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

Chiara Agrati, Alessandra Sacchi, Veronica Bordoni, Eleonora Cimini, Stefania Notari, Germana Grassi, Rita Casetti, Eleonora Tartaglia, Eleonora Lalle, Alessandra D’Abramo, Concetta Castilletti, Luisa Marchioni, Yufang Shi, Andrea Mariano, Jin Wen Song, Ji Yuan Zhang, Fu Sheng Wang, Chao Zhang, Gian Maria Fimia, Maria R. CapobianchiMauro Piacentini, Andrea Antinori, Emanuele Nicastri, Markus Maeurer, Alimuddin Zumla, Giuseppe Ippolito

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalCell Death and Differentiation
DOIs
StateAccepted/In press - 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Agrati, C., Sacchi, A., Bordoni, V., Cimini, E., Notari, S., Grassi, G., Casetti, R., Tartaglia, E., Lalle, E., D’Abramo, A., Castilletti, C., Marchioni, L., Shi, Y., Mariano, A., Song, J. W., Zhang, J. Y., Wang, F. S., Zhang, C., Fimia, G. M., ... Ippolito, G. (Accepted/In press). Expansion of myeloid-derived suppressor cells in patients with severe coronavirus disease (COVID-19). Cell Death and Differentiation. https://doi.org/10.1038/s41418-020-0572-6