COVID-19: a probable role of the anticoagulant Protein S in managing COVID-19-associated coagulopathy

Aging (Albany NY). 2020 Aug 19;12(16):15954-15961. doi: 10.18632/aging.103869. Epub 2020 Aug 19.

Abstract

The COVID-19 pandemic has caused monumental mortality, and there are still no adequate therapies. Most severely ill COVID-19 patients manifest a hyperactivated immune response, instigated by interleukin 6 (IL6) that triggers a so called "cytokine storm" and coagulopathy. Hypoxia is also associated with COVID-19. So far overlooked is the fact that both IL6 and hypoxia depress the abundance of a key anticoagulant, Protein S. We speculate that the IL6-driven cytokine explosion plus hypoxemia causes a severe drop in Protein S level that exacerbates the thrombotic risk in COVID-19 patients. Here we highlight a mechanism by which the IL6-hypoxia curse causes a deadly hypercoagulable state in COVID-19 patients, and we suggest a path to therapy.

Keywords: ACE2; COVID-19; IL6; Protein S; coagulopathy; cytokine storm; hypoxia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Anticoagulants / metabolism
  • Anticoagulants / pharmacology
  • Betacoronavirus / physiology
  • COVID-19
  • Coronavirus Infections* / blood
  • Coronavirus Infections* / immunology
  • Coronavirus Infections* / therapy
  • Cytokine Release Syndrome* / blood
  • Cytokine Release Syndrome* / virology
  • Disease Management
  • Humans
  • Hypoxia* / blood
  • Hypoxia* / etiology
  • Hypoxia* / immunology
  • Interleukin-6 / blood
  • Pandemics*
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral* / blood
  • Pneumonia, Viral* / immunology
  • Pneumonia, Viral* / therapy
  • Protein S* / metabolism
  • Protein S* / pharmacology
  • SARS-CoV-2
  • Severity of Illness Index
  • Thrombophilia / immunology*

Substances

  • Anticoagulants
  • Interleukin-6
  • Protein S
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2