How flu infections trigger heart damage

Researchers from Mount Sinai have uncovered a possible explanation for why a flu infection can lead to heart disease. They’ve shown from work with mouse models and human data how the immune system that is triggered with influenza A can damage the heart.

“We have known for years that the frequency of heart attacks increases during flu season, yet outside of clinical intuition, scant evidence exists of the underlying mechanisms of that phenomenon,” Filip Swirski, Ph.D., director of the Cardiovascular Research Institute at the Icahn School of Medicine at Mount Sinai, said in a news release.

The work of Swirski and his colleagues has shed light on a specific pathway, the antiviral cytokine type 1 interferon, a factor that leads to the damage of the heart following a severe flu infection. These findings, published recently in Immunity, offer promise of new therapies to prevent this damage, Swirski said.

Influenza A is responsible for an estimated 1 billion infections globally each year. Although most infections resolve, some can become severe. During the 2023-2024 flu season, approximately 28,000 Americans died from the flu.

Swirski and his colleagues showed that in mice shortly after infection, the influenza virus infects a type of white blood cell, pro-dendritic cell 3. The pro-dendritic cell 3 expresses high concentrations of the chemokine receptor CCR2. In the heart, pro-dendritic cell 3 infects cardiomyocytes, which have a primary role in the contraction of the heart muscle, and produce large amounts of type 1 interferon. Type 1 interferon is a family of cytokines that the immune system produces to fight the influenza virus. In the heart, however, type 1 interferon damages cardiomyocytes and compromises heart function.

“Pro-dendritic cell 3 acts as a ‘Trojan horse’ of the immune system during influenza infection,” said Jeffrey Downey, Ph.D., a member of Swirski’s laboratory and lead author of the study.

Additionally, Swirski and his colleagues studied autopsies of 35 patients who had died from flu. They found that 85% had at least one cardiovascular comorbidity, such as hypertension, and the majority had multiple comorbidities, including atherosclerosis and cardiac fibrosis. These patients are more susceptible to the heart-damaging consequences of influenza infection. Researchers found in the autopsies that patients with comorbidities had more pronounced cardiac damage.

“The data suggest that the most severe manifestations of influenza infection occur in people with preexisting cardiovascular disease,” researchers wrote. “The damage to the heart is not, strictly speaking, the result of the infection… Rather, it is the festering anti-viral IFN-1 [type 1 interferon] host response against cardiomyocytes that appears to be essential.”

Researchers stress that there are still several unanswered questions, including how the virus is transferred from monocytes to cardiomyocytes and why the heart attracts pro-dendritic cell 3, as well as whether the data gathered here can be clinically translated for a possible treatment. Swirski and his team are collaborating with Lior Zangi, Ph.D., associate professor of Medicine and Genetics and Genomic Sciences, at the Icahn School of Medicine at Mount Sinai, to develop a possible mRNA therapeutic to reduce the risk of cardiac damage.

The study was supported by grants from the National Heart, Lung, and Blood Institute and the Charles H. Revson Foundation.