SARS-CoV-2 Infection Triggers Pro-Atherogenic Inflammatory Responses in Human Coronary Vessels

Authors

Natalia Eberhardt
Maria Gabriela Noval
Ravneet Kaur
Letizia Amadori
Michael Gildea
Swathy Sajja
Dayasagar Das
Burak Cilhoroz
O'Jay Stewart
Dawn M Fernandez
Roza Shamailova
Andrea Vasquez Guillen
Sonia Jangra
Michael Schotsaert
Jonathan D Newman
Peter Faries
Thomas Maldonado
Caron Rockman
Amy Rapkiewicz
Kenneth A Stapleford
Navneet Narula
Kathryn J Moore
Chiara Giannarelli

Publication Date

10-1-2023

Journal

Nature Cardiovascular Research

Abstract

Patients with coronavirus disease 2019 (COVID-19) present increased risk for ischemic cardiovascular complications up to 1 year after infection. Although the systemic inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely contributes to this increased cardiovascular risk, whether SARS-CoV-2 directly infects the coronary vasculature and attendant atherosclerotic plaques remains unknown. Here we report that SARS-CoV-2 viral RNA is detectable and replicates in coronary lesions taken at autopsy from severe COVID-19 cases. SARS-CoV-2 targeted plaque macrophages and exhibited a stronger tropism for arterial lesions than adjacent perivascular fat, correlating with macrophage infiltration levels. SARS-CoV-2 entry was increased in cholesterol-loaded primary macrophages and dependent, in part, on neuropilin-1. SARS-CoV-2 induced a robust inflammatory response in cultured macrophages and human atherosclerotic vascular explants with secretion of cytokines known to trigger cardiovascular events. Our data establish that SARS-CoV-2 infects coronary vessels, inducing plaque inflammation that could trigger acute cardiovascular complications and increase the long-term cardiovascular risk.

Comments

Supplementary Materials

PMID: 38076343