COVID-19 Literature Situation Report May 26, 2021

• An analysis of 936,423 SARS-CoV-2 RT-PCR-positive samples from hospitalized and non-hospitalized persons in Germany found that high viral loads (> 109 copies per swab) were found in 8% of subjects, 1/3 of whom were pre-symptomatic, asymptomatic, or mildly symptomatic. The mean number of days from onset of viral shedding to peak viral load was 4.3. Additionally, persons infected with the B.1.1.7 variant had a 1.05 higher mean log10 viral load and a 2.6-fold higher probability of cell culture replication than persons infected with non-B.1.1.7 strains. These results indicate that some individuals with mild or no symptoms may be as infectious as persons with severe infection.

Jones et al. (May 25, 2021). Estimating Infectiousness throughout SARS-CoV-2 Infection Course. Science. https://doi.org/10.1126/science.abi5273

• A novel molecular test for detection of SARS-CoV-2 called SARSeq (saliva analysis by RNA sequencing) demonstrated sensitivity approximately equal to existing RT-PCR tests, high specificity, and low cost while utilizing equipment available in most molecular biology facilities. The test can be run on up to 36,000 samples in parallel with a turnaround time of 12-24 hours, which could be beneficial for conducting widespread population-level surveillance for SARS-CoV-2.

Yelagandula et al. (May 2021). Multiplexed Detection of SARS-CoV-2 and Other Respiratory Infections in High Throughput by SARSeq. Nature Communications. https://doi.org/10.1038/s41467-021-22664-5

• [Pre-print, not peer-reviewed] An evaluation of a rapid testing program among 1141 resident students and staff at a university in British Columbia found that the use of rapid antigen tests was feasible, inexpensive, and increased sensitivity for detection of active SARS-CoV-2 infections. The testing program utilized the BD Veritor COVID-19 rapid antigen test and participants were invited to test up to 3 times per week. Mean number of tests per person was 3 and mean duration between tests was 7 days. 25 RT-PCR positive tests and 8 false positive rapid antigen tests were detected, all of whom were asymptomatic. 98% of participants reported rapid antigen testing was acceptable or very acceptable and 97% reported they would come back again for another test. The authors suggest that rapid antigen screening programs could potentially interrupt transmission chains and reduce overall community spread of COVID-19.

Wong et al. (May 26, 2021). Feasibility and Utility of Rapid Antigen Testing for COVID-19 in a University Residence a Cross Sectional Study. Pre-print downloaded May 26 from https://doi.org/10.1101/2021.05.24.21257732

• [Pre-print, not peer-reviewed] A systematic review and meta-analysis (n = 10 studies, n = 1,173 patients) of randomized controlled trials found that the use of ivermectin for treatment of COVID-19 did not reduce all-cause mortality, length of hospitalization, adverse events, or viral clearance. Trials of ivermectin for the treatment of mild to moderate COVID-19 in low- and middle-income countries (N=9) and Spain were included. The authors note that the quality of evidence was low or very low for all outcomes but concluded their results do not support the use of ivermectin for treatment of COVID-19.

Roman et al. (May 25, 2021). Ivermectin for the Treatment of COVID-19 A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Pre-print downloaded May 26 from https://doi.org/10.1101/2021.05.21.21257595

• [Pre-print, not peer-reviewed] A comparison of commercially available SARS-CoV-2 antibody assays found that the Roche Anti-SARS-CoV-2 anti-nucleocapsid Total Antibody test (Roche) detected antibodies for at least seven months after confirmed natural infection with while sensitivity of the Abbott Anti-SARS-CoV-2 anti-nucleocapsid IgG (Abbott) declined over time. Among serum samples from healthcare workers (N=5,788) with previously confirmed SARS-CoV-2 infection, 41% tested positive on Abbott and 95% tested positive on Roche. Sensitivity of the Abbott test started to decline at 150 days following natural infection, while Roche positivity was retained for the entire 210-day study period. These results may indicate that the Roche antibody test is better suited than Abbott to population-based studies of SARS-CoV-2 serology, though the authors note that the relationship between serologic response and functional immunity needs to be more clearly defined.

Allen et al. (May 26, 2021). SARS-CoV-2 Antibody Testing in Healthcare Workers a Comparison of the Clinical Performance of Three Commercially Available Antibody Assays. Pre-print downloaded May 26 from https://doi.org/10.1101/2021.05.25.21257772

• [Pre-print, not peer-reviewed] A study comparing antibody responses in 155 previously SARS-CoV-2 infected individuals found a single dose of the Pfizer-BioNTech vaccine provided neutralizing antibody titers exceeding those produced following two vaccine doses in 49 previously uninfected healthcare workers. Additionally, pre-vaccination neutralization titers in persons with previous infection were associated with higher neutralization titers after vaccination, independent of disease severity or time since infection up to 15 months after SARS-CoV-2 infection. Serum samples from a random selection of 20 participants with previous infection and one dose also demonstrated cross-neutralization of variants B.1.351, P.1, and B.1.1.7.  The authors suggest these findings support implementation of a single-dose mRNA vaccine strategy in persons with prior SARS-CoV-2 infection.

Gils et al. (May 25, 2021). Single-Dose SARS-CoV-2 Vaccine in a Prospective Cohort of COVID-19 Patients. Pre-print downloaded May 26 from https://doi.org/10.1101/2021.05.25.21257797

• [Pre-print, not peer-reviewed] A cohort study of 63 hospital healthcare workers in Spain who received 2 doses of the Pfizer-BioNTech vaccine found that those with a previous SARS-CoV-2 infection developed a 126-fold increase in antibody levels after 1 dose and maintained higher antibody levels than SARS-CoV-2 naïve workers after the 2nd dose. Healthcare workers with history of SARS-CoV-2 infection did not experience an increase in antibodies after the second dose, while SARS-CoV-2 naïve workers had a significant increase in antibody levels. The authors suggest these results may indicate the persistence of strong immunologic memory in persons with past SARS-CoV-2 infection and that vaccination of these persons could potentially be postponed as a strategy to optimize vaccine allocation.

