CALIFORNIA, US – Scientists have identified a biological mechanism that helps explain why mRNA-based Covid-19 vaccines can, in rare cases, trigger heart inflammation in some adolescents and young men — a finding that could pave the way for safer vaccine designs in the future.
The research, published on December 10 in Science Translational Medicine by Stanford Medicine, shows that the vaccines can occasionally activate a specific inflammatory pathway that temporarily affects the heart muscle, a condition known as myocarditis.
Myocarditis linked to Covid-19 vaccination remains uncommon and is mostly reported among adolescent and young adult males.
Symptoms can include chest pain, shortness of breath, fever and heart palpitations, typically appearing one to three days after vaccination. Most cases are mild, resolve quickly and do not result in long-term heart damage.
Despite heightened public concern, scientists stress that the condition affects only a tiny fraction of vaccine recipients compared with the billions of doses administered worldwide.
Estimates suggest myocarditis occurs in about one in 140,000 people after a first dose and one in 32,000 after a second dose, with the highest risk — around one in 16,750 — seen in males under 30.
Covid-19 infection itself is about ten times more likely to cause myocarditis than vaccination.
Two-step immune response identified
To understand the cause, researchers analysed blood samples from vaccinated individuals, including those who developed myocarditis.
They found that mRNA vaccines can, in rare cases, trigger a two-step immune response involving the cytokines CXCL10 and interferon-gamma (IFN-γ).
Laboratory experiments showed that macrophages exposed to the vaccine produced CXCL10, which then prompted T cells to release IFN-γ.
Together, these inflammatory signals attracted immune cells into heart tissue, leading to temporary injury.
The findings were confirmed using young male mice and human cardiac spheroid models.
Crucially, when researchers blocked these cytokines, heart damage was reduced without weakening the vaccine’s ability to protect against Covid-19.
Potential pathway to safer vaccines
The team also explored ways to reduce the inflammatory response and found that genistein — a soy-derived compound with anti-inflammatory properties — significantly reduced heart injury in experimental models.
Although genistein is poorly absorbed in its natural oral form, concentrated versions showed promise in protecting heart tissue.
Researchers said similar inflammatory mechanisms may also affect other organs, including the lungs, liver and kidneys, suggesting broader applications for future therapies.
While CXCL10 and IFN-γ play a vital role in defending the body against viral infections, the study found that excessive activation can, in rare cases, be harmful to the heart.
Other vaccines have also been associated with myocarditis, though symptoms are generally milder and less frequently reported.
Vaccines remain safe, WHO says
The World Health Organisation (WHO) continues to affirm that Covid-19 vaccines are safe and effective.
Most side effects are mild and short-lived, such as pain at the injection site, fatigue, headache or mild fever. Serious adverse events, including myocarditis, remain extremely rare.
WHO maintains that the benefits of vaccination — including protection against severe illness, hospitalisation and death — far outweigh the risks, and says vaccine safety monitoring remains ongoing as new scientific evidence emerges.
The study was supported by the US National Institutes of Health and the Gootter-Jensen Foundation.
