mRNA-based COVID-19 vaccines have been proven safe and effective against the deadly pandemic. However, like all medical interventions, they have some risks. One is that a very small number of vaccinated people develop inflammation in and around their heart—conditions called myocarditis, pericarditis, or a combination of the two, myopericarditis. These side effects usually strike men in their teens and early 20s, usually after the second dose of the vaccine. Fortunately, the conditions are usually mild and resolve on their own.
Because of the rarity and mildness of these conditions, studies have concluded, and experts agree that the benefits of vaccination outweigh the risks—teenage males and young adults should be vaccinated. In fact, they are more likely to develop myocarditis or pericarditis from a COVID-19 infection than from a COVID-19 vaccination. According to a large 2022 study led by researchers at Harvard University and the Centers for Disease Control and Prevention, the group with the highest risk of myocarditis and pericarditis after vaccination—males aged 12 to 17-found 35.9 cases per 100,000 (0.0359 percent) after a second dose of the vaccine, while the rate almost doubled after infection with COVID-19 in the same age group, with 64.9 cases per 100,000 (0.0649 percent)
However, the conditions are a bit of a puzzle. Why do so few get this complication after vaccination? Why does it seem to only affect the heart? How does damage occur? And what does it all mean for the many other mRNA-based vaccines currently being developed?
A new study in Science Immunology provides some new insight. The study, led by researchers at Yale University, took a deep dive into the immune responses among 23 people—mostly boys and ranging in age from 13 to 21—who developed myocarditis and/or pericarditis. after vaccination.
Explore the possibilities
Since the rare event was first noticed, immunologists and other experts have hypothesized that the vaccine may trigger a number of aberrant immune responses that would explain the fluttering hearts, such as in an autoimmune response or an allergic reaction. And a new study rules some of it out.
Researchers used blood samples from a subset of patients to look at immune responses and compared them with those from matched vaccinated controls. They first compared antibodies against SARS-CoV-2 and found no evidence of “overexuberant” or enhanced antibody responses against the virus that may explain myocarditis and pericarditis. Anti-SARS-CoV-2 antibody responses in the two groups were similar, with patients with heart conditions having similar, if not slightly blunted, antibody responses.
The researchers next checked for auto-antibodies, that is, the antibodies stimulated by the vaccine that are wrongly directed against a person’s body rather than the virus. They used an established screening tool to scan for autoantibodies against more than 6,000 human proteins and molecules. The researchers identified more than 500 of the tests related to heart tissue. They found no relative increase in the number of autoantibodies compared to controls, suggesting that an autoimmune response is unlikely.
The researchers then took a broad, unbiased approach to compare the profiles of immune responses in patients and controls. They found distinct immune signatures between the two groups, with patients showing higher levels of immune signaling chemicals (cytokines) linked to acute, systemic inflammation. And those cytokines are accompanied by a corresponding increase in inflammatory cellular responses, particularly cytotoxic T cells. In addition, the gene expression profiles of those T cells showed the potential to cause cardiac tissue damage.
Together, the researchers concluded that the most likely explanation is that in these rare cases of myocarditis and pericarditis, the vaccine is spurring a general, strong inflammatory response that leads to the heart tissue inflammation and damage.
“The immune systems of these individuals are somewhat altered and produce more cytokines and cellular responses,” senior study author Carrie Lucas, professor of immunobiology at Yale, said in a statement. .
While the study offers a possible answer to the “how,” it doesn’t answer all the questions—including some of the whys, such as why young men? And why the heart? Researchers have noted that young men, especially in their late teens, are the most common group to develop myocarditis in general, from any cause. Medical experts do not know why this is the case, but hypothesize that it is due to a combination of environment, genetics, and hormones, especially testosterone. As for why the heart seems to be unusually damaged, co-author Akiko Iwasaki, also a professor of immunobiology at Yale, speculates that it may be because the heart is constantly working and has limited potential for regeneration. -or the tissue, which makes it. more susceptible to inflammation.
Finally, it remains unclear what exactly in the vaccine ignites the intensified inflammatory response to lipid nanoparticles in vaccines carrying SARS-CoV-2 mRNA or the SARS-CoV-2 mRNA itself. Preliminary evidence suggests that both substances may stimulate inflammatory responses on their own. The authors hypothesize that the two components may work together to produce the exaggerated response, but researchers need more data and research to understand this and further optimize the vaccines’ safety profile. .
For now, the finding that an inflammatory response is behind the cases will help guide treatment and prevention. A Canadian study from last year suggested that extending the interval between doses of the mRNA vaccine could reduce the likelihood of myocarditis and pericarditis in young men. However, the new study may provide some relief when it does — inflammation that resolves on its own is less of a difficult-to-treat autoimmune response.