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

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. StaplefordNavneet Narula, Kathryn J. Moore, Chiara Giannarelli

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish
Pages (from-to)899-916
Number of pages18
JournalNature Cardiovascular Research
Volume2
Issue number10
DOIs
StatePublished - Oct 2023

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