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

• DOI: 10.1038/s41419-020-03125-1
• Publication Date: 2020-10-27T14:04:21Z
• Authors: Alessandra Sacchi; Germana Grassi; Veronica Bordoni; Patrizia Lorenzini; Eleonora Cimini; Rita Casetti; Eleonora Tartaglia; Luisa Marchioni; Nicola Petrosillo; Fabrizio Palmieri; Gianpiero D’Offizi; Stefania Notari; Massimo Tempestilli; Maria Rosaria Cap...; Emanuele Nicastri; Markus Maeurer; Alimuddin Zumla; Franco Locatelli; Andrea Antinori; Giuseppe Ippolito; Chiara Agrati
• Keywords: Pathogenesis; Myeloid-derived Suppressor Cell

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