Study: Long-Term Prognosis of Patients With Myocarditis Attributed to COVID-19 mRNA Vaccination, SARS-CoV-2 Infection, or Conventional Etiologies. Image Credit: SrideeStudio / Shutterstock.com

Nationwide study reveals that while myocarditis linked to COVID-19 mRNA vaccines shows less severe long-term outcomes, young, healthy men may still face months of follow-up care and medical management, raising crucial considerations for future vaccine recommendations.

In a recent study published in JAMA Network, researchers determine whether coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) vaccines increase the risk of myocarditis.

COVID-19 and myocarditis

Myocarditis is a common and potentially severe medical condition caused by inflammation of the myocardium, the muscular tissue of the heart. It is characterized by a reduction in the heart’s blood pumping efficiency and symptoms including chest pain, shortness of breath, and rapid or irregular heartbeats.

Although myocarditis often self-corrects, severe cases may require months or even years of medical intervention to resolve, thereby resulting in significant debilitation and economic burden to affected patients and their families.

Observational studies have suggested an association between the COVID-19 mRNA vaccines mRNA-1273 and BNT162b2 and an increased incidence of myocarditis, with one report identifying a 30-fold increased risk following the second mRNA-1273 dose.

However, studies aiming to establish a correlation between COVID-19 vaccination and myocarditis do not have sufficient follow-up time following disease diagnosis and have failed to address myocarditis severity or management across origins.

Since COVID-19 is associated with an increased myocarditis risk, and vaccines have been proven to significantly reduce the risk of COVID-19 and improve post-COVID outcomes, understanding the impacts of COVID-19 vaccination would allow clinicians and policymakers to clarify the benefits and possible risks associated with vaccinations across relevant demographics.

About the study

The present study aims to examine the incidence of myocarditis and subsequent cardiovascular complications following vaccination and COVID-19. The researchers also examined long-term disease management 18 months following the contraction of the disease in terms of the number of drug prescriptions and medical procedures.

Data for the study were obtained from the French National Hospital Discharge Database (PMSI), National Health Data System (SNDS), French national COVID-19 vaccination database (VAC-SI), and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) diagnosis testing database (SI-DEP), which collectively comprise the entire French population of 67 million individuals. The International Classification of Diseases and Related Health Problems, 10^th Revision (ICD-10) codes were used to define and identify both myocarditis and COVID-19.

Study data collection was restricted to December 2020 through June 2022 and only included individuals between 12 and 49 years old. For the analysis, study participants were classified as postvaccine myocarditis if they were hospitalized within seven days following COVID-19 mRNA vaccination or post-COVID-19 myocarditis if they were hospitalized within 30 days of COVID-19 diagnosis without prior immunization. Conventional myocarditis included patients diagnosed with myocarditis from any other origin.

Data collection included demographics, vaccination status, medical histories, medical procedures, hospital visits, or drug prescriptions following the myocarditis diagnosis. The incidence and outcomes of myocarditis were evaluated through Cox regression models weighted for the type of myocarditis. The risk of developing myocarditis was modeled using multinomial multivariable logistic regression models corrected for sociodemographics and comorbidities.

Study findings

During the study period, 4,635 individuals were hospitalized for myocarditis, 12% of whom were classified as postvaccine, 6% as post-COVID-19, and 82% as conventional myocarditis. About 67% of postvaccine myocarditis patients developed symptoms following the second vaccination dose.

Myocarditis type evaluations revealed that postvaccine myocarditis patients were younger, with a mean age of 25.9 years, and more likely to be male with a lower history of chronic disease as compared with conventional myocarditis. In contrast, post-COVID-19 myocarditis patients were older with a mean age of 31, more likely to be diagnosed with comorbidities, and less frequently male at 67% as compared to 84% of postvaccine myocarditis patients.  

Clinical outcomes over 18 months of follow-up were most severe in the post-COVID-19 and conventional myocarditis cohorts, both of which resulted in 4% mortality rates as compared to 0.2% in the postvaccination cohort. Hospitalization reports presented similar trends, with 5.8%, 4%, and 3.2% of conventional, post-COVID-19, and postvaccination patients requiring hospitalization, respectively. However, drugs and medical procedures in all cohorts were not statistically different from each other.

Conclusions

Although COVID-19 mRNA vaccination was associated with an increased incidence of subsequent myocarditis as compared to other disease origins, the subsequent clinical outcomes, including mortality, were significantly attenuated in this cohort. The current study identified younger male individuals, especially those receiving their second mRNA vaccine dose, as the highest-risk population, thus highlighting the need for preventive clinical follow-up between seven and 30 days following vaccination.