Research funded by the National Institutes of Health (NIH) found that SARS-CoV-2 can directly infect coronary artery tissue and increase inflammation in atherosclerotic plaques, which may be responsible for the increased risk of heart attack and stroke after COVID-19. In severe cases, a strong inflammatory response occurs throughout the body, which may contribute to the increased risk. But it's unclear whether the SARS-CoV-2 virus that causes COVID-19 also directly affects blood vessels.
To find out, a research team funded by the National Institutes of Health and led by Dr. Chiara Giannarelli of New York University School of Medicine analyzed coronary artery tissue samples from eight people who died from COVID-19 between May 2020 and May 2021. The findings were recently published in the journal Nature Cardiovascular Research.
The team found SARS-CoV-2 viral RNA in the coronary artery tissue of all patients. They found more viral RNA in the artery walls compared with surrounding fat tissue. Many of the infected cells are macrophages, a type of white blood cell that engulfs pathogens. The more macrophages there are, the more viral RNA there is in the sample.
Atherosclerosis is a disease in which the buildup of plaque made of fat, cholesterol and other substances causes the arteries to narrow. This narrowing restricts blood flow and, if the plaque ruptures, can cause blood clots that can lead to a heart attack or stroke. Factors such as high blood pressure and smoking increase the risk.
Macrophages also help clear cholesterol from blood vessels. When macrophages are filled with cholesterol, they are called foam cells. Foam cells accumulate in arteries to form plaque, a hallmark of atherosclerosis. The research team confirmed that SARS-CoV-2 can infect human macrophages and foam cells in culture dishes. Foam cells are more susceptible to infection than macrophages. This may explain why patients with atherosclerosis are more susceptible to COVID-19.
In both cell types, infection relies on a protein on the cell surface called neuroxin. Turning off the neural protein gene in these cells reduces infection. Blocking the virus from binding to neural proteins also reduces infection.
Infection triggers multiple inflammatory pathways in macrophages and foam cells. These cells also release molecules known to cause heart attacks and strokes. In arterial plaques surgically removed from patients, the researchers saw an inflammatory response following infection with SARS-CoV-2, much like those seen in cultured cells.
The findings suggest that SARS-CoV-2 may increase the risk of heart attacks and strokes by infecting artery wall tissue, including associated macrophages. This triggers inflammation of atherosclerotic plaques, which can lead to heart attack or stroke.
"These results reveal a possible link between pre-existing heart problems and the virus that causes COVID-19, and that the immune cells most involved in atherosclerosis may serve as reservoirs for the virus, giving it a chance to persist in the body for long periods of time," said Dr. Michelle Oliver of the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH). "We have known from the early days of the pandemic that people infected with COVID-19 are at increased risk of cardiovascular disease or stroke within a year of infection. We believe we have found one of the reasons."
Going forward, the authors plan to further investigate potential links between arterial infections and Long-COVID. They also want to know whether their findings also apply to newer SARS-CoV-2 variants.