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Major alterations in the mononuclear phagocyte landscape associated with COVID-19 severity.
Kvedaraite, Egle; Hertwig, Laura; Sinha, Indranil; Ponzetta, Andrea; Hed Myrberg, Ida; Lourda, Magda; Dzidic, Majda; Akber, Mira; Klingström, Jonas; Folkesson, Elin; Muvva, Jagadeeswara Rao; Chen, Puran; Gredmark-Russ, Sara; Brighenti, Susanna; Norrby-Teglund, Anna; Eriksson, Lars I; Rooyackers, Olav; Aleman, Soo; Strålin, Kristoffer; Ljunggren, Hans-Gustaf; Ginhoux, Florent; Björkström, Niklas K; Henter, Jan-Inge; Svensson, Mattias.
  • Kvedaraite E; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, 171 77 Stockholm, Sweden; egle.kvedaraite@ki.se.
  • Hertwig L; Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, 171 77 Stockholm, Sweden.
  • Sinha I; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, 171 77 Stockholm, Sweden.
  • Ponzetta A; Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, 171 77 Stockholm, Sweden.
  • Hed Myrberg I; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, 171 77 Stockholm, Sweden.
  • Lourda M; Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, 171 77 Stockholm, Sweden.
  • Dzidic M; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, 171 77 Stockholm, Sweden.
  • Akber M; Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, 171 77 Stockholm, Sweden.
  • Klingström J; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, 171 77 Stockholm, Sweden.
  • Folkesson E; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, 171 77 Stockholm, Sweden.
  • Muvva JR; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, 171 77 Stockholm, Sweden.
  • Chen P; Department of Infectious Diseases, Karolinska University Hospital, 171 77 Stockholm, Sweden.
  • Gredmark-Russ S; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, 171 77 Stockholm, Sweden.
  • Brighenti S; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, 171 77 Stockholm, Sweden.
  • Norrby-Teglund A; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, 171 77 Stockholm, Sweden.
  • Eriksson LI; Department of Infectious Diseases, Karolinska University Hospital, 171 77 Stockholm, Sweden.
  • Rooyackers O; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, 171 77 Stockholm, Sweden.
  • Aleman S; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, 171 77 Stockholm, Sweden.
  • Strålin K; Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care, Karolinska Institutet, 171 77 Stockholm, Sweden.
  • Ljunggren HG; Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, 171 77 Stockholm, Sweden.
  • Ginhoux F; Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, 171 77 Stockholm, Sweden.
  • Björkström NK; Division of Anesthesiology and Intensive Care, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, 141 52 Huddinge, Sweden.
  • Henter JI; Department of Infectious Diseases, Karolinska University Hospital, 171 77 Stockholm, Sweden.
  • Svensson M; Division of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, 171 77 Stockholm, Sweden.
Proc Natl Acad Sci U S A ; 118(6)2021 02 09.
Article in English | MEDLINE | ID: covidwho-1042803
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Mononuclear Phagocyte System / SARS-CoV-2 / COVID-19 Type of study: Observational study / Prognostic study Limits: Adult / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Mononuclear Phagocyte System / SARS-CoV-2 / COVID-19 Type of study: Observational study / Prognostic study Limits: Adult / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: English Year: 2021 Document Type: Article