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

• Published in: Cell death and differentiation Vol. 27; no. 11; pp. 3196 - 3207
• Main Authors: Agrati, Chiara, Sacchi, Alessandra, Bordoni, Veronica, Cimini, Eleonora, Notari, Stefania, Grassi, Germana, Casetti, Rita, Tartaglia, Eleonora, Lalle, Eleonora, D’Abramo, Alessandra, Castilletti, Concetta, Marchioni, Luisa, Shi, Yufang, Mariano, Andrea, Song, Jin-Wen, Zhang, Ji-Yuan, Wang, Fu-Sheng, Zhang, Chao, Fimia, Gian Maria, Capobianchi, Maria R., Piacentini, Mauro, Antinori, Andrea, Nicastri, Emanuele, Maeurer, Markus, Zumla, Alimuddin, Ippolito, Giuseppe
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2020; Nature Publishing Group
• Subjects: 13/21; 13/31; 631/250/255; 692/699/255; Adult; Apoptosis; Betacoronavirus - pathogenicity; Biochemistry; Biomedical and Life Sciences; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD95 antigen; Cell activation; Cell Biology; Cell Cycle Analysis; Convalescence; Coronavirus Infections - immunology; Coronavirus Infections - virology; Coronaviruses; COVID-19; Cytokines - metabolism; Cytotoxicity; Disease Progression; Effector cells; Female; Humans; Immune response; Inflammation; Inflammation - immunology; Interleukin 6; Leukocytes (mononuclear); Life Sciences; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Lymphopenia; Myeloid-Derived Suppressor Cells - cytology; Myeloid-Derived Suppressor Cells - immunology; Neutrophilia; Pandemics; Peripheral blood; Pneumonia, Viral - immunology; Pneumonia, Viral - virology; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Stem Cells; Suppressor cells
• ISSN: 1350-9047; 1476-5403; 1476-5403
• DOI: 10.1038/s41418-020-0572-6

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.