The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients. The clinical presentation of myocarditis after vaccination was usually mild.
BACKGROUND
Approximately 5.1 million Israelis had been fully immunized against coronavirus disease 2019 (Covid-19) after receiving two doses of the BNT162b2 messenger RNA vaccine (Pfizer–BioNTech) by May 31, 2021. After early reports of myocarditis during adverse events monitoring, the Israeli Ministry of Health initiated active surveillance.
METHODS
We retrospectively reviewed data obtained from December 20, 2020, to May 31, 2021, regarding all cases of myocarditis and categorized the information using the Brighton Collaboration definition. We analyzed the occurrence of myocarditis by computing the risk difference for the comparison of the incidence after the first and second vaccine doses (21 days apart); by calculating the standardized incidence ratio of the observed-to-expected incidence within 21 days after the first dose and 30 days after the second dose, independent of certainty of diagnosis; and by calculating the rate ratio 30 days after the second dose as compared with unvaccinated persons.
RESULTS
Among 304 persons with symptoms of myocarditis, 21 had received an alternative diagnosis. Of the remaining 283 cases, 142 occurred after receipt of the BNT162b2 vaccine; of these cases, 136 diagnoses were definitive or probable. The clinical presentation was judged to be mild in 129 recipients (95%); one fulminant case was fatal. The overall risk difference between the first and second doses was 1.76 per 100,000 persons (95% confidence interval [CI], 1.33 to 2.19), with the largest difference among male recipients between the ages of 16 and 19 years (difference, 13.73 per 100,000 persons; 95% CI, 8.11 to 19.46). As compared with the expected incidence based on historical data, the standardized incidence ratio was 5.34 (95% CI, 4.48 to 6.40) and was highest after the second dose in male recipients between the ages of 16 and 19 years (13.60; 95% CI, 9.30 to 19.20). The rate ratio 30 days after the second vaccine dose in fully vaccinated recipients, as compared with unvaccinated persons, was 2.35 (95% CI, 1.10 to 5.02); the rate ratio was again highest in male recipients between the ages of 16 and 19 years (8.96; 95% CI, 4.50 to 17.83), with a ratio of 1 in 6637.
CONCLUSIONS
The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients. The clinical presentation of myocarditis after vaccination was usually mild.
During a nationwide vaccination campaign conducted from December 2020 through May 2021 involving more than 5 million residents, the Israeli Ministry of Health recorded 136 cases of definite or probable myocarditis that had occurred in temporal proximity to the receipt of two doses of the BNT162b2 mRNA vaccine — a risk that was more than twice that among unvaccinated persons.
This association was highest in young male recipients within the first week after the second dose. In our study, definite or probable cases of myocarditis among persons between the ages of 16 and 19 years within 21 days after the second vaccine dose occurred in approximately 1 of 6637 male recipients and in 1 of 99,853 female recipients.
In most cases, symptoms of myocarditis developed within a few days after the second dose of vaccine.
The mechanism of vaccine-induced myocarditis is not known but may be related to the active component of the vaccine, the mRNA sequence that codes for the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or to the immune response that follows vaccination.