Ontanon et al. (May 26, 2021). Influence of Past Infection with SARS-CoV-2 on the Response to the BioTech Pfizer BNT162b2 MRNA Vaccine in Health Care Workers Kinetics and Durability of the Humoral Response. Pre-print downloaded May 26 from https://doi.org/10.1101/2021.05.25.21257788

• [Pre-print, not peer-reviewed] All (n = 20) breakthrough infections detected among fully vaccinated University of Washington healthcare workers involved a variant of concern, compared to a background rate of 68% of community cases being caused by a variant of concern across WA state during the same time period (N=5,174).  Additionally, variants that have been reported to be less effectively neutralized by antibodies from post-vaccinated individuals (P.1, B.1.351, B.1.427, and B.1.429) were identified in 60% of breakthrough infections and only 37% of all community cases. No breakthrough infections resulted in hospitalization, and 15 of 18 with available clinical information reported symptoms. Vaccination status was not available or reported for community cases, despite the availability of vaccination for the general population during the study period in WA State (Feb-Apr 2021). 

McEwen et al. (May 25, 2021). Variants of Concern Are Overrepresented among Post-Vaccination Breakthrough Infections of SARS-CoV-2 in Washington State. Pre-print downloaded May 26 from https://doi.org/10.1101/2021.05.23.21257679

• Patients admitted after trauma who were found to have COVID had higher rates of mortality (9% vs. 2%) and pneumonia (8% vs. 0), and a longer mean length of stay (7.5 days vs. 3 days) compared to patients without COVID-19, according to a retrospective, propensity-matched cohort study (n = 159) of patients presenting to 11 Level-I and II trauma centers in California. The two groups had similar rates of mechanical ventilation, ventilator days, complications, and discharge disposition. However, only two of 53 patients with COVID-19 died of respiratory failure, suggesting that other physiologic pathways may increase mortality risk. The authors call for additional studies to confirm these results and identification of predisposing factors associated with higher mortality in trauma patients with COVID-19.

Yeates et al. (May 25, 2021). COVID-19 in Trauma: A Propensity-Matched Analysis of COVID and Non-COVID Trauma Patients. European Journal of Trauma and Emergency Surgery. https://doi.org/10.1007/s00068-021-01699-9

• Lower testosterone concentrations during hospitalization were associated with increased disease severity, inflammation, and mortality in a cohort of 152 male COVID-19 patients. This association remained after controlling for other known risk factors for severe COVID-19, including age, BMI, comorbidities, smoking, and race. Testosterone concentrations were similar among those who presented with severe illness and those who developed severe illness during their hospital stay, which suggests testosterone may be a biomarker for risk of severe disease. 

Dhindsa et al. (May 25, 2021). Association of Circulating Sex Hormones With Inflammation and Disease Severity in Patients With COVID-19. JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2021.11398

• Veterans with a history of COVID-19 were more likely to screen positive for internalizing psychiatric disorders (depression, anxiety, and/or PTSD), substance use disorders, and current suicidal ideation compared to veterans without a history of COVID-19, according to a nationally representative, prospective cohort of 3,078 US veterans. In multivariable analysis, pre-pandemic psychiatric symptom severity and COVID-related stressors were the strongest independent predictors of internalizing disorders. Pre-pandemic suicidal ideation, greater loneliness, and lower household income were the strongest independent predictors of current suicidal ideation, while pre-pandemic community integration was associated with lower risk of suicidal ideation. These results may suggest that US veterans who survived COVID-19 may require focused psychiatric health prevention and treatment efforts.

Na et al. (May 2021). Mental Health and Suicidal Ideation in US Military Veterans with Histories of COVID-19 Infection. BMJ Military Health. https://doi.org/10.1136/bmjmilitary-2021-001846

• [Pre-print, not peer-reviewed] A modeling study of SARS-CoV-2 transmission in the US population found that allocating monoclonal antibodies (mAbs) as post-exposure prophylaxis (PEP) and treatment of persons with COVID-19 in combination with a vaccination program could substantially reduce infections and mortality. Allocation of mAbs as PEP to persons >65 years of age averted up to 17% of infections and 41% of SARS-CoV-2 associated deaths relative to vaccine alone. The authors suggest that the benefits of mAbs for early treatment and PEP could be enhanced in scenarios where rapid vaccine deployment is not feasible.  

Kamal et al. (May 25, 2021). Monoclonal Antibody Treatment Prophylaxis and Vaccines Combined to Reduce SARS CoV-2 Spread. Pre-print downloaded May 26 from https://doi.org/10.1101/2021.05.21.21257624

• A review of sentinel surveillance data on influenza-like illness in Mexico found a marked decrease in influenza diagnoses in outpatient clinics and public hospitals, influenza positivity rates, and confirmed severe influenza cases in the 10 weeks following implementation of lockdown measures in 2020 compared to the same period in 2019. The authors conclude that measures to mitigate transmission of SARS-CoV-2 was more effective for reducing transmission of influenza, which may be partially explained by differences in transmission mechanisms, virulence, and/or underlying population immunity.  

Arellanos-Soto et al. (Dec 24, 2021). Decline in Influenza Cases in Mexico after the Implementation of Public Health Measures for COVID-19. Scientific Reports. https://doi.org/10.1038/s41598-021-90329-w