The COVID-19 LST Report

In today's episode we discuss:

—Climate: Infectious Disease Society of America (IDSA) made 4 strong recommendations for preventing COVID-19 infection in health care personnel. A pulmonologist and interventional cardiologist from the Cleveland Clinic and Emory University critique recently published IDSA guidelines for preventing COVID-19 infection in healthcare workers. They argue the recommendation to use either respirators or surgical masks conflicts with Centers for Disease Control guidance to use respirators, and believe the guidelines are missing recommendations on proper gloving strategies, which are crucial to avoid self-contamination. The authors suggest the IDSA must clarify these points to alleviate confusion for healthcare workers who are inundated with recommendations from multiple organizations.

—Transmission & Prevention: A retrospective observational study conducted by physicians at the Military Instruction Hospital during April 2020 found that among 1,739 crew members aboard a French aircraft carrier in April 2020, 64% tested positive for COVID-19 via real-time polymerase chain reaction (RT-PCR), with there being significant variations in symptomatic presentation and antibody development. This article suggests viral circulation in local outbreaks requires further testing and analysis.

—Management: Remdesivir for adults with COVID-19 may decrease time on mechanical ventilation. A multi-specialty team from Minnesota and Oregon conducted a systematic review of 5 randomized-controlled trials evaluating remdesivir as a treatment for adults with COVID-19. They found that a 10-day course of remdesivir may reduce the proportion of patients receiving mechanical ventilation (RR: 0.71 [CI, 0.56 to 0.90]; 3 RCTs), but was associated with a statistically insignificant decrease in mortality (RR: 0.93 [95% CI, 0.82 to 1.06]; 4 RCTs) compared to control groups. Authors suggest that remdesivir use probably confers little to no mortality benefit, but may improve recovery by reducing time on mechanical ventilation.

—Adjusting Practice During COVID-19: Methodological quality has been lower in some COVID-19 clinical research. As part of a systemic review of COVID-19 research quality, a team of molecular biologists, physicians, and statisticians from the University of Ottawa compared the quality of 686 research articles published during the COVID-19 pandemic to 593 historical controls matched for journal and study design published pre-pandemic. COVID-19 publications had a shorter time to acceptance (13.0 vs. 110 days, p<0.0001) and lower methodological quality scores compared to historical controls. Authors suggest the push for rapid research during the pandemic may result in lower quality research, and highlight the need for higher quality evidence.

—R&D: Diagnosis & Treatments: SARS-CoV-2 lethal infected with K18-hACE2 transgenic mice may offer post-exposure protection. Researchers from the Israel Institute for Biological Research in Ness-Ziona, Israel analyzed the efficacy of monoclonal MD65 antibodies in K18-hACE2 transgenic mice with SARS-CoV-2 infection, finding a greater survival rate compared to mice without MD65 antibodies, in the setting of both prophylactic and post-exposure administration, as well as decreased viral load in lung tissue. 

We are an affiliated group of medical students, PhDs, and physicians keeping up with the latest research on SARS-CoV-2 / COVID-19. We find the newest articles, read them, grade their level of evidence, and bring you the bottom line. Our goal is to empower you to take the best care of yourself and those in your care. 

Our Story:

What did University of Washington third-year medical student Jasmine Rah do when her training program was suspended due to COVID-19? She teamed up with her mentor, Dr. Will Smith, an ER Doctor on the front lines of fighting COVID-19 who is also a UW clinical professor and Col. with the US Army Reserves, to launch the daily COVID-19 Literature Surveillance Team.

In just the first five months of 2020, more than ten thousand papers have been published regarding COVID-19. This is more than twice the number of publications on influenza or malaria for the entire year of 2019.  Many of these articles were just researchers desperate to share the findings in the hopes of helping others. However, many articles covered the same topic and many were of poor quality, highlighting the need for assistance in parsing through data, especially during the time of crisis in order to develop situational awareness.

