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The overall risk of myocarditis – inflammation of the heart muscle – is substantially higher immediately after being infected with COVID-19 than it is in the weeks following vaccination for the coronavirus, a large new study in England shows.

The of nearly 43 million people was published Monday in the ľ¹ÏÖ±²¥ journal Circulation.

"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," the study's lead author, Martina Patone, said in a news release. She is a statistician at the University of Oxford Nuffield Department of Primary Health Care Sciences in 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," Patone said.

Myocarditis is the inflammation of the middle layer of the heart muscle wall, known as the myocardium. It is uncommon and typically triggered by a viral infection. Myocarditis can weaken the heart muscle as well as the electrical system that keeps the heart pumping normally. The condition may resolve on its own or with treatment, or it may lead to lasting heart damage.

Previous research from around the world, including reports from the Centers for Disease Control and Prevention, has shown a potential increased risk of myocarditis after receiving an mRNA COVID-19 vaccine.

In the new study, researchers analyzed records from England's National Immunization database for nearly 43 million people 13 or older who had received at least one dose of a COVID-19 vaccine between Dec. 1, 2020 and Dec. 15, 2021. More than 21 million had received three doses of the vaccine – the initial two-shot regimen plus a booster. Nearly 6 million tested positive for COVID-19 either before or after receiving a vaccine. During the one-year study period, 2,861 people – or 0.007% – were hospitalized or died with myocarditis.

The analysis showed people infected with COVID-19 before receiving a vaccine were 11 times more at risk for developing myocarditis within 28 days of testing positive for the virus. But that risk was cut in half if a person was infected after receiving at least one dose of a COVID-19 vaccine.

The risk for myocarditis increased after receiving the first dose of the AstraZeneca vaccine, and after a first, second and booster dose of the Pfizer or Moderna vaccine. But the risk of myocarditis associated with the vaccine was lower than the risk associated with COVID-19 infection before or after vaccination – with one exception. Men under 40 who received a second dose of the Moderna vaccine had a higher risk of myocarditis following vaccination. The Pfizer and Moderna mRNA vaccines are available in the U.S.

"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," co-author Nicholas Mills said in the release. Mills is a professor and the Butler British Heart Foundation Chair of Cardiology at the University of Edinburgh in Scotland. "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."

For example, women 40 and older receiving a first or third dose of the Pfizer vaccine had a respective three and two extra cases of myocarditis per 1 million women vaccinated. But there were an estimated 51 extra cases of myocarditis associated with COVID-19 infection before vaccination.

Among men under 40, there were an estimated four extra cases of myocarditis associated with the first dose of the Pfizer vaccine and 14 extra cases with the first dose of the Moderna vaccine for every 1 million men vaccinated. That risk rose with the second dose for all three vaccines studied and was highest for Moderna's, which had an additional 97 myocarditis cases per 1 million. For unvaccinated men under 40 with COVID-19, there were 16 additional myocarditis cases per million.

"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," study co-author Julia Hippisley-Cox said in the release. She is a professor of clinical epidemiology and general practice at the University of Oxford.

"The SARS-CoV-2 virus continues to shift, and more contagious variants arise," she said. "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."

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