Expansion of myeloid-derived suppressor cells in patients with severe coronavirus disease (COVID-19)

Cell Death Differ. 2020 Nov;27(11):3196-3207. doi: 10.1038/s41418-020-0572-6. Epub 2020 Jun 8.


SARS-CoV-2 is associated with a 3.4% mortality rate in patients with severe disease. The pathogenesis of severe cases remains unknown. We performed an in-depth prospective analysis of immune and inflammation markers in two patients with severe COVID-19 disease from presentation to convalescence. Peripheral blood from 18 SARS-CoV-2-infected patients, 9 with severe and 9 with mild COVID-19 disease, was obtained at admission and analyzed for T-cell activation profile, myeloid-derived suppressor cells (MDSCs) and cytokine profiles. MDSC functionality was tested in vitro. In four severe and in four mild patients, a longitudinal analysis was performed daily from the day of admission to the early convalescent phase. Early after admission severe patients showed neutrophilia, lymphopenia, increase in effector T cells, a persisting higher expression of CD95 on T cells, higher serum concentration of IL-6 and TGF-β, and a cytotoxic profile of NK and T cells compared with mild patients, suggesting a highly engaged immune response. Massive expansion of MDSCs was observed, up to 90% of total circulating mononuclear cells in patients with severe disease, and up to 25% in the patients with mild disease; the frequency decreasing with recovery. MDSCs suppressed T-cell functions, dampening excessive immune response. MDSCs decline at convalescent phase was associated to a reduction in TGF-β and to an increase of inflammatory cytokines in plasma samples. Substantial expansion of suppressor cells is seen in patients with severe COVID-19. Further studies are required to define their roles in reducing the excessive activation/inflammation, protection, influencing disease progression, potential to serve as biomarkers of disease severity, and new targets for immune and host-directed therapeutic approaches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Betacoronavirus / pathogenicity*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • COVID-19
  • Coronavirus Infections / immunology
  • Coronavirus Infections / virology*
  • Cytokines / metabolism
  • Disease Progression
  • Female
  • Humans
  • Inflammation / immunology
  • Lymphocyte Activation / immunology*
  • Myeloid-Derived Suppressor Cells / cytology*
  • Myeloid-Derived Suppressor Cells / immunology
  • Pandemics
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / virology*
  • SARS-CoV-2


  • Cytokines