Interferon 1 Responsible for Causing Cardiac Events During Influenza Infection, With Jeffrey Downey, PhD

Researchers at Mount Sinai have located a cellular mechanism responsible for the correlation between influenza and cardiovascular disease, according to a recent publication.1

The connection between influenza and cardiac events has long been studied, with research from 2018 determining that patients were 6 times more likely to have a heart attack in the week after receiving a flu diagnosis. Via data obtained from the Flu and Other Respiratory Viruses Research (FOREVER) cohort, investigators saw a substantial association between respiratory infections and acute myocardial infarction.2

Additionally, a study from the CDC in 2020 found that cardiac events were quite common in patients hospitalized for influenza infection. After examining >80,000 patients over 8 flu seasons, investigators found that almost 12% experienced an acute cardiovascular event. Older age, tobacco use, diabetes, and renal disease were significantly associated with increased risk as well.3

“There’s always been an appreciation that influenza is bad for the heart; if you have a large number of cardiovascular comorbidities, influenza is going to be worse,” Jeffrey Downey, PhD, a postdoctoral student at the Swirski laboratory at Icahn School of Medicine at Mount Sinai, told HCPLive in an exclusive interview. “But we provided mechanistic insight as to why this may be, showing that influenza has the capacity to leave lasting scars.”

Downey and colleagues investigated the autopsies of 35 hospitalized patients who died of influenza. With these data, they discovered that >85% had ≥1 significant cardiovascular comorbidity, including hypertension, atherosclerosis, and cardiac fibrosis. Additionally, the team uncovered the mechanism causing cardiac damage.1

Briefly after infecting the lungs, the influenza virus targeted a circulating myeloid pro-dendritic cell 3 (pro-DC3), which expressed high concentrations of chemokine receptor CCR2. The heart attracts pro-DC3 due to its production of CCL2 – after entering the heart, the virus leaves pro-DC3 and infects cardiomyocytes to trigger production of type 1 interferon (IFN-1). In turn, IFN-1 receptors engaging with cardiomyocytes cause tissue damage and compromise heart function.4

Based on mouse models, the team developed a hypothetical treatment involving the dampening of IFN-1 receptors exclusively in cardiomyocytes. This protected the heart and preserved anti-viral immunity in the lung. Downey and colleagues hypothesized that a systemic delivery of modified RNA therapy to the heart’s muscle cells would modulate the IFN-1 signaling pathway.1

Although this study is purely hypothesis-generating, and actual attempts at treatment are far in the future, Downey and colleagues are actively researching the use of a safe and effective systemic delivery method of this modified RNA therapeutic directly into the heart’s muscle cells rather than a direct injection used in the proof-of-concept study introducing the mod-RNA pathway. Additionally, further investigation is being conducted into pro-DC3 itself, aiming to determine the reason for its susceptibility to influenza and whether this is mirrored across other infections like SARS or COVID-19.1

“Moving forward, something we should always be paying attention to is that getting through influenza may not be the only goal,” Downey said. “The main thing we should be focusing on is still prevention and mitigation of infection, but in those with high risk, we should potentially be looking at some immunotherapies that can dampen immunological pathways activated specifically in the heart.”

Editor’s Note: Downey reports no relevant disclosures.

References

1. Mount Sinai Hospital. Mount Sinai scientists uncover link between influenza and heart disease. Eurekalert. February 9, 2026. Accessed February 12, 2026. https://www.eurekalert.org/news-releases/1115515

2. Kwong JC, Schwartz KL, Campitelli MA, et al. Acute myocardial infarction after laboratory-confirmed influenza infection. New England Journal of Medicine. 2018;378(4):345-353. doi:10.1056/nejmoa1702090

3. Chow EJ, Rolfes MA, O’Halloran A, et al. Acute cardiovascular events associated with influenza in hospitalized adults. Annals of Internal Medicine. 2020;173(8):605-613. doi:10.7326/m20-1509

4. Downey J, Oliveira-Coelho A, Kiss MG, et al. Influenza hijacks myeloid cells to inflict type-I interferon-fueled damage in the heart. Immunity. Published online February 9, 2026. doi:10.1016/j.immuni.2025.12.011