Neutrophil elastase inhibitor (sivelestat) may be a promising therapeutic option for management of acute lung injury/acute respiratory distress syndrome or disseminated intravascular coagulation in COVID-19

J Clin Pharm Ther. 2020 Dec;45(6):1515-1519. doi: 10.1111/jcpt.13251. Epub 2020 Aug 28.

Abstract

What is known and objective: This article summarizes the effects of sivelestat on acute lung injury/acute respiratory distress syndrome (ALI/ARDS) or ARDS with coagulopathy, both of which are frequently seen in patients with COVID-19.

Comment: COVID-19 patients are more susceptible to thromboembolic events, including disseminated intravascular coagulation (DIC). Various studies have emphasized the role of neutrophil elastase (NE) in the development of DIC in patients with ARDS and sepsis. It has been shown that NE inhibition by sivelestat mitigates ALI through amelioration of injuries in alveolar epithelium and vascular endothelium, as well as reversing the neutrophil-mediated increased vascular permeability.

What is new and conclusions: Sivelestat, a selective NE inhibitor, has not been evaluated for its possible therapeutic effects against SARS-CoV-2 infection. Based on its promising beneficial effects in underlying complications of COVID-19, sivelestat could be considered as a promising modality for better management of COVID-19-induced ALI/ARDS or coagulopathy.

Keywords: COVID-19; acute lung injury/acute respiratory distress syndrome; coagulopathy; neutrophil elastase inhibitor; sivelestat.

Publication types

  • Review

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / etiology
  • COVID-19 / complications
  • COVID-19 Drug Treatment*
  • Disseminated Intravascular Coagulation / drug therapy*
  • Disseminated Intravascular Coagulation / etiology
  • Glycine / analogs & derivatives*
  • Glycine / therapeutic use
  • Humans
  • Proteinase Inhibitory Proteins, Secretory / therapeutic use*
  • Respiratory Distress Syndrome / drug therapy*
  • Respiratory Distress Syndrome / etiology
  • Sulfonamides / therapeutic use*
  • Treatment Outcome

Substances

  • Proteinase Inhibitory Proteins, Secretory
  • Sulfonamides
  • sivelestat
  • Glycine