Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting.
Level 3 - non-randomized controlled study
Non-randomized matched cohort study using national electronic health records
PubMed 34432976 · doi:10.1056/NEJMoa2110475
What was done
Using electronic health record data from Israel's largest healthcare organization, vaccinated individuals were individually matched to unvaccinated controls by sociodemographic and clinical variables across multiple potential adverse events (excluding individuals with prior diagnoses of each specific event). Risk ratios (RR) and risk differences (RD) at 42 days post-vaccination were estimated using Kaplan-Meier methods. A parallel analysis was conducted comparing matched SARS-CoV-2-infected individuals to uninfected controls for the same set of outcomes.
What was found
The vaccinated and matched control groups each included a mean of 884,828 persons. Vaccination was associated with increased risks of: - Myocarditis: RR 3.24 (95% CI, 1.55 to 12.44); RD 2.7 events per 100,000 persons (95% CI, 1.0 to 4.6) - Lymphadenopathy: RR 2.43 (95% CI, 2.05 to 2.78); RD 78.4 events per 100,000 persons (95% CI, 64.1 to 89.3) - Appendicitis: RR 1.40 (95% CI, 1.02 to 2.01); RD 5.0 events per 100,000 persons (95% CI, 0.3 to 9.9) - Herpes zoster: RR 1.43 (95% CI, 1.20 to 1.73); RD 15.8 events per 100,000 persons (95% CI, 8.2 to 24.2) In comparison, SARS-CoV-2 infection was associated with a much higher risk of myocarditis (RR 18.28; 95% CI, 3.95 to 25.12; RD 11.0 events per 100,000 persons; 95% CI, 5.6 to 15.8) and additional serious events, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia.
Why it matters
This nationwide study provides population-level safety data showing that while BNT162b2 vaccination carries a small excess risk of myocarditis, the absolute risk of cardiac and thromboembolic complications is substantially higher after natural SARS-CoV-2 infection.
Limits
As an observational cohort study, residual confounding remains possible despite matching. Follow-up was restricted to 42 days post-vaccination or post-infection. The study relied on electronic health records from a single country and did not evaluate longer-term adverse events beyond the 6-week window.
Cited by
- supports A New England Journal of Medicine study from Israel analyzing approximately one million subjects per arm found that the risk of myocarditis and pericarditis was higher after SARS-CoV-2 infection than after Pfizer-BioNTech vaccination.