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Myocarditis risk significantly higher after COVID-19 infection vs. after a COVID-19 vaccine

sarah Jonas

DALLAS, August 22, 2022 — In a detailed analysis of nearly 43 million people, ages 13 and older, who received at least one dose of a COVID-19 vaccine in England, the risk of myocarditis in unvaccinated individuals after COVID-19 infection was at least 11 times higher compared to people who developed myocarditis after receiving a COVID-19 vaccine or booster dose between December 1, 2020 and December 15, 2021, according to new research published today in the American Heart Association’s flagship, peer-reviewed journal Circulation.

Several previous studies and reports from public health agencies around the world including the U.S. Centers for Disease Control and Prevention have highlighted a possible connection and potentially increased risk of myocarditis after receiving an mRNA COVID-19 vaccine, generating considerable scientific, policy and public interest .

Typically trigged by a viral infection, myocarditis is the inflammation of the middle layer of the wall of the heart muscle, the myocardium. This condition is uncommon and may temporarily or permanently weaken the heart muscle and the heart’s electrical system, which keeps the heart pumping normally. An episode of myocarditis may resolve on its own or with treatment, and may result in lasting damage to the heart. In the general population not during a global pandemic, it is estimated that approximately 10 to 20 people per 100,000 are diagnosed with myocarditis each year, according to the American Heart Association’s 2021 scientific statement on myocarditis.

“We found that across this large dataset, the entire COVID-19-vaccinated population of England during an important 12-month period of the pandemic when the COVID-19 vaccines first became available, the risk of myocarditis following COVID-19 vaccination was quite small compared to the risk of myocarditis after COVID-19 infection,” says first author of the study Martina Patone, Ph.D., a statistician at the Nuffield Department of Primary Health Care Sciences at the University of Oxford in Oxford, England. “This analysis provides important information that may help guide public health vaccine campaigns, particularly since COVID-19 vaccination has expanded in many parts of the world to include children as young as 6 months old.”

In this study, Patone and colleagues evaluated England’s National Immunization database of COVID-19 vaccinations for all people ages 13 or older who had received at least one dose of the ChAdOx1 (a two-dose adenovirus-vector COVID-19 vaccine developed by the University of Oxford and AstraZeneca, most similar to the one-dose Johnson & Johnson/Janssen COVID-19 vaccine available in the U.S.), the Pfizer-BioNTech or the Moderna COVID-19 vaccine (the same mRNA vaccines available in the U.S.) between December 1, 2020 and December 15, 2021. This dataset totaled nearly 43 million people, which included more than 21 million who had received a booster dose of any of the COVID-19 vaccines (meaning they had received a total of 3 doses of a COVID-19 vaccine). The database detailed the type of COVID-19 vaccines received, dates received and dose sequencing, along with individual demographic information including age and sex for each individual. Nearly 6 million people tested positive for COVID-19 infection either before or after COVID-19 vaccination during the study period.  

England’s National Immunization database records were then cross-referenced and matched to the national offices with data on COVID-19 infection, hospital admission and death certificates for the same time period, December 1, 2020 through December 15, 2021. Individuals were classified based on age and sex to reveal which groups had the highest risk of myocarditis after a COVID-19 vaccine or after COVID-19 infection and hospitalization. The authors used the self-controlled case series (SCCS) method, which was developed to estimate the relative incidence of an acute event in a pre-defined post-vaccination risk period (1-28 days), compared to other times (pre-vaccination or long after vaccination). Being a within-person comparison, the analyses were controlled to adjust for any fixed characteristics, including sex, race or ethnicity, or chronic health conditions.

In the overall dataset of nearly 43 million people, the analyses found:

Risk of COVID-19 vaccine-associated myocarditis among women:

Risk of COVID-19 infection-associated myocarditis among women:

Risk of COVID-19 vaccine-associated myocarditis among men:

Risk of COVID-19 infection-associated myocarditis among men:

“It is important for the public to understand that myocarditis is rare, and the risk of developing myocarditis after a COVID-19 vaccine is also rare. This risk should be balanced against the benefits of the COVID-19 vaccines in preventing severe COVID-19 infection. It is also crucial to understand who is at a higher risk for myocarditis and which vaccine type is associated with increased myocarditis risk, ” said Professor Nicholas Mills, Ph.D., the Butler British Heart Foundation Chair of Cardiology at the University of Edinburgh and a co-author of the paper.

“These findings are valuable to help inform recommendations on the type of COVID-19 vaccines available for younger people and may also help shape public health policy and strategy for COVID-19 vaccine boosters. The SARS-CoV-2 virus continues to shift, and more contagious variants arise; our hope is that this data may enable a more well-informed discussion on the risk of vaccine-associated myocarditis when considered in contrast to the net benefits of COVID-19 vaccination,” said another co-author Julia Hippisley-Cox, F.R.C.P., professor of clinical epidemiology and general practice at the University of Oxford.

Authors noted there are two unanswered questions that likely require further investigation. The first is about myocarditis risk among children ages 13-17 because there were too few cases of myocarditis to quantify the risk specific to this age group. Secondly, researchers were not able to directly compare the death rate after COVID-19 infection vs. death after COVID-19 vaccination since the database only included people who had received at least one COVID-19 vaccine. More expansive data and a different analysis are still needed to address these questions and numerous other COVID-19 topics.

The study has two notable limitations. The number of cases of myocarditis among individuals who received a booster dose of the ChAdOx1 or Moderna vaccines was too small to calculate the risk of myocarditis. Additionally, researchers cannot exclude the possibility of over- or under-estimated risk due to misclassification of any health information in the database, though the U.K.’s National Health Service is known to provide timely and accurate data.

Additional co-authors are Xue W. Mei, Ph.D.; Lahiru Handunnetthi, Ph.D.; Sharon Dixon, M.R.G.C.P.; Francesco Zaccardi, Ph.D.; Manu Shankar-Hari, Ph.D.; Peter Watkinson, M.D.; Kamlesh Khunti, F.R.G.C.P.; Anthony Harden, Ph.D.; Carol A.C. Coupland, Ph.D.; Keith M. Channon, M.D., F.R.C.P.; and Aziz Sheikh, M.D. Authors’ disclosures are listed in the manuscript.

The study received funding from an HDR-UK Research and Innovation grant, as well as support from the University of Oxford’s COVID-19 Research Response Fund.  

Studies published in the American Heart Association’s scientific journals are peer-reviewed. The statements and conclusions in each manuscript and do not necessarily reflect the Association’s policy or position. The Association makes no representation or guarantee as to their accuracy or reliability. The Association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific Association programs and events. The Association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers and health insurance providers and the Association’s overall financial information are available here.

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