Vaccine safety monitoring systems worldwide have reported cases of myocarditis/pericarditis after mRNA-based COVID-19 vaccines (Pfizer-BioNTech and Moderna), especially among younger male persons 0 to 7 days after they received dose 2 (1, 2). Less is known about the incidence of myocarditis/pericarditis after booster doses.

To estimate the incidence of myocarditis/pericarditis during days 0 to 7 after mRNA vaccination by age, sex, dose number, and product.

The Vaccine Safety Datalink (VSD) is a collaborative of 8 integrated health care delivery systems with comprehensive medical records that has conducted active, population-based surveillance of prespecified outcomes after COVID-19 vaccination since December 2020 (1, 3). We identified all potential cases of myocarditis/pericarditis in emergency department and inpatient settings 1 to 98 days after vaccination, using myocarditis/pericarditis–specific ICD-10 codes, among 5- to 39-year-old persons (Table). We validated cases through review of medical records with physician adjudication and classified according to the Centers for Disease Control and Prevention case definition (1).

From 14 December 2020 through 31 May 2022 (persons 18–39 years) and 20 August 2022 (persons 5–17 years), 320 potential cases of myocarditis/pericarditis were identified 1 to 98 days after 6 992 340 vaccine doses as part of primary series COVID-19 vaccination, with 224 (70%) verified. Of these, 137 (61%) occurred 0 to 7 days after vaccination; 18 were after the first dose (of 3 562 311 doses administered) and 119 were after the second dose (of 3 430 029 doses administered).

In all age groups, incidence per million doses 0 to 7 days after vaccination was numerically higher in male than in female persons and after dose 2, although confidence intervals were wide and overlapped across sex for some age groups. Incidence was highest for male adolescents ages 12 to 15 years and 16 to 17 years following dose 2 (Table).

From 24 September 2021 through 20 August 2022, 101 potential cases of myocarditis/pericarditis were identified 1 to 98 days after 1 848 723 first booster doses, with 77 (76%) verified with a median onset of 4.5 days after vaccination; 39 cases (51%) were verified in the first week versus 38 during the subsequent 13 weeks.

In all age groups, incidence 0 to 7 days after first booster was higher for male compared to female persons, with adolescent males having the highest incidence in 16- to 17-year-olds and in 12- to 15-year-olds. In adults for whom both vaccine products were available, post-booster incidence was higher in male than in female adults and higher in males aged 18 to 29 compared to males aged 30 to 39.

In this population-based surveillance, we found that myocarditis/pericarditis 0 to 7 days after mRNA vaccination in persons aged 5 to 39 years occurred in approximately 1 in 200 000 doses after the first dose and 1 in 30 000 doses after second dose of the primary series, and 1 in 50 000 doses after the first booster. The incidence varied markedly by age and sex, however, with a disproportionate number of cases occurring in male persons, notably among adolescents after dose 2 and first boosters.

Our observed incidence after first boosters was generally higher than after dose 1, consistent with reporting from Israel (4). However, in contrast to this earlier report, we did not consistently observe a lower incidence after the first booster than after the second dose in the primary vaccination series. Incidence rates of myocarditis/pericarditis observed in the VSD population were higher, particularly after first boosters, than those reported to the U.S. Vaccine Adverse Event Reporting System (VAERS), but patterns noted by sex and age subgroups were similar (2, 5). Rates from VAERS may be lower because of the passive nature of VAERS reporting versus VSD's identification of cases using active surveillance. Both VSD and VAERS found incidence rates during days 0 to 7 after vaccination that were higher than the prepandemic background rates noted by Oster and colleagues (2); however, prepandemic rates may not be directly comparable with post vaccination rates because underdiagnosis of myocarditis/pericarditis in this age range was more likely prepandemic than post vaccination when surveillance was greater.

This study was strengthened by active surveillance of a large diverse population and by verification of cases through medical record review and physician adjudication. Important limitations include the lack of a control group, precluding causal inference. Cases were also identified only in emergency or inpatient settings using myocarditis/pericarditis–specific ICD-10 codes. Thus, cases were not identified if they were seen only in outpatient settings or if they received less-specific diagnosis codes such as chest pain (R07.9). Further limitations included potential reporting and ascertainment bias, potential differences between individuals who received Moderna versus Pfizer vaccines, and underreporting of SARS-CoV-2 infection.

Our findings can inform risk–benefit analyses, which thus far have consistently found the benefits of mRNA vaccination greatly outweigh the risks. Continued communication with patients and providers about risk for myocarditis/pericarditis after mRNA COVID-19 vaccination, as well as ongoing population-based safety surveillance, is warranted.