Publication date: Jun 23, 2025

By the end of 2021, U. S. spike (S) antibody seroprevalence from 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 IgG and infection-induced (nucleocapsid [N]) total Ig antibodies from a national blood donor sub-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 increase from 1380 binding antibody units (BAU)/mL in quarter (Q) 1 2022 to 1720 BAU/mL in Q4 2022. In Q4, S antibody levels were lowest in the infection-only group (median: 75 BAU/mL) and higher in the vaccine-only (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% CI 4120-6550) 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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