COVID-19 Literature Situation Report June 7, 2021

• [Pre-print, not peer-reviewed] A study of the impact of Washington State’s exposure notification tool, WA Notify, in mitigating the spread of COVID-19 during the first four months of implementation found that based on an estimated COVID-19 case fatality of 1.4%, WA Notify saved 30-120 lives over this period. A model was run on a range of secondary attack rates (5.1-13.7%) and quarantine effectiveness (53–64%); assuming a 12% secondary attack rate and 53% quarantine effectiveness, 6,240 cases were expected to be averted statewide during the four-month period. 

Segal et al. (June 7, 2021). Early Epidemiological Evidence of Public Health Value of WA Notify a Smartphone-Based Exposure Notification Tool Modeling COVID-19 Cases Averted in Washington State. Pre-print downloaded Jun 7 from https://doi.org/10.1101/2021.06.04.21257951

• [Pre-print, not peer-reviewed] A study in the UK suggested that many SARS-CoV-2 cases were S-gene positive, a pattern associated with the B.1.617.2 variant, which the authors suggest may become dominant over B.1.1.7. In early 2021, the majority of positive SARS-CoV-2 tests in England were genomically sequenced (74% in April 2021), with the sequencing subject to processing delays: 21% of sequencing results were available within 1 week, 44% within 2 weeks, and 66% within 3 weeks (as of 27th May 2021). S-gene positive cases were estimated to be doubling every 7 days overall in England, and as rapidly as every 5 days in some regions with known outbreaks of B.1.617.2. The authors suggest prioritizing sequencing of S-gene positive cases in countries where this variant is newly detected.

Challen et al. (June 7, 2021). Early Epidemiological Signatures of Novel SARS-CoV-2 Variants Establishment of B.1.617.2 in England. Pre-print downloaded Jun 7 from https://doi.org/10.1101/2021.06.05.21258365

• [Pre-print, not peer-reviewed] A study conducted in Ontario, Canada found that household secondary attack rates were 20.2% for wild-type, 25.1% for B.1.1.7, 27.2% for B.1.351 or P.1, and 23.3% for non-variants of concern (VOC) mutations in SARS-CoV-2. Cases were grouped into households based on reported residential address: 7,555 (28%) were wild-type, 17,058 (63%) were B.1.1.7, 1674 (6%) were B.1.351 or P.1, and 601 (2%) were non-VOC mutations. In adjusted analyses, index cases infected with the B.1.1.7, B.1.351, and P.1 VOC had the highest transmissibility (B.1.1.7 aOR = 1.5, B.1.351 or P.1 aOR = 1.6). 

Brown et al. (June 4, 2021). Comparative Household Secondary Attack Rates Associated with B.1.1.7 B.1.351 and P.1 SARS-CoV-2 Variants. Pre-print downloaded Jun 7 from https://doi.org/10.1101/2021.06.03.21258302

• [Pre-print, not peer-reviewed] A study investigating SARS-CoV-2 genetic diversity in the US using sequences publicly available prior to December 15th, 2020, when vaccination was initiated in the U.S., found that the regional distribution of COVID-19 cases varied by pandemic phase and was not always correlated with the level of viral sequencing in different regions. In Phase 1 (winter/spring 2020), sequences were dominated by the D614G spike mutation and by Phase 3 (fall 2020), genetic diversity of the viral population had tripled and at least 54 new amino acid changes had emerged at frequencies above 5%, several of which were within known antibody epitopes. The authors suggest that these findings highlight the need to track the evolution of SARS-CoV-2 variants in the U.S.

Capoferri et al. (June 4, 2021). 2020 SARS-CoV-2 Diversification in the United States Establishing a Pre-Vaccination Baseline. Pre-print downloaded Jun 7 from https://doi.org/10.1101/2021.06.01.21258185

• Treatment with monoclonal antibody (mAb) therapy, including casirivimab/imdevimab and bamlanivimab, was associated with a significant reduction in the frequency of hospitalization compared to controls not receiving mAb treatment (1.7% vs. 24%) in a retrospective study of 617 outpatients with COVID-19 classified as high-risk (n = 175 received mAb). There were no COVID-19-related deaths in the mAb group vs. 12 (2.7%) among controls (p=0.024). The authors note that the mAb group was older, was more likely to be male, had more comorbidities, and a higher COVID-19 risk score.

