Immunity, endothelial injury and complement-induced coagulopathy in COVID-19

Nat Rev Nephrol. 2021 Jan;17(1):46-64. doi: 10.1038/s41581-020-00357-4. Epub 2020 Oct 19.


In December 2019, a novel coronavirus was isolated from the respiratory epithelium of patients with unexplained pneumonia in Wuhan, China. This pathogen, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a pathogenic condition that has been termed coronavirus disease 2019 (COVID-19) and has reached pandemic proportions. As of 17 September 2020, more than 30 million confirmed SARS-CoV-2 infections have been reported in 204 different countries, claiming more than 1 million lives worldwide. Accumulating evidence suggests that SARS-CoV-2 infection can lead to a variety of clinical conditions, ranging from asymptomatic to life-threatening cases. In the early stages of the disease, most patients experience mild clinical symptoms, including a high fever and dry cough. However, 20% of patients rapidly progress to severe illness characterized by atypical interstitial bilateral pneumonia, acute respiratory distress syndrome and multiorgan dysfunction. Almost 10% of these critically ill patients subsequently die. Insights into the pathogenic mechanisms underlying SARS-CoV-2 infection and COVID-19 progression are emerging and highlight the critical role of the immunological hyper-response - characterized by widespread endothelial damage, complement-induced blood clotting and systemic microangiopathy - in disease exacerbation. These insights may aid the identification of new or existing therapeutic interventions to limit the progression of early disease and treat severe cases.

Publication types

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

MeSH terms

  • Angiotensin-Converting Enzyme 2 / physiology
  • Blood Coagulation Disorders / etiology*
  • COVID-19 / complications*
  • COVID-19 / immunology
  • COVID-19 / therapy
  • Complement Pathway, Classical
  • Complement System Proteins / physiology*
  • Endothelium, Vascular / physiopathology*
  • Humans
  • Immunization, Passive
  • Kidney Diseases / etiology
  • SARS-CoV-2 / immunology*


  • Complement System Proteins
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2

Supplementary concepts

  • COVID-19 serotherapy