalation of support or death. 40% of the subgroup died vs. 26% of others. Follow-up was > 28 days or until death.
      • Marked factor V activity elevation in severe COVID-19 is associated with venous thromboembolism. 8/24/2020. Stefely JA. Am J Hematol.
        This article studies Factor V association with COVID-19 in 102 patients. This is a well-done study and offers possible clinical effects on care and future routes for investigation. The authors found an extraordinary level of factor V elevation in COVID-19 patients which had not been observed in any patient group in the past. A number of other clotting parameters were also analyzed. This patient group consisted primarily of those representing severe cases requiring ventilators. Factor V changes were associated with the wide variety of other clotting parameters and clinical events. This reviewer is not surprised at alterations in factor V levels since this disease is associated with an incredible degree of activation of clotting and related systems.

      August 31, 2020

      August 26, 2020

      August 25, 2020

      August 19, 2020

      • Delirium and encephalopathy in severe COVID-19: a cohort analysis of ICU patients. 8/8/20. Helms J. Crit Care.
        Following up on the concept that neurotropism of the SARS-CoV-2 virus has been confirmed, French investigators focused on the neurological status of 140 consecutive patients with COVID-19 linked ARDS (mean age 62, 71% male) to determine the incidence of delirium and abnormal neurological exams. 84% developed delirium and of those, 69% presented with agitation and 63% had long-tract signs. Of 28 patients who underwent lumbar puncture and MRI, 65% had perfusion abnormalities and 61% had signs of a disturbed blood brain barrier, 64% showed inflammatory signs in CSF and one was PCR positive for SARS-CoV-2 in CSF. Delirium associated with ARDS and COVID-19 is a distinct entity caused by the corona virus which prolongs and complicates recovery, both short term and possibly in the long term as well.
      • Prominent coagulation disorder is closely related to inflammatory response and could be as a prognostic indicator for ICU patients with COVID-19. 8/8/20. Liu Y. J Thromb Thrombolysis.
        Interesting discussion highlighting interrelationship between inflammatory and coagulation systems; suggests coagulation abnormalities (PT, D-Dimer, FDP and AT III) can predict deterioration and mortality; also notes the neutrophil/lymphocyte ratio is a potential inflammatory marker in disease. Recognizes importance of prophylactic thromboprophylaxis and accurate timing of systemic anticoagulation.
      • Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients. 8/12/20. Remmelink M. Crit Care.
        The authors found in this study of 17 patients, a great heterogeneity of COVID-19-associated organ injury and the remarkable absence of any specific viral lesions, even when RT-PCR identified the presence of the virus in many organs. Pulmonary findings revealed early-stage diffuse alveolar damage 15/17; microthrombi in small lung arteries in 11 patients and no evidence of myocarditis, hepatitis, or encephalitis. Onset of symptoms and death ranged from 2 to 40 days.

      August 17, 2020

      • Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK. 6/8/20. Knight M. BMJ.
        At all 194 obstetric units in the United Kingdom, 4.9 per 1000 pregnant women (n=427) were hospitalized with confirmed SARS-CoV-2 infection between March 1, 2020 and April 14, 2020. Sixty-nine percent were overweight or obese. Fifty-eight percent had symptom onset >32 weeks gestational age. By study end, 62% (n=266) had completed pregnancy with 259 live births, 3 still births and 4 lost pregnancies. Of those, 74% (n=196) were term births,16% (n=42) had C/section “due to COVID-19,” and 44% (n=114) had C/section for other reasons. Among all hospitalized, 10% needed ICU, 1% were placed on ECMO, and 1% died. Five percent of 265 infants were RNA+ for SARS-CoV-2. Results resemble USA reports.
      • COVID-19 and Dexamethasone: A Potential Strategy to Avoid Steroid-Related Strongyloides Hyperinfection. 7/30/20. Stauffer WM. JAMA.
        Dexamethasone is recommended for critically ill COVID-19 patients. One of its uncommon preventable complications is strongyloides hyperinfection caused by a nematode (roundworm). Seroprevalence of strongyloides ranges from 10-15% among migrants from less developed countries. The infection can last a lifetime. Hyperinfection appears to be independent of dose or duration of steroid. Its possibility should be considered if the patient deteriorates acutely. For outpatients, the authors recommend screening for strongyloides and treating with ivermectin if positive. For inpatients, they recommend presumptive treatment with ivermectin for patients not previously tested or treated for strongyloides.
      • Impact of the Coronavirus Infection in Pregnancy: A Preliminary Study of 141 Patients. 7/7/20. Nayak AH. J Obstet Gynaecol India.
        They studied 141 pregnant COVID positive women and 836 pregnant controls in Mumbai, India from April 1, 2020 to May 15, 2020. COVID-19 did not have a major adverse effect on maternal or newborn outcomes. Mortality was 2% and morbidity was low among COVID-positive mothers. Out of a total of 131 babies tested, only 3 tested positive on first swab and all tested negative on day 5. Vertical transmission of COVID-19 infection from mother to newborn was rare. This study reports fewer adverse outcomes than some others.

      August 14, 2020

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

      August 12, 2020

      August 10, 2020

      August 5, 2020

      • EDITORIAL: COVID-19: a complex multisystem disorder. 6/30/20. Roberts CM. Br J Anaesth.
        COVID-19 has extensive effects on virtually all the organs. The virus binds to angiotensin converting enzyme 2 (ACE2) receptors present in vascular endothelial cells, lungs, heart, brain, kidneys, intestines, liver, pharynx, and other tissue. It can directly injure these organs. In addition, systemic disorders caused by the virus lead to organ malfunction. It can cause cytokine storm which can culminate in death. It causes inflammation, endotheliitis, vasoconstriction, hypercoagulability, and edema. Lymphocytopenia, elevated D-dimer, elevated fibrin degradation products (FDPs), and disseminated intravascular coagulation (DIC) are observed. Deep vein thrombosis (DVT), venous thromboembolism, pulmonary embolism (PE), systemic and pulmonary arterial thrombosis and embolism, and ischemic stroke are reported. In the heart, it can cause acute coronary syndrome, congestive heart failure, myocarditis, and arrhythmias. Kidney injury is usually secondary to systemic abnormalities. Stroke occurs even in young patients. Delirium and seizures are common. Anosmia and impaired sense of taste are reported. Psychological problems are common among patients as well as providers. Stool may contain virus. Lactate dehydrogenase may be elevated. Various skin manifestations including patchy erythematous rash are reported. Injury to an organ may become apparent long after the acute infection has subsided. Different organs may be affected at different times. Chronic injury may occur. Rehabilitation can be long and difficult.

      August 3, 2020

      • Characteristics and Strength of Evidence of COVID-19 Studies Registered on ClinicalTrials.gov. 7/27/20. Pundi K. JAMA Intern Med.
        As an indication of how difficult it is to obtain quality data, this evaluation of 1,551 clinical studies of COVID-19 patients listed on ClinicalTrials.gov up to May 19, 2020 found that only 29.1% were designed in a way that the results could possibly change clinical practice (i.e., be classified as Level 2 evidence by the Oxford Centre for Evidence-Based Medicine level of evidence framework). In the 664 randomized clinical studies included, only 14% included mortality as a primary or composite outcome (arguably the most important research question). The authors state that, “Even before results are known, most studies likely will not yield meaningful scientific evidence at a time when rapid generation of high-quality knowledge is critical.”

      July 31, 2020

      • COVID-19 pandemic and the skin: what should dermatologists know? 3/24/20. Darlenski R. Clin Dermatol.
        Skin manifestations of COVID-19 are like those of other viruses and chronic inflammatory diseases like acne, eczema, psoriasis, and rosacea. Vascular problems associated with skin manifestations can be neurogenic, microthrombotic, or immune complex-mediated.
        Of the patients with skin manifestations, a majority have patchy erythematous rash. Some have widespread urticaria or hives. A few also have chickenpox-like fluid-filled vesicles or blisters. They can have measles-like rashes. The most affected area is the trunk. Itching is mild or absent. Some patients have skin eruptions at symptom onset, and others after hospitalization. Lesions usually heal in a few days. Skin manifestations do not correlate with the severity of COVID-19.
        Patients may develop livedo reticularis. It is a purplish net-like discoloration of the skin, often a result of blood clotting abnormalities. Lacy, dusky rashes, including dead skin cells are observed on the arms, legs, and buttocks. They are associated with hypercoagulability. Petechiae are present. Nonpruritic blanching livedoid vascular eruption, possibly due to vaso-occlusion may be present. They appear as mottled, netlike red or pink patches. Also present are chilblains, which are purplish, slightly firm and often tender. COVID toes and fingers have frostbite-like areas with red or purple rash or hive-like eruption.
      • Distinct clinical and immunological features of SARS-COV-2-induced multisystem inflammatory syndrome in children. 7/23/2020. Lee PY. J Clin Invest.
        The authors retrospectively studied 28 confirmed cases of multisystem inflammatory syndrome in children at Boston Children’s Hospital from March to June 2020. Pediatric Multisystem Inflammatory Syndrome that includes classic features of Kawasaki disease, heterogeneous manifestations of systemic inflammation and shock. These children may exhibit heart failure, shock and coronary artery abnormalities, with a disproportionate representation among Blacks and Hispanics. Preexisting risk factors include obesity, asthma and heart disease. Acute respiratory distress syndrome was not a feature, but instead preponderance of cardiac complications including ventricular dysfunction and coronary abnormalities. The degree of inflammation as measured by CRP and procalcitonin is much greater in these children compared to those patients with COVID-19 pneumonia. Rapid diagnosis, multidisciplinary management and suppression of systemic inflammation was associated with a favorable outcome.
      • Genomewide association study of severe Covid-19 with respiratory failure. 6/17/20. Ellinghaus D. N Engl J Med.
        Genetic differences may in part explain the difference in response of different persons to SARS-CoV-2. They compared hospitalized patients with respiratory failure with controls. They studied 835 patients and 1255 controls from Italy and 775 patients and 950 controls from Spain.
        They found 3p21.31 gene cluster is a genetic susceptibility locus. Patients with blood group A were found to be at a higher risk of infection (odds ratio, 1.45) and develop more severe symptoms. Patients with blood type O were found to be at a lower risk of infection (odds ratio, 0.65). Although the results are statistically significant, the effect size is small. Results on the association with blood group has been reviewed by the SAB in several articles previously.

      July 29, 2020

      • Characterization of experimental and clinical bioaerosol generation during potential aerosol-generating procedures. 7/15/20. Doggett N. Chest.
        This prospective study from Toronto quantified aerosol production pre and post two presumed aerosol generating procedures (AGPs); intubations in pigs (n=16) and elective bronchoscopies in human adults (n=39). Though overall, there was a significant reduction in larger particle aerosols during the procedures, and no significant increase in small particle aerosolization during the procedures, some bronchoscopies did produce significantly increased small particle aerosols. The authors conclude that the variability of aerosol generation reinforces the need for PPE during AGPs, and that more research is needed, especially in the more uncontrolled environments typical of a COVID-19 surge.
      • Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System. 7/20/20. Bilaloglu S. JAMA.
        This research letter reports retrospective data analysis from 3,334 consecutive hospitalized COVID-19 patients from four NYC hospitals. “Most” received low-dose thromboprophylaxis. Sixteen percent experienced thrombotic events defined as DVT, PE, MI, or CVA (no screening). ICU patients: 13.6% venous, 18.6% arterial. Ward points: 3.6% VTE, and 8.4% arterial. Mortality with event was 43% vs. 21% without. Age, male sex, Hispanic ethnicity, CAD, prior MI, and higher D-dimer at hospital presentation were associated with a thrombotic event, but not BMI or current smoking Hx.

      July 27, 2020

      • Pulmonary immune responses against SARS-CoV-2 infection: harmful or not? 7/19/20. Guillon A. Intensive Care Med.
        A brief, well written review of the literature on COVID-19 immune responses claiming that the critical processes occur primarily in the lung and that the immune injury phase of the disease is not well described as a generalized “cytokine storm.” A T-cell subpopulation called innate T-cells appears to be diminished and have impaired function in peripheral blood but is found in increased numbers and activation in the airways of these patients.

      July 24, 2020

      July 22, 2020

      • Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report. 7/17/20. The RECOVERY Collaborative Group. N Engl J Med.
        Click here to take this CME activity.Review by the SAB
        These authors (Nuffield /Oxford) provide preliminary results (recruitment ended on June 8) of the controlled, open-label-randomized evaluation of COVID-19 Therapy (RECOVERY) trial of dexamethasone in patients hospitalized with COVID-19. The primary outcome was mortality within 28 days after randomization.
        In patients hospitalized with COVID-19, the use of dexamethasone (6mg either IV or PO up to 10 days) resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support (may harm). In a 2:1 randomization, 2,104 patients received dexamethasone and 4,321 received the usual care. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82). There was a trend showing the greatest absolute and proportional benefit among patients who were receiving invasive mechanical ventilation (11.5 by chi square test for trend). Patients in the dexamethasone group had a shorter duration of hospitalization than those in the usual care group (median, 12 days vs. 13 days) and a greater probability of discharge alive within 28 days (rate ratio, 1.10; 95%). It is likely that the beneficial effect of glucocorticoids in severe viral respiratory infections is dependent on a selection of the right dose, at the right time, in the right patient. Viral replication peaks in the second week of illness in SARS, while viral shedding in SARS-CoV-2 appears to be higher early in the illness and declines, thereafter when dexamethasone is most effective. At that stage, the disease may be dominated by immunopathological elements, with active viral replication playing a secondary role.
      • Hospitalization and Mortality among Black Patients and White Patients with Covid-19. 6/25/20. Price-Haywood EG. N Engl J Med.
        Review by the SAB
        By Heinrich Wurm, on behalf of the SAB
        This retrospective cohort study takes a critical look at incidence, mortality and concomitant risk factors among black and white non-Hispanic members of the Ochsner integrated delivery health system.
        Black patients far exceeded white non-Hispanics in getting infected (70 vs. 30% of enrolled patients were PCR positive), requiring hospital admission (77%) and dying (71%). But black race was not independently associated with a higher mortality (HR death vs. white race 0.89; 95 CI, 0.68-1.17) when adjustments for differences in socio-demographic and clinical characteristics were made.
        Blacks had a greater prevalence of underlying disease (obesity, diabetes, hypertension, chronic kidney disease), presented with higher levels of inflammatory markers, elevated creatinine and were more likely to live in low-income areas and receive public insurance. Greater occupational exposure in service industries and higher incidence of morbid obesity and chronic kidney disease were also discussed.
      • Neurobiology of COVID-19. 6/30/20. Fotuhi H. J Alzheimer’s Dis.
        Review by the SAB
        By Heinrich Wurm, on behalf of the SAB
        This review by a panel of U.S. experts goes beyond analyzing neurological manifestations of COVID-19 and provides us with plausible and well-illustrated pathophysiological theories and a 3-stage evolution of a condition termed Neuro-COVID. A synopsis of worrisome post-COVID-19 neurological sequelae, ranging from poor memory and slow processing speed to lasting depression, Parkinson’s, multiple sclerosis and Alzheimer’s, concludes this remarkable publication and points us towards a future of COVID-related sequelae.
      • Race, Postoperative Complications, and Death in Apparently Healthy Children. 7/1/20. Nafiu OO. Pediatrics.
        In a retrospective article of over 170,000 healthy children with care provided by anesthesiologists, African American children suffered more postsurgical complications, especially bleeding and death.

      July 20, 2020

      • Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. 7/15/20. Mathew D. Science.
        Review by the SAB
        By Dr. Uday Jain, on behalf of the SAB
        Previously uncharted role of lymphocytes in COVID-19 is discussed. A wide variability in immune response was observed among hospitalized COVID-19 patients. Responses were barely detectable in about one-fifth of the patients. This was associated with pathology due to the virus and reduced survival. Remaining patients had CD8 and/or CD4 T lymphocyte and plasmablast responses that were heterogeneous among the patients and were divided into immunotypes. In many patients who became seriously ill with Covid-19, helper and killer cells do not work well cooperatively. An overabundance of helper cells is proinflammatory. An overabundance of killer T cells is not ideal but consistent with survival.
      • Therapeutic Plasma Exchange: A potential Management Strategy for Critically Ill COVID-19 Patients. 7/16/20. Tabibi S. J Intensive Care Med.
        Review by the SAB
        By Dr. Lydia Cassorla, on behalf of the SAB
        This report briefly discusses various approaches currently being investigated to treat SARS-CoV-2 with a focus on potential benefits of therapeutic plasma exchange (TPE). TPE may alleviate the need for polypharmacy to combat various cytokines along with their associated side effects and necessary adjustments for comorbidities. TPE has been used to treat H1N1-associated ARDS, myasthenia gravis, Kawasaki disease, early septic shock, and various multi-organ dysfunction syndrome phenotypes including thrombocytopenia purpura. Reports of its use to treat severe COVID-19 are reviewed. TPE appears generally safe. Concerns involve blood supply, availability, and potentially cost. A proposed set of criteria that overlap with those for convalescent plasma and Spectra Optia Apheresis System is outlined, including early ARDS, severe disease, and life-threatening disease. Clinical trials are underway.