The 50+ strong group of physicians, medical students, and other experts review every COVID-19 related study that is published each day, grades its level of evidence (aka scientific integrity) based on the Center for Oxford scheme, and summarizes delivering the BLUF- Bottom Line Up Front (it's a reporters dream come true!).

Their concept is to enable providers to "Stay Informed. Read Less. Do More." This effort is 100% volunteer, free, and open access. With the need to share information quickly to combat COVID-19 many leading medical journals have suspended peer review, which means more people have access to more information more quickly- but it also means there is a lot of noise. The COVID-19 LST cuts through this noise to get doctors and health care workers on the front lines the scientifically-sound information they need, quickly, to save lives.

Though it was initially created to guide clinical decision making, it grew to also guide policymakers, various agencies of Government, researchers, students and laypersons.  Through COVID-19 LST, we now understand the very important role of screening/summarizing evidence in an unbiased manner and the critical role of a literature surveillance team.  Critical members of COVID-19 LST were then invited to join in founding the non-profit, the Literature Surveillance Team or theLST.org. The next step is now to continue our process for other topics with clinical significance in the future.

In today's episode we discuss:

—Epidemiology

· What does the literature say about face mask usage against COVID-19? A large international, interdisciplinary group summarize the evidence supporting mask wearing to mitigate the spread of COVID-19. They reviewed direct epidemiological evidence, population-level impacts, transmission characteristics, laboratory-based source control experiments, personal protective equipment efficacy research, sociological considerations, and implementation policies. Authors conclude all evidence indicates mask wearing effectively reduces viral droplet transmission and should be encouraged by officials to help minimize the spread of COVID-19.

—Understanding the Pathology: ABO blood group showed minimal differences in SARS-CoV-2 antibody response but blood group B had higher neutralizing antibody titers. A multicenter prospective cohort study conducted by Johns Hopkins University, Mississippi Valley Regional Blood Center in Springfield, IL, Washington University School of Medicine in St. Louis, MO, Mayo Clinic in Rochester, MN, and National Institute of Health in Baltimore, MD involved 202 individuals who were eligible to donate COVID-19 convalescent plasma at the beginning of the pandemic. They found there was no difference in anti-SARS-CoV-2 spike IgA or IgG between ABO groups, but significantly higher neutralizing antibody (nAb) titers were present in blood group B (44%) compared to blood groups A (25%), O (20%) and AB (0%). These findings suggest blood group B may have higher nAb titers after recovery from COVID-19 infection and thus greater protection against future infection with SARS-CoV-2, however further studies correlating ABO blood groups and disease severity are needed to further support these findings.

—Transmission & Prevention: Further robust research is necessary to deduce the link, if any between COVID-19 vaccination efficacy and obesity. Researchers from Harvard Medical School, Massachusetts General Hospital and ConscienHealth in Pittsburgh refute previous speculations that obesity could be associated with reduced efficacy of the COVID-19 vaccines. Data from Phase 3 vaccine trial results show Pfizer-BioNTech has 95.4% efficacy (CI: 86.0 - 99.1%) in people with obesity compared to 94.8% (CI: 87.4-98.3%) in people without obesity and Moderna efficacy of 91.2% (CI:32.0-98.9%) in people with severe obesity and 94.8% (CI: 89.3-96.8%) overall. Since obesity is one of the most significant risk factors for severe outcomes from COVID-19, these authors suggest that ongoing placebo-controlled vaccine trials designed with necessary power for detecting differences among classes of obesity are important for post-vaccine risk stratification and public health strategy. 

 · A nanomechanical study found SARS-CoV-2 to survive best on polystyrene compared to other tested inanimate surfaces. A nanomechanical study by researchers in Alberta, Canada and Changsha, Shenzhen, and Guangdong, China tested SARS-CoV-2 survival on four different surfaces and found that the spike protein on the outer surface of the SARS-CoV-2 virion, which is responsible for transmission via fomites, survived the best on polystyrene, then stainless steel, then gold, and then on glass, suggesting that fomite transmission of SARS-CoV-2 is prevalent and that more surfaces need to be tested to get a better understanding for both prevention and tracking transmission of the virus.

