The cumulative risk of myocarditis/myopericarditis among global mRNA-1273 recipients

By Bhavana KunkalikarReviewed by Danielle Ellis, B.Sc.Jun 8 2022

In a recent study published in Clinical Infectious Diseases, researchers analyzed the incidence of myocarditis among coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA)-1273 vaccinees.

Various studies have reported a causal association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and myocarditis. Moreover, evidence shows the incidence of myocarditis among individuals vaccinated with the mRNA-1273 COVID-19 vaccine.

About the study

In the present study, researchers assessed the cumulative risk of the incidence of myocarditis or myopericarditis among individuals who had received the mRNA-1273 COVID-19 vaccine.

The team reviewed reports of potential myopericarditis and myocarditis documented in the Moderna global safety database between 18 December 2020 and 15 February 2022. The data collected from this database included adverse events reported by individuals globally. The team queried the database for valid cases reporting myopericarditis and myocarditis. Available references were used to develop a systematic approach that characterized potential reports of myocarditis after mRNA vaccination and assessed causality.

The Brighton Collaboration case definition for myocarditis was used to classify individual cases into five categories: (1) level 1- definitive case, (2) level 2- probable case, (3) level 3- possible case, (4) level 4- a reported event with insufficient evidence; and (5) level 5- not a case of myopericarditis or myocarditis based on diagnostic evidence and clinical findings. The team also used the World Health Organization–Uppsala Monitoring Centre standardized case causality assessment tool to evaluate the likelihood of a case causally associated with the vaccine.

The global proportion of mRNA-1273 vaccinees was estimated according to the data retrieved through the Centers for Disease Control and Prevention (CDC), the European CDC, the public health agency of Canada, the Swiss federal office of public health, and Our World in Data on 16 February 2021. 

Results

The team estimated that between 18 December 2020 and 15 February 2022, 568,668,391 doses of the mRNA-1273 COVID-19 vaccine were administered, and 477,932 individual cases were reported, including 1,819,802 adverse events. The individual cases reported comprised 3027 cases of myopericarditis or myocarditis. Among these, 72% of the cases were reported by a healthcare professional involved in the patient’s therapy, and 97.5% had serious adverse events, including 1.5% reporting a fatal outcome. Almost 21% of the cases reported COVID-19 recovery, while 1.6% recovered with sequelae and 25.7% were recovering.

The team noted that 40.3% of the total cases were from the European economic area (EEA), 25.2% from the US, 11.5% from Asia, 5.1% from Switzerland, 8.5% from the UK, 8.8% from Canada, and less than 1% from the Middle East and Australia. The median age of the study population was 29 years, while 75% of the cases were reported in men.

The study results showed that the number of myopericarditis or myocarditis corresponded to the overall reporting rate of 9.23 per 100,000 person-years, irrespective of the time of disease onset. The observed reporting rate among individuals who had received the mRNA-1273 vaccine varied significantly with respect to age and gender.

Furthermore, the reporting rate for males was 14.54 per 100,000 person-years, and for females was 4.11 per 100,000 person-years. Across different age groups, the reporting rate was 29.29 per 100,000 person-years among individuals aged between 18 and 24 years. When adjusted according to age and gender, younger males under 40 years had the highest reporting rates for myopericarditis or myocarditis. Overall, the observed reporting rates for myopericarditis or myocarditis post-mRNA-1273 vaccination resulted in a rate ratio of 1.03.

When the study was restricted to cases reported within seven days of a known COVID-19 dose, the observed reporting rate for the vaccinees per 100,000 doses was higher after administering the second vaccine dose. The highest rates reported within seven days of vaccination were observed after the second dose among males aged less than 39 years, specifically those between 18 and 24 years. Comparing the observed rates to the expected rates resulted in a rate ratio of 8.88 for males aged between 18 to 24 years within seven days of the second vaccine dose. The team noted that the rates were lower after the third dose than after the second dose.      

Conclusion

Overall, the study findings showed that myopericarditis or myocarditis was a rare event in mRNA-1273 COVID-19 vaccine recipients. The researchers believe that the benefits of mRNA-1273 vaccination outweigh the potential risk of vaccine-associated myocarditis.