Impact of Sex and Age on mRNA COVID-19 Vaccine-Related Side Effects in Japan

ABSTRACT mRNA COVID-19 vaccination was initiated worldwide in late 2020, and its efficacy has been well reported. However, studies about vaccine-related side effects are sparse. A total of 262 health care workers who received mRNA COVID-19 vaccine BNT162b2 were recruited, and their vaccine-related side effects were investigated. Impact of sex and age on the side effects was statistically analyzed. A higher number of vaccine-related side effects among females versus males was identified (median 3 versus 2, P < 0.05, after the first dose, and 5 versus 2.5, P < 0.01, after the second dose). General fatigue, headache, chills, and fever were the culprit adverse symptoms. In multivariate analysis, females had an increasing number of side effects after receiving their first (B = 0.7; 95% confidence interval [CI], 0.2 to 1.2) and second (B = 1.5; 95% CI, 0.7 to 2.2) vaccine doses compared to that of males. In age analysis, the older group (≥60 years old) had a lower number of side effects than the younger group (B = −0.5 with a 95% CI of −1.1 to −0.02 after the first vaccine dose, and B = −2.1 with a 95% CI of −2.9 to −1.2 after the second vaccine dose). Additionally, prolonged time to recovery was found among females (P = 0.003 after the first dose; P = 0.008 after the second dose). Specifically, symptoms of general fatigue, headache, itching, swelling at the injection site, and dizziness were the culprit symptoms affecting recovery time. Several cutaneous and membranous symptoms, including “COVID arm,” were identified among females. These results highlight the impact of sex and age on side effects from mRNA COVID-19 vaccine and will aid in creating a safer vaccine. IMPORTANCE We demonstrate sex- and age-related impact on mRNA COVID-19 vaccine-related side effects, with a higher number and frequency of side effects and prolonged time to recovery in females compared to males and negative correlation between age and vaccine-related side effects. Identification of unique age- and sex-specific adverse symptoms will provide the opportunity to better understand the nature of sex- and age-associated immunological differences and develop safer and more efficacious vaccines.