COVID-19 Literature Situation Report June 15, 2021

• SARS-CoV-2 antibodies were detected in persons from diverse geographic regions in the US prior to the first syndromic cases identified by PCR, according to analysis of samples collected as part of the All of Us study. The All of Us study was started in 2018 and has enrolled a diverse population of US adults from all 50 states. Participation in the study includes repeated collection of blood samples. Using a two-tiered serologic testing algorithm to define seropositive individuals (positive on Abbott with subsequent seropositive on EURUOIMMUN), the authors reanalyzed serum specimens from January to March 2020 and determined that SARS-CoV-2 may have been circulating in Illinois, Wisconsin and Massachusetts as early as January 2020.

Althoff et al. (June 15, 2021). Antibodies to SARS-CoV-2 in All of Us Research Program Participants, January 2-March 18, 2020. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciab519

• Genomic surveillance of SARS-CoV-2 cases identified an expanding US-specific sub-lineage of the B.1.1.7 (Alpha) variant. This sub-lineage is characterized with sequential acquisition of a membrane protein mutation, V20L, in November 2020 and a spike mutation, D178H, in early February 2021. The proportion of B.1.1.7 (Alpha) isolates in the US belonging to this sub-lineage increased from 0.15% in February to 1.8% in April 2021. The sub-lineage comprises 37% of B.1.1.7 (Alpha) isolates in Washington State to date and has also been detected in 30 other states. Phylogenetic analysis suggests the sub-lineage may have originated from either California or Washington, while structural analysis suggests the D178H mutation may affect neutralization capacity of antibodies targeting the N terminal domain. [EDITORIAL NOTE: A pre-print version of this article was summarized in this report on May 19, 2021.]

Shen et al. (June 14, 2021). Rapidly Emerging SARS-CoV-2 B.1.1.7 Sub-Lineage in the United States of America with Spike Protein D178H and Membrane Protein V70L Mutations. Emerging Microbes & Infections. https://doi.org/10.1080/22221751.2021.1943540

• SARS-CoV-2 antibody responses were shown to increase over time in a study of plasma collected up to 63-129 days following symptom resolution from 18 patients recovered from COVID-19 when using direct double Ag-sandwich assays (Ortho Total Ig and Roche Total Ig). By contrast, measurements from indirect binding assays showed a declining antibody response. Due to their stability over time, the authors suggest using direct double sandwich assays for serosurveillance studies.

Di Germanio et al. (June 14, 2021). SARS-CoV -2 Antibody Persistence in COVID-19 Convalescent Plasma Donors: Dependency on Assay Format and Applicability to Serosurveillance. Transfusion. https://doi.org/10.1111/trf.16555

• In solid organ transplant recipients, a third dose of a COVID-19 vaccine was not able to elicit detectable anti-SARS-CoV-2 antibody responses in 53% of participants in a cohort study (n=30). Prior to receiving the third dose, 80% of patients did not have detectable antibody responses. All patients were fully vaccinated with mRNA vaccines (57% Pfizer-BioNTech, 43% Moderna), and received the third dose after a median of 67 days (50% Johnson & Johnson-Janssen, 30% Moderna, 20% Pfizer-BioNTech). Participants were assessed for an antibody response after a median of 14 days after the third vaccination.

Werbel et al. (June 15, 2021). Safety and Immunogenicity of a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series. Annals of Internal Medicine. https://doi.org/10.7326/L21-0282

• 82% of individuals recovered from COVID-19 maintained RBD-specific IgG titers, RBD-specific B cells, and neutralizing activities between 6-12 months after infection, according to analysis of 68 recovered individuals, suggesting long-lived immunity to COVID-19. In 41% of participants who received an mRNA vaccine, vaccination increased IgG responses by 30-fold, neutralizing activity by 50-fold, and circulating number of memory B cells by 9-fold. Sera from vaccinated individuals also showed robust neutralizing activity against variants of concern and neutralization breadth (the ability to neutralize a diverse panel of viruses) increased over time.

Wang et al. (June 14, 2021). Naturally Enhanced Neutralizing Breadth against SARS-CoV-2 One Year after Infection. Nature. https://doi.org/10.1038/s41586-021-03696-9

• Self-reported allergic symptoms following the first dose of a COVID-19 mRNA vaccine was associated with a 5-fold increase in odds of not completing the second dose after adjusting for demographics, vaccine manufacturer, wave of vaccine eligibility, and other confounders in a prospective cohort of healthcare employees in Boston. Among 61,057 employees who received a first dose, incomplete vaccination occurred in 3% (43 of 1,261) of those who self-reporting allergic symptoms compared to 0.6% of those who did not report allergic symptoms. Self-reported severe allergic symptoms were rare (n=6) and associated with markedly increased odds of not completing the vaccination course (aOR=23).

Robinson et al. (June 11, 2021). Allergic Symptoms after mRNA COVID-19 Vaccination and Risk of Incomplete Vaccination. The Journal of Allergy and Clinical Immunology: In Practice. https://doi.org/10.1016/j.jaip.2021.05.031

• As of May 8, 2021, 16% (22,197 of 135,968) of pregnant women identified in CDC’s Vaccine Safety Datalink, which includes integrated health systems from 7 US states, have received ≥1 dose of a COVID-19 vaccine during pregnancy. Of those initiating vaccination 68% have completed either a 1- or 2-dose series. Vaccination during pregnancy was highest among women aged 35-49 years (23%) and lowest among those aged 18-24 years (6%), and higher among Asian (25%) and white women (20%) compared to Hispanic (12%) and Black women (6%).

