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Title: Major alterations in the mononuclear phagocyte landscape associated with COVID-19 severity
Authors: Kvedaraite, Egle
Hertwig, Laura
Sinha, Indranil
Ponzetta, Andrea
Myrberg, Ida Hed
Lourda, Magda
Dzidic, Majda
Akber, Mira
Klingström, J.
Folkesson, Elin
Muvva, Jagadeeswara Rao
Chen, Puran
Gredmark-Russ, Sara
Brighenti, Susanna
Norrby-Teglund, Anna
Eriksson, Lars, I
Rooyackers, Olav
Aleman, Soo
Strålin, K.
Ljunggren, Hans-Gustaf
Ginhoux, Florent 
Björkström, N.K.
Henter, Jan-Inge
Svensson, Mattias
Karolinska KI/K COVID-19 Study Group.
Keywords: COVID-19
Issue Date: 21-Jan-2021
Publisher: National Academy of Sciences
Citation: Kvedaraite, Egle, Hertwig, Laura, Sinha, Indranil, Ponzetta, Andrea, Myrberg, Ida Hed, Lourda, Magda, Dzidic, Majda, Akber, Mira, Klingström, J., Folkesson, Elin, Muvva, Jagadeeswara Rao, Chen, Puran, Gredmark-Russ, Sara, Brighenti, Susanna, Norrby-Teglund, Anna, Eriksson, Lars, I, Rooyackers, Olav, Aleman, Soo, Strålin, K., Ljunggren, Hans-Gustaf, Ginhoux, Florent, Björkström, N.K., Henter, Jan-Inge, Svensson, Mattias, Karolinska KI/K COVID-19 Study Group. (2021-01-21). Major alterations in the mononuclear phagocyte landscape associated with COVID-19 severity. Proceedings of the National Academy of Sciences of the United States of America 118 (6) : e2018587118. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Dendritic cells (DCs) and monocytes are crucial mediators of innate and adaptive immune responses during viral infection, but misdirected responses by these cells may contribute to immunopathology. Here, we performed high-dimensional flow cytometry-analysis focusing on mononuclear phagocyte (MNP) lineages in SARS-CoV-2-infected patients with moderate and severe COVID-19. We provide a deep and comprehensive map of the MNP landscape in COVID-19. A redistribution of monocyte subsets toward intermediate monocytes and a general decrease in circulating DCs was observed in response to infection. Severe disease coincided with the appearance of monocytic myeloid-derived suppressor cell-like cells and a higher frequency of pre-DC2. Furthermore, phenotypic alterations in MNPs, and their late precursors, were cell-lineage-specific and associated either with the general response against SARS-CoV-2 or COVID-19 severity. This included an interferon-imprint in DC1s observed in all patients and a decreased expression of the coinhibitory molecule CD200R in pre-DCs, DC2s, and DC3 subsets of severely sick patients. Finally, unsupervised analysis revealed that the MNP profile, alone, pointed to a cluster of COVID-19 nonsurvivors. This study provides a reference for the MNP response to SARS-CoV-2 infection and unravels mononuclear phagocyte dysregulations associated with severe COVID-19. © 2021 National Academy of Sciences. All rights reserved.
Source Title: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
DOI: 10.1073/pnas.2018587118
Rights: Attribution 4.0 International
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