Stanford study explains why COVID vaccine can trigger myocarditis, especially in younger men

A Stanford-led study provides new clues about why the COVID-19 vaccine can trigger myocarditis, a rare inflammation of the heart, particularly in younger men. The researchers focused on two immune proteins, CXCL10 and IFN-gamma, that appear to be elevated in people who develop vaccine-associated myocarditis. The work, conducted with Ohio State University, analyzed blood samples from vaccinated people with and without myocarditis to understand the immune pathway behind the condition.

Myocarditis after vaccination remains very rare. In the study's numbers, myocarditis occurs in about 1 in 140,000 people after the first dose and about 1 in 32,000 after the second dose. Among men 30 and younger, the rate rises to about 1 in 16,750. Symptoms can include chest pain, shortness of breath, fever and palpitations, typically appearing one to three days after vaccination. A commonly used lab marker is elevated cardiac troponin, which signals heart muscle injury. Most patients recover with monitoring, and there is no vascular blockage as in a classic heart attack.

The study aimed to uncover the cause of the myocarditis signal. By examining blood from vaccinated people with and without myocarditis, the researchers found that those who developed myocarditis had elevated levels of two cytokines, CXCL10 and IFN-gamma, produced by immune cells. These molecules can amplify inflammation, and the team says they are major drivers of the condition. The researchers note that while these cytokines are necessary for fighting infections, excessive levels can become toxic and contribute to tissue injury.

In mouse and human heart tissue models, high levels of these cytokines led to signs of inflammation similar to mild myocarditis. Importantly, the researchers found that targeted blocking of CXCL10 and IFN-gamma reduced heart damage in these experimental systems without shutting down the entire immune response to the vaccine. The authors say this points to a possible future approach to prevent or treat myocarditis in people at higher risk while keeping the benefits of vaccination intact.

In addition to the cytokines identified, the researchers noted that genistein, an estrogen-like compound found in soybeans, reduced inflammation in lab tests. That finding has not yet been tested in people and remains exploratory. The authors caution that the work is preclinical and further clinical studies are needed to confirm whether targeted interventions are safe and effective in humans. The researchers stressed that vaccines remain a crucial tool against COVID-19, given the much higher risk of myocarditis from infection than from vaccination.

The study was funded by the National Institutes of Health and the Gootter-Jensen Foundation. The research team also noted that most data came from experimental systems, which cannot fully capture how myocarditis develops and resolves in real patients. Clinicians say that the findings could guide future clinical trials but do not change current vaccination guidance.