      July 17, 2020

      • COVID-19 Disease Severity Risk Factors for Pediatric Patients in Italy. 7/16/20. Bellino S. Pediatrics.
        Click here to take this CME activity.Review by the SAB
        By Dr. Jay Pryzbylo, on behalf of the SAB
        This large pediatric study demonstrates that infection by COVID-19 increases with age (severe illness in the youngest) is uncommon in the pediatric age group with only 1.8% of total infections over all ages. The study reported only 4 deaths, all in children with complex underlying medical issues.
      • Covid-19: What do we know about “long covid”? 7/14/20. Mahase E. BMJ.
        Review by the SAB
        By Dr. Barry Perlman, on behalf of the SAB
        This non-peer reviewed article discusses “Long COVID,” a term used for lasting effects after recovering from COVID-19 infection or symptoms that persist longer than expected.
        Ongoing health problems may include “breathing difficulties, enduring tiredness, reduced muscle function, impaired ability to perform vital everyday tasks, and mental health problems such as post-traumatic stress disorder, anxiety, and depression.”
        HNS England will be launching an online portal for those with long-term effects of COVID-19 to communicate with nurses, physiotherapists, and mental health specialists.
        A Facebook “long Covid Support group” has >7000 members, and the hashtag “longcovid” enables personal experiences to be shared on social media.
        Research on the long-term effects of COVID-19 infection is needed. The Post-hospitalization COVID-19 Study plans to follow 10,000 UK patients for a year, but it will not include milder cases that didn’t require hospital care.
      • Neurological manifestations of COVID-19: a systematic review. 7/15/20. Nepal G. Crit Care.
        Review by the SAB
        By Dr. Heinrich Wurm, on behalf of the SAB
        This well-organized review of the world literature up to May 20, 2020 analyses 37 articles, many of them case reports. The authors critically review each neurological symptom or disease entity currently known to exist with the intent to provide practitioners with an overview of a host of manifestations ranging from mild headaches to taste and smell disorders to strokes, hemorrhage and central and peripheral nervous system inflammatory reactions like encephalo-myelits and Guillain-Barré syndrome.
      • Relationship between ABO blood group distribution and clinical characteristics in patients with COVID-19. 6/21/20. Wu Y. Clin Chim Acta.
        Review by the SAB
        By Lydia Cassorla, on behalf of the SAB
        Retrospective case controlled study of Wuhan patients admitted to a single Chinese hospital 1/20/20 – 3/5/20. 187 study patients were admitted with COVID-19 while 1991 control patients were COVID negative individuals admitted during the same time period. The proportion of patients with type A blood in the COVID-19 group was significantly higher than that in the control group (36.90% vs. 27.47%, P = 0.006), while the proportion of patients with type O blood in the COVID-19 group was significantly lower than that in the control group (21.92% vs. 30.19%, P = 0.018). Blood group A patients had a higher risk of COVID-19 than non-A blood group patients. (OR = 1.544, 95% CI = 1.122–2.104, P = 0.006). Blood group O patients had a lower risk of COVID-19 than non-O blood group patients (OR = 0.649, 95% CI = 0.457–0.927, P = 0.018).

      July 15, 2020

      • Clinical Implications of SARS-CoV-2 Infection in the Viable Preterm Period. 7/3/20. Gulersen M. Am J Perinatol.
        Review by the SAB
        The authors in this article conducted a retrospective, logistic regression analysis for preterm birth (PTB) from boroughs in New York of patients diagnosed with COVID-19 infection with pregnancy between 23 and 37 weeks of gestation during March and April of 2020. PTB was noted to be in two groups: 23 to 33 weeks (n = 7/36) and the other one was 34+ (n = 18/29) with p= 0.0001. Most women with COVID-19 infection in the early preterm period recovered and were discharged home. The majority of PTB were indicated and not due to spontaneous preterm labor. Delivery during the current admission was noted as statistically significant for the group of patients with 34+ weeks. No correlation was noted with severity of the COVID-19 disease grade or treatment regimes (antibiotics and antimalarial) but no interleukins or steroids were given to the late group. Gestational age at diagnosis of COVID-19 infection had an odds ratio of 2.9.
      • Risk factors for myocardial injury and death in patients with COVID-19: insights from a cohort study with chest computed tomography. 7/8/20. Ferrante G. Cardiovasc Res.
        Review by the SAB
        By Dr. Philip Lumb, on behalf of the SAB
        Interesting study reporting admission CT Scan results on 332 consecutive patients with documented COVID-19 disease. Of these, 123 had myocardial injury defined as high-sensitivity troponin I above 20 ng/ml. Included patients had a median follow up of 12 days with 20.5% (68) deaths. Co-morbidities and course are well described; however, CT findings are consistent with lung involvement in COVID-19.
        The study concludes that “myocardial injury, as assessed by cardiac troponins, occurs in approximately one third of COVID-19 cases and is associated with an adjusted two-fold mortality increase. An increased PA diameter, as assessed on chest CT, is an independent predictor of both myocardial injury and death.”
      • Tocilizumab for treatment of mechanically ventilated patients with COVID-19. 7/11/20. Somers EC. Clin Infect Dis.
        Click here to take this CME activity.Review by the SAB
        By Dr. David Clement, on behalf of the SAB
        An observational, controlled study of 154 adult, ventilated COVID-19 patients, half of whom received tocilizumab. Tocilizumab-treated patients had a 45% reduction in hazard of death, improved status on some secondary outcomes, and twice as many superinfections. Extensive tables, figures and statistical analysis provide insight.  A randomized study is needed to confirm these findings.

      July 13, 2020

      • Characteristics and serological patterns of COVID-19 convalescent plasma donors: optimal donors and timing of donation. 7/6/20. Li L. Transfusion.
        Review by the SAB
        By Dr. Barry Perlman, on behalf of the SAB
        Study from Wuhan, China of 49 blood donors who recovered from mild-moderate COVID-19 to determine optimum convalescent plasma donor strategy.
        Nucleocapsid (N) and Spike protein receptor-binding domain (S-RBD) antibodies were measured by ELISA assay. S-RBD ELISA results were correlated with a SARS-CoV-2 viral neutralization assay, as the authors state that recent studies suggest that S-RBD antibodies may provide immunity.
        N specific IgM declined 3 weeks after infection and reached low levels after 6 weeks. S-RBD and N specific Ig G increased after 4 weeks from symptom onset.
        Those who donated > 28 days from symptom onset, and whose fever > 38.5°C or lasted longer than 3 days, had higher levels of S-RBD IgG.
        Further studies with larger sample size, plasma from asymptomatic donors, and clinical validation are needed.
      • COVID-19 Clinical Trials: Unravelling a Methodological Gordian Knot. 7/7/20. Mathioudakis AG. J Thromb Thrombolysis.
        Review by the SAB
        By Dr. Lance Lichtor, on behalf of the SAB
        During a pandemic, in part because of the limit in a patient population that might shrink in the coming months, clinical trials might need to enroll a patient for more than 1 trial. In addition, because of the need to get information out quickly, interim data meta-analyses (or network meta-analyses) powered to evaluate key outcomes, may be useful. At least, strategies and methodologies need to be developed to allow the best use of data collected.
      • How to Quantify and Interpret Treatment Effects in Comparative Clinical Studies of COVID-19. 7/7/20. McCaw ZR. Ann Intern Med.
        Review by the SAB
        By Dr. Jay Pryzbylo, on behalf of the SAB
        Concise but in depth explanation using the example of two previously published articles to demonstrate that the statistical techniques used do not necessarily accurately describe the outcomes achieved. At issue is that negative outcomes (e.g., deaths) are not adequately accounted for in positive outcome statistical evaluation (days to recovery). The authors advance a method to do so that alters the outcomes of the studies.
      • Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19. 6/29/20. Arshad S. Int J Infect Dis.
        Review by the SAB
        By Dr. Barry Perlman, on behalf of the SAB
        Multi-center retrospective observational study of 2,541 consecutive RT-PCR confirmed COVID-19 admissions from March 10 to May 2 in Detroit to determine impact of hydroxychloroquine +- azithromycin on inpatient mortality.
        Standard, uniform treatment guidelines established by a system-wide interdisciplinary COVID-19 task force also included corticosteroids and tocilizumab, which were used in 68% and 4.5% respectively.
        In hospital mortality:
        • Overall 18%
        • No hydroxychloroquine or azithromycin 26%
        • Azithromycin alone 22%
        • Hydroxychloroquine + azithromycin 20%
        • Hydroxychloroquine alone 13.5%
        • Mortality predictors were age > 65, CKD, decreased O2 sat on admit, ventilator use, and in contrast to previous studies, white race.

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

      July 10, 2020

      • Incidence of pulmonary embolism in non-critically ill COVID-19 patients. Predicting factors for a challenging diagnosis. 6/29/20. Mestre-Gómez B. J Thromb Thrombolysis.
        Review by the SAB
        By Dr. Barry Perlman, on behalf of the SAB
        Retrospective review of EMR data of 452 consecutive patients admitted to the general ward with COVID-19 (based on WHO clinical criteria and/or RT-PCR) in Madrid to determine the incidence of PE in non-critically ill COVID-19 patients and identify predictive factors.
        • 91 of these patients had CT pulmonary angiography (CTPA) to rule out PE, with 29 (32%) positive for acute PE.
        • Incidence of PE was 6.4% — 29/452 patients.
        • Of note, 79% were receiving prophylactic LMWH at the time PE was diagnosed
        • PE was not associated with a significantly increased risk of ICU admission or mortality
        • Multivariate analysis showed lack of history of dyslipidemia and elevated D-dimer were independent predictors of PE.
        • D-Dimer peak median was 2x higher in PE patients. Cut off predictor was > 5000 ug/dl.
        • Patients with history of dyslipidemia had a 9x lower risk of PE. It is not known if this is due to statin use prior to admission. Hospital statin administration was not significantly different among the two groups.

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

      July 8, 2020

      July 6, 2020

      • Compassionate Use of Tocilizumab for Treatment of SARS-CoV-2 Pneumonia. 6/23/20. Jordan SC. Clin Infect Dis.
        Review by the SAB
        By Dr. Heinrich Wurm, on behalf of the SAB
        Single center review by a multidisciplinary team from Cedars-Sinai following 27, mostly intubated, patients with confirmed SARS-CoV-2 pneumonia who received a single dose of 400 mg tocilizumab intravenously under a compassionate use protocol. Decreasing vasopressor support and oxygen requirements as well as lower C-reactive protein levels and temperature were observed in a majority of subjects monitored to assess anti-inflammatory effectiveness and clinical improvement.
        Tocilizumab proved beneficial in reducing inflammation and improving clinical outcome including mortality. Final proof of the drug’s efficacy awaits a placebo-controlled trial, now underway.

      July 1, 2020

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

      June 8, 2020

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

      June 5, 2020

      • Impact of anticoagulation prior to COVID-19 infection: a propensity score-matched cohort study
        May 27. Tremblay D. Blood.
        Opinion from SAB Member: Dr. Joseph Anthony Caprini, Dr. Anil Hingorani
        JC: This is a very clever analysis looking at patients who did or did not have therapeutic anticoagulation prior to developing the viral infection as a result of their underlying condition. The same analysis was done in patients on antiplatelet therapy. The results showed no benefit of either anticoagulation or antiplatelet therapy in changing all-cause mortality, mechanical ventilation, and hospital admission. They comment that the results of this study do not rule out the possibility that among some groups of patients suffering from the virus therapeutic anticoagulation following diagnosis may be important and beneficial. They further comment that their findings agree with the current recommendations of the American Society of Hematology that state that the benefit of therapeutic anticoagulation in patients with COVID-19 is unknown.
        AH: These data are from Mount Sinai. The authors use retrospective propensity matching for anticoagulation usage before COVID-19 diagnosis. No benefit of any single anticoagulation type was noted. The article suggests we may need multiple types of treatment. This paper is novel and raises good questions.
      • Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study
        May 29. CovidSurg Collaborative. The Lancet.
        Opinion from SAB Member: Dr. Anil Hingorani, Dr. Joseph Anthony Caprini
        AH: 30-day results of an international cohort study assessing postoperative outcomes in 1128 adults with COVID-19 who were undergoing a broad range of surgeries. SARS-CoV-2 infection was diagnosed postoperatively in more than two-thirds of the patients (806 [71·5%]). The primary outcome was overall postoperative mortality at 30 days, and the rate was high at 23·8% (268 of 1128 patients). Pulmonary complications occurred in 577 (51·2%) patients and 30-day mortality in these patients was 38·0% (219 of 577).
        JC: This represents a very important study demonstrating a high incidence of relatively severe complications including death postoperatively. There are obvious flaws in this study as expressed by both the authors and in the subsequent editorial. Nevertheless, these data emphasize the importance of improved preventative measures including the vaccine as well as a multimodal therapeutic approach involving drugs representing hematologic immunologic and inflammatory pathways.

      June 3, 2020

      June 1, 2020

      May 29, 2020

      • Covid-19, Angiogenesis, and ARDS Endotypes
        May 21. Hariri L. The New England Journal of Medicine.
        Opinion from SAB Member: Dr. Anil Hingorani, Dr. Louis McNabb
        AH: Editorial points out limitations of the Ackermann paper: n=7, none intubated, only 20% with noninvasive ventilation. Exact correlation with the time course of the disease and the findings are not clear.
        LM: Complimentary article to Ackermann’s paper suggesting that the small vessel disruption in COVID-19 may represent a specific ARDS histologic phenotype.
      • Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19
        May 21. Ackermann M. The New England Journal of Medicine.
        Opinion from SAB Member: Dr. Anil Hingorani, Dr. Louis McNabb
        AH: This is an autopsy study of 7 COVID-19 patients compared to 7 H1N1 patients, age and gender matched with 10 controls. Tests performed: histology, electron microscopy and gene array. Widespread thrombosis with microangiopathy were seen. COVID-19 patients had more alveolar capillary microthrombi and new vessel growth–predominantly through a mechanism of intussusceptive angiogenesis. Gene analysis also showed more angiogenesis.
        LM: This study compared lung histology of 7 patients dying of COVID-19 vs. 7 patients dying of influenza. Key Points: 1) COVID-19 patients had 9 times more capillary micro-thrombi, 2) Disrupted capillary cell membranes with intracellular virus were seen, 3) Perivascular t-cell infiltration was seen, and 4) COVID-19 patients had 2.7 more times new vessel growth through the mechanism of intussusceptive angiogenesis.
      • The association of low serum albumin level with severe COVID-19: a systematic review and meta-analysis. May 26. Aziz M. Crit Care.
        Meta-analysis of 11 studies with 910 patients finding a significantly lower admission serum albumin (3.5 g/dL) in severe COVID-19 patients than in those with non-severe disease (4.0 g/dL). Of note, patient mean age was 48. The primary cause and clinical significance of this difference is not known.

      May 28, 2020

      • Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization. May 14. Zuo T. Gastroenterology.
        Pilot, prospective comparison of fecal microbiomes in samples from 15 hospitalized COVID-19 patients in Hong Kong with samples from 6 patients hospitalized with community acquired pneumonia and 15 controls. Samples were collected 2-3 times a week until hospital discharge. Samples from COVID-19 patients had increased opportunistic pathogens and decreased beneficial commensals. Bacterial levels remained low and altered from a healthy microbiome even after RT-PCR tests became negative and respiratory symptoms had resolved. COVID-19 patients treated with antibiotics showed a larger change from a healthy microbiome. Baseline (but after admission) Coprobaccillus, Clostriium ramosum, and Clostridium hathewayi correlated with COVID-19 severity, while amounts of the anti-inflammatory Faecalibacterium inversely correlated with severity. Several Bacteroides species, which down regulate ACE2 expression, inversely correlated with viral load, suggesting that it may play a protective role. Study is limited by small sample size, unknown baseline microbiome prior to disease onset, lack of patients with asymptomatic or mild COVID-19.
      • Famotidine Use is Associated with Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Propensity Score Matched Retrospective Cohort Study. May 14. Freedberg DE. Gastroenterology.
        This retrospective cohort study from a single NY institution looked at the relationship between famotidine exposure of Covid-19 patients within 24 hours of hospitalization and death or endotracheal intubation from hospital day 2 to 30. They studied all Covid-19 positive patients from 2/25/20-4/13/20. 84 patients, representing 15% of 1,620 analyzed, were in the famotidine exposed group. Doses and route of adminstration varied. Median length of treatment was 5.8 days. Adjusted hazard risk of death or intubation was 0.42. PPIs did not show a protective effect. Next, 784 patients w/o COVID-19 were analyzed and famotidine exposure did not show a protective effect. A lower peak ferritin value was observed among famotidine-exposed patients, supporting the hypothesis that cytokine release in famotidine exposed patients may be lower in the setting of Covid-19. An untargeted computer modeling analysis identified famotidine as one of the highest-ranked matches for drugs predicted to bind 3CL (3), a SARS-CoV-2 protease.