Jenks et al. (June 6, 2021). Early Monoclonal Antibody Administration Can Reduce Both Hospitalizations and Mortality in High-Risk Outpatients with COVID-19. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciab522

• A study of the effectiveness of neutralizing antibody titers (NAbTs) against the B.1.617.2 SARS-CoV-2 variant, first identified in India and now widely circulating in the UK, found that two doses of the Pfizer-BioNTech vaccine elicited anti-wild-type spike antibodies in all participants, while NAbTs were reduced 5.8-fold against B.1.617.2 relative to wild-type, a significantly greater reduction than against B.1.1.7, but similar to the reduction observed against B.1.351. The authors note that these data are insufficient to assess the extent to which the reduction in NAbTs will impact vaccine efficacy. 

Wall et al. (June 2021). Neutralising Antibody Activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 Vaccination. The Lancet. https://doi.org/10.1016/S0140-6736(21)01290-3

• Over a period of 3 weeks, an outbreak at a long-term care facility in Ontario, Canada likely originating from an unvaccinated staff member infected with the B.1.351 variant sickened 4 staff members (2 fully vaccinated, 1 single dose, one unvaccinated) and 9 fully vaccinated residents. Two unvaccinated staff members had infections due to other variants (one B.1.1.7, and one B.1.617.2) and 3 (1 fully vaccinated, 2 single dose) had positive tests with concentrations too low to identify lineage. Genomic analysis revealed that all B.1.351 genomes were highly related. 138 of 139 residents were fully vaccinated with the Pfizer vaccine, with doses received between January 9th and March 18th, 2021. Of 243 staff, 204 (84%) received at least one dose of an mRNA vaccine (122 fully vaccinated, and 82 with second dose delayed as per Canadian vaccination strategy). 

Vanker et al. (June 6, 2021). Adverse Outcomes Associated with SARS-CoV-2 Variant B.1.351 Infection in Vaccinated Residents of a Long Term Care Home, Ontario, Canada. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciab523

• [Pre-print, not peer-reviewed] A study of SARS-CoV-2 infections among employees of the Cleveland Clinic Health System found that after adjusting for the slope of the epidemic curve, age, and job type, vaccination was associated with a significantly reduced risk of infection (HR = 0.03), corresponding to a vaccine effectiveness of 97.1%. Vaccine effectiveness was 89.2% at 7 days and 95.0% at 14 days after the first dose. Among 46,866 employees, 28,223 (60%) were vaccinated by the end of the study period, and only 15 (0.7%) of the 2,154 SARS-CoV-2 infections during the study occurred among those who were vaccinated. 

Shrestha et al. (June 5, 2021). Effectiveness of MRNA COVID-19 Vaccines among Employees in an American Healthcare System. Pre-print downloaded Jun 7 from https://doi.org/10.1101/2021.06.02.21258231

• A study assessing the avidity, or binding strength, of IgG among 217 participants in Austria soon after SARS-CoV-2 infection and 7-8 months later found that avidity increased from 18% to 42% and did not diminish among older participants. High avidity was associated with a residual neutralization capacity in 97% of participants (211/217). The authors suggest that robust immunity may persist for 7-8 months after infection and is not impaired in older individuals. 

Pichler et al. (June 2021). Marked Increase in Avidity of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Antibodies 7-8 Months after Infection Is Not Diminished in Old Age. The Journal of Infectious Diseases. https://doi.org/10.1093/infdis/jiab300

• Reports from seven cases of acute myocarditis (inflammation of the heart) or myopericarditis among adolescent males who developed chest pain within four days of receiving the Pfizer-BioNTech vaccine and were hospitalized found that six of seven patients had negative SARS-CoV-2 nucleocapsid antibody assays (indicating no prior infection), and all patients’ symptoms resolved quickly. Three patients were treated with non-steroidal anti-inflammatory drugs and 4 received intravenous immune globulin and corticosteroids. Diagnostic evaluation for other myocarditis etiologies, including respiratory pathogens from nasopharyngeal swabs, and diagnostics for other infectious agents, were all negative. 