The rest of the reports can be found here: https://www.covid19lst.org/reports 

In today's episode we discuss:

—Epidemiology: Seroprevalence of SARS-CoV-2 antibodies in over 6000 healthcare workers show increased occupational risk. Physicians and laboratory scientists from Spain conducted a cross-sectional study of 6,038 healthcare workers (HCW) across 4 regions in Spain to assess the seroprevalence of IgG anti-SARS-CoV-2 antibodies. They found 11% of HCW (n=662) had IgG against SARS-CoV-2, with those with high (OR: 2.06; 95%CI: 1.63-2.62) and moderate (OR: 1.77; 95%CI: 1.32-2.37) risk exposures more likely to have antibodies. Because this rate of seropositivity is slightly higher than in the general Spanish population, authors suggest their data confirm the occupational risk of SARS-CoV-2 infection among HCW with working in a clinical environment.

—Adjusting Practice During COVID-19: There was an effect of the COVID-19 pandemic process on STEMI patients’ timeline? An interdisciplinary group of cardiology researchers from hospitals in Samsun and Sivas, Turkey, performed a combined observational analysis as well as chart review to assess the effects that the COVID-19 pandemic has had on the management of ST elevation myocardial infarction (STEMI) patients. They concluded that there was a delayed time to first medical contact (61 minutes in non-pandemic times versus 190 minutes during the pandemic), as well as a delayed time for patients to leave their house after their onset of symptoms (30 minutes in non-pandemic times versus 165 minutes during the pandemic). While this implies that there may need to be widespread analysis of medical responses to patients experiencing STEMI, the authors do comment on the fact that the COVID-19 burden in areas studied was relatively small when compared to hotspots around the world. Further investigation is required in areas that can represent a patient population more severely burdened by COVID-19, however these results suggest an opportunity for quality improvement changes to more efficiently manage patients with STEMI during the pandemic and improve outcomes.

—R&D: Diagnosis & Treatments: Fluvoxamine when compared to placebo can decrease clinical deterioration in outpatients with symptomatic COVID-19. A double-blind randomized clinical trial, conducted by physicians from Washington University in St. Louis, analyzed the efficacy of fluvoxamine (100 mg 3 times daily for 15 days) against a placebo to decrease clinical deterioration of COVID-19 in non-hospitalized patients with confirmed SARS-CoV-2 infection within 7 days and oxygen saturation 92% or greater. Clinical deterioration (defined as development of both 1) shortness of breath or hospitalization for shortness of breath or pneumonia and 2) oxygen saturation less than 92% on room air or need for supplemental oxygen to achieve oxygen saturation of 92% or greater) occurred in 0 of 80 patients in the fluvoxamine group and in 6 of 72 patients in the placebo group without a significant increase in adverse events. 

—Transmission & Prevention: Genomic evidence of points to in-flight transmission of SARS-CoV-2 despite predeparture testing. A study by the New Zealand Ministry of Health looking at the points of infection and transmission of SARS-CoV-2 in 86 people returning to New Zealand through an international flight from Dubai, UAE. Passengers were placed in managed isolation and quarantine and tested for SARS-CoV-2 on their third and twelfth day after their return; 7 passengers subsequently tested positive for COVID-19.

In today's episode we discuss:

—Epidemiology: Do we need routine COVID-19 testing of Emergency Department staff? A study from the University of Washington uses a mathematical model based on the Diamond Princess cruise ship data to predict detection of SARS-CoV-2 in asymptomatic health care workers (HCWs) in the emergency department in regions with high COVID-19 rates. Results revealed that within six months, weekly testing in asymptomatic HCWs would reduce infection rates by 3 to 5.9% when the transmission constant is 1.219e-4 new infections/person^2, while a transmission constant of 3.660e-4 new infections/person^2 would result in reduction of infections by 11 to 23%. The authors urge more frequent testing in asymptomatic HCWs to help reduce the rate of SARS-CoV-2 infection.

