Vascular Disease and Thrombosis in SARS-CoV-2 Infected Rhesus Macaques
Malika Aid
Kathleen Busman-Sahay
Samuel J. Vidal
Amanda J. Martinot
Jacob D. Estes
Dan H. Barouch
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Published:October 09, 2020DOI:https://doi.org/10.1016/j.cell.2020.10.005
Abstract
The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world. Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details underlying these processes remain to be determined. In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2. To define key molecular pathways associated with SARS-CoV-2 pathogenesis in macaques, we performed transcriptomic analyses of bronchoalveolar lavage (BAL) and peripheral blood and proteomic analyses of serum. We observed macrophage infiltrates in lung and upregulation of macrophage, complement, platelet activation, thrombosis, and proinflammatory markers, including C-reactive protein, MX1, IL-6, IL-1, IL-8, TNFα, and NF-κB. These results suggest a model in which critical interactions between inflammatory and thrombosis pathways lead to SARS-CoV-2 induced vascular disease. Our findings suggest potential therapeutic targets for COVID-19.
