ABSTRACT
Background Antibody response duration following SARS-CoV-2 infection tends to be variable and depends on severity of disease and method of detection. Study design and methods COVID-19 convalescent plasma (CCP) from 18 donors was collected longitudinally for a maximum of 63 - 129 days following resolution of symptoms. All the samples were initially screened by the Ortho Total Ig test to confirm positivity and subsequently tested with 7 additional direct sandwich or indirect binding assays (Ortho, Roche, Abbott, Broad Institute) directed against a variety of antigen targets (S1, RBD, and NC), along with 2 neutralization assays (Broad Institute live virus PRNT and Vitalant Research Institute Pseudovirus RVPN). Results The direct detection assays (Ortho Total Ig total and Roche Total Ig) showed increasing levels of antibodies over the time period, in contrast to the indirect IgG assays that showed a decline. Neutralization assays also demonstrated declining responses; the VRI RVPN pseudovirus had a greater rate of decline than the Broad PRNT live virus assay. Discussion These data show that in addition to variable individual responses and associations with disease severity, the detection assay chosen contributes to the heterogeneous results in antibody stability over time. Depending on the scope of the research, one assay may be preferable over another. For serosurveillance studies, direct, double Ag-sandwich assays appear to be the best choice due to their stability; in particular, algorithms that include both S1 and NC based assays can help reduce the rate of false-positivity and discriminate between natural infection and vaccine-derived seroreactivity.
Subject(s)
COVID-19ABSTRACT
Background To identify blood donors eligible to donate Coronavirus Disease-2019 (COVID-19) Convalescent Plasma (CCP), a large blood center began testing for antibodies to SARS-CoV-2, the etiologic agent of COVID-19. We report the seroprevalence of total immunoglobulin directed against the S1 spike protein of SARS-CoV-2 in US blood donors. Methods Unique non-CCP donor sera from June 1-July 31, 2020 were tested with the Ortho VITROS Anti-SARS-CoV-2 total immunoglobulin assay (positive: signal-to-cutoff (S/C) =>1). Donor age, sex, race/ethnicity, ABO/RhD, education, and experience were compared to June and July 2019. Multivariate regressions were conducted to identify demographics associated with the presence of antibodies and with S/C values. Results Unique donors (n=252,882) showed an overall seroprevalence of 1.83% in June (1.37%) and July (2.26%), with the highest prevalence in northern New Jersey (7.3%). In a subset of donors with demographic information (n=189,565), higher odds of antibody reactivity were associated with non-Hispanic Native American/Alaskan (NH-NAA/A) and Black (NH-B), and Hispanic (H) race/ethnicity, age 18-64, middle school or lesser education, blood Group A, and never or non-recent donor status. In positive donors (n=2,831), antibody signal was associated with male sex, race/ethnicity (NH-NAA/A, NH-B and H) and geographic location. Conclusions Seroprevalence remains low in US blood donors but varies significantly by region. Temporal trends in reactivity may be used to gauge the effectiveness of public health measures. Before generalizing these data from healthy donors to the general population however, rates must be corrected for false positive test results among low prevalence test subjects and adjusted to match the wider demography.