      May 27, 2020

      • Critically ill patients with COVID-19 in New York City
        May 19. Grasselli. The Lancet.
        Opinion from SAB Member: Dr. Jagdip Shah
        This editorial describes the study by Matthew J. Cummings, et al as a high-quality example of research even when facing an overwhelming clinical workload. The authors claim that further studies are required to improve and personalize patient treatment, with particular attention to the role of initial non-invasive respiratory support strategies, timing of intubation, optimal setting of mechanical ventilation, and efficacy and safety of immunomodulating agents and anticoagulation strategies.
      • Detection of SARS-CoV-2 in human breastmilk. May 21 Groß. Lancet.
        In this study of 2 women with severe COVID-19 disease, one mother shed SARS-CoV-2 RNA from breast milk for 4 days. Interesting but a small study.
      • Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study
        May 19. Cummings. The Lancet.
        Opinion from SAB Member: Dr. Jagdip Shah
        1150 adults were admitted in this prospective study from 2 hospitals (Columbia, New York). Both hospitals were able to utilize more than double the ICU surge capacity. 257 were critically ill with confirmed COVID-19. The median age of patients was 62 years, 67% were men, 82% of patients had at least one chronic illness, (HTN, DM, BMI > 30). A high incidence of critical illness among racial and ethnic minorities in this pandemic is noted. 39% of patients had died and 37% remained hospitalized, 79% patients had to be mechanically ventilated for 18 days, 66% of 257 patients received vasopressors and 31% RRT. The authors present extensive respiratory and critical illness parameters on the first day of critical illness (medians): SOFA = 11, lowest PaO2:FiO2 = 129 mmHg, plateau airway pressure = 27 cmH2O, highest PEEP = 15 cmH2O.
        In the multivariable Cox model, older age (HR 1.31 per 10-year increase), chronic cardiac disease (HR 1.76), chronic pulmonary disease (HR 2.94), higher concentrations of interleukin-6 (HR 1.11 per decile increase), and higher concentrations of D-dimer (HR 1.10 per decile increase) were independently associated with in-hospital mortality. Univariate and multivariate HRs being somewhat similar suggest a higher confidence in the study and the group composition.
        Patients hospitalized with COVID-19 had a high frequency of invasive mechanical ventilation, extrapulmonary organ dysfunction, and substantial in-hospital mortality.
      • Features of 20‚133 UK patients in hospital with Covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study
        May 22. Docherty. BMJ.
        Opinion from SAB Member: Dr. David M. Clement
        This is a somewhat different twist on the numerous studies describing symptoms, co-morbidities and outcomes with COVID-19 inpatients. It is a prospective, observational cohort study from the UK of 20,100 inpatients who were tracked with a pandemic protocol written before the SARS-CoV-2 pandemic in response to the H1N1 and MERS epidemics. An army of 2,468 research nurses, administrators and medical students collected data using a pre-pandemic standardized form and protocol in 208 hospitals on about a third of RT-PCR positive patients. Of note, symptoms were present in overlapping clusters reflecting organ systems involved (lung, GI, musculoskeletal and musculo-cutaneous). Overall, symptoms, comorbidities and outcomes were somewhat similar to previous studies: 41% of patients were discharged alive, 26% died and 34% were still inpatients. In ICU patients, 32% died and 41% were still admitted. The utility of pre-pandemic preparation for many facets of care was apparent.
      • Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy
        May 15. George. Lancet Respir Med.
        Opinion from SAB Member: Dr. Louis McNabb, Dr. Edward S. Schulman
        LM: This is an opinion article raising the issue of long-term pulmonary fibrosis in survivors of severe COVID-19 pneumonia/ARDS. The authors discuss the logic for considering anti-fibrotic drugs such as: pirfenidone and nintedanib. They also discuss many other experimental anti-fibrotic drugs and their potential mechanism of action in COVID-19.
        ESS: While it may eventually become pertinent to consider the theoretical role of anti-fibrotic agents in the treatment of COVID-19, it must be noted that we do not yet know the natural history of lung injury in survivors and whether fibrosis is a persistent feature. With regards to pirfenidone and nintedanib, these agents carry significant side-effect profiles including nausea, vomiting, diarrhea and liver injury that may preclude their use in critically ill COVID-19 patients. Furthermore, the authors of this paper acknowledge relationships including “personal fees with the companies marketing pirfenidone and nintedanib.”
      • Pulmonary fibrosis secondary to COVID-19: a call to arms?
        May 15. Spagnolo. Lancet Respir Med.
        Opinion from SAB Member: Dr. Louis McNabb
        This is a short article pointing out the potential for a large population of COVID-19 survivors with residual pulmonary fibrosis and its consequences.
      • Therapy with agents acting on the renin-angiotensin system and risk of SARS-CoV-2 infection
        May 22. Gnavi. Clinical Infectious Diseases.
        Opinion from SAB Member: Dr. Jay Przybylo
        This is a study with controls demonstrating that patients treated with ACE inhibitors (ACEi) or Angiotensin II Receptor Blockers (ARBs), in particular those with diabetes or cardiovascular disease, were not more susceptible to SARS-CoV-19 infection due to drug therapy.

      May 22, 2020

      • Tracheostomy in the COVID-19 era: global and multidisciplinary guidance
        May 15. McGrath. Lancet Respir Med.
        Opinion from SAB Member: Dr. Jay Przybylo
        Presented by an international, multidisciplinary team, this article attempts to limit “conflicting recommendations” that have arisen in this pandemic regarding tracheostomies. Using COVID-19 as the example, the paper reviews the history of pandemics, searches the literature for guidance, and describes the issues of tracheostomy–in non-COVID-19 patients less than 50% of trached patients survive to leave the hospital and 12% are functional at 1 year while in COVID-19 the statistics are worse, suggesting a longer wait prior to tracheostomy. Using data on the infectious nature of COVID-19, the wait allows the detectable virus to drop below 50% of patients while allowing antibodies to become detectable in most. With this timing, the incidence of trach is 0.5%. The location of the procedure and the optimal procedure are discussed. The care of patients with emphasis on healthcare provider safety is discussed. The paper contains multiple, easily interpretable tables and graphs. Not a science paper with statistics and errors supplied, this paper promotes standards that can (should) be met worldwide.

      May 21, 2020

      • Cardiovascular implications of the COVID-19 pandemic: a global perspective
        May 10. Boukhris. Canadian Journal of Cardiology.
        Opinion from SAB Member: Dr. Jagdip Shah
        Cardiologists from across the world provide a holistic review of the present and future of their acute and chronic issues with clinical practice in this article. The article provides a comprehensive overview with evidence-based input of the pathophysiology and the dynamic cardiovascular implications of COVID-19. The authors have made an excellent effort to explain pathophysiology for noncardiac conditions, drug implication and their interactions as well. They noted that the information in references here is contemporary and relevant. It offers a detailed recommendation of existing pathways of care, the role of modern technologies (AI, social media, smartphones, telemedicine, etc.) to tackle the patient care issues in this pandemic, which other specialties can adopt. This is a practical, realistic proposal of novel management algorithms for the most common acute cardiac conditions with excellent tables and figures that are easy to read and follow.
        Although respiratory symptoms dominate the clinical presentation, COVID-19 is known to have potentially serious cardiovascular consequences, including myocardial injury, myocarditis, acute coronary syndrome, pulmonary embolism, stroke, arrhythmias, heart failure, and cardiogenic shock. The cardiac manifestations of COVID-19 may be related to the adrenergic drive, systemic inflammatory milieu and cytokine-release syndrome caused by SARS-CoV-2, direct viral infection of myocardial and endothelial cells, hypoxia due to respiratory failure, electrolytic imbalances, fluid overload, and side effects of certain COVID-19 medications known to be in practice currently.
      • Cardiovascular Safety of Potential Drugs for the Treatment of Coronavirus Disease 2019
        May 20. Aggarwal. The American Journal of Cardiology.
        Opinion from SAB Member: Dr. J. Lance Lichtor
        Any drug might have an effect on the heart. The authors have provided a nice summary of the cardiac safety of various drugs used to treat patients with COVID-19, including chloroquine/hydroxychloroquine, azithromycin, remdesivir and lopinavir/ritonavir, interferon-alpha, and briefly concerning some other therapies.
      • Neurologic complications of COVID-19
        May 10. Bridwell. American Journal of Emergency Medicine.
        Opinion from SAB Member: Dr. W. Heinrich Wurm
        Announced by the authors as, “A practical review of the literature aimed at the emergency medicine clinician”, this review of 60 recent papers dealing with the neurological impact of COVID-19 adds value for the clinician without being superficial. The avenues of direct viral assault via endothelial ACE-2 receptors, retrograde migration via the nasopharynx into the olfactory system, or via transsynaptic transmission, are highlighted, as well as the impact of secondary events like the systemic inflammatory response evoked by the virus and its impact on the blood brain barrier or the effect hypoxia may exert on cerebral autoregulation.
        In addition to highlighting clinical presentations, this review points to pre-existing neurological disease like stroke and Parkinson’s as an important risk factor not only for added neurological complications, but for severity of illness and mortality. A table listing the side effects of various pharmaceuticals used to treat COVID-19 provides another helpful addition for the practitioner.
      • The Relationship between Status at Presentation and Outcomes among Pregnant Women with COVID-19. 5/20/20. London V. Am J Perinatol.
        Review by the SAB
        By Dr. Lydia Cassorla, on behalf of the SAB
        This is a single-center retrospective cohort study of pregnant women who tested positive for COVID-19 at one Brooklyn hospital from March 15 to April 15, 2020. Fifty-five SARS-CoV-2 positive pregnant women were followed to term and 1 had fetal demise at 17 weeks. Among parturients with COVID-19 symptoms at presentation (n = 33), 16 (48.5%) had Cesarean delivery, 9 (27.3%) had preterm birth <37 weeks of whom 7 were C/Section for maternal respiratory distress. Twelve (26%) required respiratory support including 1 who required mechanical ventilation. Among those who were asymptomatic at presentation (n = 22), 6 (27%) had Cesarean delivery, and there were no preterm births. Pregnant women who present without symptoms remained asymptomatic to a greater degree than has been reported from cohorts of older individuals. Initially, patients were only tested because of symptoms of potential exposure. Universal testing began during the study period and 13.3% of 76 asymptomatic patients tested after that date were COVID-19 positive. Of 48 neonates tested on day 0 by PCR, none tested positive for COVID-19. Conclusion: Pregnant women with COVID-19-related symptoms have a high rate of severe disease and preterm birth due to Cesarean delivery to treat maternal respiratory distress.

      May 20, 2020

      • Are Gastrointestinal Symptoms Specific for COVID-19 Infection? A Prospective Case-Control Study from the United States. May 19. Chen. Gastroenterology.
        Though this is the first prospective study of GI symptoms in COVID-19 patients, its findings are not surprising. This study from Baltimore was a prospective, case-controlled study of 340 consecutive patients tested by RT-PCR. Symptoms of anorexia and diarrhea, combined with the loss of smell and taste and fever predicted a positive test with 99% specificity. No mention is made of how patients were chosen for RT-PCR testing, no discussion of the influence of false negative test was given, and no patients under 18 yo were included.
      • COVID-19 update: Covid-19-associated coagulopathy
        May 15. Becker. Journal of Thrombosis and Thrombolysis.
        Opinion from SAB Member: Dr. Anil Hingorani, Dr. Lydia Cassorla, Dr. Joseph Anthony Caprini
        AH: This article contains very detailed data on COVID-19 and its effects on coagulopathy that includes basic science.
        LC: This comprehensive and detailed analysis of COVID-19 associated coagulopathy (bleeding and thrombosis phenotypes) is a deep dive into both what is known and speculation about pathophysiology. Overlapping and distinguishing features relative to DIC and thrombotic microangiopathies (including TTP, HUS, pre/eclampsia) are reviewed. Lab features of COVID coagulopathy more resemble DIC, with the exception of the absence of low platelet count. A useful table for comparison is provided. Virchow’s triad of pro-thrombotic factors holds strong. (Abnormal blood flow, vascular injury and abnormalities within the circulating blood). US and international guidelines regarding thromboprophylaxis are reviewed as the world awaits more definitive data from ongoing clinical trials.
        JC: This is an incredibly important paper describing the sophisticated array of changes associated with this viral infection. It is must reading for those interested in learning more about the pathophysiology of the disease. There are too many important points in this paper to repeat otherwise we would rewrite the paper. Most sentences are packed with information. What is important for all of us to understand is that this viral infection is much more than the coagulation system gone wild. In addition, no amount of heparin anticoagulation will be the answer to controlling the morbidity and mortality associated with this disease. The important take away is a concept introduced nearly 50 years ago by the famous hematologist Oscar Ratnoff. He described a “tangled hemostatic web” where contact activation pathways of the blood beginning with factor XII (Hageman factor) resulted in a triggering of platelet, coagulation, fibrinolysis, complement, and kallikrein pathways. The clinical result was not only thrombosis but also systemic vascular changes consistent with activation of both the inflammatory and immunologic pathways. The implications of this work quite clearly involved therapeutic approaches not only involving anticoagulation but also perhaps antiplatelet, anti-fibrinolytic, anti-inflammatory, and anti-immunologic therapy. We know there are various stages of the disease and introducing these modalities at different times may also be important. I personally feel that this knowledge intensifies my zeal for providing early and adequate anticoagulation to these patients along with anti-inflammatory and anti-immunologic therapy to prevent the progression of the disease.
      • Below are three recent literature reviews on neurological manifestations and complications of COVID-19 as well as possible psychiatric and neuropsychiatric effects on patients that are now available. Relying primarily on case reports and pre COVID-19 coronavirus research there is strong suspicion that SARS-CoV-2 gains access to both the central and peripheral nervous system directly and possibly to a larger extent than observed in SARS or MERS. While the etiological mechanisms of anosmia remain unclear, this early sign may be a clue to the neurotropism of the SARS-CoV-2 virus. Separating primary neurologic injury from secondary effects of severe illness, hypoxia, hyper-inflammatory state and multi-organ failure, represents an additional hurdle. While new onset psychiatric illness is unlikely to follow COVID-19 recovery, patients are prone to suffer post-traumatic stress disorder and its complex symptomatology.
        • Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review
          Apr 28. Montalvan. Clinical Neurology and Neurosurgery.
          Opinion from SAB Member: Dr. W. Heinrich Wurm
          This is a systematic review of 67 studies dealing with neurological manifestations of COVID-19, including encephalitis, Guillain Barre, multiple sclerosis, and stroke, but also reviewing available evidence of neurotropism of CoV observed during SARS and MERS. Direct viral access to the CNS through the cribriform plate and olfactory bulb and dissemination via trans-synaptic transfer to the peripheral nervous system remains under investigation, as is the invasion of the medullary cardiorespiratory center as a postulated cause of refractory respiratory failure observed in COVID-19. Future research into the expression of ACE2 receptors in neurological tissues could be the key to some of these questions.
        • Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic
          May 18. Rogers. The Lancet Psychiatry.
          Opinion from SAB Member: Dr. W. Heinrich Wurm
          This systematic review and meta-analysis of 70+ papers deals primarily with psychiatric sequelae of SARS-CoV and MERS-CoV and suggests that among patients admitted to hospital for severe SARS or MERS coronavirus infections, delirium is common acutely, whereas post-traumatic stress disorder, depression, anxiety, and fatigue are common in the following months. COVID-19 patients are likely to experience delirium, confusion, agitation, and altered consciousness, as well as symptoms of depression, anxiety, and insomnia but at this point there is not enough data to determine the overall extent and impact of such sequelae. Based on their review, the authors believe there is no indication that COVID-19 results in new onset mental illness.
        • Neurological manifestations and complications of COVID-19: A literature review
          Apr 24. Ahmad. Journal of Clinical Neuroscience.
          Opinion from SAB Member: Dr. W. Heinrich Wurm
          Narrative review covering the neurological manifestations of COVID-19 based on an English language literature search which at the time of submission (April 24th) consisted of only two series: one retrospective chart review from China (245 patients, 45% neurologic involvement), and one observational study from France (58 patients, 84% neurological involvement). Following a brief discussion of SARS-CoV2’s access to central and peripheral neurons, the authors postulate the two prime mechanisms responsible for neurological injury to be hypoxia and the COVID-19 immune response. What follows are a series of case reports of central and peripheral nervous system effects, including encephalopathies, encephalitis, and strokes, as well as anosmia, myelitis, Guillian Barre syndrome and a poorly defined but not infrequently seen syndrome of skeletal muscle damage accompanied by CPK elevations, severe muscle pain and signs of concomitant kidney and liver injury. The authors conclude with a call for clinicians to track and report more detailed information on neurological manifestations of COVID-19.
      • Unique Patterns of Cardiovascular Involvement in COVID-19. May 11. Hendren. J Card Fail.
        The authors described the variable presentations of cardiac involvement in COVID-19 within the broader spectrum of symptomatic SARS-CoV-2 infection, something that has previously been proposed. There are two phenotypes: cardiac involvement superimposed on top of the typical pulmonary predominate symptoms or isolated or predominate cardiac presentation. Though fever is common with typical pulmonary involvement, not so in the predominate cardiac phenotype. The troponin level with an isolated cardiac presentation can be absent or markedly elevated depending on the presentation. Though with a cardiac predominate disease there may be chest pain due to a myocardial infarction, patients with COVID-19 disease superimposed on pulmonary disease. Much speculation.

