COVID-19 Literature Situation Report June 14, 2021

• A study comparing the Abbott SARS-CoV-2 nucleocapsid IgG, Beckman-Coulter SARS-CoV-2 spike IgG, and Roche Anti-SARS-CoV-2 nucleocapsid total antibody assays found that all three demonstrated 100% specificity, and sensitivities of 98%, 93%, and 90%, respectively. After the exclusion of samples from immunocompromised patients, all assays exhibited ≥95% sensitivity. In sequential samples collected from the same individuals, the Roche nucleocapsid antibody assay showed continually increasing signal intensity, with maximal values observed at the last time point examined, while the Beckman spike IgG antibody signal peaked between 14-28 days post-positive SARS-CoV-2 PCR test and steadily declined in subsequent samples.

Poore et al. (June 2021). A Comparison of SARS-CoV-2 Nucleocapsid and Spike Antibody Detection Using Three Commercially Available Automated Immunoassays. Clinical Biochemistry. https://doi.org/10.1016/j.clinbiochem.2021.05.011

• A study conducted between March and July 2020 that assessed the association between COVID-19 mortality and different treatment combinations found that anticoagulation treatment alone was associated with significantly reduced mortality for both patients receiving intensive care and non-intensive care. The four treatment combinations studied were anticoagulation only (OR=0.2), anticoagulation and remdesivir (OR=0.3), anticoagulation and corticosteroids (OR=0.5), and anticoagulation, corticosteroids and remdesivir (OR=0.4). After adjusting for demographic characteristics, clinical characteristics, and all treatment combinations, there was an absolute decrease in the mortality rate by 2.5% between early and late periods of the study. 

Coppock et al. (2021). COVID-19 Treatment Combinations and Associations with Mortality in a Large Multi-Site Healthcare System. PloS One. https://doi.org/10.1371/journal.pone.0252591

• Younger age and medical occupation were independent predictors of vaccine hesitancy according to results from a survey of individuals working on a military base in Ohio, administered between November 2020 and January 2021. Among 816 survey respondents, 185 (23%) self-identified as vaccine hesitant. The vaccine hesitant group reported more concern about short-term side effects (43% vs. 26%), long-term side effects (82% vs. 50%), vaccine effectiveness (23% vs. 5%), being infected with COVID-19 from the vaccine (10% vs. 5%), and worry about misinformation/political agenda (43% vs. 31%); these differences were heightened among younger participants. The non-hesitant group was more likely to recommend the COVID-19 vaccine to a friend or family member than the vaccine hesitant group (93% vs. 20%) as were those in the older (≥31 years) age group (79% vs. 67%) and non-medical personnel (81% vs. 52%).

Theis et al. (June 2021). Perceptions and Concerns Regarding COVID-19 Vaccination in a Military Base Population. Military Medicine. https://doi.org/10.1093/milmed/usab230

• A study of 24 breakthrough SARS-CoV-2 infections among fully vaccinated US Military Health System beneficiaries indicated that most infections (67%) occurred among those without comorbid conditions, 57% reported close contact with a COVID-19 case in the past month, and no case of breakthrough infection resulted in hospitalization. Sequencing from 10 of 13 qPCR-positive specimens indicated the presence of variants of concern or interest including B.1.1.7 (Alpha) (n=2), P.1 (Gamma) (n=1), and B.1.429 (Epsilon) (n=2) in addition to other strains not classified as variants of concern or interest, including B.1.1 (n=1), B.1.1.519 (n=1), B.1.2 (n=2), and B.1.243 (n=1).

Pollett et al. (June 2021). The SARS-CoV-2 MRNA Vaccine Breakthrough Infection Phenotype Includes Significant Symptoms, Live Virus Shedding, and Viral Genetic Diversity. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciab543

• A study of SARS-CoV-2 vaccination in 177 different communities in Israel indicated that for every 20 percentage point increase in the proportion of individuals who were vaccinated in a given population, the positive test fraction for the unvaccinated population decreased approximately two-fold, which the authors suggest shows that vaccination provides indirect protection to unvaccinated individuals. Findings from the study indicated that across communities, the positive test fraction in the unvaccinated cohort decreased in proportion to the rate of vaccination in each community.

