For years, doctors have observed a troubling pattern. Heart attacks tend to rise during flu season. Until now, the biological explanation behind that connection was not fully understood. New research from scientists at the Icahn School of Medicine at Mount Sinai is shedding light on exactly how severe influenza infections can harm the heart and potentially trigger serious cardiovascular events.
The findings could open the door to new treatments and reinforce the importance of flu prevention, especially for people with existing heart conditions.
The study was led by Filip Swirski, PhD, Director of the Cardiovascular Research Institute at the Icahn School of Medicine at Mount Sinai, along with lead author Jeffrey Downey, PhD, and collaborators including Lior Zangi, PhD. Their work was published in the journal Immunity and combines human tissue analysis with laboratory experiments and animal models.
Swirski explained the significance of the research, saying, “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.”
What Scientists Found About Severe Flu and the Heart
The researchers examined tissue samples from hospitalized patients who died from influenza. They discovered that the virus does not only affect the lungs. In severe cases, it can indirectly damage the heart through immune system activity.
A specific type of immune cell called pro-dendritic cell 3 becomes infected in the lungs. Instead of stopping the virus, these cells travel through the bloodstream to the heart, carrying the infection with them.
Once inside the heart, the immune cells trigger the production of a powerful inflammatory protein known as type 1 interferon. This protein causes heart muscle cells, called cardiomyocytes, to die, which weakens the heart’s ability to pump blood effectively.
Downey described this process vividly, saying, “The pro-dendritic cell 3 acts as the Trojan horse of the immune system during influenza infection, becoming infected in the lung, trafficking the virus to the heart, and disseminating it to cardiomyocytes.”
The Mount Sinai team studied autopsies from 35 patients who died after being hospitalized with influenza. More than 85 percent of these patients had at least one major cardiovascular condition, such as hypertension. Many had multiple conditions, including atherosclerosis and cardiac fibrosis.
These findings highlight that people with underlying heart disease are especially vulnerable when they develop severe influenza.
Laboratory experiments also produced encouraging results. Researchers tested a modified mRNA therapy designed to control the interferon pathway responsible for heart damage. In animal models and test systems, the treatment reduced signs of cardiac injury, lowered troponin levels, and improved heart pumping function as measured by left ventricular ejection fraction.
Downey noted, “By injecting a novel mod-RNA therapeutic that modulates the IFN-1 signaling pathway, we reduced levels of cardiac damage and improved cardiac function.”
The newly discovered mechanism centers on immune system overreaction rather than direct viral destruction alone.
Normally, interferon proteins help the body fight infections. But in this case, excessive interferon production in the heart leads to unintended collateral damage. The immune response that is meant to protect the body instead harms heart tissue.
This discovery helps explain why influenza can increase the risk of heart attacks and other cardiovascular events during and shortly after infection.
Researchers believe the study offers hope for new therapies that could protect the heart during severe infections.
Swirski emphasized the potential impact, stating, “These findings offer great promise for the development of new therapies, which are desperately needed since there are currently no viable clinical options to prevent cardiac damage.”
He also pointed to the broader implications for infectious disease treatment, noting that pathogens are constantly evolving and medical strategies must evolve with them.
Why Vaccination and Prevention Matter
The research also suggests that flu vaccination may provide protection not only against infection but also against related heart complications. By preventing severe illness, vaccination could reduce the chances of immune driven cardiac damage.
Scientists are now working on improved ways to deliver the experimental mRNA therapy to heart tissue safely and effectively. They are also studying why the pro-dendritic cell 3 is particularly susceptible to influenza and how it might be harnessed for protective purposes.
The discovery changes how experts view influenza. It is not simply a respiratory illness. In severe cases, it can trigger a cascade of immune events that directly damage the heart.
By identifying the cellular pathway involved, researchers have taken a major step toward preventing one of the most dangerous complications of the flu.
