JAK Inhibition as a New Treatment Strategy for Patients with COVID-19

Int Arch Allergy Immunol. 2020;181(6):467-475. doi: 10.1159/000508247. Epub 2020 May 11.

Abstract

After the advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the outbreak of coronavirus disease 2019 (COVID-19) commenced across the world. Understanding the Immunopathogenesis of COVID-19 is essential for interrupting viral infectivity and preventing aberrant immune responses before a vaccine can be developed. In this review, we provide the latest insights into the roles of angiotensin-converting enzyme II (ACE2) and Ang II receptor-1 (AT1-R) in this disease. Novel therapeutic strategies, including recombinant ACE2, ACE inhibitors, AT1-R blockers, and Ang 1-7 peptides, may prevent or reduce viruses-induced pulmonary, cardiac, and renal injuries. However, more studies are needed to clarify the efficacy of these therapeutics. Furthermore, considering the common role of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in AT1-R expressed on peripheral tissues and cytokine receptors on the surface of immune cells, potential targeting of this pathway using JAK inhibitors (JAKinibs) is suggested as a promising approach in patients with COVID-19 who are admitted to hospitals. In addition to antiviral therapy, potential ACE2- and AT1-R-inhibiting strategies, and other supportive care, we suggest other potential JAKinibs and novel anti-inflammatory combination therapies that affect the JAK-STAT pathway in patients with COVID-19. Since the combination of MTX and baricitinib leads to outstanding clinical outcomes, the addition of baricitinib to MTX might be a potential strategy.

Keywords: Angiotensin receptor blocker; Angiotensin-converting enzyme inhibitor; Bricitinib; Cytokine; JAK inhibitors; JAK-STAT pathway; Methotrexate.

Publication types

  • Review

MeSH terms

  • Angiotensin I / therapeutic use*
  • Angiotensin-Converting Enzyme 2
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Antiviral Agents / therapeutic use*
  • Azetidines / therapeutic use*
  • Betacoronavirus / drug effects
  • Betacoronavirus / immunology
  • Betacoronavirus / pathogenicity
  • COVID-19
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / immunology
  • Coronavirus Infections / virology
  • Disease Progression
  • Gene Expression Regulation
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology
  • Humans
  • Janus Kinases / antagonists & inhibitors
  • Janus Kinases / genetics*
  • Janus Kinases / immunology
  • Methotrexate / therapeutic use*
  • Molecular Targeted Therapy / methods
  • Pandemics*
  • Peptide Fragments / therapeutic use*
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / immunology
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / epidemiology
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / virology
  • Purines
  • Pyrazoles
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / immunology
  • SARS-CoV-2
  • STAT Transcription Factors / antagonists & inhibitors
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / immunology
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Sulfonamides / therapeutic use*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antiviral Agents
  • Azetidines
  • Peptide Fragments
  • Purines
  • Pyrazoles
  • Receptor, Angiotensin, Type 1
  • STAT Transcription Factors
  • Sulfonamides
  • Angiotensin I
  • Janus Kinases
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)
  • baricitinib
  • Methotrexate