Seroprevalence of anti-SARS-CoV-2 antibodies in a cohort of New York City metro blood donors using multiple SARS-CoV-2 serological assays: Implications for controlling the epidemic and "Reopening".

Projections of the stage of the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pandemic and local, regional and national public health policies to limit coronavirus spread as well as "reopen" cities and states, are best informed by serum neutralizing antibody titers measured by reproducible, high throughput, and statically credible antibody (Ab) assays. To date, a myriad of Ab tests, both available and FDA authorized for emergency, has led to confusion rather than insight per se. The present study reports the results of a rapid, point-in-time 1,000-person cohort study using serial blood donors in the New York City metropolitan area (NYC) using multiple serological tests, including enzyme-linked immunosorbent assays (ELISAs) and high throughput serological assays (HTSAs). These were then tested and associated with assays for neutralizing Ab (NAb). Of the 1,000 NYC blood donor samples in late June and early July 2020, 12.1% and 10.9% were seropositive using the Ortho Total Ig and the Abbott IgG HTSA assays, respectively. These serological assays correlated with neutralization activity specific to SARS-CoV-2. The data reported herein suggest that seroconversion in this population occurred in approximately 1 in 8 blood donors from the beginning of the pandemic in NYC (considered March 1, 2020). These findings deviate with an earlier seroprevalence study in NYC showing 13.7% positivity. Collectively however, these data demonstrate that a low number of individuals have serologic evidence of infection during this "first wave" and suggest that the notion of "herd immunity" at rates of ~60% or higher are not near. Furthermore, the data presented herein show that the nature of the Ab-based immunity is not invariably associated with the development of NAb. While the blood donor population may not mimic precisely the NYC population as a whole, rapid assessment of seroprevalence in this cohort and serial reassessment could aid public health decision making.

High-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19.

As Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to spread, characterization of its antibody epitopes, emerging strains, related coronaviruses, and even the human proteome in naturally infected patients can guide the development of effective vaccines and therapies. Since traditional epitope identification tools are dependent upon pre-defined peptide sequences, they are not readily adaptable to diverse viral proteomes. The Serum Epitope Repertoire Analysis (SERA) platform leverages a high diversity random bacterial display library to identify proteome-independent epitope binding specificities which are then analyzed in the context of organisms of interest. When evaluating immune response in the context of SARS-CoV-2, we identify dominant epitope regions and motifs which demonstrate potential to classify mild from severe disease and relate to neutralization activity. We highlight SARS-CoV-2 epitopes that are cross-reactive with other coronaviruses and demonstrate decreased epitope signal for mutant SARS-CoV-2 strains. Collectively, the evolution of SARS-CoV-2 mutants towards reduced antibody response highlight the importance of data-driven development of the vaccines and therapies to treat COVID-19.

Low Seroprevalence of SARS-CoV-2 in Rhode Island blood donors during may 2020 as determined using multiple serological assay formats.

BACKGROUND: Epidemic projections and public health policies addressing Coronavirus disease (COVID)-19 have been implemented without data reporting on the seroconversion of the population since scalable antibody testing has only recently become available. METHODS: We measured the percentage of severe acute respiratory syndrome- Coronavirus-2 (SARS-CoV-2) seropositive individuals from 2008 blood donors drawn in the state of Rhode Island (RI). We utilized multiple antibody testing platforms, including lateral flow immunoassays (LFAs), enzyme-linked immunosorbent assays (ELISAs) and high throughput serological assays (HTSAs). To estimate seroprevalence, we utilized the Bayesian statistical method to adjust for sensitivity and specificity of the commercial tests used. RESULTS: We report than an estimated seropositive rate of RI blood donors of approximately 0.6% existed in April-May of 2020. Daily new case rates peaked in RI in late April 2020. We found HTSAs and LFAs were positively correlated with ELISA assays to detect antibodies specific to SARS-CoV-2 in blood donors. CONCLUSIONS: These data imply that seroconversion, and thus infection, is likely not widespread within this population. We conclude that IgG LFAs and HTSAs are suitable to conduct seroprevalence assays in random populations. More studies will be needed using validated serological tests to improve the precision and report the kinetic progression of seroprevalence estimates.

Serological Assays Estimate Highly Variable SARS-CoV-2 Neutralizing Antibody Activity in Recovered COVID-19 Patients.

The development of neutralizing antibodies (NAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following infection or vaccination is likely to be critical for the development of sufficient population immunity to drive cessation of the coronavirus disease of 2019 (COVID-19) pandemic. A large number of serologic tests, platforms, and methodologies are being employed to determine seroprevalence in populations to select convalescent plasma samples for therapeutic trials and to guide policies about reopening. However, the tests have substantial variations in sensitivity and specificity, and their ability to quantitatively predict levels of NAbs is unknown. We collected 370 unique donors enrolled in the New York Blood Center Convalescent Plasma Program between April and May of 2020. We measured levels of antibodies in convalescent plasma samples using commercially available SARS-CoV-2 detection tests and in-house enzyme-linked immunosorbent assays (ELISAs) and correlated serological measurements with NAb activity measured using pseudotyped virus particles, which offer the most informative assessment of antiviral activity of patient sera against viral infection. Our data show that a large proportion of convalescent plasma samples have modest antibody levels and that commercially available tests have various degrees of accuracy in predicting NAb activity. We found that the Ortho anti-SARS-CoV-2 total Ig and IgG high-throughput serological assays (HTSAs) and the Abbott SARS-CoV-2 IgG assay quantify levels of antibodies that strongly correlate with the results of NAb assays and are consistent with gold standard ELISA results. These findings provide immediate clinical relevance to serology results that can be equated to NAb activity and could serve as a valuable roadmap to guide the choice and interpretation of serological tests for SARS-CoV-2.

COVID19 antibody detection using lateral flow assay tests in a cohort of convalescent plasma donors.

OBJECTIVE: COVID19 has caused a global and ongoing pandemic. The need for population seroconversion data is apparent to monitor and respond to the pandemic. Using a lateral flow assay (LFA) testing platform, the seropositivity in 63 New York Blood Center (NYBC) Convelescent Plasma (CP) donor samples were evaluated for the presence of COVID19 specific IgG and IgM. RESULTS: CP donors showed diverse antibody result. Convalescent donor plasma contains SARS-CoV-2 specific antibodies. Weak antibody bands may identify low titer CP donors. LFA tests can identify antibody positive individuals that have recovered from COVID19. Confirming suspected cases using antibody detection could help inform the patient and the community as to the relative risk to future exposure and a better understanding of disease exposure.