European Study Details Risk of Myocarditis Following COVID-19 Vaccination

Rickard Ljung, MD, PhD, MPH

New research from investigators in Europe provides an overview of the risk of myocarditis following SARS-CoV-2 vaccination in a cohort of more than 23,000,000 residents from 4 countries.

An analysis of data from nationwide health registers in Denmark, Finland, Norway, and Sweden, results of the study provide insight into the risk of myocarditis and pericarditis following SARS-CoV-2 vaccination based on vaccine type as well as by patient sex and age, with results demonstrating the greatest risk was observed following the second dose of mRNA vaccines among young men aged 16-24 years.

Few topics in the history of medicine have received as much attention as the potential for myocarditis during the COVID-19 pandemic, both from contracting SARS-CoV-2 and following vaccination. As the pandemic has continued and more data has been accumulated, researchers’ ability to provide insight into this apparent increase in risk has grown as well. With this in mind, a team of investigators from Europe led by Rickard Ljung, MD, PhD, MPH, of the Karolinksa Institute in Sweden, designed their study to with the intent of adding to the current knowledge base surrounding risk of myocarditis and pericarditis following vaccination.

The study was designed as a meta-analysis of data from 4 population-based cohort studies conducted using a common protocol among patients in Denmark, Finland, Norway, and Sweden. These studies included all patients aged 12 years and older in 2021 who were residents on January 1, 2017, and were alive and still residing within the country on December 27, 2020, with the exception of those with any myocarditis or pericarditis in inpatient or outpatient hospital care from January 1, 2017-December 26, 2020.

The primary outcome of interest for the study was the incidence of the first inpatient hospital admission based on primary per secondary discharge diagnosis for myocarditis or pericarditis from December 27, 2020, onward. Secondary outcomes of interest were myocarditis or pericarditis combined from either inpatient or outpatient hospital care. The incidence rate ratios (IRRs) and excess rates were calculated using Poisson regression models comparing rates of myocarditis or pericarditis within the first 28 days following vaccination against those of unvaccinated

Among the 23,122,522 individuals identified for inclusion in the current study, 81% were vaccinated by the end of the study period, with 17,129,982 residents (74%) having received 2 doses and 1, 681, 930 residents (7%) having received 1 dose of SARS-CoV-2 vaccines. Investigators noted 487,751 of 1,238,004 (39%) aged 12-15 years, 2,009,995 of 2,675,558 persons (75%) aged 16-24 years of age, 3,736,517 of 5,046,164 persons (74%) aged 25-39 years, and 12,579,805 of 14,162,796 persons (89%) aged 40 years or older had received at least 1 dose of a SARS-CoV-2 vaccine.

Within the first 28 days following vaccination, a total of 1077 incident myocarditis cases and 1149 incident pericarditis cases occurred among the study cohort. Upon analysis, investigators identified 105 myocarditis cases following administration of the first dose of BNT162b2 and 115 myocarditis cases following the second dose. For mRNA-1273 vaccines, investigators observed 15 myocarditis cases following administration of the first dose and 60 cases following the second dose.

Based on results observed in the study, data suggested for males and females 12 years or older who received a homologues schedule, the second dose was associated with higher risk of myocarditis, with adjusted IRRs of 1.75 (95% CI, 1.43-2.14) for BNT162b2 and 6.57 (95% CI, 4.64-9.28) for mRNA-1273 vaccines. Further analysis demonstrated the adjusted IRRs for myocarditis were 5.31 (95% CI, 3.68-7.68) for the second dose of BNT162b2 and 13.83 (95% CI, 8.08-23.68) for the second dose of mRNA-1273 among males aged 16-24 years.

When assessing the number of excess events per 100,000 vaccines, results indicated the number of excess events per 100,000 vaccinees after the second dose of BNT162b2 was 5.55 (95% CI, 3.70-7.39) and 18.39(95% CI, 9.05-27.72) after the second dose of mRNA-1273. Investigators noted the trends for risks of pericarditis were similar to those observed for risk of myocarditis following vaccination.

“The risks of myocarditis and pericarditis were highest within the first 7 days of being vaccinated, were increased for all combinations of mRNA vaccines, and were more pronounced after the second dose. A second dose of mRNA-1273 had the highest risk of myocarditis and pericarditis, with young males aged 16 to 24 years having the highest risk,” investigators wrote.

This study, “SARS-CoV-2 Vaccination and Myocarditis in a Nordic Cohort Study of 23 Million Residents,” was published in JAMA Cardiology.