      May 19, 2020

      • Angiotensin II infusion in COVID-19-associated vasodilatory shock: a case series
        May 15. Zangrillo. Critical Care.
        Opinion from SAB Member: Dr. Philip Lumb
        This research letter details a trial of angiotensin II (ANGII) in 16 patients with vasodilatory shock resistant to high dose catecholamine (norepinephrine > 0.25 mcg/kg/min) as either first line or rescue infusion in a compassionate use protocol. Patients demonstrated improvement in oxygenation parameters associated with ANGII infusion; catecholamines were withdrawn or significantly reduced after 24 hours. Small series with interesting and favorable results.
      • Risk Factors of Severe Disease and Efficacy of Treatment in Patients Infected with COVID-19: A Systematic Review, Meta-Analysis and Meta-Regression Analysis. May 14. Zhang. Clin Infect Dis.
        This is an extensive meta-analysis and meta-regression of 45 studies (Asia only) with 4,203 patients, noted rates of intensive care unit (ICU) admission (10.9%), mortality (4.3%) and acute respiratory distress syndrome (ARDS) (18.4%). The investigators followed up with the regression analysis of these patients and studied the associations with the key epidemiological features, clinical characteristics, laboratory investigations, radiological findings, treatment details for outcomes of COVID-19. The investigators have statistically significant proof for their finding that: 1. elevated LDH is a significant predictive marker of ARDS; 2. Both elevated leukocyte count and elevated LDH suggests clinically a secondary infection and its complication on multi-systems which also predict the mortality; 3. Treatment with the anti-retroviral drug lopinavir-ritonavir was not associated (antiviral treatment likely to be all 6, 4 or 2 drugs) with any additional significant benefit on complications or outcome; and 4. corticosteroids were associated with possible harm.
        Strength: Extensive statistical proof while addressing biases. The publications included were GRADE (A method of exclusion) then addressed by several filters for the non-validity, has excellent graphs and tables. The secondary outcome (infection – 8.9% cardiac injury 7.8 %..) noted. Subgroup analysis for antiviral drugs and steroids are also complementary to the investigation.
        Weakness: No mention of -> Prone benefits, convalescent plasma therapy OR HCQ, LDH and its association with shock or antiviral Meds. Asian patients only (High tobacco?).
      • Smell and taste alterations in Covid-19: a cross-sectional analysis of different cohorts
        May 14. Paderno. Allergy & Rhinology.
        Opinion from SAB Member: Dr. J. Lance Lichtor
        In this study of a little over 500 patients who were either hospitalized or in quarantine with laboratory confirmed SARS-CoV-2 disease, whose data was collected between March 27 and April 1 via survey, the prevalence of olfactory and gustatory dysfunction was greater than 50%. There was a higher prevalence in home-quarantined patients (79% vs 72%). Hospitalized patients, though, had more dyspnea and a lower rate of flu-like syndrome. Indeed, because of a severe clinical condition and a decrease in oral intake, the perception of olfactory and gustatory dysfunction in the inpatient setting was likely lower than for outpatients. Outpatients were also younger, healthier, were less likely to smoke, and were more likely female.
      • Understanding pathophysiology of hemostasis disorders in critically ill patients with COVID-19
        May 15. Joly. Intensive Care Medicine.
        Opinion from SAB Member: Dr. Anil Hingorani, Dr. Joseph Anthony Caprini
        AH: This review of the literature of COVID-19 and its effects on coagulation is complete and bridges into the clinical effects of this knowledge.
        JC: This paper describes a number of interesting observations regarding the pathophysiology and clinical manifestations of this disease. The focus of this paper on heparin, while important, does not adequately reflect to the reader what is involved in the correlation between pathophysiology and various treatment modalities. The Becker paper captures more fully the myriad of pathophysiologic mechanisms, and provides a good source for the interested reader regarding these interactions in COVID-19. The bottom line for the treating physician is there is going to be a combination of therapeutic modalities including heparin at various stages of the disease needed to blunt the pathophysiologic changes described in this paper. Thromboelastography is mentioned in this paper as a possible way to measure the sum total of these effects using a global test. I’m a strong proponent of this method, having worked with it for many years, but it is not quite ready for clinical application except in prospective studies correlating the results with known hemostatic tests. Reminding us that evidence-based data is not available for full anticoagulation isn’t very helpful, especially since there are a number of reports showing a variety of beneficial effects with these treatment doses.

      May 16, 2020

      • A Game Plan for the Resumption of Sport and Exercise After Coronavirus Disease 2019 (COVID-19) Infection
        May 13. Phelan. JAMA Cardiology.
        Opinion from SAB Member: Dr. Barry Perlman
        Expert consensus opinion from members of the American College of Cardiology’s Sports & Exercise Cardiology Council, with input from national leaders in sports cardiology, regarding when those recovered from COVID-19 can return to recreational or competitive sports. Acute cardiac injury, based on elevated troponin, EKG changes, or ECHO abnormalities, occur in up to 22% of hospitalized COVID-19 patients. After myocarditis, return to play should require “normalization of ventricular function, absence of biomarker evidence of inflammation, and absence of inducible arrhythmias.” ECHO, stress testing, and rhythm monitoring are used to determine risk stratification after 3-6 months of exercise restriction. An algorithm is provided based on COVID-19 testing and symptoms: 1) Asymptomatic COVID-19 positive athletes or those who have detected antibodies indicating prior infection can slowly resume activity after 2 weeks; 2) If mild or moderate symptoms, a minimum of 2 weeks cessation of exercise training after symptoms resolve is recommended, and if cardiovascular evaluation including cardiac biomarkers and imaging reveal evidence of cardiac involvement, myocarditis return-to-play guidelines should be followed; 3) For those who were hospitalized or had more severe COVID-19, myocarditis return-to-play guidelines should be followed, and if cardiac biomarkers and imaging are normal after cardiac reevaluation graded, resumption of exercise can start at a minimum of 2 weeks after symptom resolution.
      • AGA Institute Rapid Review of the GI and Liver Manifestations of COVID-19, Meta-Analysis of International Data, and Recommendations for the Consultative Management of Patients with COVID-19
        May 1. Sultan. Gastroenterology.
        Opinion from SAB Member: Dr. David M. Clement
        This is an excellent paper from the American Gastroenterological Association for frontline workers wanting to understand and care for patients with GI disease during the COVID-19 pandemic. It starts with a detailed meta-analysis (47 studies with 10,890 patients) of GI symptoms and abnormal LFTs in patients with COVID-19. Overall, 10% of COVID-19 patients had GI symptoms and 15% had elevations of AST and/or ALT. Both GI symptoms and elevated LFTs were more common outside China. Occasionally, GI symptoms presented before other COVID-19 symptoms. Though fecal RT-PCR testing is commonly positive, culture of SARS-CoV-2 is rarely successful. Numerous tables are included, such as the GI side effects of commonly used COVID-19 drugs. Based on all pooled information, guidelines are presented for frontline providers dealing with GI symptoms in the COVID-19 era. These include, among others, checking for other etiologies of GI symptoms in outpatients, following LFTs on COVID-19 inpatients, not testing stool, and following outpatients with GI symptoms alone in case they develop COVID-19.
      • Anaesthesia and intensive care in obstetrics during the COVID-19 pandemic. May 6. Morau. Anaesth Crit Care Pain Med.
        This is a complete recommendation list to all personnel, how to prepare for COVID-19 environments at labor and delivery (L&D) room. The author points out that L&D cannot afford to hold back and has to continue to perform the duty irrespective of the pandemic which is of high transmissibility and infectivity of this virus. The authors have provided management skills required for this disease in detail regarding all system involvements and their complications that pertain to parturient. The authors review the antenatal, post and intra natal care, role of triage, role of testing for COVID-19, anesthetic care, pain treatment, staff training…and stresses the need for PPE but be prepared for telemedicine where it’s possible, infection control, and a need to be vigilant of known complications to mother/fetus and offers practical points. A helpful guide to all L&D staff.
      • Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19. May 12. Liang. JAMA Intern Med.
        Developed a prediction model for composite end point of ICU admit, need for a ventilator, and death based on ten variables: cxray abnormality, age, hemoptysis, dyspnea, unconsciousness, # of comorbidities, cancer hx, neutrophil/lymphocyte ratio, LDH, and direct bilirubin.
      • Gastrointestinal and Liver Manifestations of COVID-19. Mar 1. Agarwal. J Clin Exp Hepatol.
        A brief literature review of GI symptoms and elevated LFTs in COVID-19 patients. Mostly data from China, somewhat dated.

      May 15, 2020

      May 14, 2020

      • Liver injury is associated with severe Coronavirus disease 2019 (COVID-19) infection: a systematic review and meta-analysis of retrospective studies. May 10. Parohan. Hepatol Res.
        From 212 articles from around the world (English & non-English literature), 20 articles were selected from various sources by Iranian investigators, 3,428 patients were entered in meta-analysis with complete records. They followed by a systematic review and meta-analysis, analyzing the laboratory findings and trying to ascertain the mechanism of liver injury caused by COVID-19 infection. Here is an excellent effort for the collection, analyzing and applying of appropriate statistics for the data by the authors. They noted that a mild to moderate derangement of liver profile (AST, ALT, total Bilirubin and Albumin levels) was associated with severe outcome from COVID-19 infection. But offer a limited inference of mode of injury except to point out a derangement of endothelial ACE2 cells in liver and or in biliary tree, perhaps toxicity of anti-viral drugs and inflammatory cytokine production abnormality or maybe part of MOF.
      • RAAs inhibitors and outcome in patients with SARS-CoV-2 pneumonia. A case series study. May 9. Conversano. Hypertension.
        Retrospective, observational study of 191 confirmed COVID-19 patients from one Italian hospital. 50% had HTN, and 70% of those were on ACEI or ARBs. 28 patients were still hospitalized at the end of the study. Age, HF, and CKD were univariate predictors of mortality, but HTN and ACEI/ARB treatment were not.

      May 13, 2020

      • Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019. May 12. Shi. Eur Heart J.
        No real news here, but large number of cases and associated data illustrate that cardiac involvement is an important predictor of death with COVID-19. All consecutive patients admitted to Renmin Hospital of Wuhan University between 1/1/20 and 2/23/20 with laboratory-confirmed COVID-19 were included in this retrospective study. Data from 671/1001 unique severe cases with adequate information was analyzed. Study period ended on a given date, not with definitive outcome. A great deal of data is presented, not only regarding myocardial injury. 62(9.2%) died of whom 75.8% had elevated initial cardiac troponin (cTnl), vs 9.7% of survivors. Among many other factors, (none surprising), elevated cTnI, CK-MB and NT-ProBNP levels were predictors of risk for in-hospital death, along with age, CV morbidities and inflammatory response. cTnI > 0.026 ng/mL was associated with a hazard ratio of 4.56.
      • Characteristics and outcomes of patients hospitalized for COVID-19 and cardiac disease in Northern Italy. May 9. Inciardi. Eur Heart J.
        A retrospective case review of 92 consecutive COVID-19 patients admitted to a single center in Italy. Those with pre-existing heart disease (AF, CHF, CAD) had higher rates of thrombo-embolic and pulmonary complications, and higher death rates.
      • Clinical and histological characterization of vesicular COVID-19 rashes: A prospective study in a tertiary care hospital
        May 8. Fernandez‐Nieto. Clinical and Experimental Dermatology.
        Opinion from SAB Member: Dr. Barry Perlman
        There are now many reports of COVID-19 patients presenting with or having associated cutaneous lesions. This is a prospective observational study of vesicular lesions in 24 COVID-19 patients in Spain. 29% had prior history of dermatologic conditions. 75% had a disseminated pattern with the rest having a more localized one. Median rash duration was 10 days. Rashes developed a median 14 days after COVID-19 diagnosis, prior to COVID-19 treatment in 71%. Skin biopsy in 2 patients showed histology consistent with viral infection. PCR tests performed on vesicular fluid in 4 patients were negative in 4/4 for SARS-CoV-2 and herpes virus.
      • Clinical course of severe and critical COVID-19 in hospitalized pregnancies: a US cohort study. 5/12/20. Pierce-Williams RAM. Am J Obstet Gynecol MFM.
        Review by the SAB
        By Dr. Jay Pryzbylo, on behalf of the SAB
        Data-rich, multicenter study of COVID-19 severe and critically ill women in third trimester pregnancy. Of the many findings, critically ill women required intubation, delivered prematurely mostly for maternal risk, the newborns were COVID-19 negative, 1 of 64 women required a tracheostomy. Matched to a non-pregnant control group, pregnancy did not alter outcome.
      • Coronavirus Disease-2019 with Dermatologic Manifestations and Implications: An Unfolding Conundrum. May 9. Almutairi. Dermatol Ther.
        4 categories of dermatological effects of COVID-19 are discussed:
        1. Cutaneous manifestations. Include urticaria, varicella-like vesicles, transient livedoid eruptions, livedoid vasculopathy, purpuric eruptions, lichenoid photodermatitis, erythroderma, photo-contact dermatitis, and generalized pustular figurate erythema
        2. Skin changes from lifestyle alterations, such as prolonged PPE contact and excessive personal hygiene
        3. Medication adverse cutaneous effects. For example, chloroquine and hydroxychloroquine can aggravate pre-exisitng psoriases or cause potentially severe cutaneous reactions
        4. Effect on primary skin diseases and their treatment. Guidelines recommend continuing immune-modulating treatments despite COVID-19
      • Cutaneous manifestations of the Coronavirus Disease 2019 (COVID-19): a brief review. May 7. Tang. Dermatol Ther.
        Review of 14 PubMed articles on cutaneous manifestations of COVID-19 in 88 patients. Skin lesions were typically erythematous, urticarial, or vesicular. 1 patient had no other symptoms.
      • Cutaneous Signs in COVID-19 Patients: A Review
        May 10. Wollina. Dermatologic Therapy.
        Opinion from SAB Member: Dr. Barry Perlman
        Detailed review describing reported cutaneous symptoms of COVID-19. ACE2 receptors are found in skin and adipose tissue. SARS-CoV-2 associated pulmonary and cutaneous fibrosis both involve transdifferentiation of adipocytes or lipo-fibroblasts into myofibroblasts. Adipocytes can act as a viral reservoir. The different cutaneous manifestations are described, along with differential diagnosis and associated COVID-19 presentation. Chilblain-like acral eruptions, purpuric and erythema multiforme-like lesions have been seen in children and young adult patients with asymptomatic or mild COVID-19. Acro-ischemic lesion and maculopapular rash are often seen in adult patients with more severe disease. Urticaria with pyrexia can be an early symptom of SARS-CoV-2 infection. Attention to cutaneous signs may aid in diagnosis, triage, and risk stratification of COVID-19 patients.

      May 12, 2020

      • In-hospital cardiac arrest outcomes among patients with COVID-19 pneumonia in Wuhan, China
        Apr 2. Shao. Resuscitation.
        Opinion from SAB Member: Dr. David M. Clement
        This study documents the poor outcomes for in-hospital cardiac arrest (IHCA) in severe COVID-19 patients. It is a retrospective, observational study from China, of 136 patients with IHCA. Most were monitored, had witnessed arrests, and received CPR in under a minute. Most IHCA had respiratory causes, 94% had asystole or PEA, and only 6% had shockable rhythms. Return of spontaneous circulation was achieved in 13%, with 3% surviving at least 30 days and only one patient surviving with an acceptable neurologic outcome at 30 days.
      • Misinformation During the Coronavirus Disease 2019 Outbreak: How Knowledge Emerges From Noise
        Apr 1, 2020. Rochwerg. Critical Care Explorations.
        Opinion from SAB Member: Dr. Lydia Cassorla
        This well articulated narrative review by authors from Canada, New Zealand, and the US outlines the challenges and opportunities for both the media and researchers to develop knowledge in the face of an information storm. Much of the media is driven by corporate interests rather than a desire to meticulously vet sources and research quality, fanning hysteria. There are important benefits to the “live update” culture, however, consumers are advised to carefully consider the reliability of their sources in both lay press and medical publications. During a pandemic, conventional research and publishing practice are out of synch with the need for rapid information and dissemination, as they require months to years. Major publications have prioritized and made accessible COVID-19 related work to help overcome barriers to rapid, peer-reviewed work and combat misinformation. Nonetheless, some reports remain questionable. The concept of “living guidelines”, frequently updated as evidence emerges, is discussed. The authors highlight the benefit of advance planning to accelerate clinical trials, governmental support, targeted funding and collaboration with industry to optimize the reliability of research output when pandemics occur.
      • Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials. Dec. 18, 2003. Smith. BMJ.
        Parachute use to prevent death and major trauma when jumping from aircraft: randomized controlled trial. The study highlights a. The importance of the conclusion when writing and reading a manuscript and b. Randomization might not always be possible: in designing studies, investigators must always consider equipoise.
      • Seven alternatives to evidence based medicine. Dec. 19, 1999. Isaacs. BMJ.
        A short, easy to read, tongue in cheek (maybe) analysis of decision making styles when there is inadequate evidence on which to base a clinical decision. Cheer up! We have all been there in the past, and frequently find ourselves in this situation with COVID-19.

