Beneficial non-anticoagulant mechanisms underlying heparin treatment of COVID-19 patients

EBioMedicine. 2020 Sep:59:102969. doi: 10.1016/j.ebiom.2020.102969. Epub 2020 Aug 25.

Abstract

Coronavirus disease-2019 (COVID-19) is associated with severe inflammation in mainly the lung, and kidney. Reports suggest a beneficial effect of the use of heparin/low molecular weight heparin (LMWH) on mortality in COVID-19. In part, this beneficial effect could be explained by the anticoagulant properties of heparin/LMWH. Here, we summarise potential beneficial, non-anticoagulant mechanisms underlying treatment of COVID-19 patients with heparin/LMWH, which include: (i) Inhibition of heparanase activity, responsible for endothelial leakage; (ii) Neutralisation of chemokines, and cytokines; (iii) Interference with leukocyte trafficking; (iv) Reducing viral cellular entry, and (v) Neutralisation of extracellular cytotoxic histones. Considering the multiple inflammatory and pathogenic mechanisms targeted by heparin/LMWH, it is warranted to conduct clinical studies that evaluate therapeutic doses of heparin/LMWH in COVID-19 patients. In addition, identification of specific heparin-derived sequences that are functional in targeting non-anticoagulant mechanisms may have even higher therapeutic potential for COVID-19 patients, and patients suffering from other inflammatory diseases.

Keywords: COVID-19; Heparanase; Heparin; Inflammation; Low molecular weight heparin.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Betacoronavirus / isolation & purification
  • Betacoronavirus / physiology
  • COVID-19
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / pathology
  • Coronavirus Infections / virology
  • Glucuronidase / antagonists & inhibitors
  • Glucuronidase / metabolism
  • Heparin / metabolism
  • Heparin / pharmacology
  • Heparin / therapeutic use*
  • Heparin, Low-Molecular-Weight / metabolism
  • Heparin, Low-Molecular-Weight / pharmacology
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Histones / blood
  • Histones / metabolism
  • Humans
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / pathology
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Virus Internalization / drug effects

Substances

  • Anti-Inflammatory Agents
  • Heparin, Low-Molecular-Weight
  • Histones
  • Heparin
  • heparanase
  • Glucuronidase