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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19
Immunity, Volume 54, No. 11, Year 2021
Notification
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Description
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. © 2021 Elsevier Inc.
Authors & Co-Authors
Schlabe, Stefan
Germany, Bonn
Universitätsklinikum Bonn
Blüthgen, Nils
Germany, Berlin
Freie Universität Berlin
Germany, Berlin
Humboldt-universität zu Berlin
Strassburg, Christian P.
Germany, Bonn
Universitätsklinikum Bonn
Su, Yapeng
United States, Seattle
Institute for Systems Biology
Yuan, Dan
United States, Seattle
Institute for Systems Biology
Chen, Daniel G.
United States, Seattle
Institute for Systems Biology
Goldman, Jason D.
United States, Seattle
Institute for Systems Biology
United States, Seattle
Swedish Medical Center, Seattle
United States, Renton
Providence St. Joseph Health
United States, Seattle
University of Washington
Rosenstiel, Philip C.
Germany, Kiel
Universitätsklinikum Schleswig-holstein Campus Kiel
Latz, Eicke
Germany, Bonn
Universität Bonn
Haniffa, Muzlifah A.
United Kingdom, Newcastle
Newcastle University
United Kingdom, Hinxton
Wellcome Sanger Institute
United Kingdom, Newcastle
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
Heath, James R.
United States, Seattle
Institute for Systems Biology
United States, Seattle
University of Washington
Kümmerer, Beate Mareike
Germany, Bonn
Universität Bonn
Keitel, Verena
Germany, Dusseldorf
Heinrich-heine-universität Düsseldorf
Jensen, Björn Erik Ole
Germany, Dusseldorf
Heinrich-heine-universität Düsseldorf
Kurth, Florian
Germany, Berlin
Charité – Universitätsmedizin Berlin
Altmüller, Janine
Unknown Affiliation
Angelov, Angel
Unknown Affiliation
Aschenbrenner, Anna C.
Germany, Bonn
Deutsches Zentrum Für Neurodegenerative Erkrankungen
Germany, Bonn
Universität Bonn
Netherlands, Nijmegen
Radboud University Medical Center
Bals, Robert
Unknown Affiliation
Becker, Anke
Unknown Affiliation
Bezdan, Daniela
Unknown Affiliation
Bitzer, Michael
Unknown Affiliation
Bonifacio, Ezio E.
Unknown Affiliation
Bork, Peer
Unknown Affiliation
Blum, Helmut
Unknown Affiliation
Casadei, Nicolas L.P.
Unknown Affiliation
Clavel, Thomas
Unknown Affiliation
Cornberg, Markus
Unknown Affiliation
De La Rosa-Velazquez, Inti Alberto
Unknown Affiliation
Diefenbach, Andreas
Unknown Affiliation
Dilthey, Alexander T.
Unknown Affiliation
Fischer, Nicole
Unknown Affiliation
Förstner, Konrad U.
Unknown Affiliation
Ganzenmueller, Tina
Unknown Affiliation
Goesmann, Alexander
Unknown Affiliation
Göpel, Siri
Unknown Affiliation
Grundhoff, Adam T.
Unknown Affiliation
Grundmann, Hajo J.
Unknown Affiliation
Hain, Torsten
Unknown Affiliation
Hanses, Frank
Unknown Affiliation
Hehr, Ute
Unknown Affiliation
Hoeper, Marius M.
Unknown Affiliation
Hübschmann, Daniel
Unknown Affiliation
Hummel, Michael
Unknown Affiliation
Iftner, Thomas
Unknown Affiliation
Illig, Thomas
Unknown Affiliation
Janssen, Stefan
Unknown Affiliation
Kalinowski, Jörn
Unknown Affiliation
Kallies, René
Unknown Affiliation
Keller, Andreas C.
Unknown Affiliation
Keppler, Oliver Till
Unknown Affiliation
Klein, Christoph A.
Unknown Affiliation
Korbel, Jan O.
Unknown Affiliation
Kremsner, Peter G.
Unknown Affiliation
Kühnert, Denise
Unknown Affiliation
Kurth, Ingo
Unknown Affiliation
Li, Yang
Unknown Affiliation
Ludwig, Kerstin Urte
Unknown Affiliation
Makarewicz, Oliwia
Unknown Affiliation
Marz, Manja
Unknown Affiliation
McHardy, Alice Carolyn
Unknown Affiliation
Nahnsen, Sven
Unknown Affiliation
Nöthen, Markus Maria
Unknown Affiliation
Ntoumi, Francine
Unknown Affiliation
Nurnberg, Peter N.
Unknown Affiliation
Ossowski, Stephan
Unknown Affiliation
Overmann, Jörg
Unknown Affiliation
Peter, Silke
Unknown Affiliation
Pfeffer, Klaus
Unknown Affiliation
Pink, Isabell
Unknown Affiliation
Protzer, Ulrike
Unknown Affiliation
Ralser, Markus
Unknown Affiliation
Riess, Olaf H.
Unknown Affiliation
Ripke, Stephan
Unknown Affiliation
Rocha, Ulisses
Unknown Affiliation
Scheithauer, Simone
Unknown Affiliation
Schmid-Burgk, Jonathan Leo
Unknown Affiliation
Sczyrba, Alexander
Unknown Affiliation
Singh, Yogesh
Unknown Affiliation
Sonnabend, Michael S.
Unknown Affiliation
Stegle, Oliver
Unknown Affiliation
Stoye, Jens
Unknown Affiliation
Theis, Fabian J.
Unknown Affiliation
Ulas, Thomas
Unknown Affiliation
Vehreschild, Jörg Janne
Unknown Affiliation
Velavan, Thirumalaisamy P.
Unknown Affiliation
Walker, Andreas
Unknown Affiliation
Walter, Jörn E.
Unknown Affiliation
Wieczorek, Dagmar
Unknown Affiliation
Ziebuhr, John
Unknown Affiliation
Nattermann, Jacob K.
Germany, Bonn
Universitätsklinikum Bonn
Statistics
Citations: 131
Authors: 91
Affiliations: 16
Identifiers
Doi:
10.1016/j.immuni.2021.09.002
ISSN:
10747613
Research Areas
Cancer
Covid
Study Design
Cohort Study