Background: Increased risk of myocarditis/pericarditis (m/p) has been reported in younger males receiving the original monovalent Pfizer-BioNTech COVID-19 vaccine (BNT162b2). A US post-approval safety study [EUPAS43468] was conducted in recipients of the primary series and initial booster dose of BNT162b2.
Objectives: To assess the risk of m/p following receipt of BNT162b2 in the US.
Methods: Using data from 5 health insurers participating in the Sentinel System, BNT162b2 vaccinees aged ≥6 months were identified from 11 December 2020 to 18 April 2023. Comparator individuals were matched to vaccinees (up to a 2:1 ratio) with ≥1 year of prior enrollment on age, sex, US state, calendar month, and propensity score. Comparators for the primary series had no prior COVID-19 vaccination and for booster doses had received 2 doses of BNT162b2 without a third dose.
M/p was identified with diagnosis codes in days 1-21 (primary definition) and days 1-7 and 1-14 (secondary definitions) after the index date. Hazard ratios (HR) were estimated using Cox models. Secondary analysis using a self-controlled risk interval design (SCRI) was also performed. Results are reported separately for the primary series and for the initial booster dose in the overall population and stratified by age, sex, and dose number.
Results: A total of 7.3 million (M) primary series vaccinees were matched to 14.5 M unexposed individuals; 2.1 M booster dose recipients were matched to 3.4 M comparator individuals. In the overall population, the HR for primary series vaccination was 1.15 (95% confidence interval [CI], 1.03-1.30) and 1.09 (95% CI, 0.77-1.54) for the initial booster dose.
In subgroup analyses, the highest HR estimates for the primary series were after dose 2 in males aged 12-17 years (HR 12.22, 95% CI 5.51-27.11), males aged 18-24 years (HR 3.63, 95% CI 1.94-6.80), and females aged 18-24 years (HR 4.33, 95% CI 1.65-11.40). The highest HR estimates for booster doses were in males aged 12-17 years (HR 4.92, 95% CI 1.01-24.09), 18-24 years (HR 5.16, 95% CI 1.39-19.24), and 30-39 years (HR 8.22, 95% CI 0.95-71.27).
Sensitivity analyses using 7- and 14-day risk intervals also yielded HR estimates > 1; the highest HR estimates were with the 7-day risk interval (primary series HR, 1.61; 95% CI, 1.34-1.93; booster dose HR, 1.81; 95% CI, 1.07-3.08). Results from the secondary SCRI design were consistent with the primary cohort analysis (primary series incidence rate ratio [IRR], 1.46; 95% CI, 1.18-1.80; booster dose IRR, 1.14; 95% CI, 0.83-1.57).
Conclusions: Consistent with prior observational studies and the US and EU labels for BNT162b2, increased risks of m/p were observed, with the highest increased risks in males aged 12-24 years in the week after vaccination.
Kawai A, Fuller CC, Hawrusik R, Iyer GS, Koram N, Agan AA, Alam S, Avula R, Brown J, Burk J, Connolly JG, Daniels K, DeFor T, DeVries A, Diessner B, Djibo DA, Ezzy S, Cai B, Layton JB, Dea K, Tetreault-Langlosi P, Lyons J, Love S-AM, Mayer S, Ma Q, McMahill-Walraven CN, Nolan MB, Oyedele N, Peters A, Reynolds JS, Taggert E, Wideman K, Ziyadeh NJ, Gilsenan A, Platt R. Risk of Myocarditis/Pericarditis After Receipt of Pfizer-BioNTech COVID-19 Vaccine: Results from a Post-approval Safety Study in the US. 42nd Annual International Society for Pharmacoepidemiology Conference; 2026 Sep 1; Milan, Italy.
