Stanford Study Links Immune Proteins CXCL10 and IFN-Gamma to Post-Vaccine Myocarditis

An interdisciplinary Stanford study, published in Science Translational Medicine, identifies two immune proteins that may drive rare myocarditis after mRNA COVID-19 vaccination, particularly among young men. The incidence is about 1 in 140,000 after the first dose and about 1 in 32,000 after the second dose, with risk rising to roughly 1 in 16,750 for males 30 and younger. Symptoms commonly include chest pain, shortness of breath, fever and palpitations, and elevated cardiac troponin levels can indicate heart muscle injury.

Researchers from Stanford Cardiovascular Institute and The Ohio State University analyzed blood samples from vaccinated people, some with myocarditis and some without. They found two proteins, CXCL10 and IFN-gamma, released by immune cells, that amplify inflammation. The study team says these two are the major drivers of myocarditis, with Wu, the director of the Stanford Cardiovascular Institute, explaining that these cytokines are essential for fighting viruses but can become toxic in large amounts.

In tests using mouse and human heart tissue models, high levels of these cytokines produced signs of heart irritation similar to mild myocarditis. The researchers showed that blocking these two cytokines reduced heart damage in the models without shutting down the overall immune response. The study also noted that genistein, a compound found in soybeans, reduced inflammation in laboratory tests, though it has not yet been tested in humans.

Although vaccines have an excellent safety record, rare cases of myocarditis can lead to hospitalization or serious illness. The researchers note that a COVID-19 infection is about 10 times more likely to cause myocarditis than vaccination with mRNA vaccines. They added that mRNA vaccines remain an essential tool against COVID-19, and the findings offer a potential path to make future vaccines safer without reducing benefits.

Limitations include that most data came from experimental systems, such as mice and human cells in the lab, which may not fully reflect clinical cases. Clinical studies will be needed to confirm whether targeted therapies that block CXCL10 and IFN-gamma are safe and effective. The authors stressed that the findings do not change current vaccination guidance and that this work is a preclinical step.

Funding came from the National Institutes of Health and the Gootter-Jensen Foundation. The researchers say the findings could point to ways to prevent or mitigate myocarditis in people at higher risk while maintaining the protective benefits of vaccination, but more work is required before any new treatment becomes available.