Longitudinal serologic and viral testing post-SARS-CoV-2 infection and post-receipt of mRNA COVID-19 vaccine in a nursing home cohort--Georgia, October 2020-April 2021

ImportanceThere are limited data describing SARS-CoV-2-specific immune responses and their durability following infection and vaccination in nursing home residents. ObjectiveTo evaluate the quantitative titers and durability of binding antibodies detected after SARS-CoV-2 infection and subsequent COVID-19 vaccination. DesignA prospective longitudinal evaluation included nine visits over 150 days; visits included questionnaire administration, blood collection for serology, and paired anterior nasal specimen collection for testing by BinaxNOW COVID-19 Ag Card (BinaxNOW), reverse transcription polymerase chain reaction (RT-PCR), and viral culture. SettingA nursing home during and after a SARS-CoV-2 outbreak. Participants11 consenting SARS-CoV-2-positive nursing home residents. Main Outcomes and MeasuresSARS-CoV-2 testing (BinaxNOW, RT-PCR, viral culture); quantitative titers of binding SARS-CoV-2 antibodies post-infection and post-vaccination (beginning after the first dose of the primary series). ResultsOf 10 participants with post-infection serology results, 9 (90%) had detectable Pan-Ig, IgG, and IgA antibodies and 8 (80%) had detectable IgM antibodies. At first antibody detection post-infection, two-thirds (6/9, 67%) of participants were RT-PCR-positive but none were culture positive. Ten participants received vaccination; all had detectable Pan-Ig, IgG, and IgA antibodies through their final observation [≤]90 days post-first dose. Post-vaccination geometric means of IgG titers were 10-200-fold higher than post-infection. Conclusions and RelevanceNursing home residents in this cohort mounted robust immune responses to SARS-CoV-2 post-infection and post-vaccination. The augmented antibody responses post-vaccination are potential indicators of enhanced protection that vaccination may confer on previously infected nursing home residents.

Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines

IntroductoryThe evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of many new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccines. To ascertain and rank the risk of VOCs and VOIs, we analyzed their ability to escape from vaccine-induced antibodies. The variants showed differential reductions in neutralization and replication titers by post-vaccination sera. Although the Omicron variant showed the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retained moderate neutralizing activity against that variant. Therefore, vaccination remains the most effective strategy to combat the COVID-19 pandemic.

Seroprevalence of SARS-CoV-2 Antibodies in Seattle, Washington: October 2019-April 2020

Estimating prevalence of SARS-CoV-2 antibodies is important to determine disease burden. We tested residual samples from 763 Seattle-area adults for SARS-CoV-2 antibodies. Prevalence rose from 0% to 1.2% between October 2019-April 2020, suggesting a small percentage of this metropolitan-area cohort had been infected with SARS-CoV-2 at that time.

Seroprevalence of Antibodies to SARS-CoV-2 in Six Sites in the United States, March 23-May 3, 2020

ImportanceReported cases of SARS-CoV-2 infection likely underestimate the prevalence of infection in affected communities. Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected. ObjectiveTo estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the United States. DesignSerologic testing of convenience samples using residual sera obtained for routine clinical testing by two commercial laboratory companies. SettingConnecticut (CT), south Florida (FL), Missouri (MO), New York City metro region (NYC), Utah (UT), and Washington States (WA) Puget Sound region. ParticipantsPersons of all ages with serum collected during intervals from March 23 through May 3, 2020. ExposureSARS-CoV-2 virus infection. Main outcomes and measuresWe estimated the presence of antibodies to SARS-CoV-2 spike protein using an ELISA assay. We standardized estimates to the site populations by age and sex. Estimates were adjusted for test performance characteristics (96.0% sensitivity and 99.3% specificity). We estimated the number of infections in each site by extrapolating seroprevalence to site populations. We compared estimated infections to number of reported COVID-19 cases as of last specimen collection date. ResultsWe tested sera from 11,933 persons. Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein ranged from 1.13% (95% confidence interval [CI] 0.70-1.94) in WA to 6.93% (95% CI 5.02-8.92) in NYC (collected March 23-April 1). For sites with later collection dates, estimates ranged from 1.85% (95% CI 1.00-3.23, collected April 6-10) for FL to 4.94% (95% CI 3.61-6.52) for CT (April 26-May 3). The estimated number of infections ranged from 6 to 24 times the number of reported cases in each site. Conclusions and relevanceOur seroprevalence estimates suggest that for five of six U.S. sites, from late March to early May 2020, >10 times more SARS-CoV-2 infections occurred than the number of reported cases. Seroprevalence and under-ascertainment varied by site and specimen collection period. Most specimens from each site had no evidence of antibody to SARS-CoV-2. Tracking population seroprevalence serially, in a variety of specific geographic sites, will inform models of transmission dynamics and guide future community-wide public health measures. Key findingsO_ST_ABSQuestionC_ST_ABSWhat proportion of persons in six U.S. sites had detectable antibodies to SARS-CoV-2, March 23-May 3, 2020? FindingsWe tested 11,933 residual clinical specimens. We estimate that from 1.1% of persons in the Puget Sound to 6.9% in New York City (collected March 23-April 1) had detectable antibodies. Estimates ranged from 1.9% in south Florida to 4.9% in Connecticut with specimens collected during intervals from April 6-May 3. Six to 24 times more infections were estimated per site with seroprevalence than with case report data. MeaningFor most sites, evidence suggests >10 times more SARS-CoV-2 infections occurred than reported cases. Most persons in each site likely had no detectable SARS-CoV-2 antibodies.

Validation of a SARS-CoV-2 spike ELISA for use in contact investigations and serosurveillance

Since emergence of SARS-CoV-2 in late 2019, there has been a critical need to understand prevalence, transmission patterns, to calculate the burden of disease and case fatality rates. Molecular diagnostics, the gold standard for identifying viremic cases, are not ideal for determining true case counts and rates of asymptomatic infection. Serological detection of SARS-CoV-2 specific antibodies can contribute to filling these knowledge gaps. In this study, we describe optimization and validation of a SARS-CoV-2-specific-enzyme linked immunosorbent assay (ELISA) using the prefusion-stabilized form of the spike protein [1]. We performed receiver operator characteristic (ROC) analyses to define the specificities and sensitivities of the optimized assay and examined cross reactivity with immune sera from persons confirmed to have had infections with other coronaviruses. These assays will be used to perform contact investigations and to conduct large-scale, cross sectional surveillance to define disease burden in the population.