COVID Heart Injuries Traced Back to Infected Arterial Plaque, Inflammation

Scientists found that the SARS-CoV-2 virus can directly infiltrate atherosclerotic plaques in coronary arteries and trigger an inflammatory response, providing one mechanism for how COVID-19 infection can lead to cardiovascular complications in some people.

Directly infected atherosclerotic tissue was found in both people who died with severe COVID-19 and underlying atherosclerosis and an ex vivo model of human vascular explants. Infection in either setting produced an inflammatory response and induced the secretion of pro-atherogenic cytokines such as interleukin (IL)-6 and IL-1β, reported Chiara Giannarelli, MD, PhD, of NYU Grossman School of Medicine in New York City, and colleagues.

“Considering that plaque inflammation promotes disease progression and contributes to plaque rupture, our results provide a molecular basis for how SARS-CoV-2 infection of coronary lesions can contribute to the acute cardiovascular manifestations of COVID-19, such as myocardial infarction,” Giannarelli’s group wrote in Nature Cardiovascular Research.

In a press release, study co-author Natalia Eberhardt, PhD, of NYU Langone Health, said that the “findings provide for the first time a direct mechanistic link between COVID-19 infection and the heart complications it provokes. The virus creates a highly inflammatory environment that could make it easier for plaque to grow, rupture, and block blood flow to the heart, brain, and other key organs.”

The study goes beyond prior research that has shown that a systemic inflammatory response, the cytokine storm, can occur and contribute to increased cardiovascular risk. It was also previously established that some people recovering from COVID-19 undergo a brief period of localized myocardial inflammation accompanied by cardiac injury and higher levels of systemic inflammatory blood markers.

In the current study, SARS-CoV-2 was found to target plaque macrophages, especially cholesterol-loaded primary macrophages, which in turn orchestrated the over-reactive inflammatory response. The virus also showed a stronger tropism for arterial lesions than adjacent perivascular fat.

“This study reiterates the notion that true viral myocarditis by direct tropism of the cardiomyocytes is not the main mechanism of cardiovascular injury, and instead points towards the vascular origin of the cardiac symptoms and findings,” Valentina Puntmann, MD, PhD, of Goethe University Frankfurt in Germany, told MedPage Today via email.

“Secondly, the preference of viral tropism for lipid-laden macrophages, also known as the foam cells, in the early vascular lesions is an extremely relevant finding, because these lesions are present ubiquitously, without a need for any severe atherosclerotic manifestations such as heart attacks or strokes,” she noted. “The combination of early vascular lesions and COVID-19 infection appears to uncover a human vascular weak spot.”

For this study, the authors used coronary autopsy specimens from eight New York City patients with confirmed COVID-19 from May 2020 to May 2021.

All eight individuals had coronary artery disease and three or more cardiovascular risk factors. Mean age was 69.6 years, and 75% were men.

Giannarelli and colleagues identified infected plaque macrophages as the site of SARS-CoV-2 replication in human coronary arteries. Macrophages residing in vascular tissue can undergo self-renewal, contributing to their long-term staying power, the researchers noted.

“These results shed light onto a possible connection between preexisting heart issues and long COVID symptoms,” said Giannarelli in a statement. “It appears that the immune cells most involved in atherosclerosis may serve as a reservoir for the virus, giving it the opportunity to persist in the body over time.”

Puntmann noted it remains to be shown “whether the immune response borne by the infected foam cell macrophages in response to the virus may account for the vascular antigen presentation moment and a trigger of subsequent immune dysregulation, a crucial missing piece of evidence underlying the chronic inflammatory microvascular injury behind the cardiac and other clinical manifestations of long COVID.”

The study authors acknowledged their small and relatively sick sample and cautioned against extrapolating their findings to younger, healthy individuals, or those affected by other viral strains.

“Despite these limitations, our study highlights the hyperinflammatory response orchestrated by SARS-CoV-2-infected plaque macrophages and foam cells as a mechanistic link between infection of atherosclerotic coronary vessels and acute cardiovascular complications of COVID-19,” they wrote.

Inflammation has gained recognition as a factor in cardiovascular disease in recent years. The concept reached a new milestone this summer, when the FDA made colchicine (Lodoco) the first anti-inflammatory drug to win an indication for cardiovascular prevention in adults with established atherosclerotic disease or multiple risk factors.

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