Estimated US Trends in SARS-CoV-2 Spike Antibody Concentrations and Correlation to Risk of First-Time Infections Based on Blood Donations, 2022.

Jones, Jefferson M; Grebe, Eduard; Lartey, Isaac; Stone, Mars; Spencer, Bryan R; Akinseye, Akitunde; Molina Manrique, Irene; Fink, Rebecca V et al. · J Infect Dis · 2025

cross_sectional · Level IV

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Abstract

By the end of 2021 in the United States, spike (S) antibody seroprevalence from coronavirus disease 2019 (COVID-19) vaccination, infection, or both (hybrid immunity) reached over 90%. With high seroprevalence, quantitative antibody concentrations are needed to characterize population immunity. We measured quantitative S antibody concentrations in a national blood donor cohort and evaluated their correlation with protection against infection. One blood specimen per quarter in 2022 was tested for quantitative S immunoglobulin G (IgG) and infection-induced (nucleocapsid [N]) total Ig antibodies from a national blood donor cohort of 106 969 people. Median S antibody concentrations were calculated by quarter and by history of vaccination and infection. Among vaccinated donors without N antibodies, protection (measured as 1 minus hazard ratios compared with unvaccinated donors) against N antibody seroconversion was estimated by S antibody concentration. Median S antibody levels were compared using the Kruskal-Wallis tests. Median S antibody concentrations increased from 1380 binding antibody units (BAU)/mL in quarter 1 of 2022 to 1720 BAU/mL in quarter 4 of 2022. In quarter 4, S antibody levels were lowest in the infection-only group (median, 75 BAU/mL) and higher in the vaccine-only group (median, 1950 BAU/mL) and hybrid immunity group (median, 2550 BAU/mL). Protection against first-time infection increased with higher antibody concentrations; 5010 BAU/mL (95% confidence interval, 4120-6550 BAU/mL) was associated with 50% protection. During 2022, this nationwide study showed mildly increased S IgG concentrations over time among blood donors. Vaccination and hybrid immunity resulted in higher antibody concentrations than infection alone. Higher antibody concentrations were associated with increased protection from infection.

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