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

Cell. 2020 Nov 25;183(5):1354-1366.e13. doi: 10.1016/j.cell.2020.10.005. Epub 2020 Oct 9.


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.

Keywords: IFNα; SARS-CoV-2; coagulation; collagen; complement; macrophage; platelet; thrombosis; vWF; vascular.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Animals
  • Bronchoalveolar Lavage
  • C-Reactive Protein / analysis
  • COVID-19 / blood
  • COVID-19 / complications*
  • COVID-19 / immunology*
  • COVID-19 / pathology
  • Complement Activation
  • Cytokines / blood
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / immunology
  • Inflammation / virology
  • Lung / pathology
  • Macaca mulatta
  • Macrophages / immunology
  • Male
  • Platelet Activation
  • SARS-CoV-2 / genetics*
  • Thrombosis / blood
  • Thrombosis / complications*
  • Thrombosis / pathology
  • Transcriptome
  • Vascular Diseases / blood
  • Vascular Diseases / complications*
  • Vascular Diseases / pathology


  • Cytokines
  • C-Reactive Protein