Marshall et al. (June 4, 2021). Symptomatic Acute Myocarditis in Seven Adolescents Following Pfizer-BioNTech COVID-19 Vaccination. Pediatrics. https://doi.org/10.1542/peds.2021-052478

• A longitudinal study of convalescent plasma donors (n = 228) detected anti-SARS-CoV-2 antibodies in 97% of donors at initial presentation, and found that 91.4% of the 116 donors presenting for repeat timepoints had detectable IgG levels up to 11 months post-symptom recovery. The VITROS® Anti-SARS-CoV-2 Total and IgG assays, and an in-house fluorescence reduction neutralization assay, were used to test samples. 63% of donors had detectable neutralizing titers, while 25% had neutralizing levels that dropped to an undetectable titer over time. The authors suggest their results indicate that immunological memory lasts for at least 11 months after recovery from COVID-19.

De Giorgi et al. (June 2021). Naturally Acquired SARS-CoV-2 Immunity Persists for up to 11 Months Following Infection. The Journal of Infectious Diseases. https://doi.org/10.1093/infdis/jiab295

• No major safety problems were detected following the first or second dose of either of the two mRNA SARS-CoV-2 vaccines in a study of electronic health records from US nursing home residents (n = 8,553) between December 18, 2020 and March 7, 2021. The analysis of pre-specified adverse events did not detect statistical signals for any pre-specified outcomes, including anaphylaxis, seizures, Guillain-Barre Syndrome, or myocarditis.

Bardenheier et al. (May 2021). Adverse Events Following MRNA SARS-CoV-2 Vaccination among U.S. Nursing Home Residents. Vaccine. https://doi.org/10.1016/j.vaccine.2021.05.088

• [Pre-print, not peer-reviewed] A study using electronic health record data from 54 clinical sites in the National COVID Cohort Collaborative found that people living with HIV (PLWH, n=13,170) had a higher risk of COVID-19 death and hospitalization after adjusting for age and sex. The associations were attenuated, but remained significant, after adjusting for smoking status, BMI, and comorbidities (death aOR = 1.4, hospitalization = 1.2). PLWH were more likely to have severe COVID-19 when only controlling for demographics, smoking, and BMI, although the estimated risk was obviated after controlling for comorbidities. Analysis for effect modification found that the HIV-associated risk was higher among older people, males, and Black/African American individuals. 

Yang et al. (June 6, 2021). The Role of HIV Infection in the Clinical Spectrum of COVID-19 a Population-Based Cohort Analysis Based on US National COVID Cohort Collaborative (N3C) Enclave Data. Pre-print downloaded Jun 7 from https://doi.org/10.1101/2021.06.03.21258324

• Among patients with COVID-19 (n=306), high plasma levels of angiotensin converting enzyme 2 (ACE2) at hospital admission were associated with increased illness severity within 28 days (OR = 1.8), and plasma ACE2 was significantly higher among patients with hypertension. Circulating ACE2 was also significantly higher in patients with COVID-19 with pre-existing heart conditions and kidney disease. The authors suggest that ACE2 may predict COVID-19 disease outcome.

Kragstrup et al. (June 4, 2021). Plasma ACE2 Predicts Outcome of COVID-19 in Hospitalized Patients. PLOS ONE. https://doi.org/10.1371/journal.pone.0252799

• A mathematical model fit to data from King County, Washington found that in a scenario where masks only lowered viral exposure by about 50%, they were still effective at controlling SARS-CoV-2 transmission, and moderately efficacious masks would reduce exposure viral load ten-fold among people who get infected despite masking in the era before vaccines were available, potentially limiting infection severity. Additional benefits were predicted with an increase in masking compliance from 75% of people masking 75% of the time to 90% of people masking 90% of the time. The model also found that in the absence of additional interventions, mask wearing decreased Re from 1.3–1.5 to ~ 1.0 between June and September 2020.

Goyal et al. (Dec 4, 2021). Slight Reduction in SARS-CoV-2 Exposure Viral Load Due to Masking Results in a Significant Reduction in Transmission with Widespread Implementation. Scientific Reports. https://doi.org/10.1038/s41598-021-91338-5