Milman et al. (June 2021). Community-Level Evidence for SARS-CoV-2 Vaccine Protection of Unvaccinated Individuals. Nature Medicine. https://doi.org/10.1038/s41591-021-01407-5

• [Pre-print, not peer-reviewed] The presence of SARS-CoV-2 anti-nucleocapsid antibodies at baseline was associated with almost 80% protection against SARS-CoV-2 re-infection for a period of at least eight months, according to a study of healthcare workers (HCW) in Switzerland. Among 4,818 participants, 144 (3%) were seropositive at baseline. Among 2,713 participants with ≥1 SARS-CoV-2 test during follow-up, 3 of 67 (4.5%) seropositive individuals reported a positive result, compared to 547 of 2,646 (20.7%) seronegative participants (RR=0.22).

Kohler et al. (June 12, 2021). Impact of Baseline SARS-CoV-2 Antibody Status on Syndromic Surveillance and the Risk of Subsequent Covid-19 – a Prospective Multicentre Cohort Study. Pre-print downloaded Jun 14 from https://doi.org/10.1101/2021.06.09.21258422

• [Pre-print, not peer-reviewed] As part of the Phase 3 randomized trial for the Novavax SARS-CoV-2 vaccine, a sub-study found that co-administration of an influenza vaccine resulted in no change in influenza vaccine immune response, and a slight reduction in antibody responses to the Novavax vaccine. The authors suggest that this could indicate the viability of combined vaccinations. SARS-CoV-2 vaccine efficacy in this sub-study was 87.5% compared to an efficacy in the main study of 89.8%. 

Heath et al. (June 13, 2021). Safety Immunogenicity and Efficacy of a COVID-19 Vaccine (NVX-CoV2373) Co-Administered With Seasonal Influenza Vaccines. Pre-print downloaded Jun 14 from https://doi.org/10.1101/2021.06.09.21258556

• SARS-CoV-2 RNA levels, as determined by cycle threshold (Ct) values, were significantly higher in symptomatic compared to asymptomatic individuals, and no significant differences in RNA levels were detected between adults and children, according to results from a community-based cross-sectional study in King County, Washington. Among 555 SARS-CoV-2–positive participants, 47 of 123 children (38%) were asymptomatic compared to 31 of 432 (7%) adults, and children with symptoms reported fewer symptoms than symptomatic adults. 

Chung et al. (June 2021). Comparison of Symptoms and RNA Levels in Children and Adults With SARS-CoV-2 Infection in the Community Setting. JAMA Pediatrics. https://doi.org/10.1001/jamapediatrics.2021.2025

• A cohort study of children and adolescents (n=671) from France, Germany, Spain, Singapore, the UK, and the US found varying trends in COVID-19 hospitalizations and complications between countries, with hospitalizations in the cohort mirroring those of national-level pediatric hospitalization trends for most countries with available data. Laboratory values for 16 assays were analyzed, which indicated elevated levels of inflammatory markers, including C-reactive protein, ferritin, and procalcitonin. Common complications included cardiac arrhythmias (15%), viral pneumonia (13%), and respiratory failure (11%). Few children were treated with COVID-19–directed medications.

Bourgeois et al. (June 2021). International Analysis of Electronic Health Records of Children and Youth Hospitalized With COVID-19 Infection in 6 Countries. JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2021.12596

• [Pre-print, not peer-reviewed] A cohort study of children and adolescents (n=1,501) who were admitted to the hospital between March 18, 2020 and April 30, 2021 in Germany and who tested positive for SARS-CoV-2 found that although approximately half of the cohort was not admitted to the hospital due to COVID-19, 72% had infection-related symptoms during hospitalization. Pre-existing conditions, including respiratory disorders, and neurological, neuromuscular, and cardiovascular diseases, were present in 28% of participants. In a fully adjusted model, patient age, trisomy 21, coinfections and primary immunodeficiencies were significantly associated with intensive care treatment. 