      May 11, 2020

      • Respiratory advice for the non-respiratory physician in the time of COVID-19
        May 4. Bennett. Clinical Medicine Journal.
        Opinion from SAB Member: Dr. David M. Clement
        A pre-print review from the British Thoracic Society mostly describing one approach to the pre-ICU respiratory care of hospitalized COVID-19 patients. The emphasis is on coordinated assessments, cooperation between personnel, and the systematic alteration of respiratory treatments as patient parameters hit certain thresholds. Healthcare worker safety and efficiency, do-not-intubate preferences (“ceilings of care”), proning before intubation, oxygen therapy (esp. CPAP) and triggers for transfer to the ICU are reviewed. Several tables and diagrams help explain this strategy.
      • Should COVID-19 take advice from rheumatologists?
        May 7. Kernan. Lancet Rheumatology.
        Opinion from SAB Member: Dr. J. Lance Lichtor
        Anakinra is a drug that has had success treating patients with auto-inflammatory diseases and now, there is evidence that the drug may also be useful in managing patients with COVID-19 disease who also have acute respiratory distress syndrome. The authors summarized the results seen in the study “Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study” (below). As the authors note: “these and other emerging data rightly focus more attention on the host inflammatory response and might herald a shift in how we approach the host-virus relationship.”
      • Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study
        May 7. Cavalli. Lancet Rheumatology.
        Opinion from SAB Member: Dr. J. Lance Lichtor
        The authors first noted that of 16 patients treated between March 10 and March 17, 2020 with COVID-19, ARDS, and hyper-inflammation who were managed with CPAP outside of the ICU, that 21-day survival was 56%. Another similar group of patients receive low dose anakinra (100 mg twice a day) and did not do much better. But when instead high-dose intravenous anakinra (5 mg/kg twice daily) was used, survival increased to 90% at 21 days.
      • Targeting the inflammatory cascade with anakinra in moderate to severe COVID-19 pneumonia: case series. May 6. Aouba. Ann Rheum Dis.
        When some people are fighting a COVID-19 infection, it may not be the virus itself that’s causing distress, but the exaggerated host response in the form of a cytokine storm the body uses to fight off the infection. In this letter to the editor, the authors used anakinra, an anti-IL-1 blocking drug, in this study administered subcutaneously for 9 consecutive patients with SARS-CoV-2 infection confirmed by reverse transcription-PCR on nasopharyngeal swabs hospitalized in a non-ICU, with oxygen flow of ≤6L/min, and C reactive-protein levels ≥50mg/L. One patient developed acute respiratory failure 6 hours after the first and only dose of anakinra, leading to premature treatment cessation and ICU admission. The other 8 patients had good outcomes and C reactive protein (CRP) levels decreased steadily but only partially by 6 days in all, and normalized in 5/8 patients by day 11. In addition, at last followup, all patients were alive. The study was not randomized, but the results are promising.

      May 9, 2020

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

      May 8, 2020

      • Autoimmune hemolytic anemia associated with Covid-19 infection. May 7. Lazarian. Br J Haematol.
        Opinion from SAB Members: Drs. Philip Lumb and Joseph Anthony Caprini
        PL: Series of 7 Covid-19 positive patients from six different French and Belgian hospitals who developed autoimmune hemolytic anemia during admission. Patient demographics presented with associated co-morbidities; timeframe consistent with development of cytokine storm. Authors recommend screening for presence of a lymphoid clone in patients with Covid-19 infections and autoimmune cytopenias.
        JAC: The abstract states it well and I include it here- “Although the pathophysiology underlying severe Covid‐19 remains poorly understood, accumulating evidence argue for hyperinflammatory syndrome causing fulminant and fatal cytokines release associated with disease severity and poor outcome (Mehta et al, 2020).
        However, the spectrum of complications is broader and include among others various autoimmune disorders such as autoimmune thrombocytopenia, Guillain-Barré and antiphospholipid syndrome (Zhang et al, 2020; Zulfiqar et al, 2020; Toscano et al, 2020). In this report we describe 7 patients from 6 French and Belgian Hospitals who developed a first episode of autoimmune hemolytic anemia (AIHA) during a Covid-19 infection.”
      • Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study
        May 6. Wichmann. Annals of Internal Medicine.
        Opinion from SAB Member: Dr. Lydia Cassorla, Dr. Joseph Anthony Caprini
        LC: This fascinating report from Hamburg Germany describes the findings of complete autopsy reports, as mandated by law, of the first 12 consecutive known COVID-19 deaths in their city. “In all cases the cause of death was in the lungs or the pulmonary vascular system”. Unsurprisingly, patients were older (10/12 >60 yrs) and all had pre-existing co-morbidities and pneumonia at death. They trended obese with BMI of >30 in 5 and nearly 30 in a sixth. The focus of the report is on the high incidence (7/12 or 58%) of venous thrombosis with 4/12 dying of PE. D-dimer was measured in 5 patients on admission, all elevated. 3/5 of those with elevated D-dimer had venous thrombosis including 2 PE deaths. 3 patients had some form of anticoagulation therapy, including 2 PE deaths. There is a trove of additional information in this report as each death resulted in a full autopsy, a post mortem total body CT in all but 2, histopathology and virology. SARS–CoV-2 RNA was present in high titers in the lungs in all, and in the blood in 6/10. The authors suggest that their findings support proactive anticoagulant therapy for hospitalized patients as well as potentially for outpatients. JC: In this autopsy study of 12 consecutive patients who died of COVID-19, we found a high incidence of deep venous thrombosis (58%). One third of the patients had a pulmonary embolism as the direct cause of death. Furthermore, diffuse alveolar damage was demonstrated by histology in 8 patients (67%). The CT images of the ground glass appearance in the lungs is chilling. They indicate the need for more than heparin and some have raised the possibility of steroids. The association between fatal outcomes and pre-existing risk factors, particularly CV disease is also striking.

      May 7, 2020

      • ACE2, COVID-19, and ACE Inhibitor and ARB Use during the Pandemic: The Pediatric Perspective. May 6. South AM. Hypertension.
        A thorough description of the effect of COVID-19 on renin-angiotensin including perspective particular to pediatrics including small percentage of affected patients. The significance is that pediatrics is the focus with the conclusion: At this time, there is no evidence that children with hypertension, cardiovascular disease, or chronic kidney disease, and/or those who are taking ACE inhibitors or ARBs, are at increased risk of SARS-CoV-2 infection or more-severe COVID-19.
      • Coronavirus disease 2019 (COVID-19) and the renin-angiotensin system: a closer look at angiotensin-converting enzyme 2 (ACE2)
        May 5. Zemlin. Annals of Clinical Biochemistry: International Journal of Laboratory Medicine.
        Opinion from SAB Member: Dr. Barry Perlman
        In depth review of SARS-CoV-2, COVID-19, the renin-angiotensin system, the relationship between ACE2 and COVID-19, use of ACE-I and ARB with COVID-19, and possible RAS related targets for COVID-19 treatment.
      • Early recovery following new onset anosmia during the COVID-19 pandemic – an observational cohort study. May 6. Hopkins C. J Otolaryngol Head Neck Surg.
        Post-viral loss of sense of smell accounts for up to 40% of anosmia cases. Nasal respiratory and epithelial cells and olfactory epithelial cells have high levels of ACE2. Survey of 382 patients with presumed COVID-19 — only 15 had been tested and of those 80% were positive. 86% had complete anosmia and 12% had severe anosmia. For 17% this was their only symptom. 80% reported improvement in 1 week. Recovery plateaued after 3 weeks. Limitation of study was low rate of confirmatory COVID-19 testing.
      • High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study
        May 4. Helms. Intensive Care Medicine.
        Opinion from SAB Member: Dr. Louis McNabb, Dr. Joseph Anthony Caprini
        LM: Study of 150 patients in an ICU setting. The main clinical threat was PE at 16%. There was a high incidence of catheter clotting, particularly for patients on dialysis (28/29). Most of patients were on at least prophylactic anticoagulation. 67% of patients were still intubated at time of data analysis, which may have led to underestimation of thrombotic risk, Lupus anticoagulant was found in 50/57 patients. No DIC was noted, but this result may reflect early termination of the study. Curiously, non-COVID-19 patients with ARDS had higher D-dimer levels. JC: In a prospective cohort study, we have shown that sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients with COVID-19 ARDS during their ICU stay, mainly pulmonary embolisms (25 patients, 16.7%). Despite anticoagulation, a high number of patients with COVID-19 ARDS developed life-threatening thrombotic complications, meaning that higher anticoagulation targets than in usual critically ill patients should probably be considered.
      • Incidence of venous thromboembolism in hospitalized patients with COVID-19
        May 5. Middeldorp. Journal of Thrombosis and Haemostasis.
        Opinion from SAB Member: Dr. Louis McNabb
        This is an article describing 198 hospitalized patients of which 38% were in the ICU. 20% were diagnosed with VTE, of which 13% were symptomatic. Most patients were on prophylactic anticoagulation in the medical units. Patients in the ICU received BID prophylactic anticoagulation (double standard regimen). The key point to this paper is that clinicians need to be vigilant looking for VTE in patients with less severe COVID-19 disease.
      • Interim Guidance for Basic and Advanced Life Support in Children and Neonates With Suspected or Confirmed COVID-19. May 6. Topjian A. Pediatrics.
        A prepublication Scientific Statement from the American Association of Critical Care Nurses and including authorship of physicians across North America. A step by step guide to resuscitating children from time of birth on with special attention to COVID-19.
      • Olfactory Dysfunction: A Highly Prevalent Symptom of COVID-19 With Public Health Significance. May 6. Sedaghat AR. Otolaryngol Head Neck Surg.
        In this state of the art review, the scientific evidence that relates to olfactory dysfunction in the face of COVID-19 is reviewed. A high prevalence of olfactory dysfunction is noted in patients with COVID-19 using objective measures of olfactory testing. Also, the presence of olfactory dysfunction might also be useful to predict patients who might develop COVID-19. Most patients with olfactory dysfunction will note improvement after 1-2 weeks just as symptoms of COVID-19 improve.
      • The Prevalence of Olfactory and Gustatory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-analysis. May 6. Tong JY. Otolaryngol Head Neck Surg.
        In this meta-analysis of 10 studies, all published in 2020, that included patients from studies in North America, Europe, and Asia, 1600 patients were analyzed. Over 50% of patients had some level of olfactory dysfunction and almost 50% had some level of gustatory dysfunction. For many patients also, olfactory dysfunction was a presenting symptom. Screening patients for olfactory dysfunction may be indicative of COVID-19 infection.
      • Understanding Observational Treatment Comparisons in the Setting of Coronavirus Disease 2019 (COVID-19)
        May 5. Thomas. JAMA Cardiology.
        Opinion from SAB Member: Dr. J. Lance Lichtor
        In this editorial, concerning patients with COVID-19, hypertension, diabetes, and cardiovascular disease may be vulnerable and are more likely to be taking angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs). Based on the Mehta study (below), patients taking those drugs can continue taking the drugs given the current pandemic given the fact that these patients are not more likely to be susceptible to the disease, though based on a secondary analysis, the severity of disease might be greater in terms of need for hospitalization and ICU admission. Yet, it’s possible also that the presence of cardiovascular disease and other comorbidities lowers the threshold on the part of referring clinicians to hospitalize and move to the ICU those individuals considered to be at higher risk than the general population. These secondary findings, though real, should not be considered as causal.
        • Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19)
          May 5. Mehta. JAMA Cardiology.
          Opinion from SAB Member: Dr. J. Lance Lichtor
          As has been discussed in previous articles this newsletter has referenced, SARS-CoV-2 binds to the extracellular domain of the transmembrane angiotensin-converting enzyme 2 (ACE2) receptor to gain entry into host cells; patients who are taking angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers are theoretically at an increased risk for becoming infected with SARS-CoV-2 or may have worse outcomes; upregulation of angiotensin-converting enzyme 2 may improve outcomes in infection-induced acute lung injury in patients with SARS-CoV or SARS-CoV-2 infections; and in certain high-risk patients, the withdrawal of ACEIs or ARBs may be harmful. In this retrospective analysis of 18,472 patients tested for SARS-CoV-2, taking either an angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers was not associated with an increase in the likelihood of testing positive for SARS-CoV-2 infection.
      • Venous thromboembolism and heparin use in COVID-19 patients: juggling between pragmatic choices, suggestions of medical societies
        May 4. Profidia. Journal of Thrombosis and Thrombolysis.
        Opinion from SAB Member: Dr. Lydia Cassorla, Dr. Joseph Anthony Caprini
        LC: This editorial states that while most guidelines are currently recommending antithrombotic prophylaxis for all hospitalized COVID-19 patients, and full anticoagulation for a subset, questions remain about which population may benefit from therapeutic doses of anticoagulation. It is a call to share data via registries and arrive at a consensus at a time when randomized controlled clinical trials may not be able to answer the question in a timely manner. JC: This is a very good discussion from the data driven point of view including extrapolation of pre-existing data to the clinical presentation and course of patients with COVID-19. Unfortunately, it is a whole new ball game and we need to learn on the job.

      May 6, 2020

      • Management of acute ischemic stroke in patients with COVID-19 infection: Report of an international panel
        May 3. Qureshi. International Journal of Stroke.
        Opinion from SAB Member: Dr. Barry Perlman
        Multinational expert consensus for management of acute ischemic stroke in COVID-19 patients. 5% incidence of acute ischemic stroke is noted in COVID-19 patients, and such events are associated with older age, hepatic and renal dysfunction, HTN, DM, cerebrovascular disease, and elevated D-dimers. Mortality rate of 38% dependent on severity of COVID-19 infection. Possible undiagnosed COVID-19 infection should be suspected in patients with acute stroke, as some may have difficulty communicating due to the stroke. Since renal insufficiency is common with COVID-19 infection, risk of contrast-induced nephropathy should be considered prior to neuroimaging. Coagulation assessment can help determine risk benefit of IV rt-PA. Mechanical thrombectomy with low threshold for intubation and general anesthesia may be considered on case-by-case basis. Single or dual antiplatelet therapy may be considered for patients who do not receive IV rt-PA or mechanical thrombectomy. Risk of healthcare provider infection and mitigation strategies are also discussed.
      • Medical treatment options for COVID-19. May 4. Delang. Eur Heart J Acute Cardiovasc Care.
        There is an urgent need for treatment for this COVID-19 pandemic from all quarters of the world. Several clinical trials with COVID-19 patients are evaluating “repurposed drugs”, but there is no uniformity in timing, duration of treatment and study endpoints. Currently, there are registered clinical trials pertaining to one or more clinical outcomes in 66% of the studies, virological in 23%, radiological in 8%, or immunological in 3%. Repurposing of existing antiviral and immunomodulating drugs is an important strategy, because the safety profile of these drugs is well known. In the solidarity (started in April worldwide), a clinical trial launched by the WHO, is appealing due to simplicity. On 7 March 2020, the most frequently evaluated antiviral therapies were lopinavir/ritonavir (LPV/r) (n=15), chloroquine (n= 11), arbidol (n= 9), hydroxychloroquine (n= 7), favipiravir (n=7) and remdesivir (n= 5). Immune modulating drugs: IL-6 inhibitors – receptor antagonist – Tocilizumab (Actemra) and Granulocyte-macrophage colony-stimulating factor. Both critical role immune response and/or macrophage activation syndrome (MAS).

