17 January 2022

Changes in the blood may underlie cardiac thrombosis in COVID-19 patients, according to a new US study.

Researchers at Yale University, New Haven, and Brigham and Women’s Hospital, Boston, examined tissue samples of hearts from patients who died early in the pandemic. While they found expected thromboses within heart vessels, they also identified there were no changes in the endothelial cells lining the heart that are typically observed in thromboses.

Instead, they found hypercoagulability of the blood caused by activated neutrophils. Their findings are published in The American Journal of Pathology.

Lead investigator Dr Jordan Pober, from the Yale University School of Medicine’s Department of Immunobiology, said: “My laboratory has a long history of defining endothelial cell alterations that produce pathologies, including thrombosis, and we expected to confirm the widely held assumption that local endothelial cell alterations were responsible for thrombosis of the cardiac vessels in COVID-19 patients.

“Instead, we found that the cardiac thrombi contained neutrophils that expressed changes known to promote coagulation, including changes that are associated with cell death and inflammation.”

Dr Pober and his colleagues examined heart tissue from seven patients who died from COVID-19, before anticoagulation treatment was commonly administered.

These samples were compared to tissue from 12 controls who did not die from COVID-19, six of whom had cardiac disease.

Thrombosis was the most common pathological finding in the COVID-19 group, with a greatly elevated frequency of microthrombi and number of macrothrombi compared to the negative controls.

Despite the thrombosis in the COVID-19 group, there was no evidence of myocyte death or acute inflammation typically associated with myocardial infarction.

When the researchers examined the heart vessels for signs of endothelial cell injury, they failed to find endothelial changes at sites of thrombosis.

Instead, they saw that the cardiac thrombi in four of the six COVID-19 patients contained neutrophils that expressed procoagulant changes in the blood, such as citrullination of histones associated with formation of neutrophil extracellular traps (NETs).

“Our data challenge the view that alterations in the heart vessel wall are the primary cause of COVID-19 cardiac thrombosis,” said Dr Pober.

“Current treatments of severe COVID-19 include anticoagulation, but the best strategy is still not clear. In light of our findings, reducing neutrophil responses could be an important target for therapeutic intervention.”

Dr Peter Libby, a cardiologist and vascular biologist at Boston’s Brigham and Women’s Hospital and the Harvard Medical School, added: “The finding of neutrophil involvement in the smaller blood vessels that course through the heart muscle in COVID-19 extends our understanding of cardiac injury that we often see in patients with severe SARS-CoV-2 infection.”

Source:

Johnson JE, McGuone D, Xu ML, Jane-Wit D, Mitchell RN, Libby P, and Pober JS (2022) “Coronavirus Disease 2019 (COVID-19) Coronary Vascular Thrombosis: Correlation with Neutrophil but Not Endothelial Activation.” American Journal of Pathology, doi: 10.1016/j.ajpath.2021.09.004

Link: https://ajp.amjpathol.org/article/S0002-9440(21)00429-6/fulltext

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