Early expansion of myeloid-derived suppressor cells inhibits SARS-CoV-2 specific T-cell response and may predict fatal COVID-19 outcome

• Published in: Cell death & disease Vol. 11; no. 10; p. 921
• Main Authors: Sacchi, Alessandra, Grassi, Germana, Bordoni, Veronica, Lorenzini, Patrizia, Cimini, Eleonora, Casetti, Rita, Tartaglia, Eleonora, Marchioni, Luisa, Petrosillo, Nicola, Palmieri, Fabrizio, D’Offizi, Gianpiero, Notari, Stefania, Tempestilli, Massimo, Capobianchi, Maria Rosaria, Nicastri, Emanuele, Maeurer, Markus, Zumla, Alimuddin, Locatelli, Franco, Antinori, Andrea, Ippolito, Giuseppe, Agrati, Chiara
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.10.2020; Springer Nature B.V
• Subjects: 13/21; 38/77; 692/420/254; 692/699/255/2514; Aged; Antibodies; Area Under Curve; Betacoronavirus - immunology; Betacoronavirus - isolation & purification; Betacoronavirus - metabolism; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Culture; Coronavirus Infections - immunology; Coronavirus Infections - mortality; Coronavirus Infections - pathology; Coronavirus Infections - virology; Coronaviruses; COVID-19; Female; Humans; IL-1β; Immunology; Interferon-gamma - metabolism; Interleukin 6; Interleukin 8; Interleukin-1beta - blood; Interleukin-6 - blood; Life Sciences; Lymphocytes T; Male; Middle Aged; Myeloid-Derived Suppressor Cells - cytology; Myeloid-Derived Suppressor Cells - immunology; Neutrophils - cytology; Neutrophils - immunology; Neutrophils - metabolism; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Pandemics; Peptides - immunology; Peptides - metabolism; Plasma levels; Pneumonia, Viral - immunology; Pneumonia, Viral - mortality; Pneumonia, Viral - pathology; Pneumonia, Viral - virology; Proportional Hazards Models; ROC Curve; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Suppressor cells; Survival Rate; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transforming Growth Factor beta - blood; Transforming Growth Factor beta - metabolism; Tumor necrosis factor-α; γ-Interferon
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-020-03125-1

The immunological mechanisms underlying the clinical presentation of SARS-CoV-2 infection and those influencing the disease outcome remain to be defined. Myeloid-derived suppressor cells (MDSC) have been described to be highly increased during COVID-19, however, their role remains elusive. We performed an in depth analysis of MDSC in 128 SARS-CoV-2 infected patients. Polymorphonuclear (PMN)-MDSC expanded during COVID-19, in particular in patients who required intensive care treatments, and correlated with IL-1β, IL-6, IL-8, and TNF-α plasma levels. PMN-MDSC inhibited T-cells IFN-γ production upon SARS-CoV-2 peptides stimulation, through TGF-β- and iNOS-mediated mechanisms, possibly contrasting virus elimination. Accordingly, a multivariate regression analysis found a strong association between PMN-MDSC percentage and fatal outcome of the disease. The PMN-MDSC frequency was higher in non-survivors than survivors at the admission time, followed by a decreasing trend. Interestingly, this trend was associated with IL-6 increase in non-survivors but not in survivors. In conclusion, this study indicates PMN-MDSC as a novel factor in the pathogenesis of SARS-CoV2 infection, and open up to new therapeutic options.