Sex differences in the long-term tolerability of BNT162b2 in children and adolescents

BACKGROUND: Sex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the sex differences in the tolerability of BNT162b2 in children younger than 18 years in Germany. METHODS: A post-hoc analysis of retrospectively collected tolerability data, collected through an authentication-based survey of legal guardians of children vaccinated with BNT162b2 under the age of 18 years (CoVacU18-study). Primary outcome was the frequency of the four most common post-vaccination symptom categories (local, general, musculoskeletal symptoms, fever) reported after the 1st-4th doses. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interactions between sex and age group effects on post-vaccination symptoms were assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines. RESULTS: Three thousand two hundred twenty-eight participants (median age 5.7 years, male 49.6%). In logistic regression, female sex was associated with higher odds of local symptoms (OR = 1.28 [95% CI: 1.17-1.40], p < 0.05), general symptoms (OR = 1.27 [1.13-1.44], p < 0.05), and musculoskeletal symptoms (OR = 1.27 [1.03-1.56], p < 0.05). Interactions between sex and age groups existed for post-vaccination local symptoms. Following non-BNT162b2 childhood vaccinations, female sex was not associated with odds of any post-vaccination symptoms. No relevant interaction existed between vaccine types (BNT162b2 vs non-BNT162b2) and sex for the association with post-vaccination symptoms. CONCLUSION: Sex differences exist in post-vaccination symptoms after BNT162b2 administration in young children and adolescents. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies.