Groundbreaking Evidence Reveals Direct Infection of Atherosclerotic Plaques by COVID Virus
New research has uncovered unprecedented evidence indicating the direct infection of atherosclerotic plaques in the coronary arteries by the virus responsible for COVID, leading to a persistent inflammatory response. This finding not only sheds light on the correlation between COVID and the heightened risk of cardiovascular events, but also serves as a catalyst for innovative therapeutic approaches.
Dr. Chiara Giannarelli, senior investigator and associate professor of medicine and pathology at New York University’s Grossman School of Medicine, shared, “Our study reveals the presence of viral debris within the arteries, accompanied by a significant inflammatory response. We can now explore strategies to control this inflammation.” Giannarelli emphasizes that COVID affects the entire body and demonstrates an extraordinary ability to manipulate the immune system. She explains, “Our findings may offer an explanation for this phenomenon.”
Furthermore, Giannarelli stresses the importance of doctors and patients being mindful of the increased risk of cardiovascular issues following a SARS-CoV-2 infection, urging them to closely monitor traditional risk factors like blood pressure and cholesterol. Dr. Peter Hotez, professor of molecular virology and microbiology at Baylor College of Medicine, concurs, stating, “This study solidifies the connection between severe acute respiratory syndrome coronavirus and direct infection of coronary artery plaques, resulting in the production of inflammatory substances. This ultimately helps us understand why COVID patients frequently experience heart disease.”
When questioned about whether this direct infection of vascular plaques is exclusive to SARS-CoV-2 or may also occur with other viruses, both Giannarelli and Hotez agree that it is likely a distinct effect of COVID. Giannarelli expresses her skepticism, saying, “While it is possible, I find it unlikely that other viruses infect coronary arteries in the same manner.” Hotez emphasizes that while other viruses can provoke heart inflammation, such as myocarditis, none have been observed to stimulate the sequence of events leading to coronary artery inflammation as exhibited by COVID.
Though it is known that influenza is associated with a heightened risk of cardiovascular events, there has been no evidence thus far that it directly impacts coronary arteries. Hotez suggests that these fresh findings regarding SARS-CoV-2 could inspire a renewed investigation into this possibility with influenza.
COVID’s Impact on Heart Disease
In a recent publication in Nature Cardiovascular Research, Giannarelli and her colleagues analyzed human autopsy tissue samples obtained from the coronary arterial walls of COVID patients who succumbed to the disease during the early stages of the pandemic. They discovered an accumulation of viral RNA within atherosclerotic plaques in the coronary arteries, particularly concentrated in lipid-rich macrophage foam cells present in the plaques. “Our data conclusively demonstrates the ability of severe acute respiratory syndrome coronavirus to infect and replicate within macrophages located within the coronary vasculature,” the researchers assert.
These findings indicate that the virus disproportionately replicates in foam cells compared to other macrophages, implying that these cells may serve as reservoirs for viral debris within the atherosclerotic plaque. Giannarelli explains, “Our study has illuminated the virus’s targeting of lipid-rich macrophages in atherosclerotic lesions. This is a groundbreaking revelation with significant implications.”
Giannarelli adds, “We have also discovered that the virus persists within these foam cells, potentially stimulating long-term, low-grade inflammation in the vasculature. This persistent inflammation could contribute to the prolonged cardiovascular manifestations observed in COVID-recovered patients.”
The researchers note that macrophages residing in vascular tissue have the capacity for self-renewal and can remain in the tissue for many years, suggesting that these macrophages may act as viral reservoirs for SARS-CoV-2 RNA in atherosclerotic plaques. Utilizing an ex vivo model, the researchers also demonstrated that atherosclerotic tissue can be directly infected by the virus. Infection of vascular tissue, similar to cultured macrophages and foam cells, triggered an inflammatory response. This response led to the secretion of proatherogenic cytokines like interleukin-6 and interleukin-1 beta, known to play a role in the development of atherosclerosis and increased cardiovascular risk.
The researchers report, “Considering that plaque inflammation promotes disease progression and contributes to plaque rupture, our results provide a molecular basis for how infection of coronary lesions can contribute to acute cardiovascular manifestations of COVID-19, such as myocardial infarction.” They also discovered a higher accumulation of viral RNA in the coronary vasculature of three patients with acute ischemic cardiovascular manifestations, providing further evidence of the link between infection and cardiovascular risk.
Giannarelli notes that the patients included in the study passed away in New York during the early stages of the pandemic, before vaccines were available. She states, “These individuals were unvaccinated and likely had limited immunity against the initial viral strains.” Hotez notes that when COVID-19 first emerged, it was widely believed within the medical and scientific communities that it would primarily resemble the initial SARS viral infection, which primarily affected the respiratory system. “However, it became evident early on that this virus was causing significant cardiovascular and thromboembolic diseases. This study provides insights into the underlying mechanisms.”
Affecting More Than the Lungs
Hotez highlights a recent study which reported a 5% increase in cardiovascular deaths during the years 2020–2022 compared to before the pandemic. He explains, “These spikes in cardiovascular deaths corresponded to specific waves of COVID, the first occurring during the initial wave with the original virus, and the second during the Delta wave. Hence, there is no doubt that this virus contributes to excess cardiovascular mortality, and this research seemingly elucidates the underlying mechanism.”
Furthermore, Hotez suggests that the cardiovascular risk may persist long after the acute infection has subsided. He remarks, “When people discuss long COVID, the focus tends to be on the neurological effects such as brain fog and depression. Yet, cardiac insufficiency and other cardiovascular events must also be considered as components of long COVID.”
Giannarelli’s team is currently investigating whether patients with long COVID harbor the virus in their coronary arteries. She emphasizes that these studies were made possible through the collaboration of experts in cardiovascular disease, virology, and infectious diseases. She comments, “To gain a better understanding of the impact of viral infections on patients and their clinical manifestations, we need to foster more collaborations like this.”
Hotez asserts that these new findings will have significant implications for the future. “COVID is still prevalent; the number of cases in the US has been steadily increasing in recent months, resulting in numerous hospitalizations,” he warns. Although it may be impractical to request a cardiology consultation for every COVID patient, Hotez acknowledges that certain individuals, particularly older individuals or those who experienced severe cases of COVID, may now be more prone to developing cardiovascular disease. He concludes, “We must remain vigilant in monitoring these patients for cardiovascular issues and perhaps be more proactive in managing their cardiovascular risk factors.”
The study received funding from the US National Institutes of Health, the American Heart Association, and the Chan Zuckerberg Initiative. The full text is available online at Nature Cardiovascular Research. For further updates, follow Medscape on Facebook, Twitter, Instagram, and YouTube.
