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ARDS Due to COVID-19 Linked to Heart Damage Risk

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New data from NIH investigators show acute respiratory distress syndrome from COVID-19 infection may trigger heart inflammation in patients.

ARDS Due to COVID-19 Linked to Heart Damage Risk

Matthias Nahrendorf, MD

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Acute respiratory distress syndrome (ARDS) caused by viral infections including SARS-CoV-2 may cause inflammation of cardiac macrophages resulting in compromised heart health, according to new data from the National Institutes of Health (NIH).

Namely, NIH investigators have observed in mouse models that COVID-19 may increase the risk of heart damage without even infecting heart tissue.

“What this study shows is that after a COVID infection, the immune system can inflict remote damage on other organs by triggering serious inflammation throughout the body – and this is in addition to damage the virus itself has directly inflicted on the lung tissue,” senior author Matthias Nahrendorf, MD, PhD, professor of radiology at Harvard Medical School, said in an accompanying statement. “These findings can also be applied more generally, as our results suggest that any severe infection can send shockwaves through the whole body.”

The new findings published to Circulation today considered the effect of viral ARDS-related immune signals on cardiac macrophage subsets, systemic inflammation and overall cardiovascular health. As they noted, viral infections are closely associated with increased risk of ARDS, systemic inflammation and secondary heart issues in patients.

Nahrendorf and colleagues sought to understand whether SARS-CoV-2 infecting the heart directly was responsible for increased cardiac risks, or whether infection in a patient’s lung was severe enough to trigger changes to heart macrophages. “Lung macrophage subsets change during ARDS, but the role of heart macrophages in cardiac injury during viral ARDS remains unknown,” they noted.

The team assessed cardiac macrophage subsets through immunofluroscence histologies derived from 21 deceased patients with COVID-19 and SARS-CoV-2-associated ARDS, compared with 33 patients who died from other causes. They additionally compared the cardiac immune cell dynamics in mice followed SARS-CoV-2 infection with induced ARDS.

Investigators found that SARS-CoV-2 in humans was associated with increased total counts of cardiac macrophages, as well as a greater proportion of inflammation-promoting C-C chemokine receptor type 2 positive (CCR2+) macrophages. In the mouse models, SARS-CoV-2 and ARDS was shown to trigger “profound remodeling of cardiac resident macrophages, recapitulating the clinical expansion of CCR2+ macogrphages.”

“This was a critical question and finding the answer opens up a whole new understanding of the link between this serious lung injury and the kind of inflammation that can lead to cardiovascular complications,” Michelle Olive, PhD, associate director of the Basic and Early Translational Research Program at the NIH’s National Heart, Lung, and Blood Institute (NHLBI), said in the statement. “The research also suggests that suppressing the inflammation through treatments might help minimize these complications.”

Indeed, the investigators additionally found that treating the mice with replicant ARDSwith a TNF inhibitor resulted in reduced cardiac monocyctes and CCR2+ macrophages while preserving cardiac function, providing hope that available targeted therapies may help to reduce the risk of cardiac damage in patients with ARDS due to viral infection.

Nahrendorf stated such a treatment like a TNF inhibitor may be used preventively in COVID-19 patients with pre-existing conditions, or those identified to be at risk of severe outcomes due to SARS-CoV-2 associated ARDS.

References

  1. Grune J, Bajpai G, Ocak PT, et al. Virus-Induced Acute Respiratory Distress Syndrome Causes Cardiomyopathy Through Eliciting Inflammatory Responses in the Heart. Circulation. Published online March 20, 2024. doi:10.1161/CIRCULATIONAHA.123.066433
  2. NIH. Severe lung infection during COVID-19 can cause damage to the heart. Press release. Published March 20, 2024. https://www.nih.gov/news-events/news-releases/severe-lung-infection-during-covid-19-can-cause-damage-heart
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