SARS-CoV-2 Vaccination and Myocarditis in a Nordic Cohort Study

Quick Takes

  • This is a population-based cohort study of 23.1 million individuals aged ≥12 years, from four Nordic countries, which aims to assess the incidence and determinants of SARS-CoV-2 vaccine-related myocarditis.
  • mRNA vaccines were associated with an increased risk of myocarditis and pericarditis, with 4-7 excess events in 28 days per 100,000 BNT162b2 vaccinees, and 9-28 excess events per 100,000 mRNA-1273 vaccinees.
  • Risks were highest in younger men compared to women, and more pronounced after the second dose. Otherwise, prevalence of comorbidities did not differ between unvaccinated and vaccinated myocarditis.

Study Questions:

What is the risk of myocarditis and pericarditis following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination by vaccine product, vaccination dose number, sex, and age?

Methods:

The purpose of this population-based cohort study is to assess the incidence and determinants of myocarditis/pericarditis related to the SARS-CoV-2 vaccine. The study leverages nationwide health registers on SARS-CoV-2 vaccination across Denmark, Finland, Norway, and Sweden, combining a total of 23.1 million individuals aged ≥12 years. The cohort was followed from December 27, 2020, until incident myocarditis/pericarditis, censoring, or October 5, 2021 (study end). The primary outcome was hospitalization for myocarditis or pericarditis within the 28-day period post first or second dose vaccination. Rates of myocarditis or pericarditis in the 28-day period following vaccination was compared with rates during the unvaccinated time period.

Results:

Among 23,122,522 Nordic residents aged ≥12 years (50.2% women, 81% vaccinated by study end, 65% with BNT162b2 [Pfizer-BioNTech], 10% mRNA-1273 [Moderna], and 6% AZD1222 [AstraZeneca]), there were 1,077 incident myocarditis events and 1,149 incident pericarditis events. The incidence rate during the unvaccinated period was 9.7 per 100,000 person-years for men, and 4.3 per 100,000 person-years for women. There were no differences in the prevalence of comorbidities between vaccinated and unvaccinated cases. For individuals receiving 2 doses of the same vaccine (homologous schedule), there were between 4 and 7 excess events in 28 days per 100,000 vaccinees after BNT162b2, and between 9 and 28 excess events per 100,000 vaccinees after mRNA-1273. The adjusted incidence rate ratios (IRRs) for men and women ≥12 years old combined who received a homologous schedule, the second dose was associated with higher risk of myocarditis, with adjusted IRRs of 1.75 (95% confidence interval [CI], 1.43-2.14) for BNT162b2 and 6.57 (95% CI, 4.64-9.28) for mRNA-1273. Among males 16-24 years of age, adjusted IRRs were 5.31 (95% CI, 3.68-7.68) for a second dose of BNT162b2 and 13.83 (95% CI, 8.08-23.68) for a second dose of mRNA-1273. IRRs for women were lower across age groups. Estimates for pericarditis were similar.

Conclusions:

Messenger RNA (mRNA) vaccines are associated with an increased risk of myocarditis, with men and those receiving the mRNA-1273 vaccine being at relatively higher risk.

Perspective:

This is the largest study examining the risks of SARS-CoV-2–related myocarditis, with individual-level data spanning four countries and long follow-up. In addition to confirming earlier findings of an association between mRNA vaccines and myocarditis, the shear sample size of the study allows delving into details of this association, including the impact of age, sex, vaccine dose, and type. The described associations persisted after account for various confounders including geographic location. The majority of individuals did receive the BNT162b2 vaccine; however, the sample size is large enough to make confident conclusions regarding both the BNT162b2 and the mRNA-1273 vaccines. The higher risk associated with mRNA-1273 was previously described and is presumed to be related to its overall larger dose and increased immunogenicity compared to BNT162b2. What the study does not determine is whether there are major health consequences related to the myocarditis/pericarditis attributed to vaccination. Thus far, studies focused on clinical outcomes of patients diagnosed with vaccine-related myocarditis suggest the vast majority experience a full recovery. Several societies have thus highlighted that the benefit of vaccination for SARS-CoV-2 in adults far outweighs the risk of myocarditis. Much less is known with regard to the risk of vaccine-related myocarditis in young children (<12 years); a population under close scrutiny, given the risk–benefit ratio of vaccination may be higher compared to adults.

Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Pericardial Disease, Prevention, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Prevention, CHD and Pediatrics and Quality Improvement, Acute Heart Failure

Keywords: Adolescent, COVID-19 Vaccines, Heart Failure, Mass Vaccination, Myocarditis, Pericarditis, Primary Prevention, Risk, SARS-CoV-2, Vaccination


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