Research supported by the NIH clarifies the connection between COVID-19 infection and a higher risk of stroke and cardiovascular disease.
According to a National Institutes of Health-funded study, the virus that causes COVID-19, SARS-CoV-2, can directly infect heart arteries and cause the fatty plaque inside arteries to become highly inflamed, increasing the risk of heart attack and stroke. The results, which were published in the journal Nature Cardiovascular Research, may provide some insight into why some COVID-19 carriers are more likely to develop cardiovascular disease or, in the event that they already do, to experience an increased risk of heart-related complications.
Researchers in the study concentrated on elderly patients who died from COVID-19 and had atherosclerotic plaque, a fatty buildup. The findings, however, may have wider ramifications for anyone infected with COVID-19, as the researchers discovered that the virus replicates and infects the arteries regardless of the degree of plaque.
“We have known that individuals who had COVID-19 have an increased risk for cardiovascular disease or stroke up to one year after infection since the early days of the pandemic,” stated Michelle Olive, Ph.D., acting associate director of the National Heart, Lung, and Blood Institute (NHLBI), a division of the National Institutes of Health. “We think we have identified one of the causes,”
While prior research has demonstrated that SARS-CoV-2 can enter the brain and lungs directly, little is known about how it affects the coronary arteries. Researchers understood that the body’s immune system sends in white blood cells called macrophages to help clear the virus once it has entered the cells. Macrophages also aid in the removal of cholesterol from the arteries; however, when they become overloaded with the material, they change into a different kind of cell known as foam cells.
The idea behind this was that if SARS-CoV-2 was able to infect arterial cells directly, the normally lethal macrophages might exacerbate the inflammation already present in the plaque, according to Chiara Giannarelli, M.D., Ph.D., senior author of the study and associate professor of pathology and medicine at New York University’s Grossman School of Medicine. Giannarelli and her colleagues confirmed the presence of COVID-19 in tissues taken from the coronary arteries and plaque of patients who had passed away, in order to test their theory. Next, they infected SARS-CoV-2 in a lab dish using arterial and plaque cells from healthy patients, including macrophages and foam cells. They discovered that those tissues and cells had also been infected by the virus.
Furthermore, the researchers discovered that the virus infects macrophages more frequently than other arterial cells when they compared the SARS-CoV-2 infection rates. Foam cells that were high in cholesterol were the most prone to infection and had a slower rate of virus clearance. This implied that SARS-CoV-2 could be stored in foam cells within the atherosclerotic plaque. Increased plaque accumulation and, consequently, an increased number of foam cells may exacerbate or prolong COVID-19.
After the plaque was infected with the virus, the researchers focused on the inflammation they thought would happen. They swiftly recorded the release of chemicals called cytokines, which are known to exacerbate inflammation and encourage the development of additional plaque. Foam cells and infected macrophages released the cytokines. According to the researchers, this could help explain why COVID-19 infections may cause cardiovascular problems long after the initial infection in people with preexisting plaque accumulation.
According to Olive, “this study is extremely important because it adds to the larger body of work to better understand COVID-19.” This study adds to the body of research showing how the virus both infects and inflames a variety of cells and tissues. In the end, this data will help guide future studies on acute and long-term COVID.
Even though the results unequivocally demonstrate that SARS-CoV-2 can replicate and infect plaque and arterial cell macrophages, they are only applicable to the initial strains of the virus that were active in New York City between May 2020 and May 2021. The results cannot be applied to younger, healthy people because the study was done on a small cohort of older people who were all diagnosed with atherosclerosis and other medical conditions.
The NIH/NHLBI grants 1R01HL165258, R01HL153712, R35HL135799, and R01HL084312 provided funding for this work. Funding was also provided by NIDDK and NIAID.
References
Eberhardt, N., et al. SARS-CoV-2 infection triggers pro-atherogenic inflammatory responses in human coronary vessels. Nat Cardiovasc Res doi: 10.1038/s44161-023-00336-5.