      May 5, 2020

      • Acute myocardial injury is common in patients with Covid-19 and impairs their prognosis
        Apr 6. Wei. Heart.
        Opinion from SAB Member: Dr. Philip Lumb
        101 patient prospective study from January to March 10, 2020 in Sichuan, China with primary endpoints including cardiac injury defined by above normal high-sensitivity troponin T (hs-TnT) levels. Study confirms that myocardial involvement in COVID-19 is common and that elderly and patients with underlying cardiovascular disease at increased risk.
      • Cardiac considerations in patients with COVID-19
        May 1. Calvillo-Argüelles. CMAJ.
        Opinion from SAB Member: Dr. Louis McNabb
        Five key points on cardiac considerations for COVID-19 in a convenient one-page summary.
      • Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the Coronavirus Disease 2019 (COVID-19) Pandemic
        Mar 17. Driggen. JACC.
        Opinion from SAB Member: Dr. Jay Przybylo
        An exhaustive State-of-the-Art Review with complete recommendations concerning every phase of COVID-19 cardiac involvement from presentation by phone through hospitalization and including all forms of cardiac pathology to healthcare worker precautions. Multiple tables with reviews from previous studies and 100+ references included.
      • Characteristics, treatment, outcomes and cause of death of invasively ventilated patients with COVID-19 ARDS in Milan, Italy. May 1. Zangrillo. Crit Care Resusc.
        Many with COVID-19 end up requiring critical care and then die. It might be useful to better predict who might die to better plan critical care resources. Of 73 invasively ventilated patients with COVID-19 ARDS in a referral centre in Milan, Italy male sex and hypertension were disproportionately common; one in 15 patients was treated with ECMO; and one in five with RRT. Most patients received vasopressors and neuromuscular blocking agents, three out of four patients were treated with prone positioning, and three in ten received a tracheostomy. After a medical followup of 20 days, about 15% died. This was a single center study, and though more granular data was provided, this was not really a guide concerning who should or should not receive intensive care.
      • Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan, China. May 2. Wang. Crit Care.
        Retrospective study of 107 COVID-19 patients discharged from 2 hospitals in Wuhan, China.
        Week 1 after onset — fever, though dyspnea, lymphopenia, multi-lobar pulmonary infiltrates. In severe cases, thrombocytopenia, acute kidney injury acute myocardial injury and ARDS.
        Week 2. Fever, cough, systemic symptoms, and thrombocytopenia began to resolve with persistent lymphopenia in mild cases, while in severe cases leukocytosis, neutrophilia, and multi-organ dysfunction were seen.
        Week 3. Mild cases clinically resolved with persistent lymphopenia. Severe cases showed persistent lymphopenia, severe ARDS, refractory shock, anuria, coagulopathy, thrombocytopenia, and death.
        88 survived. Duration of active viral shedding in survivors was 13 days. Non-survivors were older, predominantly male, had more co-morbidites such as HTN or CV disease, and were more likely to present with with dyspnea, diarrhea. They had higher neutrrophil count, D-dimer, BUN, creatinine, HS-troponin I, CK, CK-MB, LDH, ALT, and AST and had lower platelets. Causes of death included refractory ARDS, septic shock, sudden cardiac arrest, hemorrhagic shock and AMI.
      • Coagulopathy associated with COVID-19
        May 4. Lee. CMAJ.
        Opinion from SAB Member: Dr. Louis McNabb
        5 key points in a concise one-page summary on where we are in our understanding of coagulopathy issues for COVID-19.
      • COVID-19 and acute myocardial injury: the heart of the matter or an innocent bystander?
        Apr 30. Cheng. Heart.
        Opinion from SAB Member: Dr. Philip Lumb
        Short but valuable review of myocardial involvement in COVID-19 with relevant literature reviews, and a useful table of potential mechanism and diagnostic limitations in myocardial injury. Recognizes the current therapeutic dilemmas facing clinicians in order to maximize myocardial preservation and/or recovery.
      • COVID-19 and Neonatal Respiratory Care: Current Evidence and Practical Approach. May 3. Shalish. Am J Perinatol.
        An international group of perinatologists reviewed reports of COVID-19 infections under 10 y/o noting the incidence is rare, less than 1% of all cases. In newborns the number is lower. Recommendations for care are listed.
      • Inhibitors of the Renin-Angiotensin-Aldosterone System and Covid-19
        May 1. Jarcho. The New England Journal of Medicine.
        Opinion from SAB Member: Dr. David M. Clement
        Editorial reviewing the theoretical concerns for the use of ARB/ACEI drugs during the COVID-19 epidemic, and three observational clinical studies that conclude these drugs seem not to influence the course of the disease. This is consistent with other studies and guidelines from pertinent organizations; that ARB/ACEI drugs should be continued if a patient develops COVID-19 disease.
      • Olfactory and Gustatory Dysfunction in Coronavirus Disease 19 (COVID-19)
        May 1. Luers. Clinical Infectious Diseases.
        Opinion from SAB Member: Dr. J. Lance Lichtor
        72 patients with polymerase chain reaction confirmed COVID-19 agreed to participate and were enrolled in this study. Reduced olfaction was noted in 74% and a reduced sense of taste was noted in 69%. 68% reported both symptoms. Both symptoms occurred on average on the 4th day after first symptoms were noted, though 13% noted reduced olfaction and taste on the first day of COVID-19 symptoms.
      • Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19. May 2. Reynolds. N Engl J Med.
        A retrospective, observational study from New York of 12,594 patients on various anti-hypertensive medications. Sophisticated statistical analysis showed no association of any class of drugs (including ARBs/ACEIs) and the presence or severity of COVID-19 disease.
      • The Renin-Angiotensin-Aldosterone System in Coronavirus Infection-Current Considerations During the Pandemic. May 4. Augoustides. J Cardiothorac Vasc Anesth.
        An editorial reviewing what is known, being studied, and speculated about the RAAS system’s contributions to the clinical spectrum of COVID-19 disease.

      May 2, 2020

      • Cardiovascular Consequences and Considerations of Coronavirus Infection – Perspectives for the Cardiothoracic Anesthesiologist and Intensivist During the Coronavirus Crisis
        May 1. Augoustides. Journal of Cardiothoracic and Vascular Anesthesia.
        Opinion from C19SAB: Dr. Barry Perlman
        Editorial discussing causes of cardiovascular collapse in patients with severe COVID-19, focusing on Cardiogenic shock, vasoplegic shock, acute coronary ischemia, and right ventricular failure.
      • COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options
        Apr 30. Guzik. Cardiovascular Research.
        Opinion from C19SAB: Dr. Philip Lumb, Dr. Lydia Cassorla
        PL: Detailed, research-oriented discussion on cardiovascular implications of COVID-19 infection. Mechanisms of infection described with experimental justification for potential interventions; recognizes supportive care required for most cases. Discusses (albeit briefly) progression to invasive therapies including ECMO. Basic science oriented with clearly described mechanisms and exhaustive review of available literature with references to match. LC: This comprehensive review of COVID-19 illness with a particular eye toward cardiovascular ramifications may raise more questions than it answers. However, it is well written and thoroughly referenced to be consumed when time permits careful reading. Regarding CV complications: “The most common cardiac complications include arrhythmia (AF, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury (elevated hs-cTnI and CK), fulminant myocarditis, and heart failure.” The authors point out that since cardiac manifestations often occur >15 d after onset of symptoms, they are possibly a result of host-driven phenotypes and/or secondary effects of medications. They mention that inclusion bias may result from specific factors in the area where a pandemic begins and expect data to differ as the disease population changes. Surprisingly, a history of smoking or chronic lung disease is less of a risk for poor outcomes than with SARS-CoV (2003) or MERS. HTN/CV disease are risk factors for advanced disease and death but not for infection and may partly be a proxy for age. When acute myocardial injury occurs, PCI may not always benefit patients as their ischemia may be due to Type 2 MI or myocarditis.
      • Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy
        Apr 23. Lodigiania. Thrombosis Research.
        Opinion from SAB Member: Dr. J. Lance Lichtor, Dr. Joseph Anthony Caprini
        JLL: Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. The study is based on retrospective data for 388 admitted hospitalized patients with COVID-19. All ICU patients received thromboprophylaxis and 75% of those admitted to general wards also had thromboprophylaxis. Thromboembolic events occurred in almost 8% of patients which included pulmonary embolism. A little over half of the patients with PE did not receive anticoagulant treatment. Hospital mortality was associated with a high rate of thromboembolic complications. Rapidly increasing D-dimer levels were observed in non-survivors. A true incidence is difficult to determine since, as the reader is told in the discussion, a low number of specific imaging tests were performed. JC: The low incidence of thrombotic events on the ward compared to the ICU is one feature of this series. The fact that 58% of thrombotic events were not on anticoagulation is telling. We know all patients should be on anticoagulation. That has not been their routine practice in the past in many medical patients not in ICU. The paper sends the wrong message advocating for more tests which exposes scanners and machines to risks that may be avoided. Giving everyone anticoagulation and adjusting the dose based on co-morbidities and when the D-dimers skyrocket using full dose anticoagulation. We are learning as we go along but more heparin or LMWH is the developing trend.

      May 1, 2020

      • Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases
        Apr 29. Casas. British Journal of Dermatology.
        Opinion from C19SAB: Dr. Barry Perlman
        Description of 5 clinical patterns of cutaneous lesions associated with 375 COVID-19 cases in Spain, in order of associated severity of disease: 1. Acral areas of erythema with vesicles or pustules (Pseuo-chilblain). Appears late, more common in younger patients; 2. Other Vesicular eruptions. More common in middle aged patients; 3. Urticarial lesions; 4. Maculopapular eruptions. Most common; 5. Livedo or Necrosis. Consistent with occlusive vascular disease.
      • Factors associated with mortality in patients with COVID-19. A quantitative evidence synthesis of clinical and laboratory data. Apr 20. Martins-Filho. Eur J Intern Med.
        For this meta-analysis a literature search performed January 1- April 06, 2020 led to screening 8692 titles and abstracts among which 73 full-text articles were assessed for eligibility and 69 were excluded, 11 due to potential overlapping data. Data in the report is from only four retrospective Chinese studies encompassing 852 unique patients (489 male and 363 female) with confirmed SARS-CoV-2 infection by RT-PCR: 603 survivors and 249 non-survivors. The study reports increased risk for in-hospital death in older patients (MD= 13.8, 95%CI 8.0 to 19.7), male gender (RR= 1.3, 95%CI 1.1 to 1.4), with comorbidities (RR= 1.6, 95%CI 1.4 to 2.0) and dyspnea (RR= 1.8, 95%CI 1.4 to 2.2). The report details the relative risk for death of dozens of clinical and laboratory findings. There are no surprises.
      • Hypercoagulation and Antithrombotic Treatment in Coronavirus 2019: A New Challenge. Apr 30. Violi. Thromb Haemost.
        The authors analyzed variables regarding clotting and fibrinolysis along with platelet count in COVID-19 patients, according to disease severity and survival. Tables and algorithms are clearly presented.  The conclusion of this report is to treat those with pneumonia that is severe or associated with elevated D-dimer levels but not those with mild disease without additional risk factors for thrombosis. In contrast, opinion in the US appears to be swinging toward prophylaxis in most if not all hospitalized COVID-19 patients.
      • Persistent hiccups as an atypical presenting complaint of COVID-19. Apr 30. Prince. Am J Emerg Med.
        A case report of a patient who presented with hiccups, for which a CT was obtained. This was abnormal and SARS-CoV-2 testing was positive. Hiccups resolved on hydroxychloroquine.
      • Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia
        Apr 30. Pei. Journal of the American Society of Nephrology.
        Opinion from C19SAB: Dr. Barry Perlman
        Retrospective study of EMR data from 333 COVID-19 patients hospitalized with pneumonia in China. Patients with CKD or on dialysis were excluded. 75% had hematuria, proteinuria, or acute kidney injury. 82% had suspected intrinsic AKI. Severity of pneumonia was an independent risk factor for AKI. 46% with AKI had complete recovery of kidney function within 3 weeks of illness onset. Renal involvement correlated with a 9X increased rate of mortality. No deaths occurred in patients with pre-renal AKI, or in whom hematuria or proteinuria resolved.

      April 30, 2020

      • Clinical phenotypes of SARS-CoV-2: Implications for clinicians and researchers
        Apr 11. Rello. European Respiratory Journal.
        Opinion from C19SAB: Dr. Barry Perlman
        Discussion of COVID-19 clinical experience in Italy and Spain. Lymphocytopenia, low procalcitonin, and elevated LDH and CRP are characteristic. Hypercoagulability is common, with increased risk of thrombotic and embolic events. Severe cases have elevated D-Dimer and INR, and low fibrinogen and platelet count. Use of prophylactic unfractionated heparin is suggested for all hospitalized COVID-19 patients. 5 phenotypes of COVID-19 infection are described to guide individualized therapy (Table 2): 1. Most common is benign, with fever, headache, mild respiratory symptoms, malaise. Normal CXR and no hypoxemia; 2. 80% of hospitalized patients. Hypoxemia or small CXR opacities. Should be monitored closely due to risk of rapid deterioration. Typically hypovolemia and hyper-inflamed. Good candidates for clinical trials of anti-virals, anti-inflammatories, or anti-fibrotics; 3. 15% of China hospitalizations. Greater hypoxemia and high respiratory rates. High IL6. Also candidates for clinical trials. Prone position may help avoid intubation. Consider intubation if respiratory alkalosis with increasing hyperventilation on high O2; 4. Severe hypoxemia requiring intubation. Pulmonary hypoxic vasoconstriction with normal lung compliance. Probably due to pulmonary microvascular thrombosis. Advise no delay in intubation, especially when BB coalescent lines are present in more than 3 fields. Nitric oxide or prostacyclin may be helpful. PEEP typically should be 8-10 cm H2O with tidal volumes 6-9 mL/kg. Avoid recruitment maneuvers, prone positioning; 5. Less common. Advanced disease with acute lung injury or co-infection causing high procalcitonin. More common when intubation is delayed by non-invasive ventilation treatment. Low lung compliance < 40 mL/cm H2O. Suggest ARDS strategy with high PEEP and prone positioning.
      • Fatal Invasive Aspergillosis and Coronavirus Disease in an Immunocompetent Patient. Apr 29. Blaize. Emerg Infect Dis.
        The gold standard to prove invasive disease is to show fungal invasion in tissue samples. Although at least 4 out of 6 reported patients died, there was no corroboration with autopsy findings. Also the “immunocompetent patient” had asymptomatic and untreated myelodysplastic syndrome.
      • Objective evaluation of anosmia and ageusia in COVID-19 patients: a single-center experience on 72 cases
        Apr 27. Vaira. Head & Neck.
        Opinion from SAB Member: Dr. J. Lance Lichtor
        Among 72 COVID-19 patients, almost 75% had chemosensory dysfunctions during the course of their COVID-19 disease, with taste disorders in 12%, 14% with olfactory dysfunction, and 41% with combined dysfunction. 66% had recovery of chemosensitive dysfunction, with recovery in <5 days in 19 patients. Using an objective test, 80% of these patients still revealed a certain degree of residual hypoosmia or hypogeusia after resolution of their illness.
      • Updates on What ACS Reported: Emerging Evidences of COVID-19 with Nervous System Involvement. Apr 29. Baig. ACS Chem Neurosci.
        Author claims that there is a CNS connection with COVID-19. Anosmia, dysgeusia, ataxia, and altered mental status could be early signs of the neurotropic potential of this virus. There are reported cases of acute necrotizing hemorrhagic encephalopathy (was reported in a female with a 3 day history of cough, fever, and altered mental status who was COVID-19 positive), Acute G, B & Encephalitis. This is a view point.

      April 29, 2020

      April 28, 2020

      • Cardiac injury is associated with mortality and critically ill pneumonia in COVID-19: A meta-analysis. Apr 26. Santoso. Am J Emerg Med.
        A retrospective, cardiac injury causes death. Conclusion unable to link the deaths to cytokine storm or myocarditis, but able to state all who died had elevated troponin.
      • Incidence of thrombotic complications in critically ill ICU patients with COVID-19
        Apr 13. Kloka. Thrombosis Research.
        Opinion from C19SAB: Dr. Anil Hingorani, Dr. Lydia Cassorla
        AH: This paper presents real world data on thromboembolism with COVID-19 patients in the ICU. It gives the clinician realistic expectations of the incidence of thromboembolism in these critically ill patients and explores prophylaxis strategies.
        LC: The incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital was observed for 4 weeks. (March 7-April 5, 2020). Among 184 ICU patients with proven COVID-19 pneumonia, 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still in the ICU at the conclusion of the observation period. All patients received at least standard doses of thromboprophylaxis. The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CT pulmonary angiography and/or ultrasonography confirmed venous thrombosis in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%). PE was the most frequent thrombotic complication (n = 25, 81%). Age (adjusted hazard ratio 1.05/per year) and coagulopathy were independent predictors of thrombotic complications. None developed DIC. The findings were all the more striking given that ¾ of the study patients were still in ICU at the end of the observation period. The authors recommend low molecular weight heparin prophylaxis in higher dose ranges in all ICU patients, vigilance, and a low bar for diagnostic tests to confirm thrombosis but not full therapeutic anticoagulation for all ICU patients with COVID-19 illness “even in the absence of randomized evidence”. There have been many other reports regarding the high incidence of thrombotic complications in COVID-19 patients. The question of when to use prophylactic or therapeutic anticoagulation in severely ill patients that will likely be further clarified as data and studies emerge.
        • UPDATE: Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis
          May 9. Klok. Thrombosis Research.
          Opinion from SAB Member: Dr. Louis McNabb, Dr. Anil Hingorani
          LM: This article reported on 184 COVID-19 patients in the ICU. The initial evaluation demonstrated a thrombotic rate of 31%. Follow up 17 days later showed a thrombotic rate of 49%. The PE rate was 65/184, and most patients were on prophylactic anticoagulation. Given the high risk of VTE in COVID-19 patients, we need immediate trials on regimens of anticoagulation to reduce thrombotic complications.
          AH: A review of 184 ICU COVID-19 patients in the Netherlands. The patients had a high incidence of VTE despite prophylaxis and 3% had arterial thrombosis. Patients with thrombotic complications had five-fold increased risk of all-cause death.
      • Myocarditis in a patient with COVID-19: a cause of raised troponin and ECG changes. Apr 27. Doyen. Lancet.
        Case report of COVID-19 related myocarditis. 69 yr old with history of HTN on b-blocker admitted in Nice with COVID-19 ARDS. EKG showed LVH and diffuse inverted T waves. HSTI was 9000 nl/L. ECHO showed LVH with normal wall motion and EF. Initially started on antiplatelet therapy but coronary angiography was negative. MRI was consistent with apical and inferolateral myocarditis. Negative workup for other causes of myocarditis. He was treated with hydrocortisone for 9 days and discharged from ICU after 3 weeks. Suggestion for measuring troponin and ruling out myocardial infarction if myocarditis is suspected in COVID-19 patients.
      • No SARS-CoV-2 detected in amniotic fluid in mid-pregnancy. Apr 26. Yu. Lancet Infect Dis.
        In this letter to the editor, 2 pregnant women developed COVID-19 infection early during their pregnancy and in the second trimester, the two women were both positive for SARS-CoV-2 total antibodies in their serum and negative for SARS-CoV-2 RNA in throat swabs. RT-PCR tests of the patients’ amniotic fluid collected during their second trimester were negative, and tests for SARS-CoV-2 IgM and IgG in amniotic fluid were also negative. As the authors admit, the virus might not have been detectable due to gestation age, ideally performed after 18–21 weeks’ gestation, based on Zika virus data. The sample size was also very small.
      • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vertical Transmission in Neonates Born to Mothers With Coronavirus Disease 2019 (COVID-19) Pneumonia. Apr 26. Hu. Obstet Gynecol.
        In this research letter, the authors describe 7 pregnant women diagnosed with COVID-19, who were otherwise healthy during pregnancy and who after pregnancy recovered from COVID-19. 6/7 mothers underwent C-section and for one, the baby was delivered vaginally before the C-section could be performed. 1/7 infants was positive for COVID-19, but that infant as well as the other children subsequently were without symptoms of the disease. What’s not clear is if the mothers were chosen sequentially, if there were inclusion and exclusion criteria, when the mothers acquired COVID-19 and when they recovered.

