Stanford Study Offers Clue to Rare Myocarditis After COVID Vaccination

Stanford scientists may be closing in on an explanation for a rare cardiac side effect experienced by a small number of people a few days after they received a COVID-19 shot. Fewer than 30 people in every million who are vaccinated experience brief chest pain and shortness of breath. The myocarditis primarily affects teenage boys and young men and has puzzled clinicians since the rollout of vaccines.

To investigate what might be happening inside the body after the shot, the researchers used human plasma, lab-grown heart tissue, modeling, and mice. In every lab model, the same thing happened: right after a shot — especially the second one — immune cells sent out a burst of two signaling proteins. Normally, they help the body fight viruses, but at unusually high levels, these cytokines, CXCL10 and interferon-gamma, seemed to put stress on heart cells.

The results of the study outlining this possible mechanism were published on Wednesday in Science Translational Medicine.

“When we block these two with the antibodies, the cardiac damage goes down,” said Dr. Joseph Wu, senior author of the study and director of the Stanford Cardiovascular Institute. “So we’re pretty confident that these two cytokines are probably two key players in terms of causing COVID myocarditis.”

The authors stress that these findings are lab results. The next step will be to run human clinical trials. They also said the results should not lead individuals to avoid Moderna or Pfizer COVID-19 shots. Myocarditis after an mRNA shot is extremely uncommon.

Cardiac risks are much more common and far more severe after a COVID-19 infection, which can inflame not only the heart but also the lungs and other organs.

The vaccine schedule may also be a factor. Some data suggest the risk of myocarditis is higher when the second dose follows within weeks of the first. That raises the possibility that spacing out doses — as Canada did early in the pandemic — may blunt the immune spikes that stress the heart.

One possible reason the condition affects young men more often is that estrogen may provide some protection. In mice, the researchers found that estrogen eased the inflammatory damage triggered by the cytokine surge. That led them to test genistein, a plant-based phytoestrogen found in soy, which similarly reduced inflammation in lab models.

“What we see here [in the Stanford study] is when we give this drug [genistein], we decrease the cardiac inflammation or the myocarditis,” said Dr. Amir Munir, a UCSF cardiologist not involved in the research. “However, we still keep the protective properties of the vaccine to protect against COVID.”

Understanding why myocarditis occurs is a first step toward designing safer mRNA vaccines. It may also lead to medication for myocarditis that arises outside of vaccination.

“We have no FDA-approved treatments for myocarditis,” Munir said. “Having models like this, where we can understand the mechanisms that drive myocarditis, allow us to think how we can specifically target inflammation to treat patients with it.”