Perturbations in the mononuclear phagocyte landscape associated with COVID-19 disease severity

Kvedaraite, E.; Hertwig, L.; Sinha, I.; Ponzetta, A.; Hed Myrberg, I.; Lourda, M.; Dzidic, M.; Akber, M.; Klingstrom, J.; Folkesson, E.; Muvva, R.; Chen, P.; Brighenti, S.; Norrby-Teglund, A.; Eriksson, L. I.; Rooyackers, O.; Aleman, S.; Stralin, K.; Ljunggren, H.-G.; Ginhoux, F.; Bjorkstrom, N.; Henter, J.-I.; Svensson, M.

Monocytes and dendritic cells are crucial mediators of innate and adaptive immune responses during viral infection, but misdirected responses by these cells might contribute to immunopathology. A comprehensive map of the mononuclear phagocyte (MNP) landscape during SARS-CoV-2 infection and concomitant COVID-19 disease is lacking. We performed 25-color flow cytometry-analysis focusing on MNP lineages in SARS-CoV-2 infected patients with moderate and severe COVID-19. While redistribution of monocytes towards intermediate subset and decrease in circulating DCs occurred in response to infection, severe disease associated with appearance of Mo-MDSC-like cells and a higher frequency of pre-DC2. Furthermore, phenotypic alterations in MNPs, and their late precursors, were cell-lineage specific and in select cases associated with severe disease. Finally, unsupervised analysis revealed that the MNP profile, alone, could identify a cluster of COVID-19 non-survivors. This study provides a reference for the MNP response to clinical SARS-CoV-2 infection and unravel myeloid dysregulation associated with severe COVID-19.