SARS-CoV-2 increases the risk of heart attack and stroke by causing fatty plaque in cardiac arteries to become highly inflamed, according to a new study funded by the National Institutes of Health. The findings, published in the journal Nature Cardiovascular Research, may help explain why certain people who get COVID-19 have a greater chance of developing cardiovascular disease, or if they already have it, develop more heart-related complications.
“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,” said Michelle Olive, PhD, acting associate director of the Basic and Early Translational Research Program at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH. “We believe we have uncovered one of the reasons why.”
The researchers focused on older people with atherosclerotic plaque who died from COVID-19. But the team found the virus infects and replicates in the arteries no matter the levels of plaque, so their findings could have broader implications for anybody who gets COVID-19.
Though previous studies have shown that SARS-CoV-2 can directly infect tissues such as the brain and lungs, less was known about its effect on the coronary arteries. Researchers knew that after the virus reaches cells, the body’s immune system sends in macrophages to help clear the infection. In the arteries, macrophages also help remove cholesterol, and when they become overloaded with that molecule, they morph into a specialized type of cell called foam cells.
The researchers thought that macrophages might increase inflammation in the existing plaque in SARS-CoV-2 infected arterial cells, explained senior author Chiara Giannarelli, MD, PhD, associate professor in the departments of medicine and pathology at New York University’s Grossman School of Medicine.
To test their theory, the team took tissue from the coronary arteries and plaque of people who had died from COVID-19 and confirmed the virus was in those tissues. Then they took arterial and plaque cells—including macrophages and foam cells—from healthy patients and infected them with SARS-CoV-2 in a lab dish. They found that the virus had also infected those cells and tissues.
The researchers also found that when they compared the infection rates of SARS-CoV-2, the virus infects macrophages at a higher rate than other arterial cells. Cholesterol-laden foam cells were the most susceptible to infection and unable to readily clear the virus. This suggested to them that foam cells might act as a reservoir of SARS-CoV-2 in the atherosclerotic plaque. Having more build-up of plaque, and thus a greater number of foam cells, could increase the severity or persistence of COVID-19.
Further, the team found that cytokines were released by infected macrophages and foam cells in this process. Cytokines are known to increase inflammation and promote the formation of even more plaque. This effect, the researchers surmised, may help explain why people who have underlying plaque buildup and then get COVID-19 may have cardiovascular complications long after getting the infection.
“This study is incredibly important as it adds to the larger body of work to better understand COVID-19,” said Olive. “This is just one more study that demonstrates how the virus both infects and causes inflammation in many cells and tissues throughout the body. Ultimately, this is information that will inform future research on both acute and Long COVID.”
