Phenotypical and functional alteration of unconventional T cells in severe COVID-19 patients

J Exp Med. 2020 Dec 7;217(12):e20200872. doi: 10.1084/jem.20200872.


COVID-19 includes lung infection ranging from mild pneumonia to life-threatening acute respiratory distress syndrome (ARDS). Dysregulated host immune response in the lung is a key feature in ARDS pathophysiology. However, cellular actors involved in COVID-19-driven ARDS are poorly understood. Here, in blood and airways of severe COVID-19 patients, we serially analyzed unconventional T cells, a heterogeneous class of T lymphocytes (MAIT, γδT, and iNKT cells) with potent antimicrobial and regulatory functions. Circulating unconventional T cells of COVID-19 patients presented with a profound and persistent phenotypic alteration. In the airways, highly activated unconventional T cells were detected, suggesting a potential contribution in the regulation of local inflammation. Finally, expression of the CD69 activation marker on blood iNKT and MAIT cells of COVID-19 patients on admission was predictive of clinical course and disease severity. Thus, COVID-19 patients present with an altered unconventional T cell biology, and further investigations will be required to precisely assess their functions during SARS-CoV-2-driven ARDS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD / blood
  • Antigens, Differentiation, T-Lymphocyte / blood
  • Betacoronavirus / genetics*
  • COVID-19
  • Cells, Cultured
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / virology
  • Cytokines / metabolism
  • Female
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Lectins, C-Type / blood
  • Male
  • Middle Aged
  • Mucosal-Associated Invariant T Cells / immunology
  • Mucosal-Associated Invariant T Cells / metabolism*
  • Natural Killer T-Cells / immunology
  • Natural Killer T-Cells / metabolism*
  • Pandemics
  • Phenotype*
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / virology
  • Prognosis
  • Prospective Studies
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Respiratory Distress Syndrome / immunology*
  • Respiratory Distress Syndrome / virology
  • SARS-CoV-2
  • Severity of Illness Index


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Cytokines
  • Lectins, C-Type
  • Receptors, Antigen, T-Cell, gamma-delta