Razzaghi et al. (June 15, 2021). COVID-19 Vaccination Coverage Among Pregnant Women During Pregnancy — Eight Integrated Health Care Organizations, United States, December 14, 2020–May 8, 2021. MMWR. https://doi.org/10.15585/mmwr.mm7024e2

• A study evaluating the immune responses in four infants with mild COVID-19 (median age 7 weeks old) found that compared to their parents who also had COVID-19 (n=8) and a cohort of adult controls with prior COVID-19 (n=10), infants had higher anti-SARS-CoV-2 IgG antibody levels in both sera and saliva and exhibited more robust serum neutralizing activity. Infants also had reduced production of interferon-gamma after direct ex-vivo stimulation (ELISPOT), despite a comparable frequency of SARS-specific T cells and comparable capacity for expansion with prolonged stimulation with SARS-CoV-2 antigens.

Goenka et al. (June 9, 2021). Young Infants Exhibit Robust Functional Antibody Responses and Restrained IFN-γ Production to SARS-CoV-2. Cell Reports Medicine. https://doi.org/10.1016/j.xcrm.2021.100327

• SARS-CoV-2 infections caused by the B.1.617.2 (Delta) variant of concern were at increased risk of hospitalization (HR=1.9) compared to the B.1.1.7 (Alpha) variant after adjusting for demographics, temporal trends, and comorbidities, according to an analysis of 19,543 confirmed infections and 377 hospitalizations in Scotland from April 1 to June 6, 2021. Considering the whole population cohort, estimated vaccine effectiveness 14 days after the second dose against infection was reduced against B.1.617.2 (Delta) compared to B.1.1.7 (Alpha) for the Pfizer-BioNTech (92% vs 79%) and Oxford-AstraZeneca vaccine (73% vs 60%).

Sheikh et al. (June 15, 2021). SARS-CoV-2 Delta VOC in Scotland: Demographics, Risk of Hospital Admission, and Vaccine Effectiveness. The Lancet. https://doi.org/10.1016/S0140-6736(21)01358-1

• Nearly 1 in 4 individuals hospitalized for COVID-19 had 3 or more persistent symptoms 6 months after hospital admission in a cohort study in France (n=1,137). Presence of 3 or more symptoms at 6 months was more common among women, those with 3 or more symptoms at admission, and those who were admitted to the ICU, but was not associated with age or having two or more comorbidities. At least one symptom was present in 68% of patients at 3-months and 60% at 6-month of follow-up, with fatigue, shortness of breath, joint pain, and muscle pain being the most common symptoms.

Ghosn et al. (May 10, 2021). Persistent COVID-19 Symptoms Are Highly Prevalent 6 Months after Hospitalization: Results from a Large Prospective Cohort. Clinical Microbiology and Infection. https://doi.org/10.1016/j.cmi.2021.03.012

• Emergency department (ED) visits resulting in a diagnosis for diabetic ketoacidosis (DKA) during early COVID-19 pandemic period of March to May 2020 were 70% higher than in the same period in 2019 in New York City (214 vs 106 diagnoses) according to an analysis of ED data extracted for routine quality review. By contrast, Total volume of ED visits declined by 27% from 2019 to 2020 (93,218 vs 59,009 visits).

Ditkowsky et al. (June 9, 2021). SARS-CoV-2 Infection and Associated Rates of Diabetic Ketoacidosis in a New York City Emergency Department. Western Journal of Emergency Medicine. https://doi.org/10.5811/westjem.2021.2.49634

• Incidence of all-cause mortality among a cohort of US Medicare beneficiaries residing in assisted living settings between January to August 2020 (n=425,333) was 17% higher compared to a cohort from the same time in 2019 (n=422,262). The incidence ratio was 36% higher during the peak week in April 8-14, 2020 (3.3 vs 2.2 deaths per 1,000 residents). Among the 10 states with the highest COVID-19 community spread during the study period, the incidence of all-cause mortality was 24% higher and up to 73% higher during the peak week.

Thomas et al. (June 14, 2021). Estimation of Excess Mortality Rates Among US Assisted Living Residents During the COVID-19 Pandemic. JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2021.13411

• COVID-19 transmission was correlated with season in a manner similar to influenza-like illnesses (ILI), according to a comparison between the average annual time-series for ILIs based on incidence data from 2016 till 2019 and two COVID-19 time-series during 2020/2021 in the Netherlands. The authors suggest that the high correlation seems to imply factors driving seasonality of ILIs, such as temperature, relative humidity, and seasonal allergens may also drive COVID-19 seasonality.

Hoogeveen and Hoogeveen. (June 8, 2021). Comparable Seasonal Pattern for COVID-19 and Flu-like Illnesses. One Health. https://doi.org/10.1016/j.onehlt.2021.100277

• Texas clinics in medically underserved areas (MUAs) were less likely to conduct greater than half of their visits via telehealth compared to non-MUA clinics, according to an analysis of 1,344 pooled responses from Texas primary care providers between March 27 and May 22, 2020. Restricting the analysis to responses obtained after May 1, 2020 showed that the association had attenuated, suggesting that initial telehealth barriers among MUA clinics may have resolved over time.

Adepoju et al. (May 2021). COVID-19 and Telehealth Operations in Texas Primary Care Clinics: Disparities in Medically Underserved Area Clinics. Journal of Health Care for the Poor and Underserved. https://doi.org/10.1353/hpu.2021.0073