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Small study points to possible cause of myocarditis following mRNA vaccination in young men

Researchers observed elevated levels of immune molecules that, in rare cases, could trigger inflammation in the heart.
A healthcare worker administers a dose of the Pfizer-BioNTech Covid-19 vaccine to a teenager in Philadelphia, Pa.,
A health care worker administers a dose of the Pfizer Covid vaccine to a teenager in Philadelphia in 2021.Hannah Beier / Bloomberg via Getty Images file

An overactive immune response to the mRNA Covid vaccines may be the culprit in rare cases of heart inflammation seen in some young men after they receive the shot, a small study published Friday in the journal Science Immunology suggests. 

The study was based on 23 patients ages 13 to 21 who developed myocarditis after their second dose of either the Pfizer-BioNTech or Moderna vaccine. An analysis of blood samples from nine of these patients — all of whom had gotten Pfizer — found elevated cytokine levels. 

Cytokines help coordinate the body’s immune response to pathogens, including bacteria, viruses and other invading microbes, as well as vaccines. But at too high levels, cytokines can trigger a rapid expansion of white blood cells that are capable of causing inflammation.

That’s what appears to be happening in some young men who develop myocarditis or pericarditis — two types of heart inflammation — after getting the Covid vaccine.

“It’s a little bit of a double-edged sword,” said senior study author Carrie Lucas, an associate professor of immunobiology at Yale University School of Medicine. The vaccinated individuals mount a strong immune response, she said, but that response is also causing “cells to overreact and cause tissue inflammation.”

The researchers found no evidence that antibodies that target the virus’s spike protein played a role in heart inflammation. Previous research had suggested that such antibodies may also bind to proteins in the heart tissue, causing inflammation. 

“Our findings point to inflammation-induced heart damage,” said Yale immunologist Akiko Iwasaki, another author on the study, “and rule out elevated levels of anti-spike antibodies in patients.”

Despite the study's small size, Dr. Ofer Levy, the director of the Precision Vaccines Program at Boston Children's Hospital, was optimistic about the findings.

The research, he said, could provide insight into developing treatments for vaccine-induced myocarditis. There are currently no drugs for the condition, though most people fully recover on their own.

“The better we understand what the vaccine is doing, the better we can build a better mousetrap,” said Levy, who was not involved in the study.

Dr. Leslie Cooper, the chair of the cardiology department at the Mayo Clinic in Rochester, Minnesota, said the study, though small, is “an important contribution to our understanding of the mechanisms” of vaccine-induced myocarditis in young men. Cooper was also not involved with the new research.

The findings, he said, suggest that one potential treatment for the inflammation could be a drug that targets the body's excess immune response after vaccination.

How common is myocarditis?

Myocarditis (inflammation of the heart muscle) or pericarditis (inflammation of the lining of the heart) following Covid vaccination is very rare, according to the Centers for Disease Control and Prevention. As of March 2, there have been 376 confirmed cases of myocarditis in children ages 12 to 15 after more than 25 million vaccine doses were administered, according to the agency. In teens ages 16 and 17, there have been 316 confirmed cases after more than 14 million vaccine doses were administered.

Most cases that do occur are in male teens and young adults, usually after the second dose of a primary series of either the original version of the Pfizer-BioNTech or Moderna vaccine. Those vaccines, however, are no longer in use in the U.S. after the Food and Drug Administration switched to the updated bivalent formula and moved away from a two-dose primary series. A CDC study published in January that looked at children ages 5 to 11 found no cases of myocarditis following a booster dose of the bivalent vaccine.

The patients included in the new analysis had not previously had Covid before they were vaccinated. All experienced symptoms of heart inflammation one to four days after their second dose of the Pfizer vaccine.

Although the analysis only looked at the Pfizer vaccine, Levy said it’s reasonable to extrapolate the findings to the Moderna vaccine, which also uses mRNA technology.

Other vaccines and viral infections can also cause myocarditis, Iwasaki said. Myocarditis has been reported in a small number of people who received the Novavax Covid vaccine, which doesn't use mRNA technology. And Covid itself is more likely to cause heart inflammation than mRNA vaccination. 

While the study helps explain what is driving the inflammation in people who got an mRNA vaccine, a number of questions remain. 

The findings don’t explain why the inflammation only appears to affect the heart and not other organs, Lucas, the senior study author, said. Nor do they explain why the condition affects men more than women.

The study also doesn’t give insight into what long-term health problems — if any — people may experience following vaccine-induced myocarditis, which is often milder than the kind caused by viral or bacterial infections. 

Pfizer and Moderna are both conducting long-term clinical trials to track possible health issues in the years following a diagnosis of vaccine-associated heart problems in teens and young adults. Some people who’ve developed myocarditis after a viral infection can develop scarring in the heart, reducing its ability to pump blood and circulate oxygen around the body. 

Lucas said the findings support earlier recommendations from the CDC for males ages 12 to 39 to wait up to eight weeks before getting their second dose of the primary series as a way to reduce the risk of myocarditis.

She added that the study could also help to identify biomarkers that could measure whether someone might be at risk for heart inflammation following vaccination.

The researchers said they hope larger trials will confirm their findings, although they noted that finding more participants could be difficult as the condition is very rare. 

“We were really motivated to understand this rare vaccine-associated myocarditis to hopefully make it even more rare in the future,” Lucas said.

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