SARS‐CoV‐2 immunoassays in a predominantly vaccinated population: Performances and qualitative agreements obtained with two analytical approaches and four immunoassays.

Background and Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) serosurveys are typically analysed by applying a fixed threshold for seropositivity ('conventional approach'). However, this approach underestimates the seroprevalence of anti‐nucleocapsid (N) in vaccinated individuals—who often exhibit a difficult‐to‐detect anti‐N response. This limitation is compounded by delays between the onset of infection and sample collection. To address this issue, we compared the performance of four immunoassays using a new analytical approach ('ratio‐based approach'), which determines seropositivity based on an increase in anti‐N levels. Materials and Methods: Two groups of plasma donors and four immunoassays (Elecsys total anti‐N, VITROS total anti‐N, Architect anti‐N Immunoglobulin G (IgG) and in‐house total anti‐N) were evaluated. First‐group donors (N = 145) had one positive SARS‐CoV‐2 polymerase chain reaction (PCR) test result and had made two plasma donations, including one before and one after the PCR test (median = 27 days post‐PCR). Second‐group donors (N = 100) had made two plasma donations early in the Omicron wave. Results: Among first‐group donors (97.9% vaccinated), sensitivity estimates ranged from 60.0% to 89.0% with the conventional approach, compared with 94.5% to 98.6% with the ratio‐based approach. Among second‐group donors, Fleiss's κ ranged from 0.56 to 0.83 with the conventional approach, compared with 0.90 to 1.00 with the ratio‐based approach. Conclusion: With the conventional approach, the sensitivity of four immunoassays—measured in a predominantly vaccinated population based on samples collected ~1 month after a positive test result—fell below regulatory agencies requirement of ≥95%. The ratio‐based approach significantly improved the sensitivities and qualitative agreement among immunoassays, to the point where all would meet this requirement. [ABSTRACT FROM AUTHOR]