Patients hospitalized with myocarditis after COVID-19 mRNA vaccination had a lower rate of cardiovascular complications over 18 months compared to those who developed myocarditis from other causes, while patients with myocarditis after SARS–CoV-2 infection had a similar prognosis to those with conventional cases, according to findings from a large cohort study conducted in France.
Researchers leveraged comprehensive French national health databases, including the COVID-19 vaccination and testing registries and the National Health Data System covering 67 million people. Myocarditis was identified by ICD-10 codes. Weighted Cox models compared clinical outcomes between groups, standardized to the conventional myocarditis group characteristics.
The study, published in JAMA, included 4,635 individuals aged 12 to 49 years who were hospitalized for myocarditis between December 2020 and June 2022. Of these, 558 (12%) developed myocarditis within 7 days of COVID-19 mRNA vaccination, 298 (6%) developed myocarditis within 30 days of SARS–CoV-2 infection, and 3,779 (82%) developed myocarditis from other conventional causes.
During initial hospitalization, the median length of stay was 4 days for postvaccine and conventional myocarditis cases compared to 5 days for post–COVID-19 infection myocarditis cases. No deaths occurred in the postvaccine group, while there were 4 deaths (1.3%) in the post–COVID-19 group and 17 deaths (0.5%) in the conventional group.
Most postvaccine myocarditis cases occurred after the second vaccine dose (67%) and in young males (84%). Patients who developed postvaccine cases were younger (mean age = 25.9 years) than those with post–COVID-19 cases (mean age = 31.0 years) and conventional cases (mean age = 28.3 years). Post–COVID-19 patients had more cardiometabolic comorbidities than postvaccine or conventional patients.
At 18 months, the composite outcome of rehospitalization for myopericarditis, other cardiovascular events, or all-cause death occurred in 5.7% of postvaccine myocarditis patients compared to 13.2% of conventional myocarditis patients (weighted hazard ratio [HR] = 0.55, 95% confidence interval [CI] = 0.36-0.86); in contrast, 12.1% of post-COVID-19 myocarditis patients experienced the composite outcome (weighted HR = 1.04, 95% CI = 0.70-1.52).
Postvaccine patients also had lower all-cause hospitalization rates compared to conventional cases (weighted HR = 0.64, 95% CI = 0.48-0.85), while post-COVID-19 cases remained similar (weighted HR = 1.03, 95% CI = 0.75-1.40). Sensitivity analyses excluding prior myocarditis, using historical controls, and extending the postvaccine window to 30 days showed consistent results.
From 3 to 18 months postdischarge, 21% to 51% of the patients in each group received cardiac imaging, 12% to 41% received cardiovascular medications, 5% to 12% underwent Holter monitoring, and 7% to 18% had troponin measured, with frequencies decreasing over time. This suggests ongoing medical surveillance occurs at substantive rates for these patients, regardless of their myocarditis etiology.
Limitations of the study included potential overdiagnosis of less severe postvaccine cases and lack of clinical data on exam findings; strengths included the large sample size, population-based design, and access to complete health data.
The authors noted the findings should inform ongoing risk-benefit assessments for COVID-19 mRNA vaccines.
One investigator reported receiving nonfinancial support from the French Society of Cardiology outside the submitted work. No other disclosures were reported.
