Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19

Nat Rev Immunol. 2021 May;21(5):319-329. doi: 10.1038/s41577-021-00536-9. Epub 2021 Apr 6.


Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe disease show hyperactivation of the immune system, which can affect multiple organs besides the lungs. Here, we propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels. Microthrombotic complications may contribute to acute respiratory distress syndrome (ARDS) and other organ dysfunctions. Therapeutic strategies aimed at reducing immunothrombosis may therefore be useful. Several antithrombotic and immunomodulating drugs have been proposed as candidates to treat patients with SARS-CoV-2 infection. The growing understanding of SARS-CoV-2 infection pathogenesis and how it contributes to critical illness and its complications may help to improve risk stratification and develop targeted therapies to reduce the acute and long-term consequences of this disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Blood Coagulation / immunology
  • Blood Platelets / immunology
  • COVID-19 / immunology*
  • COVID-19 / pathology*
  • Critical Illness / therapy
  • Cytokine Release Syndrome / immunology
  • Cytokine Release Syndrome / pathology*
  • Endothelium, Vascular / pathology
  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Immunity, Innate / immunology
  • Lung / blood supply
  • Lung / pathology
  • Lung / virology
  • Monocytes / immunology
  • Neutrophils / immunology
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / pathogenicity
  • Venous Thrombosis / immunology*
  • Venous Thrombosis / pathology*
  • Venous Thrombosis / prevention & control


  • Fibrinolytic Agents