Background: The U.S. Food and Drug Administration’s Biologics Effectiveness and Safety (BEST) Initiative conducted near-real-time safety monitoring of 16 adverse events (AEs) post COVID-19 mRNA vaccination that detected elevations in risk for six AEs following primary series and monovalent booster dose administration among people 65 years and older. The crude association from initial safety monitoring does not imply causality; further evaluations were performed to assess post-vaccination risk of these six AEs.
Objectives: To evaluate the association between COVID-19 mRNA vaccines and AEs with an identified increase in risk post-vaccination, from initial safety monitoring.
Methods: We conducted self-controlled case series studies of BNT162b2 and mRNA-1273 for primary series (from December 2020 through April/May 2021) and monovalent booster doses (from August 2021 through April/May 2022) separately, among Medicare beneficiaries aged 65 years and older in the Centers for Medicare & Medicaid Services claims database. Adjusted incidence rate ratio (IRRs) and attributable risk (ARs) estimates and associated 95% confidence intervals (CIs) were estimated using a conditional Poisson regression model, following primary series doses for acute myocardial infarction (AMI), pulmonary embolism (PE), immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC); and boosters for AMI, PE, ITP, Bell’s Palsy (BP), and myocarditis/pericarditis (Myo/Peri).
Results: Among 3,360,981 individuals who received 6,388,542 primary series doses and 6,156,100 individuals with monovalent booster doses of either BNT162b2 or mRNA-1273, AE counts were: AMI (3,653 primary series, 16,042 booster), inpatient PE (2,470 primary, 5,085 booster), ITP (1,085 primary, 88 booster), DIC (254 primary), BP (3,268 booster), and Myo/Peri (1,295 booster). The adjusted IRR for inpatient PE cases following BNT162b2 primary series and boosters were 1.19 (95% CI: 1.03-1.38) and 0.86 (95% CI: 0.78-0.95), respectively; and for mRNA-1273 primary series and boosters 1.15 (95% CI: 0.94 to 1.41) and 0.87 (95% CI: 0.79-0.96), respectively. The adjusted IRR and AR (per 100,000 doses) for BP following BNT162b2 and mRNA-1273 boosters were 1.17 (95% CI: 1.06-1.29) and 3.73 (95% CI: 1.38-6.08), respectively; and 1.16 (95% CI: 1.05-1.29) and 3.16 (95% CI: 1.02-5.30), respectively.
Conclusions: In these two studies of the U.S. elderly, we did not find an increased post-vaccination risk for AMI, ITP, DIC, and Myo/Peri; the results were inconsistent for PE; and there was a small, elevated BP risk after exposure to COVID-19 mRNA monovalent booster vaccines. Excess post-vaccination absolute risk of AEs was low. These results support the favorable safety profile of COVID-19 mRNA vaccines in the elderly.
