Association between adverse events after COVID-19 vaccination and anti-SARS-CoV-2 antibody concentrations, the Netherlands, May 2021 to November 2022: a population-based prospective cohort study

Abstract

Background Non-severe adverse events (AE) including pain at injection site or fever are common after COVID-19 vaccination. Aim To describe determinants of AE after COVID-19 vaccination and investigate the association between AE and pre- and post-vaccination antibody concentrations. Methods Participants of an ongoing prospective cohort study (VASCO) completed a questionnaire on AE within 2 months after vaccination and provided 6 monthly serum samples during May 2021–November 2022. Logistic regression analyses were performed to investigate AE determinants after mRNA vaccination, including pre-vaccination Ig antibody concentrations against the SARS-CoV-2 spike protein receptor binding domain. Multivariable linear regression was performed in SARS-CoV-2-naive participants to assess the association between AE and log-transformed antibody concentrations 3–8 weeks after mRNA vaccination. Results We received 47,947 completed AE questionnaires by 28,032 participants. In 42% and 34% of questionnaires, injection site and systemic AE were reported, respectively. In 2.2% of questionnaires, participants sought medical attention. AE were reported more frequently by women, younger participants (< 60 years), participants with medical risk conditions and Spikevax recipients (vs Comirnaty). Higher pre-vaccination antibody concentrations were associated with higher incidence of systemic AE after the second and third dose, but not with injection site AE or AE for which medical attention was sought. Any AE after the third dose was associated with higher post-vaccination antibody concentrations (geometric mean concentration ratio: 1.38; 95% CI: 1.23–1.54). Conclusions Our study suggests that high pre-vaccination antibody levels are associated with AE, and experiencing AE may be a marker for higher antibody response to vaccination.