BTK/ITK dual inhibitors: Modulating immunopathology and lymphopenia for COVID-19 therapy

J Leukoc Biol. 2021 Jan;109(1):49-53. doi: 10.1002/JLB.5COVR0620-306R. Epub 2020 Jul 8.


Bruton's tyrosine kinase (BTK) signaling is involved in innate immune responses and regulates the production of proinflammatory cytokines that can contribute to COVID-19 immunopathology. Clinical trials with BTK inhibitors in COVID-19 treatment have been proposed, and previous studies have attempted to investigate the therapeutic effects of ibrutinib and underlying mechanisms in treating viral pneumonia. These attempts, however, did not consider potential off target effect of BTK inhibitors on T cell differentiation, function, and survival, which may be beneficial in treatment for COVID-19. Here, we summarize the current knowledge of BTK/IL-2-inducible T-cell kinase (ITK) signaling in immunopathology and lymphopenia and discuss the potential of BTK/ITK dual inhibitors such as ibrutinib in modulating immunopathology and lymphopenia, for COVID-19 therapy.

Keywords: BTK; COVID-19; ITK; immunopathology; lymphopenia; therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase* / antagonists & inhibitors
  • Agammaglobulinaemia Tyrosine Kinase* / immunology
  • Agammaglobulinaemia Tyrosine Kinase* / metabolism
  • COVID-19 / enzymology
  • COVID-19 / immunology
  • COVID-19 Drug Treatment*
  • Cytokines / immunology
  • Humans
  • Immunity, Innate / drug effects
  • Lymphopenia* / drug therapy
  • Lymphopenia* / enzymology
  • Lymphopenia* / immunology
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / immunology
  • Protein-Tyrosine Kinases / metabolism
  • SARS-CoV-2* / immunology
  • SARS-CoV-2* / metabolism
  • Signal Transduction* / drug effects
  • Signal Transduction* / immunology


  • Cytokines
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • emt protein-tyrosine kinase