Vascular Disease and Thrombosis in SARS-CoV-2-Infected Rhesus Macaques

• Published in: Cell Vol. 183; no. 5; pp. 1354 - 1366.e13
• Main Authors: Aid, Malika, Busman-Sahay, Kathleen, Vidal, Samuel J., Maliga, Zoltan, Bondoc, Stephen, Starke, Carly, Terry, Margaret, Jacobson, Connor A., Wrijil, Linda, Ducat, Sarah, Brook, Olga R., Miller, Andrew D., Porto, Maciel, Pellegrini, Kathryn L., Pino, Maria, Hoang, Timothy N., Chandrashekar, Abishek, Patel, Shivani, Stephenson, Kathryn, Bosinger, Steven E., Andersen, Hanne, Lewis, Mark G., Hecht, Jonathan L., Sorger, Peter K., Martinot, Amanda J., Estes, Jacob D., Barouch, Dan H.
• Format: Journal Article Web Resource
• Language: English
• Published: United States Elsevier Inc 25.11.2020; Elsevier BV
• Subjects: Aged, 80 and over; Animals; Bronchoalveolar Lavage; C-Reactive Protein - analysis; coagulation; collagen; complement; Complement Activation; COVID-19 - blood; COVID-19 - complications; COVID-19 - immunology; COVID-19 - pathology; Cytokines - blood; Female; Humans; IFNα; Inflammation - blood; Inflammation - immunology; Inflammation - virology; Lung - pathology; Macaca mulatta; macrophage; Macrophages - immunology; Male; platelet; Platelet Activation; SARS-CoV-2; SARS-CoV-2 - genetics; thrombosis; Thrombosis - blood; Thrombosis - complications; Thrombosis - pathology; Transcriptome; vascular; Vascular Diseases - blood; Vascular Diseases - complications; Vascular Diseases - pathology; vWF; SARS-CoV-2; IFNα; thrombosis; vWF; collagen; platelet; macrophage; complement; vascular; coagulation
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2020.10.005

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 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. [Display omitted] •SARS-CoV-2 infection leads to macrophage infiltrates in the lung of infected macaques•SARS-CoV-2 upregulates proinflammatory cytokines and ISGs in macaques•SARS-CoV-2 upregulates complement and coagulation cascade in macaques•SARS-CoV-2 infection leads to endothelial damage and thrombosis in macaques Aid et al. show that SARS-CoV-2 causes endothelial disruption and vascular thrombosis in both human and rhesus macaques lungs by inducing an upregulation of proinflammatory cytokines. Using an approach that combines histopathology and multiomics in macaques, they show the progression to vascular disease over time, which involves complement, macrophage, cytokine, and thrombosis cascades.