Factors influencing SARS-CoV-2 IgG test sensitivity: A Bayesian analysis of seroconversion and seroreversion by time since infection, test, age and disease severity

BACKGROUND: Antibody testing is commonly used to assess past exposure to pathogens, but the interpretation is complex. We quantified test-specific SARS-CoV-2 seroconversion and seroreversion by time since PCR-confirmed infection, age and disease severity. METHODS: We combined Belgian data from laboratory SARS-CoV-2 testing, prescriptions, contact tracing and hospital surveillance collected between March 2020 and June 2021 with data from published longitudinal studies on Wantai and EuroImmun IgG serological tests. We used a hierarchical Bayesian model to estimate time-varying sensitivity of serological tests following PCR-confirmed infection. The model employed a scaled Weibull-bi-exponential distribution. We accounted for disease severity (distinguishing between asymptomatic, symptomatic, and hospitalized cases), age (i.e., age groups 18-49, 50-64, and 65-74 years) and serological test used. RESULTS: We included 44,262 serological test results: 10,864 obtained from published studies, 33,398 from Belgian laboratories. Seroconversion occurred during the six weeks following a PCR-confirmed infection. Age, disease severity and the test used strongly influenced seroconversion rates and the rate of the subsequent seroreversion. For the EuroImmun test, 82% (95% Credible Interval (CrI): 80%-84%) of symptomatic individuals in the youngest age group seroconverted, compared to 95% (CrI: 95%-96%) for the Wantai test. Seroconversion was associated with hospitalization, (OR = 8.17 (CrI: 5.56-13.72), compared to asymptomatic infection) and older age (OR = 1.65 (CrI: 1.41-1.97), compared to 18-49 year-olds). Slower seroreversion was associated with older age, hospitalization and the Wantai test. At 50 weeks, seropositivity among symptomatic 18-49 year-olds was 64% (CrI: 58%-70%) for the EuroImmun test and 95% (CrI: 94%-96%) for the Wantai test. CONCLUSION: These findings highlight the need for test-specific, time-varying sensitivity adjustments in seroprevalence studies. Such adjustments are crucial for translating seroprevalence results to cumulative incidence estimates.