—Understanding the Pathology: Dynamic changes are witnessed in anti-SARS-CoV-2 antibodies during SARS-CoV-2 infection and recovery in a retrospective analysis by bioinformatics and global health specialists in Jiangsu, China where 1,850 hospitalized patients with COVID-19 were analyzed and those with mild or moderate disease were found to develop IgG antibodies one week earlier than patients with severe disease. While spike protein and receptor-binding domain specific IgG levels were 1.5- and 2-fold higher in critically ill hospitalized patients and SARS-CoV-2 RNA-negative recovered patients, respectively, compared to those who are remained RNA-positive. These data suggest earlier development of antibodies may be protective against developing severe disease; however, those who recover from more severe disease may also have higher levels of antibodies and a shorter duration of viral shedding.

—Management: Coronary calcium scoring was found to be a predictor for outcome in COVID-19. A retrospective cohort study conducted at the University of Munich by a team of internal medicine and radiology specialists found the coronary artery calcification (CAC) score to be a significant prognostic indicator based on 109 SARS-CoV-2-infected patients. Authors found the median CAC to be 140 [IQR 1–1165] in patients with critical COVID-19, and 160 [IQR: 88–562] in patients with fatal outcome. Authors note limitations due to retrospective design and small sample size, however, these findings suggest that coronary artery disease is significantly associated with an adverse clinical outcome in COVID-19.

—Adjusting Practice During COVID-19: There is a high prevalence of deep venous thrombosis in non-severe COVID-19 patients hospitalized for a neurovascular disease. This prospective study from Strasbourg University Hospital, France evaluates 13 patients with non-severe COVID-19 and concurrent neurovascular disease for deep venous thrombosis (DVT) via doppler ultrasound scanning (DUS) of the lower limbs. Results showed that despite thromboprophylaxis, the prevalence of asymptomatic DVT was 38.5%. The authors thus advocate for the use of bedside DUS to identify DVT in patients with COVID-19 given that D-dimer, the classic marker of DVT, has been shown to correlate with COVID-19 severity and may be elevated in this population regardless of coagulable state.

In today's episode we discuss:

—Epidemiology: The authors present a case report of a 29-year-old SARS-CoV-2 positive woman with minimal, mild symptoms who underwent an uncomplicated and successful vaginal delivery to a healthy baby boy at the University of Missouri Women and Children’s Hospital in April 2020. After birth, the patient’s placenta was subsequently analyzed using hematoxylin-and-eosin (H&E) staining, which revealed evidence of general placental vascular malperfusion possibly due to hypertrophic arteriolopathy along with immunohistochemistry (IHC) staining which revealed the presence of SARS-CoV-2 in chorionic villi endothelial cells. Current literature on COVID-19 in pregnant patients is somewhat conflicting regarding morbidity, miscarriage rates, susceptibility, and the possibility of vertical transmission; the authors posit that this case is the first report of placental SARS-CoV-2 in the setting of mild COVID-19 disease, where the patient had only symptoms of mild myalgias.

—R&D: Diagnosis & Treatments: A prospective study conducted at a Malaysian COVID-19 quarantine center of 217 asymptomatic adult males, where 160 tested positive, found a far greater SARS-CoV-2 detection rate using morning salivary samples (93.1%) when compared to nasopharyngeal swabs (52.5%) (p<0.001, 45.6% concordance, 47.5% discordance). These results suggest that the higher accuracy of salivary analysis could play a role in improved diagnostics, decreasing direct healthcare worker-patient interaction and risk of transmission, improving transport preservation, reducing test wait time, and allowing for self-collection.

