Evaluation of commercially available high-throughput SARS-CoV-2 serological assays for serosurveillance and related applications

Stone, M.; Grebe, E.; Sulaeman, H.; Di Germanio, C.; Dave, H.; Kelly, K.; Biggerstaff, B.; Crews, B. O.; Tran, N.; Jerome, K.; Denny, T. N.; Hogema, B.; Destree, M.; Jones, J. M.; Thornburg, N.; Simmons, G.; Krajden, M.; Kleinman, S.; Dumont, L. J.; Busch, M. P.

SARS-CoV-2 serosurveys can estimate cumulative incidence for monitoring epidemics but require characterization of employed serological assays performance to inform testing algorithm development and interpretation of results. We conducted a multi-laboratory evaluation of 21 commercial high-throughput SARS-CoV-2 serological assays using blinded panels of 1,000 highly-characterized blood-donor specimens. Assays demonstrated a range of sensitivities (96%-63%), specificities (99%-96%) and precision (IIC 0.55-0.99). Durability of antibody detection in longitudinal samples was dependent on assay format and immunoglobulin target, with anti-spike, direct, or total Ig assays demonstrating more stable, or increasing reactivity over time than anti-nucleocapsid, indirect, or IgG assays. Assays with high sensitivity, specificity and durable antibody detection are ideal for serosurveillance. Less sensitive assays demonstrating waning reactivity are appropriate for other applications, including characterizing antibody responses after infection and vaccination, and detection of anamnestic boosting by reinfections and vaccine breakthrough infections. Assay performance must be evaluated in the context of the intended use.