Targeting JAK-STAT Signaling to Control Cytokine Release Syndrome in COVID-19

Trends Pharmacol Sci. 2020 Aug;41(8):531-543. doi: 10.1016/ Epub 2020 Jun 17.


Recent advances in the pathophysiologic understanding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has indicated that patients with severe coronavirus disease 2019 (COVID-19) might experience cytokine release syndrome (CRS), characterized by increased interleukin (IL)-6, IL-2, IL-7, IL-10, etc. Therefore, the treatment of cytokine storm has been proposed as a critical part of rescuing severe COVID-19. Several of the cytokines involved in COVID-19 employ a distinct intracellular signaling pathway mediated by Janus kinases (JAKs). JAK inhibition, therefore, presents an attractive therapeutic strategy for CRS, which is a common cause of adverse clinical outcomes in COVID-19. Below, we review the possibilities and challenges of targeting the pathway in COVID-19.

Keywords: COVID-19; JAK inhibitors; cytokine release syndrome.

Publication types

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

MeSH terms

  • Animals
  • Betacoronavirus / isolation & purification*
  • COVID-19
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / immunology
  • Coronavirus Infections / physiopathology*
  • Cytokine Release Syndrome / drug therapy
  • Cytokine Release Syndrome / immunology
  • Cytokine Release Syndrome / virology*
  • Cytokines / immunology
  • Humans
  • Janus Kinases / metabolism
  • Pandemics
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / physiopathology*
  • SARS-CoV-2
  • STAT Transcription Factors / metabolism
  • Signal Transduction / physiology


  • Cytokines
  • STAT Transcription Factors
  • Janus Kinases