      April 25, 2020

      April 24, 2020

      • Multicenter initial guidance on use of antivirals for children with COVID-19/SARS-CoV-2
        Pediatric Infectious Diseases Society. Apr 22, 2020.
        Kathleen Chiotos; Molly Hayes; David W Kimberlin; Sarah B Jones; et al
        Opinion from SAB Member: Dr. Barry Perlman
        Recommendations from a multidisciplinary panel of infectious disease physicians and pharmacists from 18 North American institutions regarding the use of antiviral treatment for severe COVID-19 infection in children.
        The panel addressed the following questions:
        1. Are antiviral agents indicated in children with COVID-19?
        2. What criteria define the pediatric population in whom antiviral use may be considered?
        3. Does presence of any underlying medical condition or characteristic warrant different criteria for antiviral use based on increased risk of COVID-19-related morbidity or mortality?
        4. What agents are preferred if antiviral therapy is offered to children with COVID-19?
        The panel concluded that most pediatric COVID-19 patients have mild disease and just require supportive care. A small proportion develop severe illness requiring respiratory support. Most of these, and some children with critical illness, also only require supportive care. In the absence of available data, possible risk factors for severe COVID-19 in children were discussed–cardiovascular or pulmonary disease, diabetes, cancer, obesity, young age, immunocompromise. On a case by case basis, if antiviral medication is used, remdesivir is recommended as the preferred agent, with hydroxychloroquine as an alternative if remdesivir is contraindicated or not available. Hydroxychloroquine/azithromycin combination and lopinavir-ritonavir are not recommended. Preferably, antivirals should be used as part of a clinical trial, but as of 4/14/20 no US trials are enrolling children < age 12. Of note, subsequent to acceptance of this manuscript, preliminary results from a hydroxychloroquine retrospective analysis and a remdesivir clinical trial, both involving adult COVID-19 patients, did not show benefit. Additional studies are ongoing.
      • Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. April 2020. Shi. The Lancet Infectious Diseases.
        Another chest CT article, this time with 81 patients.
      • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children and Adolescents: A Systematic Review. Apr 23. Castagnoli R. JAMA Pediatr.
        Italian authors, retrospective, metanalysis of literature (PUBMD, Cochrane…) from all China except one Singapore, Pediatric population with + PCR. They Identified 815 articles, selected 18 studies (Bias, exclusion criteria addressed with a referee author). N= 1065 includes 444 < 10 years age and 553 >10 but < 19. Slightly higher M >: F ratio. Software assistance, tightness of statistics – but no mention. Majority had mild symptoms, moderate < 20 patient & 1 kid < Shock. No vertical transmission but mainly contact from family. Asymptomatic manifestation for majority noted. 8 patients with rectal swab + ve in spite of – ve NP. Author concludes weakness of study: 3 month window, China factor, no adult comparison, no viral load to clinical picture or viral to immunity….
      • Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. Apr 23. Zheng S. BMJ.
        In this retrospective cohort study, 3497 respiratory, stool, serum, and urine samples were collected from 96 hospitalized Covid-19 patients and evaluated for SARS-CoV-2 RNA viral load. Disease severity was mild in 22 and severe in 74. Infection confirmed in all patients by sputum and saliva testing. RNA was detected in the stool of 55 (59%) and in the serum of 39 (41%) patients. The urine was positive in 1 patient. The median duration of virus in stool (22 days, interquartile range 17-31 days) was longer than in respiratory (18 days, 13-29 days; P=0.02) and serum samples (16 days, 11-21 days; P<0.001). The median duration of virus in the respiratory samples of patients with severe disease (21 days, 14-30 days) was longer than in patients with mild disease (14 days, 10-21 days; P=0.04). In the mild group, the viral loads peaked in respiratory samples in the second week from disease onset, whereas viral load continued to be high during the third week in the severe group. Virus duration was longer in patients > 60 yrs old and in males. 78 (81%) patients received glucocorticoids and 33 (34%) antibiotic treatment. All patients received antiviral Rx with interferon α inhalation, lopinavir-ritonavir combination, arbidol, favipiravir, and darunavir-cobicistat combination. The authors claim no deaths in this group. The main conclusions were that the virus persists for a longer time in stool than in respiratory or serum samples and that patients with more severe disease have a longer respiratory viral persistence with a greater load. This potentially affects their ability to transmit disease to others.

      April 23, 2020

      • Central Nervous System Involvement by Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2). Apr 22. Paniz-Mondolfi. J Med Virol.
        In this case report of 1, a 74 yo patient with Parkinson’s with a positive nasopharyngeal swab test for SARS-CoV-2 by real-time reverse-transcription-polymerase-chain-reaction amplification was noted to be confused when admitted. He expired on day 11 and at post-mortem, was noted to have viral particles in brain capillary endothelium and actively budding across endothelial cells, though the nature of the virus in the brain was not otherwise defined.
      • Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Feb 24. Huang. The Lancet.
        Detailed review of clinical features of COVID-19 presentation and progression from Wuhan; patient data collected prospectively on 41 patients with COVID-19 confirmed by real-time RT-PCR and next-generation sequencing admitted between December 16th, 2019 and January 2nd, 2020. Analysis and information well presented.
      • CT imaging features of 4,121 patients with COVID-19: a meta-analysis. Apr 22. Zhu. J Med Virol.
        Meta-analysis of 34 retrospective studies that describes the lung CT characteristics of patients with COVID-19. The most common charachteristics were bilateral and multi-lobar ground glass opacities. 8% of CTs were normal. Analysis did not include any clinical or outcome information, and suggested CT could help with diagnosis.
      • Faecal calprotectin indicates intestinal inflammation in COVID-19. Apr 22. Effenberger. Gut.
        Austrian PAP Letter to the Editor of GUT noting that fecal calprotectin levels are elevated in 40 COVID-19 inpatients with active diarrhea.
      • Kidney disease is associated with in-hospital death of patients with COVID-19. Mar 20. Cheng. Kidney International.
        A retrospective study, regression analysis, single center 701 (600 + 101 with possibly raised baseline serum creatinine, BUN & low GFR) patient in Wuhan with a possible renal insuffiency and one without. Preexisting renal compromise will progress to acute kidney injury and to a higher mortality. In this cohort, approximately 13% of patients had underlying kidney disease. More than 40% had evidence of abnormal kidney function and 5.1% had acute kidney injury (AKI) during their hospital stay. There was a dose dependent relationship between AKI stages and death, with an excess risk of mortality by at least 4 times among those with stage 3 AKI. Kidney disease is a major complication of COVID-19 and a significant risk factor of death. Nonetheless, the study findings suggest that early identification of those at risk, interventions to provide appropriate support, and avoidance of nephrotoxins, vigilance may help to improve the prognosis of patients with COVID-19. Sudden loss of kidney function, ACE2 association are part of hypothesis. Hazard ratio (3 to 8) with increasing proteinuria, hematuria, AK Stage 3, rising kidney markers.
      • Lung–kidney interactions in critically ill patients: consensus report of the Acute Disease Quality Initiative (ADQI) 21 Workgroup. Dec. 9, 2019. Joannidis. Intensive Care Medicine.
        Consensus report summarizing findings of a June 2018 conference on lung and kidney interactions in critical illness (18 pages, 123+ references). Using ADQI 21 methodology, including critical review of available clinical and research evidence, an international panel of pulmonologists, nephrologists and critical care specialists created clinical recommendations and suggestions for future research.
        Clinical recommendations with high quality evidence included lung protective ventilation, conservative fluid management and early recognition and treatment of pulmonary infections. Consensus statements linking AKI and ARDS were developed and the effect of ECMO and RRT on either organ system was explored.
        COVID-19 attacks both organ systems and much of this work applies to clinical scenarios clinicians face daily in critical care units around the globe. Despite its volume, this report (18 pages, 123 references), may be of value to clinicians dealing with the impact of COVID-19 on the front lines today.
      • Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized with COVID-19 in the New York City Area
        Apr 22. Richardson. JAMA.
        Opinion from SAB Member: Dr. David M. Clement, Dr. J. Lance Lichtor
        DC: This is a case review of a 12 hospital system in New York City, detailing the characteristics and outcomes of 5,700 patients admitted between March 1 and April 4. Besides the usual co-morbidities (hypertension, obesity and diabetes), only 31% of patients were febrile at triage, 14% needed ICU admission, 12% were intubated and of those intubated, 88% died. This provides an early window into the US experience. The supplementary tables provide a wealth of clinical data. JLL: In this review of 5700 patients admitted between March 1, 2020, and April 4, 2020 to any of 12 Northwell Health acute care hospitals, some clinical characteristics and outcomes were described. The median time to obtain polymerase chain reaction testing results was 15.4 hours, and common morbidities included hypertension, obesity and diabetes. 30% were febrile, almost 20% had a respiratory rate greater than 24 and almost 30% needed supplemental oxygen. The overwhelming majority had a positive COVID-19 test result on the first attempt. About 15% were treated in the ICU; 12% were treated with mechanical ventilation and 3% were treated with kidney replacement. About 20% died. Patients between 18 and 65 were more likely to be treated in the ICU, receive mechanical ventilation, compared to patients older than 65 years. Mortality rates were lower than reported in China.

      April 22, 2020

      • Audiological profile of asymptomatic Covid-19 PCR-positive cases. Apr 21. Mustafa MWM. Am J Otolaryngol.
        Viral infections can cause hearing loss. 20 confirmed positive but asymptomatic COVID-19 patients were compared with 20 controls with normal hearing. The COVID-19 patient group had significantly worse high frequency pure-tone thresholds and transient evoked otoacoustic emission amplitudes, suggesting damage to cochlea hair cells. The paper recommends further research to determine the mechanism of this effect.
      • COVID-19: impact on cancer workforce and delivery of care. Apr 20. Mayor. The Lancet Oncology.
        A Lancet “News” piece stressing the adaptations being made to care for cancer patients during COVID-19. Centralization of cancer care, telemedicine, modifying chemo and radiation treatments and splitting teams of cancer care workers are mentioned.
      • Category: Emerging Clinical Data and Guidelines
        Diarrhea is associated with prolonged symptoms and viral carriage in COVID-19
        Apr 13. Wei. Clinical Gastroenterology and Hepatology.
        Opinion from SAB Member: Dr. J. Lance Lichtor
        In this retrospective analysis of 84 patients with SARS-CoV-2, diarrhea occurred in 31% of patients, and patients with diarrhea had a higher incidence of headache, myalgia or fatigue, cough, sputum production, nausea and vomiting and duration of symptoms and hospital stays were longer for patients who had diarrhea. The digestive system is also a potential pathway for SARS-CoV-2 infection. Though the diarrhea could have been due to antibiotic use–all patients received antibiotics (46% used two antibiotics) and intestinal probiotics relieved diarrhea, which is consistent with diarrhea secondary to antibiotic use.
      • Dynamic profile of RT-PCR findings from 301 COVID-19 patients in Wuhan, China: a descriptive study. Apr 11. Xiao. J Clin Virol.
        More than 2 negative RT-PCR tests may be needed to document viral clearing. Retrospective study of of 301 Wuhan COVID-19 patients with mild – moderative symptoms. Average contagious period (positive RT-PCR test) was 20 days, with 26% still testing positive after 4 weeks. Patients < 65 converted on average earlier than older patients. 23% of the 70 patients with 3 documented consecutive RT-PCR tests had a positive test after 2 negative tests. Throat swab tests had a higher flare negative rate of 41%.
      • What Has the COVID-19 Pandemic Taught Us so Far? Addressing the Problem from a Hepatologist’s Perspective. Apr 21. Méndez-Sánchez. J Clin Transl Hepatol.
        Editorial with 12 international authors.
        The authors outline that hepatic injury during COVID-19 illness may be due to systemic inflammation, liver ischemia and hypoxia, exacerbation of pre-existing liver diseases, and drug-related liver injury. ACE2 is expressed in the epithelial cells of bile ducts “however, in the studies conducted so far, no increase in bile duct injury markers, such as gamma-glutamyl transferase and alkaline phosphatase, has been observed.” “It is a matter of debate whether COVID-19 is directly responsible for the development of liver injury, or whether the observed changes are secondary to the systemic inflammation triggered by infection.“ The authors make no specific recommendations other than to emphasize adherence to general recommendations such as social distancing and appropriate hand washing to curtail spread of the virus until treatment or vaccines are available.

      April 21, 2020

      • Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Mar 1. Liang. The Lancet Oncology.
        In this letter to the editor, the authors note that COVID-19 patients can have cancer and note that patients with cancer might have a higher incidence of COVID-19 than the general population and that patients with cancer may also have a worse outcomes with COVID-19 disease.
      • Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes. Apr 18. Han. Am J Gastroenterol.
        Patients with mild Covid-19 illness may present with GI symptoms. This study from Wuhan China identified 206 Covid-19 patients with mild disease of whom 48 had GI symptoms (nausea, vomiting, or diarrhea) alone, 69 had both GI and Respiratory symptoms, and 89 had only respiratory symptoms. All were followed until they had two consecutive daily PCR tests for SARS-CoV-2. Those who presented with GI symptoms waited longer on average to seek treatment, (16 vs. 11.6 days) a longer duration of illness until PCR tests were negative, and a greater likelihood to have positive stool tests.
      • Endoscopy in inflammatory bowel diseases during the COVID-19 pandemic and post-pandemic period
        Apr 16. Iacucci. The Lancet.
        Opinion from SAB Member: Dr. W. Heinrich Wurm
        This is an international consensus paper by 9 academic centers and 4 societies on the management of inflammatory bowel disease (IBD) and the indications for urgent endoscopy during and after the COVID-19 pandemic. The panel identified 4 clinical scenarios requiring urgent endoscopy and provides well-organized algorithms for each situation. If urgent endoscopy is indicated, ruling out COVID-19 infection and a diagnosis of irritable bowel syndrome (IBS) are high priorities, as COVID-19 infection frequently starts with GI symptomatology (52% in one study). Strict precautions are advised to protect providers and the environment from aerosolized transmission during an endoscopy. An algorithm dealing with post-pandemic gridlock in the endoscopy suite is helpful in prioritizing postponed diagnostic and therapeutic interventions.
      • Risk Factors Associated with Disease Severity and Length of Hospital Stay in COVID-19 Patients. Apr 20 Liu. J Infect.
        Pre-Proof article from China which reptrospectively studied 99 patients who recovered from COVID-19 and identified risk factors for severe disease. Since study was retrospective, did not include deaths, and had nothing new.
      • The performance of chest CT in evaluating the clinical severity of COVID-19 pneumonia: identifying critical cases based on CT characteristics. Apr 19. Lyu. Invest Radiol.
        Retrospective study from a single center in China regarding utility of CT scan in diagnosis of COVID19. N= 51. Three groups: mild, moderate, and severe. All groups were tested and scored on: 1. clinical score, 2. qualitative score, 3. quantitative, 4. AI score. Don’t know who were excluded. Stastics had fitness test besides standard tests (P…… ) Comparing mild to severe. Their conclusion: “The combined use of qualitative and quantitative indicators could distinguish cases at different clinical stages, might provide help to facilitate the fast identification and management of critical cases, thus reducing the mortality rate. Critical cases had higher total severity score (>10) and total score for crazy-paving and consolidation (>4) than ordinary cases, and had higher mean lung density (>-779HU) and full width at half maximum (>128HU) but lower relative volume of normal lung density (≦50%) than ordinary/severe cases. CT imaging findings could help to continuously monitor the treatment effects objectively in the follow-up as well as provide guidance for clinical management and treatment.”

