Inhibition of cytokine signaling by ruxolitinib and implications for COVID-19 treatment

Clin Immunol. 2020 Sep;218:108517. doi: 10.1016/j.clim.2020.108517. Epub 2020 Jun 23.

Abstract

Approximately 15% of patients with coronavirus disease 2019 (COVID-19) experience severe disease, and 5% progress to critical stage that can result in rapid death. No vaccines or antiviral treatments have yet proven effective against COVID-19. Patients with severe COVID-19 experience elevated plasma levels of pro-inflammatory cytokines, which can result in cytokine storm, followed by massive immune cell infiltration into the lungs leading to alveolar damage, decreased lung function, and rapid progression to death. As many of the elevated cytokines signal through Janus kinase (JAK)1/JAK2, inhibition of these pathways with ruxolitinib has the potential to mitigate the COVID-19-associated cytokine storm and reduce mortality. This is supported by preclinical and clinical data from other diseases with hyperinflammatory states, where ruxolitinib has been shown to reduce cytokine levels and improve outcomes. The urgent need for treatments for patients with severe disease support expedited investigation of ruxolitinib for patients with COVID-19.

Keywords: COVID-19; Coronavirus; Cytokine storm; Janus kinase; Ruxolitinib.

Publication types

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

MeSH terms

  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / pharmacology
  • Betacoronavirus / immunology
  • Betacoronavirus / pathogenicity*
  • COVID-19
  • Coronavirus Infections / complications
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / immunology
  • Coronavirus Infections / virology
  • Cytokine Release Syndrome / complications
  • Cytokine Release Syndrome / immunology
  • Cytokine Release Syndrome / prevention & control*
  • Cytokine Release Syndrome / virology
  • Cytokines / antagonists & inhibitors*
  • Cytokines / genetics
  • Cytokines / immunology
  • Drug Dosage Calculations
  • Gene Expression Regulation
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology
  • Humans
  • Janus Kinase 1 / antagonists & inhibitors
  • Janus Kinase 1 / genetics
  • Janus Kinase 1 / immunology
  • Janus Kinase 2 / antagonists & inhibitors
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / immunology
  • Lung / drug effects
  • Lung / immunology
  • Lung / pathology
  • Lung / virology
  • Pandemics
  • Pneumonia, Viral / complications
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / virology
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrazoles / pharmacokinetics
  • Pyrazoles / pharmacology*
  • SARS-CoV-2
  • Severe Acute Respiratory Syndrome / complications
  • Severe Acute Respiratory Syndrome / immunology
  • Severe Acute Respiratory Syndrome / prevention & control*
  • Severe Acute Respiratory Syndrome / virology
  • Severity of Illness Index
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • ruxolitinib
  • JAK1 protein, human
  • JAK2 protein, human
  • Janus Kinase 1
  • Janus Kinase 2