Optimizing Immunoassay-Based Selection of Donors for COVID-19 Convalescent Plasma

Abstract COVID-19 convalescent plasma (CCP) is currently administered to hospitalized COVID-19 patients under an EAU by the FDA. CCP units are selected by commercially available ELISA quantification of anti-SARS-CoV-2 (SARS2) antibodies under the rationale that higher levels of anti-SARS2 antibodies correlate with higher neutralizing capabilities and thus greater efficacy. The validity of this selection process has yet to be investigated. We analyzed serum samples from 60 convalesced donors with PCR-confirmed COVID-19. Samples were analyzed using commercial SARS2 ELISAs (DiaSorin, Euroimmun, Ortho, and Roche) and a cell-based enzyme-linked immunosorbent assay (cbELISA) that detects antibodies against the native conformation of the SARS2 spike glycoprotein (GP). Sera were also tested for neutralizing activity against wild-type SARS2 and a pseudovirus expressing the SARS2 GP. Immunoassay and neutralization values were compared to determine the precision of each immunoassay to predict differing levels of neutralizing activity, and ability of each immunoassay to identify high neutralizing activity. Results of immunoassays that apply SARS2 GP as the antigen (DiaSorin, Euroimmun, Ortho, and cbELISA) correlated well with neutralization titers measured by wild-type SARS2 or SARS2 GP-pseudotyped virus as compared with assays using other SARS2 antigens (Roche; N protein). Differences in precision of these assays were evident when samples within the top quintile or decile of immunoassay values were analyzed, with DiaSorin and Ortho assays showing superior performance in predicting neutralizing capability. We hope this approach will assist in the selection of highly neutralizing CCP units that confer greater clinical efficacy.