      April 20, 2020

      • Joint statement on safely resuming elective surgery after the COVID-19 pandemic
        Apr 17. American College of Surgeons; American Society of Anesthesiologists; Association of periOperative Registered Nurses; American Hospital Association.
        Opinion from SAB Member: Dr. Jagdip Shah
        In response to the COVID-19 pandemic, the Centers for Medicare and Medicaid Services (CMS), the U.S. Surgeon General and many medical specialties such as the American College of Surgeons and the American Society of Anesthesiologists recommended interim cancelation of elective surgical procedures. Physicians and health care organizations have responded appropriately and canceled non-essential cases across the country. Many patients have had their needed, but not essential, surgeries postponed due to the pandemic. When the first wave of this pandemic is behind us, the pent-up patient demand for surgical and procedural care may be immense, and health care organizations, physicians and nurses must be prepared to meet this demand. Facility readiness to resume elective surgery will vary by geographic location. The following is a list of principles and considerations to guide physicians, nurses and local facilities in their resumption of care in operating rooms and all procedural areas.
      • Sequential analysis of viral load in a neonate and her mother infected with SARS-CoV-2. Apr 17. Han MS. Clin Infect Dis.
        An interesting manuscript: 27-day old neonate, born almost at 39 wks and her mother were diagnosed with COVID-19. About a month after the baby was born, her mother and father developed symptoms of COVID-19 and the baby and mother both tested positive and were hospitalized. Though at its early stage, the viral load was highest in the nasopharynx, up until the 18th day it was high in the infant’s stool, when respiratory specimens were negative. It’s not clear if virus detected in stool and urine was viable, still important to wash hands after changing a diaper.

      April 17, 2020

      • COVID-19 pneumonia: different respiratory treatments for different phenotypes? Apr 16. Gattinoni L. Intensive Care Med.
        Clinical observations from experienced researchers conclude two types of lung disease exist variably in COVID-19 patients; patient presentation may depend on severity of infection, initial patient response to hypoxemia and the time from symptom onset to hospital admission. Type L is described as low elastance with retained lung compliance, low VA/Q ratio and normal lung weight. As hypoxemia worsens, patient generated large tidal volumes increase negative intrathoracic pressure which may cause further lung damage. Type H is defined as high elastance due to increased pulmonary edema, high shunt, high lung weight and high lung recruitability. Excellent discussion and physiologic explanation for managing patients with different lung support strategies and ventilatory assistance in both stages. Important discussion for all physicians engaged in treating COVID-19 patients who may present at different stages of the disease which require different ventilatory strategies which may prevent deterioration if treated early in the course.

      April 16, 2020

      April 15, 2020

      April 11, 2020

      April 10, 2020

      • Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19. Apr 9. Zhang. NEJM.
        Case report and comparison with 2 other COVID-19 patients in Wuhan who presented with coagulopathy, antiphospholipid antibodies, and multiple cerebral infarcts. SARS-CoV-2 was confirmed with RT-PCR or serologic testing. All three patients had histories of multiple co-morbidities. The case report patient was age 69 with a history of HTN, DM, and CVA. He had leukocytosis, thrombocytopenia, elevated PT. aPTT, fibrinogen, and D-dimer. Patients 2 and 3 did not have leukocytosis or as markedly elevated D-dimer, and patient 3 had a normal Plt count. All 3 showed presence of anticardiolipin IgA and anti-B2-glycoprotein I IgA and IgG antibodies, and negative lupus anticoagulant.

      April 9, 2020

      • Clinicolaboratory study of 25 fatal cases of COVID-19 in Wuhan. Apr 8. Tu. Intensive Care Med.
        An interesting read that just reaffirms what we already know about the subset of patients who are most likely to die and their abnormal lab values more likely associated with death, i.e., interleukin-6, C-reactive protein and D-dime. Single center retrospective analysis focusing on fatality markers of the disease by comparing lab data of survivors with non-survivors. Among 174 patients, mortality was 14.4%. Older males with comorbidities (diabetes, heart disease, COPD) were at higher risk and non-survivors had pronounced lymphocytopenia, abnormal coagulation, elevated D-dimer levels and showed evidence of cytokine abnormalities with high IL-6 and CRP levels.

      April 8, 2020

      April 5, 2020

      • Early Lessons From the Frontline of the 2019-nCoV. Feb. 11. Zhang. The Lancet.
        C19SAB Opinion from: Dr. Jack Lance Lichtor
        A physician working on the frontline in Wuhan explained what treating patients with this disease taught him. Though we complain in the US about the lack of early detection, a lack of understanding that patients may be contagious during the incubation period, the lack of availability of protective equipment, the inability to get certain drugs, the lack of hospital beds for patients with other diseases, and the lack of enough hospital beds for patients with COVID-19 disease, this physician explained that in China they had the same issues as we have here.
      • Preparing for a COVID-19 Pandemic: A Review of Operating Room Outbreak Response Measures in a Large Tertiary Hospital in Singapore. Mar 11. Wong. Canadian Journal of Anaesthesia.
        COVID-19 SAB Opinion from: Dr. Lydia Cassorla
        This is a well-illustrated in-depth discussion of multiple aspects of a major Singapore medical center’s approach to caring for patients in the COVID-19 era, with 72 references cited. Preparation for a pandemic involves considering the different levels in the hierarchy of controls as well as the different phases of the pandemic. In the OR setting, these measures include the modification of infrastructure and processes, management of staff and patients, infection prevention strategies, and clinical recommendations.

      April 3, 2020

      April 2, 2020

      April 1, 2020

      March 31, 2020

      March 30, 2020

      March 26, 2020

      March 25, 2020

      March 24, 2020

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      March 17, 2020

      March 16, 2020

      March 15, 2020

      March 2020

      February 2020

      • Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19) Feb 16. WHO.
        Opinion from SAB Member: Dr. Barry Perlman
        Joint Mission was a series of meetings and field visits from February 16-24, 2020 by 25 Chinese and international experts, headed by Dr. Bruce Aylward of WHO and Dr. Wannian Liang of the People’s Republic of China. The major objectives: 1) To enhance understanding of the evolving COVID-19 outbreak in China and the nature and impact of ongoing containment measures; 2) To share knowledge on COVID-19 response and preparedness measures being implemented in countries affected by or at risk of importations of COVID-19; 3) To generate recommendations for adjusting COVID-19 containment and response measures in China and internationally; and 4) To establish priorities for a collaborative program of work, research and development to address critical gaps in knowledge and response and readiness tools and activities. It was recommended that “uncompromising and rigorous” non-pharmaceutical measures to contain transmission, proactive surveillance, rapid diagnosis and isolation, and tracking and quarantine of close contacts should be employed globally.
    1. COVID-19 Patients
      September 16, 2020
      • Time-critical goals of care in the Emergency Department during COVID-19: A three-stage protocol. 6/17/20. Nakagawa S. Journal of the American Geriatric Society.
        This is an important and ethically relevant research letter discussing applicability of initiating palliative care discussions in the Emergency Department (ED) and defining a “clear goal of care” in this COVID-19 pandemic. The author proposes a simple 3-stage communication approach (1. sharing knowledge, 2. clarifying goal of care, and 3. negotiating treatment options) with the patient’s family and ED physicians that allows clinicians to quickly share the clinical picture, effectively assess the patient’s values, and make a goal recommendation for care during our rapidly progressing crisis. The 3-stage tool is very practical and saves resources while preserving the patient’s autonomy and wishes.

      July 24, 2020

      • The Structural and Social Determinants of the Racial/Ethnic Disparities in the U.S. COVID-19 Pandemic: What’s Our Role? 7/17/20. Thakur N. Am J Respir Crit Care Med.
        A call to arms for critical care and pulmonary specialists: black, Latinx, and Native Americans test positive for and die from coronavirus at higher proportion than other racial and ethnic groups. Their mortality rates far exceed the proportion of the population that these groups represent. Historically disadvantaged communities have reduced capacity to adopt preventive measures. Minority communities with low socioeconomic status (SES) and/or limited English proficiency receive less public communication during crisis and pandemics; access to testing and care is greatly limited in low-SES and minority communities. This article advocates for under-represented minority patients, who are becoming critically ill and dying at disproportionate rates.

      July 20, 2020

      • CPR in the COVID-19 Era – An Ethical Framework. 7/9/20. Kramer DB. N Engl J Med.
        Review by the SAB
        By David Clement, on behalf of the SAB
        This opinion paper provides important reading on the ethics of how the surge of patients with COVID-19 complicate standard CPR practices. An ethical framework of three crisis standards is proposed: acknowledge resource limitations, forgo CPR in certain circumstances, and impose selective constraints on CPR to ensure the safety of healthcare personnel. Hospitals need to develop such explicit crisis standards for CPR to help clinicians and the public understand when strict adherence to established resuscitation protocols may no longer be appropriate.

      May 27, 2020

      • Saving Lives Versus Saving Dollars: The Acceptable Loss for Coronavirus Disease 2019. May 18. Ashkenazi. Crit Care Med.
        This is in response to the previous article “Adult ICU Triage During the Coronavirus Disease 2019 Pandemic. Who Will Live and Who Will Die?” Recommendations to Improve Survival in CCM.
        A thought provoking reply: Care for patient vs. population and simultaneously incorporating a principal of “life for ‘Fittest for a survival’” while accepting the strategic “retrieve” in this pandemic.
        The author questions the article’s recommendation of a triage algorithm based on various criteria—except for the age.
        The formula in question is based on 1. Performance score; 2. ASA score; 3. Number of organ failures; and 4. Predicted survival. Performance score and predicted survival has indirectly incorporated the age of the patient in consideration for “greater good to great number of people / year.”
        The author makes a cerebral argument for a need for strategic pre-planning of the national capacities (based on ICU beds) and capabilities (surge of 100 + Supply + Space) of a pandemic. Here the policy maker should consider as an “acceptable loss,” which represents the ultimate balance between saving lives and keeping life routines. This includes defining the “price” that we are willing to “pay” in order to be able to save the most lives and life-years and to lower the morbidity rate while, at the same time safeguarding the economy and individuals at workplaces and the fabric of social existence. Social distancing, quarantine, tracking and monitoring are medical aspects of a pandemics but does cause a collateral damage in the area with 1. Loss of lives due to suicides; 2. Psychiatry diseases; 3.Delayed chronic treatment; 4. Domestic violence; and 5. Economic losses. An evaluation of the “acceptable loss” is a professional, financial, ethical, legal, social, cultural, and historical dilemma. The COVID-19 pandemic has shown a dichotomy of the society: “the objective element” of the lethal virus and “controlled element” of the overprotective reaction for those who are not at risk, while vulnerable populations are left unprotected.
        ICU Triage needs to be 1. Differential diagnosis with comorbidities – risks stratification of population; 2. International surge – share and care of equipment and valuable resources; 3. Awareness to differential age; and 4. Meta leadership at stages (country, state, city level). The author appeals a medical triage, acceptable loss is based on two basic principles: beneficence and distributive justice.
        In a big country that is fractured at several levels, these suggested principals will need “a well-orchestrated political will” in this pandemic. On the other side, success for a smaller, monolithic, resources poor, undemocratic country from the author’s perspective in this pandemic.

      May 14, 2020

      May 13, 2020

      • Adult ICU Triage During the Coronavirus Disease 2019 Pandemic: Who Will Live and Who Will Die? Recommendations to Improve Survival
        May 6. Sprung. Critical Care Medicine.
        Opinion from SAB Member: Dr. Jagdip Shah
        The authors review 3 methods of triage (Andorran Model, Medical Benefit, and Manchester Triage System), in 3 countries (Spain, Ecuador, and the Netherlands). They then compared results with current COVID-19 pandemic ICU care profiles. The Netherlands ICU was able to increase capacity 4-fold and was able to decrease mortality while other ICUs in Ecuador and Spain more than doubled ICU bed capacity and experienced an increased mortality of almost 2- to 3-fold. Triage is to be used only in crisis mode, not in contingency mode (e.g. when demand for ICU bed is increased >100%). Here the authors make an appeal for a flexible, simple and powerful tool implemented by a triage committee that may include doctors with relevant experience (palliative care, critical care, administration), nurses, social workers, and ethicists for ICU admission and discharge. The authors recommend a triage algorithm based on clinical estimations of the incremental survival benefit (saving the most life-years) with “first come, first served” being applied for patients with otherwise equal priorities/benefits. Prognosis is an important factor to consider with emphasis on biologic age being needed for COVID-19, specifically. Fairness by age, gender, race ethnicity, sex preference, financial status, social worth is also recommended. The triage model proposed here is based on the priority (1 to 4) label of all ICU seeking patients. The triage committee will make color coding of each patient seeking ICU based on: 1. performance score (The premorbid baseline condition using the Eastern Cooperative Oncology Group Performance Score + the Clinical Frailty Score + the Karnofsky Performance Scale), 2. ASA class, 3. SOFA score, 4. predicted survival. The triage committee reviews all ICU admitted patients Q24 hrs and also Q14 days for discharge from the ICU. The authors make a plea for health workers to get priority for treatment with a blessing from the government/communities that they serve. Administrators in the committee are likely to guide space, staff and supplies. An excellent graphic clearly written for the current pandemic is included.

      April 21, 2020

      April 13, 2020

      April 11, 2020

      April 8, 2020

      • Patients who are improving could have treatment withdrawn if others could benefit more. Apr 2. Mahase. BMJ.
        Doctors could be forced to withdraw lifesaving treatment from stable or improving patients.
      • Potential Legal Liability for Withdrawing or Withholding Ventilators During COVID-19: Assessing the Risks and Identifying Needed Reforms Apr 1. Cohen. JAMA.
        COVID-19 SAB Opinion from: Dr. Philip Lumb
        Sobering discussion on potential legal liability for physicians and organizations following triage protocols that refuse, withdraw, and reassign or withdraw lifesaving equipment (ventilators) from non-consenting patients. The discussion is well founded and provides a call for state legislatures to enact similar statutes to a ‘”Maryland statute in place since 2004, indicating that “A health care provider is immune from civil or criminal liability if the health care provider acts in good faith and under a catastrophic health emergency proclamation” with health care provider defined to include most health care facilities.”‘ The discussion notes the possibility of criminal and/or civil charges in certain situations and urges rapid action at state level to create 120-day, self-expiring legislation to hold harmless institutions and physicians who make triage decisions following defined protocols. (Reference A Framework for Rationing Ventilators and Critical Care Beds During the COVID-19 Pandemic JAMA. Mar 27, 2020. Douglas B. White MD MAS; Bernard Lo MD)

      April 3, 2020

      March 31, 2020

      March 29, 2020

      March 23, 2020

      March 18, 2020

    1. Healthcare Workers
      May 15, 2020
      • Medically Vulnerable Clinicians and Unnecessary Risk During the COVID-19 Pandemic
        May 13. Janvier. The American Journal of Bioethics.
        Opinion from SAB Member: Dr. Philip Lumb
        This is an intellectually provocative discussion on appropriate tasks for retired physician volunteers in COVID-19 areas. The article entertains appropriate conflict between “wishing to be in the front line” versus more appropriate and potentially intellectually valuable activities that entertain less risk for volunteers and the health system.
    1. Society
      April 30, 2020

      April 25, 2020

      • What the Great Pandemic Novels Teach Us
        Apr 23. Pamuk. The New York Times.
        Opinion from SAB Member: Dr. J. Lance Lichtor, Dr. David M. Clement
        JLC: Though not really a science paper, this piece shows, based on literary history, how eerily similar the current pandemic is compared to what has happened over the last 400 years in terms of initial response (denial); the carelessness, incompetence and selfishness of those in power that infuriates the masses; how institutions are unsure how to deal with many of the issues; how rumor and the spread of false information has been a universal and unprompted response, including how the disease is foreign, and is brought in with malicious intent; the intensity of suffering; and finally the terror all of us feel which shows how fragile our lives are and how we all share the same humanity. Fear may cause us to withdraw, but it also teaches us to be humble and practice solidarity.
        DC: One may question the historical accuracy of novels. During the current pandemic some countries (New Zealand, Australia and Taiwan for example) have largely avoided baseless rumors and false information. But the human tendency for such dysfunctional approaches to pandemics are wonderfully illustrated in this article.

      April 21, 2020

      • The Untold Toll – The Pandemic’s Effects on Patients without Covid-19. Apr 18. Rosenbaum. NEJM.
        An articulate, appropriately emotional and well written article on the peripheral and usually undocumented costs of COVID-19’s effects on other (frequently emergency) patient care priorities. Details experiences with delayed coronary angiography, rushed decisions to perform bilateral mastectomy, and inadequate post procedural follow-up. Timely, thoughtful and obvious future implications when “routine” access to medical care resumes.

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
      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

      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)
      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,