COVID-19 Literature Situation Report June 11, 2021

• An analysis of SARS-CoV-2 sequences isolated from farmed mink populations (N=977) and human infections in the US and Canada (N=192,806) from December 2019-March 2021 revealed that the N501T mutation was found in humans two months prior to being detected in mink populations. However, in contrast to the N501Y mutation, which is present in the B.1.1.7 (Alpha), B.1.351 (Beta), and P.1 (Gamma) variants and has been associated with higher transmissibility, the N501T mutation was not found to be associated with higher levels of transmission. The authors suggest that these results indicate that SARS-CoV-2 variants may have evolved in humans prior to being detected in mink populations.

Cai and Cai. (June 2021). SARS-CoV2 Spike Protein Gene Variants with N501T and G142D Mutation-Dominated Infections in Mink in the United States. Journal of Veterinary Diagnostic Investigation: Official Publication of the American Association of Veterinary Laboratory Diagnosticians, Inc. https://doi.org/10.1177/10406387211023481

• A retrospective cohort study from Denmark found that patients hospitalized with COVID-19 (N=2,747) who were treated with remdesivir and dexamethasone had lower odds of 30-day mortality (OR=0.47) and progression to mechanical ventilation (OR=0.36) compared to persons receiving the standard of care. However, the authors caution that because treatment was not randomized, study data does not permit the distinction between individual effects of the drugs vs. additional interventions during hospitalization on measured outcomes. However, the authors controlled for confounding factors that may have influenced treatment decisions and disease severity by using inverse probability weighted logistic regression. 

Benfield et al. (June 2021). Improved Survival among Hospitalized Patients with COVID-19 Treated with Remdesivir and Dexamethasone. A Nationwide Population-Based Cohort Study. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciab536

• [Pre-print, not peer-reviewed] A small study of Japanese healthcare workers (N=67) found that reactogenicity to a second dose of the Pfizer-BioNTech vaccine was not a predictor of subsequent IgG antibody levels. The study controlled for age, sex, and IgG levels after the first dose of vaccine. The prevalence of local and systemic reactogenicity was 2.5-times higher after the second dose compared to the first dose, with a higher severity in younger persons, and spike IgG titers increased 16-fold after the second dose.

Takeuchi et al. (June 10, 2021). Does Reactogenicity after a Second Injection of the BNT162b2 Vaccine Predict Spike IgG Antibody Levels in Healthy Japanese Subjects. Pre-print downloaded Jun 11 from https://doi.org/10.1101/2021.06.08.21258444

• Data from a voluntary surveillance program at a single medical center in Italy revealed that 11 healthcare workers who had been fully vaccinated with the Pfizer-BioNTech vaccine had SARS-CoV-2 detected in nasopharyngeal swabs and 5 of these persons had mild symptoms. The average cycle threshold (Ct) in detected infections was 19 (range 6-26). However, no cases of nosocomial transmission were documented from these healthcare workers to patients. [EDITORIAL NOTE: This article did not report the number of vaccinated health care workers from among which the 11 SARS-CoV-2-positive individuals emerged, which makes it impossible to determine the incidence of infection among fully vaccinated individuals.]

Baj et al. (June 10, 2021). Symptomatic SARS-CoV-2 Infections After Full Schedule BNT162b2 Vaccination in Seropositive Healthcare Workers: A Case Series From a Single Institution. Emerging Microbes & Infections. https://doi.org/10.1080/22221751.2021.1942230

• Compared to those who received one dose of the Pfizer-BioNTech COVID-19 vaccine, receipt of one dose of the Oxford-AstraZeneca vaccine was associated with a higher risk of idiopathic thrombocytopenic purpura (ITP), a blood disorder involving low platelet counts, during 0–27 days after vaccination (adjusted RR = 5.8), with an estimated incidence of 1.13 cases per 100,000 doses. Findings were based on a nested, incident-matched case-control study (N=2.5 million) conducted in Scotland. Confirmatory self-controlled case series analysis confirmed this association was unlikely to be due to bias, although the true risk ratio is likely lower (RR=1.2) due to the potential for overestimation of reported results due to residual confounding. Receipt of the Pfizer-BioNTech vaccine was not associated with ITP. The authors suggest that using an alternative to the AstraZeneca vaccines may be appropriate for individuals at low risk of COVID-19 if supply allows.

