SARS-CoV-2 infection triggers pro-atherogenic inflammatory responses in human coronary vessels

Area of Science:

• Cardiovascular Pathology
• Infectious Disease Immunology

Background:

• Patients with COVID-19 face elevated risks of ischemic cardiovascular complications for up to a year post-infection.
• The systemic inflammatory response to SARS-CoV-2 is implicated, but direct viral infection of coronary vasculature and plaques is unconfirmed.

Purpose of the Study:

• To investigate whether SARS-CoV-2 directly infects coronary vessels and atherosclerotic plaques.
• To determine the impact of SARS-CoV-2 infection on plaque inflammation and macrophage activity.

Main Methods:

• Detection and replication of SARS-CoV-2 viral RNA in coronary lesions from deceased COVID-19 patients.
• Analysis of viral tropism for arterial lesions versus perivascular fat, correlating with macrophage infiltration.
• Assessment of SARS-CoV-2 entry into macrophages and its dependence on neuropilin-1.
• Evaluation of SARS-CoV-2-induced inflammatory responses in cultured macrophages and human atherosclerotic explants.

Main Results:

• SARS-CoV-2 RNA was detected and replicated within coronary lesions of severe COVID-19 cases.
• The virus preferentially targeted plaque macrophages, showing greater tropism for arterial lesions than surrounding fat.
• Cholesterol-loaded macrophages exhibited increased SARS-CoV-2 entry, partly mediated by neuropilin-1.
• SARS-CoV-2 triggered significant inflammation in macrophages and vascular explants, secreting cardiovascular-event-associated cytokines.

Conclusions:

• SARS-CoV-2 directly infects coronary vessels, including atherosclerotic plaques.
• The virus induces inflammation within plaques, potentially triggering acute cardiovascular events.
• This direct vascular infection may underlie the increased long-term cardiovascular risk observed in COVID-19 patients.