Initially recognized as a mere respiratory ailment, it soon became evident that SARS-CoV-2, the virus responsible for COVID-19, was capable of affecting various organs and systems significantly beyond the lungs. Dr. Chiara Giannarelli, an associate professor at NYU Grossman School of Medicine, highlighted that early findings indicated the virus was also impacting heart health by increasing the risk of heart attacks and strokes among patients. However, the vascular system—the network of blood vessels that disseminates the virus throughout the body—was not initially the focus of research efforts.
During the spring of 2020, Giannarelli was situated at the epicenter of COVID-19 cases in New York City. Her research, which centered on the intricate relationship between inflammatory and immune cells within arteries and their contribution to atherosclerosis (a primary factor in cardiovascular disease), positioned her well to explore the broader implications of the virus. Meanwhile, other research groups honed in on the virus’s effects on heart muscle. Instances of myocarditis, an inflammation of the heart muscle, emerged as a leading cause of fatalities among COVID-19 patients.
As scientists delved into these issues, one conclusion became evident: the body’s excessive immune response to the SARS-CoV-2 virus was primarily responsible for the damage observed, as explained by Dr. DeLisa Fairweather, vice chair of translational research at the Mayo Clinic in Jacksonville, Florida. Fairweather, who authored a 2023 review in Circulation Research focused on COVID-19 and myocarditis, stated that the immune response mechanisms were similar in both COVID-related cardiovascular issues and myocarditis. “In one scenario, damage occurs in the blood vessel walls, while in another, it’s in the heart muscle,” she clarified, emphasizing that the crucial factor is how the immune system reacts to the virus.
SARS-CoV-2 is categorized as a large, enveloped RNA virus. It relies on a layer of cell membrane to fuse with healthy cells, primarily entering the body through the eyes, nose, or mouth before targeting the lungs. Cells found in both the lungs and blood vessels are rich in ACE2 receptors; these are the primary gateways the virus exploits to infiltrate host cells using a spike protein on its surface. Besides facilitating the virus’s entry, ACE2 receptors play a vital role in regulating cardiovascular health, including inflammation control. After infiltrating a host cell, the virus releases its genetic material, prompting replication.
Fairweather pointed out that the most concerning issue arises once the virus enters the host cells. It targets mitochondria, the powerhouses of the cell responsible for energy production. This hijacking creates a significant alarm for the body, leading to an intense inflammatory response and a cytokine storm, which Fairweather analogized to a DEFCON 4 alert, unnecessarily mobilizing a full force when only limited resources may be warranted. The reasons behind this exaggerated response remain unclear.
Nevertheless, researchers have established that the inflammatory cytokines summoned to assist during this response are indeed linked to atherosclerosis—the accumulation and potential rupture of plaques in the arteries, which can precipitate heart attacks and strokes. With SARS-CoV-2 associated with heightened risks of these cardiovascular events, Giannarelli and her research team sought to determine whether the virus was invading arteries and what effects it would have there.
To investigate, they examined tissue samples from autopsies of individuals who had succumbed to COVID-19 after being hospitalized. They discovered viral RNA sequences corresponding to the spike protein of SARS-CoV-2 in macrophages—immune cells located in the heart. Subsequently, they replicated a SARS-CoV-2 infection within human tissue in the lab to see whether the virus could persist and multiply in these macrophages. Although the virus showed limited capacity to reproduce infectious viral particles in macrophages, it did provoke a substantial immune response.
Interestingly, the research also revealed that white blood cells with elevated lipid levels were less adept at eradicating the virus than their counterparts. These lipid-laden cells may provide an ideal environment for the virus, enabling it to linger and sustain an inflammatory response for an extended duration, Giannarelli explained. This persistent inflammation within existing arterial plaque can give rise to fragments breaking off, ultimately resulting in heart attacks or strokes. A recent study published in Arteriosclerosis, Thrombosis, and Vascular Biology corroborated this, indicating a prolonged increased risk of heart attacks and strokes in individuals infected with the virus as far as three years following their initial infection.
Moreover, myocarditis can also surface in those infected with the virus who previously showed no signs of heart disease. Fairweather identified mast cells as a possible contributing factor, as these cells, much like macrophages, also contain ACE2 receptors. When the virus infiltrates mast cells, it amplifies the immune response, leading to the excessive inflammation associated with myocarditis.
On a positive note, Fairweather mentioned that as individuals gain immunity through vaccinations and reinfections, their bodies are expected to respond to the virus more effectively and with more balanced immune responses. While older adults, those with compromised immune systems, and individuals with pre-existing heart conditions will continue to be at risk, for the majority, the immune system is likely to become more temperate, reducing the potential threat over time.
