COVID-19 vaccination-induced antibody responses and waning by age and comorbidity status in a large population-based prospective cohort study.

Background: Information on the magnitude and duration of antibody levels after COVID-19 vaccination in different groups may be useful for prioritizing of additional vaccinations.

Methods: Serum samples were collected every six months in a prospective cohort study among adults in the Netherlands. Geometric mean concentrations (GMCs) of antibodies against the receptor binding domain of the SARS-CoV-2 spike protein were calculated after the primary series, first, and second booster vaccinations. Effects of age (18-59 vs 60-85 years) and medical risk conditions on GMC 2-6 weeks and 21-25 weeks after each vaccination, and on waning during 3-25 weeks after each vaccination, were estimated by linear regression.

Results: We included 20,640, 15,229 and 8,392 samples collected after primary, first and second booster vaccination, respectively. GMCs at 2-6 and 21-25 weeks after primary series were lower in participants with older age or medical risk conditions. After the first booster, older age was associated with lower GMC at 2-6 weeks and at 21-25 weeks. Waning after the first and second boosters (only 60-85) was not associated with age or medical risk conditions.

Conclusions: Since antibody differences by age and medical risk groups have become small with increasing number of doses, other factors such as COVID-19 disease severity rather than antibody levels are useful for prioritization of additional vaccinations.