Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting

In this study in a nationwide mass vaccination setting, the BNT162b2 vaccine was not associated with an elevated risk of most of the adverse events examined. The vaccine was associated with an excess risk of myocarditis (1 to 5 events per 100,000 persons). The risk of this potentially serious adverse event and of many other serious adverse events was substantially increased after SARS-CoV-2 infection.

Adverse Events Associated with SARS-CoV-2 Vaccination.

The effect of vaccination on the various potential adverse events included in this study is presented in Table 2. The risk was substantially higher on either the multiplicative (risk ratio) or additive (risk difference) scales in the vaccinated group than in the unvaccinated group for myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2). Vaccination was substantially protective against adverse events such as anemia, acute kidney injury, intracranial hemorrhage, and lymphopenia.

Figure S1 shows the cumulative incidence (risk) curves for each specific adverse event. Spikes in the incidence of lymphadenopathy were seen after both the first and second doses of vaccine, whereas the incidence of myocarditis spiked mainly after the second dose of vaccine.

https://www.nejm.org/doi/full/10.1056/NEJMoa2110475