Armann et al. (June 13, 2021). Risk Factors for Hospitalization Disease Severity and Mortality in Children and Adolescents with COVID-19 Results from a Nationwide German Registry. Pre-print downloaded Jun 14 from https://doi.org/10.1101/2021.06.07.21258488

• A modeling study estimating the impact of different non-pharmaceutical intervention (NPI) policies on the SARS-CoV-2 effective reproduction number (Reff) found that NPIs that included closure of schools and leisure activities and nursing home visiting bans were all associated with a median Reff below 1 when combined with either stay at home orders (median Reff 0.97) or face masks (median Reff 0.97). The authors note that the simultaneous implementation of multiple NPI policies makes it difficult to estimate the effect of any one policy, particularly school closures. Lifting restrictions on leisure activities (e.g., restaurants and gyms) was associated with increased Reff, indicating higher transmission risks, while less dramatic changes in Reff were estimated for the removal of stay-at-home orders and medical service suspension. The authors suggest that these results indicate that relaxation of some NPIs will need to be counterbalanced by continuation and/or implementation of others.

Yang et al. (June 2021). Effect of Specific Non-Pharmaceutical Intervention Policies on SARS-CoV-2 Transmission in the Counties of the United States. Nature Communications. https://doi.org/10.1038/s41467-021-23865-8

• [Pre-print, not peer-reviewed] A modeling study showed that the early SARS-CoV-2 vaccine allocation (February 19 and March 17, 2021) in the US created “vaccine deserts” – areas with localized, geographic barriers to vaccine-associated herd immunity – which the authors suggest may impact population-wide efforts to curb SARS-CoV-2 transmission. Using an empirically-parameterized spatial accessibility model that incorporated high-resolution COVID-19 burden and time-willing-to travel for vaccination, the early allocation scheme favored spatial accessibility within US metropolitan areas, in contrast to rural areas that were more likely to have both more vulnerable populations and more vaccine deserts. At the time of the analysis, the authors estimated that about 14% of the US population was living in vaccine deserts. 

Rader et al. (June 12, 2021). Spatial Accessibility Modeling of Vaccine Deserts as Barriers to Controlling SARS-CoV-2 Transmission. Pre-print downloaded Jun 14 from https://doi.org/10.1101/2021.06.09.21252858

• An online cross-sectional survey conducted in May 2020 (n=963) found that experiencing structural discrimination was associated with higher health-specific COVID-19 conspiracy beliefs, while everyday discrimination was associated with more general medical mistrust but not with health-specific COVID-19 conspiracy beliefs. In addition, higher endorsement of health-specific COVID-19 conspiracy beliefs, but not general medical mistrust, was associated with significantly lower engagement in health-specific COVID-19 conspiracy beliefs.

Smith et al. (June 2021). An Investigation of Associations Between Race, Ethnicity, and Past Experiences of Discrimination with Medical Mistrust and COVID-19 Protective Strategies. Journal of Racial and Ethnic Health Disparities. https://doi.org/10.1007/s40615-021-01080-x

• [Pre-print, not peer-reviewed] A cohort study of over 29 million adults in the UK found that compared to people without disabilities, mortality involving COVID-19 was higher both among people who self-identified as more-disabled (HR=3.1) and less-disabled (HR=1.9). Between January 24, 2020 and February 28, 2021, >100,000 people in the UK died from COVID-19-related causes, 58% of whom had disabilities. Among people aged 30-69, mortality involving COVID-19 risk was 8.5-fold higher among females who were more-disabled and 5.4-fold higher among more-disabled males. 

Bosworth et al. (June 13, 2021). Deaths Involving COVID-19 by Disability Status a Retrospective Analysis of 29 Million Adults during the First Two Waves of the Coronavirus Pandemic in England. Pre-print downloaded Jun 14 from https://doi.org/10.1101/2021.06.10.21258693