Persistence of anti-sars-cov-2 antibodies: immunoassay heterogeneity and implications for serosurveillance

Perez-Saez, Javier; Zaballa, María-Eugenia; Yerly, Sabine; Andrey, Diego O.; Meyer, Benjamin; Eckerle, Isabella; Balavoine, Jean-François; Chappuis, François; Pittet, Didier; Trono, Didier; Kherad, Omar; Vuilleumier, Nicolas; Kaiser, Laurent; Guessous, Idris; Stringhini, Silvia; Azman, Andrew S.

OBJECTIVES: Serologic studies have been critical in tracking the evolution of the COVID-19 pandemic. Data on anti-SARS-CoV-2 antibodies persistence remain sparse, especially from infected individuals with few to no symptoms. The objective of the study was to quantify the sensitivity for detecting historic SARS-COV-2 infections as a function of time since infection for 3 commercially-available SARS-COV-2 immunoassays and to explore the implications of decaying immunoassay sensitivity in estimating seroprevalence. METHODS: We followed a cohort of mostly mild/asymptomatic SARS-CoV-2-infected individuals (n=354) through 9 months after their presumed infection date and tested their serum for anti-SARS-CoV-2 antibodies with three commercially available assays; Roche-N, Roche-RBD and EuroImmun S1. We developed a latent-class statistical model to infer the specificity and time-varying sensitivity of each assay and show through simulations how inappropriately accounting for test performance can lead to biased serosurvey estimates. RESULTS: Antibodies persisted at follow-up in 74% to 100% of participants, depending on immunoassays. Model estimates indicate that both Roche assays maintain high sensitivity with the EuroImmun assay missing 40% of infections after 9 months. Simulations reveal that without appropriate adjustment for time-varying assay sensitivity, seroprevalence surveys may underestimate infection rates. CONCLUSIONS: Antibodies persist after 9 months in a cohort of mildly infected individuals with detection depending on assay choice. Appropriate assay-performance-adjustment are important for the interpretation of serologic studies in the case of decaying sensitivity after infection.