tetano
Editor, Senior Moderator
Cell Death Differ
. 2020 Jun 8.
doi: 10.1038/s41418-020-0572-6. Online ahead of print.
Expansion of Myeloid-Derived Suppressor Cells in Patients With Severe Coronavirus Disease (COVID-19)
Chiara Agrati[SUP] 1 [/SUP], Alessandra Sacchi[SUP] 1 [/SUP], Veronica Bordoni[SUP] 1 [/SUP], Eleonora Cimini[SUP] 1 [/SUP], Stefania Notari[SUP] 1 [/SUP], Germana Grassi[SUP] 1 [/SUP], Rita Casetti[SUP] 1 [/SUP], Eleonora Tartaglia[SUP] 1 [/SUP], Eleonora Lalle[SUP] 1 [/SUP], Alessandra D'Abramo[SUP] 1 [/SUP], Concetta Castilletti[SUP] 1 [/SUP], Luisa Marchioni[SUP] 1 [/SUP], Yufang Shi[SUP] 2 3 [/SUP], Andrea Mariano[SUP] 1 [/SUP], Jin-Wen Song[SUP] 4 [/SUP], Ji-Yuan Zhang[SUP] 4 [/SUP], Fu-Sheng Wang[SUP] 4 [/SUP], Chao Zhang[SUP] 4 [/SUP], Gian Maria Fimia[SUP] 1 5 [/SUP], Maria R Capobianchi[SUP] 1 [/SUP], Mauro Piacentini[SUP] 1 6 [/SUP], Andrea Antinori[SUP] 1 [/SUP], Emanuele Nicastri[SUP] 1 [/SUP], Markus Maeurer[SUP] 7 8 [/SUP], Alimuddin Zumla[SUP] 9 10 [/SUP], Giuseppe Ippolito[SUP] 11 [/SUP]
Affiliations
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.
. 2020 Jun 8.
doi: 10.1038/s41418-020-0572-6. Online ahead of print.
Expansion of Myeloid-Derived Suppressor Cells in Patients With Severe Coronavirus Disease (COVID-19)
Chiara Agrati[SUP] 1 [/SUP], Alessandra Sacchi[SUP] 1 [/SUP], Veronica Bordoni[SUP] 1 [/SUP], Eleonora Cimini[SUP] 1 [/SUP], Stefania Notari[SUP] 1 [/SUP], Germana Grassi[SUP] 1 [/SUP], Rita Casetti[SUP] 1 [/SUP], Eleonora Tartaglia[SUP] 1 [/SUP], Eleonora Lalle[SUP] 1 [/SUP], Alessandra D'Abramo[SUP] 1 [/SUP], Concetta Castilletti[SUP] 1 [/SUP], Luisa Marchioni[SUP] 1 [/SUP], Yufang Shi[SUP] 2 3 [/SUP], Andrea Mariano[SUP] 1 [/SUP], Jin-Wen Song[SUP] 4 [/SUP], Ji-Yuan Zhang[SUP] 4 [/SUP], Fu-Sheng Wang[SUP] 4 [/SUP], Chao Zhang[SUP] 4 [/SUP], Gian Maria Fimia[SUP] 1 5 [/SUP], Maria R Capobianchi[SUP] 1 [/SUP], Mauro Piacentini[SUP] 1 6 [/SUP], Andrea Antinori[SUP] 1 [/SUP], Emanuele Nicastri[SUP] 1 [/SUP], Markus Maeurer[SUP] 7 8 [/SUP], Alimuddin Zumla[SUP] 9 10 [/SUP], Giuseppe Ippolito[SUP] 11 [/SUP]
Affiliations
- PMID: 32514047
- DOI: 10.1038/s41418-020-0572-6
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.