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

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.

Category: Biochemistry

Category: Health

Funder: KAW/SciLifeLab

Funder: VR

Funder: Vinnova

Research Area: Host cell systems biology and targets

Type: Journal article

PubMed 33479167

DOI 10.1073/pnas.2018587118

Crossref 10.1073/pnas.2018587118

Publications 9.5.0