SARS-CoV-2 can infect coronary arteries and trigger heart attack, stroke, study suggests

Patient being defibrillated

Vadym Terelyuk / iStock

SARS-CoV-2 can directly infect the arteries of the heart, inflaming the fatty plaque inside and raising the risk of heart attack and stroke, suggests a small study published yesterday in Nature Cardiovascular Research.

A New York University-led team obtained 27 samples of coronary arteries and fatty, or atherosclerotic, plaque at autopsy from eight patients who died of COVID-19. They also infected arterial and plaque cells, including macrophages and foam cells, with SARS-CoV-2; the cells were extracted from healthy patients from May 2020 to May 2021, a period dominated by the wild-type virus.

Macrophages are white blood cells the immune system sends to help clear the virus. They also help sweep cholesterol from the arteries, and when they are overloaded with cholesterol, they change into another kind of macrophage called a foam cell. Foam cells ingest low-density lipoprotein (LDL, or "bad") cholesterol lining blood vessel walls.

The average patient age was 69.6 years, six of the eight patients were men, and all had evidence of coronary artery disease and at least three cardiovascular risk factors, including high blood pressure (8 patients), overweight or obesity (7), high cholesterol levels (7), type 2 diabetes (6), and chronic kidney disease (4). Some had a history of heart attack (1) or ischemic stroke.

The researchers noted that while heart attack and stroke can occur after other respiratory viral infections such as the flu, COVID-19 patients are at more than seven times the risk for stroke than flu patients, and the risk of heart attack and stroke stays elevated for up to 1 year post-infection.

Cytokines promote formation of more plaque

The researchers found SARS-CoV-2 viral RNA in coronary atherosclerotic plaques in all patients—regardless of the extent of plaque buildup, although viral replication was greatest in early-stage lesions that progress to advanced plaques. SARS-CoV-2 gravitated more toward the arterial plaques than toward the fat surrounding the arteries.

The team also showed that the virus infects macrophages at a higher rate than other arterial cells. Cholesterol-filled foam cells were the most vulnerable type of cell to infection and couldn't readily clear the virus, which the authors said suggests that foam cells store SARS-CoV-2 in atherosclerotic plaque. Patients with more plaque, and therefore more foam cells in their arteries, may be at elevated risk for severe COVID-19, the authors said.

The SARS-CoV-2–infected macrophages and foam cells released cytokines, small proteins that increase inflammation and promote the formation of even more plaque, which can break off and cause ischemic cardiovascular events such as heart attack and stroke. The researchers said this finding could explain why some COVID-19 patients with underlying plaque buildup experience cardiovascular complications long after they were infected.

Three patients had been diagnosed as having myocardial ischemia, or partial or complete blockage of a coronary artery from plaque buildup, in the hospital; one patient had a stroke, and four patients had a greater than 50% coronary artery blockage at autopsy.

Our data establish that SARS-CoV-2 infects coronary vessels, inducing plaque inflammation that could trigger acute cardiovascular complications and increase the long-term cardiovascular risk.

Except for a patient who died before hospital admission, all patients were hospitalized for, on average, 17.6 days. One patient died of a heart attack while hospitalized for the third time.

Results may not apply to younger people, other strains

"SARS-CoV-2 induced a robust inflammatory response in cultured macrophages and human atherosclerotic vascular explants with secretion of cytokines known to trigger cardiovascular events," the researchers wrote. "Our data establish that SARS-CoV-2 infects coronary vessels, inducing plaque inflammation that could trigger acute cardiovascular complications and increase the long-term cardiovascular risk."

In a press release from the National Heart, Lung, and Blood Institute (NHLBI; the study sponsor), Michelle Olive, PhD, acting associate director of the Basic and Early Translational Research Program at NHLBI, said, "Since the early days of the pandemic, we have known that people who had COVID-19 have an increased risk for cardiovascular disease or stroke up to one year after infection. We believe we have uncovered one of the reasons why."

Olive was not involved in the study.

"This is just one more study that demonstrates how the virus both infects and causes inflammation in many cells and tissues throughout the body," she added. "Ultimately, this is information that will inform future research on both acute and Long COVID.”

The researchers cautioned that the findings can't be generalized to younger, healthy people or those infected with strains that superseded the wild-type virus.


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