Kvedaraite E, Hertwig L, Indranil S, Ponzetta A, Hed Myrberg I, Magdalini Lourda M, Dzidic M, Akber M, Klingstrom J, Folkesson E, Muvva R, Chen P, Brighenti S, Norrby-Teglund A, Lars I. Eriksson LI, Rooyackers O, Aleman S, Stralin K, Ljunggren H, Ginhoux F, Bjorkstrom N, Henter J, Svensson M
Proc Natl Acad Sci U S A 118 (6) - [2020-11-17; online 2021-01-23]
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.