Simpson et al. (June 2021). First-Dose ChAdOx1 and BNT162b2 COVID-19 Vaccines and Thrombocytopenic, Thromboembolic and Hemorrhagic Events in Scotland. Nature Medicine. https://doi.org/10.1038/s41591-021-01408-4

• An in-vitro study of sera from persons fully vaccinated with the Pfizer-BioNTech vaccine found that all samples neutralized SARS-CoV-2 virus variants B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.618 (first identified in India) and B.1.525 (Eta, first identified in Nigeria). Neutralization of all variants, with the exception of B.1.617.1, was only slightly reduced compared to neutralization of wild-type SARS-CoV-2. Although neutralization of B.1.617.1 was somewhat reduced, the sera still neutralized this variant. The authors suggest that vaccination will reduce transmission of existing variants and reduce emergence of new variants. 

Liu et al. (June 2021). BNT162b2-Elicited Neutralization of B.1.617 and Other SARS-CoV-2 Variants. Nature. https://doi.org/10.1038/s41586-021-03693-y

• A small, single center study of persons hospitalized with COVID-19 in China (N=74) identified innate and adaptive immunological differences between patients with severe and non-severe disease. Specifically, patients with severe disease had lower baseline lymphocyte counts, higher neutrophil to lymphocyte ratios, and lower eosinophil counts. T-cell, B-cell, and natural killer cells were also lower among those with severe disease. The authors suggest that these results indicate that innate and adaptive immune responses are correlated with COVID-19 disease severity.

Zheng et al. (June 2021). Dynamic Changes in the Immune Response Correlate with Disease Severity and Outcomes During Infection with SARS-CoV-2. Infectious Diseases and Therapy. https://doi.org/10.1007/s40121-021-00458-y

• A retrospective cohort study of persons with SARS-CoV-2 infection diagnosed between April and June 2020 in 7 US states identified 248 cases of multisystem inflammatory syndrome in children (MIS-C) in persons <21 years of age. The corresponding incidence of MIS-C was 5.1 per 100,000 person-months and 316 persons per 1,000,000 (0.0003%) SARS-CoV-2 infections. Incidence was higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons compared to white persons and lower among those aged 16-20 compared to children <5 years of age. The authors indicate that MIS-C was a rare complication associated with SARS-CoV-2 during this time period and suggest that the study can serve as a baseline for monitoring of MIS-C after increased vaccination uptake. 

Payne et al. (June 2021). Incidence of Multisystem Inflammatory Syndrome in Children Among US Persons Infected With SARS-CoV-2. JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2021.16420

• Emergency department visits for suspected suicide attempts were 51% higher among young females aged 12-17 between February 21 and March 20, 2021 compared to the same period in 2019, according to a review of US National Syndromic Surveillance Program data. Among young males of the same age, emergency department visits for suicide attempt were up 4%. The observed increase in visits for suicide attempts began in summer 2020 and remained elevated through May 15, 2021. The authors hypothesize that these increased rates may have been affected by COVID-9 pandemic mitigation measures, resulting in a lack of connectedness to schools, teachers, and peers, barriers to mental health treatment, increases in substance use, and anxiety about family health and economic problems, which are all risk factors for suicide. 

Yard et al. (June 11, 2021). Emergency Department Visits for Suspected Suicide Attempts Among Persons Aged 12–25 Years Before and During the COVID-19 Pandemic — United States, January 2019–May 2021. MMWR. https://doi.org/10.15585/mmwr.mm7024e1

• A cross-sectional seroprevalence survey of teachers and staff (N=753) at a school in suburban Indiana conducted in July 2020 found that 1.7% of tested persons had antibodies to SARS-CoV-2. Persons with a previously confirmed SARS-CoV-2 infection had 48-fold higher odds of seropositivity compared to persons without previous infection, controlling for mask usage, travel history, symptom history, and known contact with persons with confirmed infection. In persons without previous infection, exposure to a person with confirmed infection was associated with 7-fold higher odds of seropositivity.

Lopez et al. (2021). Seroprevalence of Anti-SARS-CoV-2 IgG Antibodies in the Staff of a Public School System in the Midwestern United States. PloS One. https://doi.org/10.1371/journal.pone.0243676