ABSTRACT
Background: PMN and monocytic myeloid-derived suppressor cells (PMN-MDSCs, M-MDSCs) are immunosuppressive cells rising during infections. Aim: To characterize the dynamic of MDSCs in relation with immune parameters in COVID-19 patients followed for 3 months. Methods: 56 SARS-CoV-2 infected adult patients hospitalized at CHUV were included. Blood was obtained at inclusion and 3 months later in 21 patients, and from 10 healthy controls. Blood was stimulated with TLR ligands. Leukocyte populations and cytokines were analyzed by flow cytometry, mass cytometry, multiplex bead assay and ELISA. Results: At hospital admission, PMN-MDSCs and M-MDSCs were increased 2-4-fold in COVID-19 patients (P <0.05). PMN-MDSCs and M-MDSCs counts were higher in severe than in moderate COVID-19 patients (P <0.005). PMN-MDSCs and M-MDSCs correlated positively with EGF and HGF (P <0.05). M-MDSCs correlated positively with IL-1β, IL-7, PDGF and VEGF (P <0.05). In whole blood stimulated with TLR ligands, the proportion of TNF and IL-6- producing monocytes and DCs were reduced in patients. After 32 months, MDSCs were back to normal levels, while the production of cytokines by blood, monocytes and DCs was still largely affected. Conclusions: PMN-MDSCs and M-MDSCs were elevated and correlated with disease severity in patients analyzed at hospitalization. Innate immune blood responses were impaired in patients, which persisted for up to 3 months. Our results suggest that COVID-19 induces rapid and long-standing innate immune dysregulation.