In today's episode we discuss:

—Adjusting Practice During COVID-19: A team of cardiologists and pharmacists from hospitals in Shanghai and Wuhan, China assessed the association between mortality in hospitalized COVID-19 patients (n=535) and low molecular weight heparin (LMWH) use between January 26-March 26, 2020. They found overall adjusted odds ratio for mortality was lower in the LMWH-users vs non-users (0.20; 95% CI, 0.09-0.46), specifically in severe (0.08; 95% CI, 0.01–0.62) and critically ill cases (0.32; 95% CI ,0.10–0.996). Authors suggest LMWH appears correlated with a survival benefit in hospitalized COVID-19 patients, especially those severely and critically ill.

In today's episode we discuss:

—Climate: American physicians from Yale and the University of Maryland argue that the US government should mandate vaccination of migrant detainees against COVID-19. They assert the crowded and inadequate sanitary conditions in these facilities create epicenters for disease proliferation and that without federal mandates, states will fail to vaccinate this vulnerable population. Authors suggest such policy is both sound medical practice and a moral imperative.

—Epidemiology: A team of Spanish physicians conducted a retrospective cohort-study using the SEMI-COVID-19 Registry of 12,170 COVID-19 patients from 150 hospitals in Spain to investigate impact of arterial stiffness on mortality. They found arterial stiffness (pulse pressure greater than or equal to 60 mmHg) and systolic blood pressure (SBP) less than 120 mmHg on admission significantly and independently predicted all-cause in-hospital mortality (ORadj: 1.27, p=.0001; ORadj: 1.48, p=.0001, respectively). Authors concluded SBP and pulse pressure values on admission are independent predictors of mortality in COVID-19 patients.

—Management: A single-center retrospective cohort study of 157 hospitalized COVID-19 patients in Wuhan, China analyzed 43 demographic, clinical, and laboratory parameters and found an association between higher systolic blood pressure (SBP) on admission and increased mortality. They also utilized regression models to predict mortality and survivability based of available data and they suggest utilizing these models for risk stratification and appropriate triaging of patients to improve outcomes.

In today's episode we discuss:

—Climate: More transparency is needed for emergency use authorizations (EUA), including drugs and vaccines for COVID-19, according to a journalist writing for the Journal of the American Medical Association reporting on a recent US Government Accountability Office (GAO) report. The report calls on the Food and Drug Administration (FDA) to publicly share safety and efficacy data related to EUAs to improve public confidence during this unprecedented time.

—Epidemiology: Persistence of SARS-CoV-2 in a first trimester placenta may have led to transplacental transmission and fetal demise from an asymptomatic mother. An interdisciplinary group of researchers at Model Hospital in Mumbai, India describe a case of hydrops fetalis detected at 13 weeks gestation in an asymptomatic carrier of the SARS-CoV-2 virus. The patient tested posted for COVID-19 at 7.6 weeks of gestation and then was subsequently found to have detectable SARS-CoV2 in the amniotic fluid and placental cells at 13 weeks gestation. These findings suggest possible transplacental SARS-CoV-2 transmission and viral replication within the placenta. While there was evidence of robust placental inflammation, fetal tissue was unavailable for biopsy and therefore infection of the fetus itself is unable to be determined.

—Understanding the Pathology: Immunometabolism may be useful for inflammaging, immunosenescence, and autoimmunity in COVID-19. In this review, an interdisciplinary group of French researchers propose that inflammaging, which is chronic low-grade inflammation that occurs with aging, may be the common factor predisposing individuals with certain comorbidities to more severe COVID-19. They discuss how the underlying mechanisms of immunosenescence and chronic inflammation seen in diseases such as diabetes, hypertension, metabolic syndrome, systemic lupus erythematosus, and rheumatoid arthritis seem to predispose COVID-19 patients to the immune dysfunction and cytokine storm observed in severe disease. Thus, authors propose an immunometabolism-mediated treatment paradigm that includes metformin, rapamycin, and dimethyl fumarate.

