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 (preprint)

Importance: There are limited data describing SARS-CoV-2-specific immune responses and their durability following infection and vaccination in nursing home residents. Objective: To evaluate the quantitative titers and durability of binding antibodies detected after SARS-CoV-2 infection and subsequent COVID-19 vaccination. Design: A 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. Setting: A nursing home during and after a SARS-CoV-2 outbreak. Participants: 11 consenting SARS-CoV-2-positive nursing home residents. Main Outcomes and Measures: SARS-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). Results: Of 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 Relevance: Nursing 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.

Patient Reported Experience of Clinical Care of Osteogenesis Imperfecta (OI) During The COVID-19 Pandemic (preprint)

Background: Research on the effects of the COVID-19 pandemic on people with rare diseases is limited. Few studies compare healthcare throughout the progression of the ongoing pandemic. Aims: To assess the impact of lockdown on individuals with OI (Osteogenesis Imperfecta) across two consecutive years of the pandemic, to understand what challenges were encountered, and to analyse the experience of remote consultation. Methods: Two independent surveys were distributed in August 2020 and April 2021. The primary survey was distributed following the first lockdown, and the second survey built on the experiences reported from the initial survey. The surveys explored four key themes- effects on therapy, alternatives to consultation, effect on mental health, and perceived risks of COVID-19. Results: In the primary 2020 survey of the 110 respondents 69 (63%) had at least one appointment delayed due to lockdown, increasing to 89 of the 124 respondents (72%) in the follow-up survey. Of the 110 initial survey participants, 57 (52%) had a remote consultation, increasing to 92 of 124 (74%) in the follow-up survey. In the primary survey 63 of 91 (69%) expressed increasing anxiety due to lockdown, compared with 76 of 124 (61%) in the follow-up survey. In the primary survey 12 of 91 respondents (13%) expressed concerns at not seeing friends and family compared with 103 of 124 (83%) in the follow-up survey. In the second survey of 124 participants there were concerns regarding weight and diet (55, 44%), mobility (70, 56%), pain (71, 57%), and keeping physically active (89, 72%). The majority of participants felt they would have a worse illness and require longer rehabilitation than someone without OI (81 of 117 respondents, and 77 of 120 respectively), and the majority of participants (68%) had been vaccinated at the time of the second survey. Conclusions: The pandemic has had widespread effects on both the mental and physical health of those with OI. These repercussions are likely to be felt for years to come. On the other hand, the pandemic has also revealed that in certain situations remote consultation may prove a viable long-lasting alternative to face-to-face appointments.

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

The divergence of SARS-CoV-2 into variants of concern/interest (VOC/VOI) necessitated analysis of their impact on vaccines. Escape from vaccine-induced antibodies by SARS-CoV-2 VOC/VOIs was analyzed to ascertain and rank their risk. The variants showed differential reductions in neutralization and replication titers by the post-vaccination sera with Beta variant showing the most neutralization escape that was mechanistically driven by mutations in both the N-terminal domain and receptor-binding domain of the spike.

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

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 (preprint)

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 (preprint)

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.