ABSTRACT
Background Sex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the safety of BNT162b2 vaccine administered off-label in female and male children younger than 5 years in Germany. Methods This is a retrospective cohort study, in which we performed a post-hoc analysis of a dataset collected through an authentication-based survey of individuals having registered children aged 0-<5 years for vaccination against SARS-CoV-2 in six private practices and/or two lay person-initiated vaccination campaigns. We analyzed the safety profiles of the first 3 doses of 3-10g BNT162b2. Primary outcome was comparison in frequencies of 4 common post-vaccination symptom categories such as local, general, musculoskeletal symptoms and fever. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interaction between sex and BNT162b2 dosage was assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines. Results The dataset for the present analysis consisted of 7801 participants including 3842 females (49%) and 3977 males (51%) with an age of 3 years (median, interquartile: 2 years). Among individuals receiving 3g BNT162b2, no sex differences were noted, but after a first dose of 5 or 10g BNT162b2, local injection-site symptoms were more prevalent in girls compared to boys. In logistic regression, female sex was associated with higher odds of local symptoms, odds ratio (OR) of 1.33 (95% confidence interval [CI]: 1.15-1.55, p<0.05) and general symptoms with OR 1.21 (95% CI: 1.01-1.44, p<0.05). Following non-BNT162b2 childhood vaccinations, female sex was associated with a lower odds of post-vaccination musculoskeletal symptoms (OR: 0.29, 95% CI: 0.11-0.82, p<0.05). An active comparator analysis between BNT162b2 and non-SARS-CoV-2 vaccinations revealed that female sex positively influenced the association between BNT162b2 vaccine type and musculoskeletal symptoms. Conclusions Sex differences exist in post-vaccination symptoms after BNT162b2 administration even in young children. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies. (German Clinical Trials Register ID: DRKS00028759).
Subject(s)
COVID-19 , Fever , Musculoskeletal DiseasesABSTRACT
Background The safety of SARS-CoV-2 vaccines is unknown in children aged <5 years. Here, we retrospectively evaluated the safety of BNT162b2 vaccine used off-label in children of this age group in Germany. Methods An investigator-initiated retrospective cohort study (CoVacU5) included parents or caregivers having children aged <5 years registered for SARS-CoV-2 vaccination in outpatient care facilities in Germany. Reported short-term safety data of 1-3 doses of 3-10ug BNT162b2 in children aged 0 to <60 months are presented. Co-primary outcomes were the frequencies of 11 categories of symptoms post-vaccination with bivariate analyses and regression models adjusting for age, sex, weight and height. On-label non-SARS-CoV-2 vaccines served as controls in an active-comparator design. Results The study included 7806 representing a 41% response rate of 19,000 registered children. 338 children received the first dose of BNT162b2 at age 0-<12 months, n=1272 at age 12-24 months and n=5629 at age [≥]24 to <60 months. A 10ug dosage was more frequently associated with injection-site symptoms compared to lower dosages. The probability of any symptoms (OR: 1.62 [95% confidence interval (CI): 1.36-1.94]), injection-site, musculoskeletal, dermatological or otolaryngological symptom categories were modestly elevated after BNT12b2 compared to non-SARS-CoV-2 vaccines, whereas the probabilities of general symptoms (OR: 0.74 [95% CI: 0.64-0.85]) and fever (OR: 0.43 [95% CI: 0.35-0.51]) were lower after BNT162b2. Symptoms requiring hospitalization (n=10) were reported only at BNT162b2 dosages higher than 3ug. Conclusions The symptoms reported after BNT162b2 administration were overall comparable to on-label non-SARS-CoV-2 vaccines in this cohort of children aged <5 years.