What The Study Did: In this population-based study of almost 2.4 million people who received at least one dose of COVID-19 mRNA vaccines, acute myocarditis was rare, at an incidence of 5.8 cases per 1 million individuals after the second dose (1 case per 172,414 fully vaccinated individuals). The signal of increased myocarditis in young men warrants further investigation.
Vaccination is an essential component of the public health strategy to end the COVID-19 pandemic.1–3 Recently, there have been reports of acute myocarditis following COVID-19 mRNA vaccine administration.4–6 We evaluated acute myocarditis incidence and clinical outcomes among adults following mRNA vaccination in an integrated health care system in the US.
We included Kaiser Permanente Southern California (KPSC) members aged 18 years or older who received at least 1 dose of the BNT162b2 (Pfizer) or mRNA-1273 (Moderna) mRNA vaccine between December 14, 2020, and July 20, 2021. Potential cases of postvaccine myocarditis were identified based on reports from clinicians to the KPSC Regional Immunization Practice Committee and by identifying hospitalization within 10 days of vaccine administration with a discharge diagnosis of myocarditis. All cases were independently adjudicated by at least 2 cardiologists. We calculated incidence rates and 95% confidence intervals (CIs) of myocarditis using vaccine administration as the denominator and compared it with the incidence of myocarditis in unexposed individuals between December 14, 2020, and July 20, 2021; and with vaccinated individuals during a 10-day period 1 year prior to vaccination. Incidence rate ratios (IRRs) and 95% CIs were calculated using STATA statistical software (version 14, Stata Corp). We described the characteristics and outcomes of acute myocarditis cases. A 2-sided P < .05 was used to define statistical significance. This study was approved by the institutional review board of KPSC with a waiver of informed consent because of the observational nature of the study in the course of standard care.
Of 2 392 924 KPSC members who received at least 1 dose of COVID-19 mRNA vaccines, 50.2% received mRNA-1273 and 50.0% BNT162b2. In this cohort, 54.0% were women, 31.2% White, 6.7% Black, 37.8% Hispanic, and 14.3% were Asian individuals. Median age was 49 years (IQR, 34-64 years), 35.7% were younger than 40 years, and 93.5% completed 2 doses of vaccines. In the unexposed group of 1 577 741 individuals, median (IQR) age was 39 (28-53) years, 53.7% were younger than 40 years, 49.1% women, 29.7% White, 8.8% Black, 39.2% Hispanic, and 6.6% were Asian individuals.
There were 15 cases of confirmed myocarditis in the vaccinated group (2 after the first dose and 13 after the second), for an observed incidence of 0.8 cases per 1 million first doses and 5.8 cases per 1 million second doses over a 10-day observation window (Table 1). All were men, with a median (IQR) age of 25 (20-32) years. Among unexposed individuals, there were 75 cases of myocarditis during the study period, with 39 (52%) men and median (IQR) age of 52 (32-59) years. The IRR for myocarditis was 0.38 (95% CI, 0.05-1.40) for the first dose and 2.7 (95% CI, 1.4-4.8) for the second dose. Sensitivity analyses using vaccinated individuals as their own controls showed similar findings (Table 1).
Of the patients with myocarditis postvaccination, none had prior cardiac disease (Table 2). Eight patients received BNT162b2 and 7 received mRNA-1273. All were hospitalized and tested negative for SARS-CoV-2 by polymerase chain reaction on admission. Fourteen (93%) reported chest pain between 1 to 5 days after vaccination. Symptoms resolved with conservative management in all cases; no patients required intensive care unit admission or readmission after discharge.
In this population-based cohort study of 2 392 924 individuals who received at least 1 dose of COVID-19 mRNA vaccines, acute myocarditis was rare, at an incidence of 5.8 cases per 1 million individuals after the second dose (1 case per 172 414 fully vaccinated individuals). The signal of increased myocarditis in young men warrants further investigation.
This vaccinated cohort is unique in its racial and ethnic diversity and in receiving care at community hospitals with treatment reflective of real-world practice. Limitations of this study include the observational design; short follow-up time; absence of myocardial biopsy for definitive diagnosis; lack of uniform testing of all cases; possible more extensive workup of chest pain in vaccinated individuals during the immediate postvaccination period; and possible underdiagnosis of subclinical cases. No relationship between COVID-19 mRNA vaccination and postvaccination myocarditis can been established given the observational nature of this study.