What causes myocarditis in boys and young men after COVID vaccination? Study offers answers.

A new study may partly explain what's driving rare cases of heart inflammation, called myocarditis, in some young people who have gotten repeat doses of the mRNA COVID-19 vaccines.

The risk of developing vaccine-related myocarditis is extremely low, affecting fewer than 20 people per 1,000,000 vaccinations, according to the National Institutes of Health. Researchers at the Yale School of Medicine studied 23 participants who developed the heart condition after their second dose of COVID-19 vaccine to learn how it developed in these few cases. Authors say the study's small sample size is a testament to the condition's rarity.

“We were really motivated to understand this rare vaccine-associated myocarditis to hopefully make it even more rare in the future,” said co-lead author Carrie Lucas, associate professor of immunobiology at Yale School of Medicine.

After running a series of tests, Yale scientists discovered myocarditis may likely be caused by an overreaction from the body's natural immune system — and not from antibodies induced by COVID-19 vaccines, according to the study published Friday in Science Immunology.

Experts say the findings not only provide a clearer picture of how a small number of people react to the vaccine, but it can also help future research into who might develop the condition and more targeted therapies.

What is myocarditis? What were symptoms after COVID vaccination?

Myocarditis is inflammation of the heart muscle, according to the Centers for Disease Control and Prevention.

While severe cases can damage the heart and cause heart failure, cases of COVID vaccine-related myocarditis have typically been mild in nature, said Dr. Donald Lloyd-Jones, former president of the American Heart Association and Eileen M. Foell professor of heart research at Northwestern University’s Feinberg School of Medicine in Chicago.

"While we can see over time some scar tissue form in the heart, we can see that people can get back to doing what they do, like getting back to sports" within a month, he said.

Yale researchers found common symptoms among study participants included:

• Chest pain
• Palpitations
• Fever
• Shortness of breath
• Headaches
• Muscle pain
• Fatigue
• Nausea
• Heavy sweating
• Congestion

Who was affected by myocarditis?

The CDC says cases of myocarditis most frequently occur in teens and young adult males within seven days after receiving the second dose of an mRNA vaccine.

Yale researchers said their study further confirmed this as 87% of their participants were male and ages ranged from 13 to 21, with the average age falling around 16 years old.

How to treat vaccine-related myocarditis

If you experience any symptoms, experts say it's important to see a doctor. Most cases of vaccine-related myocarditis have been mild and resolved on its own, but health care providers have also been treating patients with steroids or non-steroidal anti-inflammatory drugs, or NSAIDs.

Myocarditis and COVID vaccine: What researchers learned

Through various testing, study authors sought to find out if vaccine-related myocarditis may be caused by four different mechanisms:

• An allergic reaction: Researchers tested whether the myocarditis could be due to hypersensitivity, or an allergic reaction, to the vaccine. But an analysis showed the pathology was not consistent with other allergic reactions and the scientists ruled out this theory.
• Vaccine-induced antibodies: Some theorized the COVID-19 vaccine could illicit such a strong immune response that the body would produce an overabundance of antibodies that could affect the heart. But antibody levels in study participants were consistent with levels in people who didn't develop myocarditis, so this was also ruled out.
• Heart-specific antibodies: Another theory was that the vaccine may produce "heart-specific" antibodies that could attack the virus as well as the heart. But researchers ruled this out when they didn't find any evidence of such antibodies in the body.
• An overreaction of the innate immune system: Bingo! Yale scientists discovered increased chemical signaling, called cytokine signaling, that may have overactivated tissue-damaging white blood cells. This shows vaccine-related myocarditis may be caused by the body's natural immunity and not adaptive immunity induced by the vaccine. It also suggests the heart may not be directly targeted but could just be an "innocent bystander," Lloyd-Jones said.

Study authors speculate this overreaction could be triggered by a number of factors that could relate to the vaccine but more research is needed to understand which factors and why. In the meantime, studies show people who are unvaccinated and contract COVID-19 are still more at risk of developing myocarditis compared to vaccine-related cases, and the vaccine continues to be important in preventing severe disease and transmission.

"This article helps us understand the mechanism by which this is happening but it doesn’t change what we know: That this is a rare complication, uniformly self-limited and very manageable and you still need to get the vaccine," Lloyd-Jones said.

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Follow Adrianna Rodriguez on Twitter: @AdriannaUSAT.

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