Complement cascade in severe forms of COVID-19: Recent advances in therapy

Eur J Immunol. 2021 Jul;51(7):1652-1659. doi: 10.1002/eji.202048959. Epub 2021 Apr 10.

Abstract

The complement system is an essential component of the innate immune system. The three complement pathways (classical, lectin, alternative) are directly or indirectly activated by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). In the most severe forms of COVID-19, overactivation of the complement system may contribute to the cytokine storm, endothelial inflammation (endotheliitis) and thrombosis. No antiviral drug has yet been shown to be effective in COVID-19. Therefore, immunotherapies represent a promising therapeutic in the immunopathological phase (following the viral phase) of the disease. Complement blockade, mostly C5a-C5aR axis blockade, may prevent acute respiratory distress syndrome (ARDS) from worsening or progression to death. Clinical trials are underway.

Keywords: C5a; COVID-19; SARS-CoV-2; complement; cytokine storm.

Publication types

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

MeSH terms

  • COVID-19 / immunology
  • COVID-19 / pathology*
  • COVID-19 Drug Treatment
  • Complement Activation / immunology
  • Complement C5a / antagonists & inhibitors*
  • Cytokine Release Syndrome / drug therapy
  • Cytokine Release Syndrome / immunology
  • Cytokine Release Syndrome / pathology*
  • Cytokines / immunology*
  • Humans
  • Immunotherapy / methods*
  • Inflammation / immunology
  • Inflammation / pathology
  • Receptor, Anaphylatoxin C5a / antagonists & inhibitors*
  • Respiratory Distress Syndrome / prevention & control
  • SARS-CoV-2 / immunology
  • Signal Transduction / immunology
  • Thrombosis / immunology
  • Thrombosis / pathology

Substances

  • C5AR1 protein, human
  • Cytokines
  • Receptor, Anaphylatoxin C5a
  • Complement C5a