—Transmission & Prevention: Intrauterine transmission of SARS-CoV-2 from COVID-19 infected pregnant women is a potential complication according to one review. Members of the Pakistan Health Research Council reviewed 16 articles (498 COVID-19 infected pregnant women) on vertical transmission of SARS-CoV-2 and found vertical transmission occurred in 4.883% of SARs-CoV-2 infected mothers (23/471), and in the 17 cases where outcomes were reported, 4 infants developed COVID-19 pneumonia, 8 required care in the neonatal intensive care unit, 4 received mechanical ventilation, and none died. Authors suggest vertical transmission is possible and that because severe neonatal complications can occur, recommend neonatal screening for infants born to mothers with SARS-CoV-2.

—Management: Do care bundles improve outcomes in patients with COVID-19 or related conditions in intensive care? A systematic review by authors from Ireland and Australia examined the literature on ICU care bundles used in the management of COVID-19 and other acute respiratory pathogens and identified 21 studies encompassing 8 countries, with care bundles most commonly including guidance on ventilator setting, restrictive fluid management, sedation, and prone positioning.

In today's episode we discuss:

—Climate: More transparency is needed for emergency use authorizations (EUA), including drugs and vaccines for COVID-19, according to a journalist writing for the Journal of the American Medical Association reporting on a recent US Government Accountability Office (GAO) report. The report calls on the Food and Drug Administration (FDA) to publicly share safety and efficacy data related to EUAs to improve public confidence during this unprecedented time.

—Epidemiology: Persistence of SARS-CoV-2 in a first trimester placenta may have led to transplacental transmission and fetal demise from an asymptomatic mother. An interdisciplinary group of researchers at Model Hospital in Mumbai, India describe a case of hydrops fetalis detected at 13 weeks gestation in an asymptomatic carrier of the SARS-CoV-2 virus. The patient tested posted for COVID-19 at 7.6 weeks of gestation and then was subsequently found to have detectable SARS-CoV2 in the amniotic fluid and placental cells at 13 weeks gestation. These findings suggest possible transplacental SARS-CoV-2 transmission and viral replication within the placenta. While there was evidence of robust placental inflammation, fetal tissue was unavailable for biopsy and therefore infection of the fetus itself is unable to be determined.

—Understanding the Pathology: Immunometabolism may be useful for inflammaging, immunosenescence, and autoimmunity in COVID-19. In this review, an interdisciplinary group of French researchers propose that inflammaging, which is chronic low-grade inflammation that occurs with aging, may be the common factor predisposing individuals with certain comorbidities to more severe COVID-19. They discuss how the underlying mechanisms of immunosenescence and chronic inflammation seen in diseases such as diabetes, hypertension, metabolic syndrome, systemic lupus erythematosus, and rheumatoid arthritis seem to predispose COVID-19 patients to the immune dysfunction and cytokine storm observed in severe disease. Thus, authors propose an immunometabolism-mediated treatment paradigm that includes metformin, rapamycin, and dimethyl fumarate.

—Transmission & Prevention: Intrauterine transmission of SARS-CoV-2 from COVID-19 infected pregnant women is a potential complication according to one review. Members of the Pakistan Health Research Council reviewed 16 articles (498 COVID-19 infected pregnant women) on vertical transmission of SARS-CoV-2 and found vertical transmission occurred in 4.883% of SARs-CoV-2 infected mothers (23/471), and in the 17 cases where outcomes were reported, 4 infants developed COVID-19 pneumonia, 8 required care in the neonatal intensive care unit, 4 received mechanical ventilation, and none died. Authors suggest vertical transmission is possible and that because severe neonatal complications can occur, recommend neonatal screening for infants born to mothers with SARS-CoV-2.

—Management: Do care bundles improve outcomes in patients with COVID-19 or related conditions in intensive care? A systematic review by authors from Ireland and Australia examined the literature on ICU care bundles used in the management of COVID-19 and other acute respiratory pathogens and identified 21 studies encompassing 8 countries, with care bundles most commonly including guidance on ventilator setting, restrictive fluid management, sedation, and prone positioning.