Suppressive myeloid cells are a hallmark of severe COVID-19

Schulte-Schrepping, J.; Reusch, N.; Paclik, D.; Bassler, K.; Schlickeiser, S.; Zhang, B.; Krämer, B.; Krammer, T.; Brumhard, S.; Bonaguro, L.; De Domenico, E.; Wendisch, D.; Grasshoff, M.; Kapellos, T. S.; Beckstette, M.; Pecht, T.; Saglam, A.; Dietrich, O.; Mei, H. E.; Schulz, A. R.; Conrad, C.; Kunkel, D.; Vafadarnejad, E.; Xu, C.-J.; Horne, A.; Herbert, M.; Drews, A.; Thibeault, C.; Pfeiffer, M.; Hippenstiel, S.; Hocke, A.; Müller-Redetzky, H.; Heim, K.-M.; Machleidt, F.; Uhrig, A.; de Jarcy, L. B.; Jürgens, L.; Stegemann, M.; Glösenkamp, C. R.; Volk, H.-D.; Goffinet, C.; Raabe, J.; Kai,

'Severe Acute Respiratory Syndrome - Coronavirus-2' (SARS-CoV-2) infection causes Coronavirus Disease 2019 (COVID-19), a mild to moderate respiratory tract infection in the majority of patients. A subset of patients, however, progresses to severe disease and respiratory failure with acute respiratory distress syndrome (ARDS). Severe COVID-19 has been associated with increased neutrophil counts and dysregulated immune responses. The mechanisms of protective immunity in mild forms and the pathogenesis of dysregulated inflammation in severe courses of COVID-19 remain largely unclear. Here, we combined two single-cell RNA-sequencing technologies and single-cell proteomics in whole blood and peripheral blood mononuclear cells (PBMC) to determine changes in immune cell composition and activation in two independent dual-center patient cohorts (n=46 + n=54 COVID-19 samples), each with mild and severe cases of COVID-19. We observed a specific increase of HLA-DR high CD11c high inflammatory monocytes that displayed a strong interferon (IFN)-stimulated gene signature in patients with mild COVID-19, which was absent in severe disease. Instead, we found evidence of emergency myelopoiesis, marked by the occurrence of immunosuppressive pre-neutrophils and immature neutrophils and populations of dysfunctional and suppressive mature neutrophils, as well as suppressive HLA-DR low monocytes in severe COVID-19. Our study provides detailed insights into systemic immune response to SARS-CoV-2 infection and it reveals profound alterations in the peripheral myeloid cell compartment associated with severe courses of COVID-19.