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

Abstract

Adverse events are potentially associated with an IgG response after the BNT162b2 vaccination for severe acute respiratory syndrome coronavirus 2. In this study, we investigated the side effects of BNT162b2 vaccination using a health questionnaire and examined its relationship with IgG antibody titers. Serum samples were collected from participants 3 months after the second vaccination, just before the third vaccination, and 1 and 3 months after the third vaccination. A total of 505 participants who received three doses of vaccination were eligible for analysis. The results showed that postvaccination body temperature correlated with anti-spike-receptor-binding domain (anti-S-RBD) antibody titers analyzed 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 with log-transformed anti-S-RBD antibody levels, whereas sex (female), body temperature, and heat sensation were positively associated after the second vaccination. After the third vaccination, body temperature, and fatigue were positively associated with log-transformed anti-S-RBD antibody levels, and sex (female) was negatively associated. These results indicate that post-vaccination fever may be a marker of increased antibody titer.