Febrile Reactions Associated with High IgG Antibody Titers after the Second and Third BNT162b2 Vaccinations in Japan.

Adverse events are potentially associated with an IgG response after BNT162b2 vaccination for severe acute respiratory syndrome coronavirus 2. In this study, we investigated the side effects of the BNT162b2 vaccine using a health questionnaire and examined its relationship with IgG antibody titers. Serum samples were collected from participants 3 months after the second vaccination, immediately before the third vaccination, and 1 and 3 months after the third vaccination. A total of 505 participants who received three doses of vaccine were eligible for inclusion in the analysis. The results showed that post-vaccination body temperature correlated with anti-spike-receptor-binding domain (anti-S-RBD) antibody titers measured 3 months after the second (r = 0.30, P < 0.001) and third (r = 0.14, P < 0.001) vaccinations. Multivariate linear regression analysis revealed that age and severe swelling were negatively associated, whereas female sex, body temperature, and heat sensation were positively associated with log-transformed anti-S-RBD antibody levels after the second vaccination. After the third vaccination, body temperature and fatigue were positively associated, and female sex was negatively associated, with the log-transformed anti-S-RBD antibody levels. These results suggest that post-vaccination fever may be a marker of a high antibody titer.