Vascular Disease and Thrombosis in SARS-CoV-2-Infected Rhesus Macaques.
Malika Aid, Kathleen Busman-Sahay, Samuel J Vidal, Zoltan Maliga, Stephen Bondoc, Carly Starke, Margaret Terry, Connor A Jacobson, Linda Wrijil, Sarah Ducat, Olga R Brook, Andrew D Miller, Maciel Porto, Kathryn L Pellegrini, Maria Pino, Timothy N Hoang, Abishek Chandrashekar, Shivani Patel, Kathryn Stephenson, Steven E Bosinger, Hanne Andersen, Mark G Lewis, Jonathan L Hecht, Peter K Sorger, Amanda J Martinot, Jacob D Estes, Dan H Barouch
Author Information
Malika Aid: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Kathleen Busman-Sahay: Oregon Health & Sciences University, Beaverton, OR 97006, USA.
Samuel J Vidal: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Zoltan Maliga: Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Stephen Bondoc: Oregon Health & Sciences University, Beaverton, OR 97006, USA.
Carly Starke: Oregon Health & Sciences University, Beaverton, OR 97006, USA.
Margaret Terry: Oregon Health & Sciences University, Beaverton, OR 97006, USA.
Connor A Jacobson: Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Linda Wrijil: Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
Sarah Ducat: Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
Olga R Brook: Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Andrew D Miller: Department of Biomedical Sciences, Section of Anatomic Pathology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
Maciel Porto: Bioqual, Rockville, MD 20852, USA.
Kathryn L Pellegrini: Yerkes Genomics Core Laboratory, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Maria Pino: Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Timothy N Hoang: Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Abishek Chandrashekar: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Shivani Patel: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Kathryn Stephenson: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Steven E Bosinger: Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Yerkes Genomics Core Laboratory, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pathology & Laboratory Medicine, Emory School of Medicine, Emory University, Atlanta, GA 30329, USA.
Hanne Andersen: Bioqual, Rockville, MD 20852, USA.
Mark G Lewis: Bioqual, Rockville, MD 20852, USA.
Jonathan L Hecht: Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Peter K Sorger: Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Amanda J Martinot: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
Jacob D Estes: Oregon Health & Sciences University, Beaverton, OR 97006, USA.
Dan H Barouch: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Electronic address: dbarouch@bidmc.harvard.edu.
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.
