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Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19.
Krämer, Benjamin; Knoll, Rainer; Bonaguro, Lorenzo; ToVinh, Michael; Raabe, Jan; Astaburuaga-García, Rosario; Schulte-Schrepping, Jonas; Kaiser, Kim Melanie; Rieke, Gereon J; Bischoff, Jenny; Monin, Malte B; Hoffmeister, Christoph; Schlabe, Stefan; De Domenico, Elena; Reusch, Nico; Händler, Kristian; Reynolds, Gary; Blüthgen, Nils; Hack, Gudrun; Finnemann, Claudia; Nischalke, Hans D; Strassburg, Christian P; Stephenson, Emily; Su, Yapeng; Gardner, Louis; Yuan, Dan; Chen, Daniel; Goldman, Jason; Rosenstiel, Philipp; Schmidt, Susanne V; Latz, Eicke; Hrusovsky, Kevin; Ball, Andrew J; Johnson, Joe M; Koenig, Paul-Albert; Schmidt, Florian I; Haniffa, Muzlifah; Heath, James R; Kümmerer, Beate M; Keitel, Verena; Jensen, Björn; Stubbemann, Paula; Kurth, Florian; Sander, Leif E; Sawitzki, Birgit; Aschenbrenner, Anna C; Schultze, Joachim L; Nattermann, Jacob.
  • Krämer B; Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
  • Knoll R; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Bonaguro L; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • ToVinh M; Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
  • Raabe J; Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
  • Astaburuaga-García R; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt- Universität zu Berlin, Institute of Pathology, Berlin, Germany; IRI Life Sciences & Institute of Theoretical Biology, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Schulte-Schrepping J; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Kaiser KM; Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
  • Rieke GJ; Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
  • Bischoff J; Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
  • Monin MB; Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
  • Hoffmeister C; Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
  • Schlabe S; Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany; German Center for Infection Research (DZIF), Germany.
  • De Domenico E; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, and University of Bonn, Bonn, Germany.
  • Reusch N; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
  • Händler K; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, and University of Bonn, Bonn, Germany.
  • Reynolds G; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
  • Blüthgen N; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt- Universität zu Berlin, Institute of Pathology, Berlin, Germany; IRI Life Sciences & Institute of Theoretical Biology, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Hack G; Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
  • Finnemann C; Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
  • Nischalke HD; Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
  • Strassburg CP; Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
  • Stephenson E; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
  • Su Y; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Gardner L; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
  • Yuan D; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Chen D; Institute for Systems Biology, Seattle, WA 98109, USA.
  • Goldman J; Institute for Systems Biology, Seattle, WA 98109, USA; Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA 98109, USA; Providence St. Joseph Health, Renton, WA 98057, USA; Division of Allergy & Infectious Diseases, University of Washington, Seattle, WA 98109, USA.
  • Rosenstiel P; Institute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, Kiel, Germany.
  • Schmidt SV; Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany.
  • Latz E; Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany.
  • Hrusovsky K; Quanterix Corporation, Billerica, MA, USA.
  • Ball AJ; Quanterix Corporation, Billerica, MA, USA.
  • Johnson JM; Quanterix Corporation, Billerica, MA, USA.
  • Koenig PA; Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany; Core Facility Nanobodies, Medical Faculty, University of Bonn, Bonn, Germany.
  • Schmidt FI; Institute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany; Core Facility Nanobodies, Medical Faculty, University of Bonn, Bonn, Germany.
  • Haniffa M; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK; NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Department of Dermatology, Newcastle Hospitals NHS Fou
  • Heath JR; Institute for Systems Biology, Seattle, WA 98109, USA; Board of Directors of Isoplexis, Branford, CT 06405, USA; Department of Bioengineering, University of Washington, Seattle, WA 98105, USA; Board of Directors of PACT Pharma, South San Francisco, CA 94080, USA.
  • Kümmerer BM; German Center for Infection Research (DZIF), Germany; Institute of Virology, Medical Faculty, University of Bonn, Bonn, Germany.
  • Keitel V; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • Jensen B; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • Stubbemann P; Department of Infectious Diseases and Respiratory Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
  • Kurth F; Department of Infectious Diseases and Respiratory Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany; German Center for Lung Research (DZL), Germany.
  • Sander LE; Department of Infectious Diseases and Respiratory Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany; German Center for Lung Research (DZL), Germany.
  • Sawitzki B; Institute of Medical Immunology, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Aschenbrenner AC; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, and Univer
  • Schultze JL; Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, and Univer
  • Nattermann J; Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany; German Center for Infection Research (DZIF), Germany. Electronic address: jacob.nattermann@ukbonn.de.
Immunity ; 54(11): 2650-2669.e14, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1442406
ABSTRACT
Longitudinal analyses of the innate immune system, including the earliest time points, are essential to understand the immunopathogenesis and clinical course of coronavirus disease (COVID-19). Here, we performed a detailed characterization of natural killer (NK) cells in 205 patients (403 samples; days 2 to 41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated interferon (IFN)-α plasma levels in early severe COVD-19 alongside increased NK cell expression of IFN-stimulated genes (ISGs) and genes involved in IFN-α signaling, while upregulation of tumor necrosis factor (TNF)-induced genes was observed in moderate diseases. NK cells exert anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for the development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates a prolonged IFN-α-induced NK cell response with poorer disease outcome.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Killer Cells, Natural / Tumor Necrosis Factor-alpha / Interferon-alpha / SARS-CoV-2 / COVID-19 Type of study: Controlled clinical trial Topics: Long Covid Limits: Humans Country/Region as subject: North America / Europa Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2021.09.002

Full text: Available Collection: International databases Database: MEDLINE Main subject: Killer Cells, Natural / Tumor Necrosis Factor-alpha / Interferon-alpha / SARS-CoV-2 / COVID-19 Type of study: Controlled clinical trial Topics: Long Covid Limits: Humans Country/Region as subject: North America / Europa Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2021.09.002