Safety of the fourth COVID-19 BNT162b2 mRNA (second booster) vaccine

ABSTRACT

COVID-19 remains a global concern due to vaccine protection waning and the emergence of immuneevasive variants. While the effectiveness of a second booster vaccine dose (i.e., fourth inoculation) is well proven, its safety has yet to be fully understood, and vaccine compliance remains low. We conducted a prospective observational study to compare the short-term effects of the first and second BNT162b2 mRNA COVID-19 vaccine booster doses. 2,019 participants received smartwatches and filled in a daily questionnaire on systemic reactions to the vaccine. We found substantial changes from baseline levels in the 72 hours post-vaccination with the second booster in both self-reported and physiological reactions measured by the smartwatches. However, no significant difference in reactions was observed between the first and second boosters. We also found that participants who experienced more severe reactions to the first booster tended to likewise experience more severe reactions to the second booster. Our work supports the safety of the second booster from both subjective (self-reported questionnaires) and objective (physiological measurements) perspectives.