%0 Journal Article
%A Krämer, Benjamin
%A Knoll, Rainer
%A Bonaguro, Lorenzo
%A ToVinh, Michael
%A Raabe, Jan
%A Astaburuaga-García, Rosario
%A Schulte-Schrepping, Jonas
%A Kaiser, Kim Melanie
%A Rieke, Gereon J
%A Bischoff, Jenny
%A Monin, Malte B
%A Hoffmeister, Christoph
%A Schlabe, Stefan
%A De Domenico, Elena
%A Reusch, Nico
%A Händler, Kristian
%A Reynolds, Gary
%A Blüthgen, Nils
%A Hack, Gudrun
%A Finnemann, Claudia
%A Nischalke, Hans D
%A Strassburg, Christian P
%A Stephenson, Emily
%A Su, Yapeng
%A Gardner, Louis
%A Yuan, Dan
%A Chen, Daniel
%A Goldman, Jason
%A Rosenstiel, Philipp
%A Schmidt, Susanne V
%A Latz, Eicke
%A Hrusovsky, Kevin
%A Ball, Andrew J
%A Johnson, Joe M
%A Koenig, Paul-Albert
%A Schmidt, Florian I
%A Haniffa, Muzlifah
%A Heath, James R
%A Kümmerer, Beate M
%A Keitel, Verena
%A Jensen, Björn
%A Stubbemann, Paula
%A Kurth, Florian
%A Sander, Leif E
%A Sawitzki, Birgit
%A Aschenbrenner, Anna C
%A Schultze, Joachim
%A Nattermann, Jacob
%A Altmüller, Janine
%A Angelov, Angel
%A Aschenbrenner, Anna C
%A Bals, Robert
%A Bartholomäus, Alexander
%A Becker, Anke
%A Becker, Matthias Kai Holger
%A Bezdan, Daniela
%A Bitzer, Michael
%A Blumert, Conny
%A Bonifacio, Ezio
%A Bork, Peer
%A Boyke, Bunk
%A Blum, Helmut
%A Casadei, Nicolas
%A Clavel, Thomas
%A Colome-Tatche, Maria
%A Cornberg, Markus
%A De La Rosa Velázquez, Inti Alberto
%A Diefenbach, Andreas
%A Dilthey, Alexander
%A Fischer, Nicole
%A Förstner, Konrad
%A Franzenburg, Sören
%A Frick, Julia-Stefanie
%A Gabernet, Gisela
%A Gagneur, Julien
%A Ganzenmueller, Tina
%A Gauder, Marie
%A Geißert, Janina
%A Goesmann, Alexander
%A Göpel, Siri
%A Grundhoff, Adam
%A Grundmann, Hajo
%A Hain, Torsten
%A Hanses, Frank
%A Hehr, Ute
%A Heimbach, André
%A Hoeper, Marius
%A Horn, Friedemann
%A Hübschmann, Daniel
%A Hummel, Michael
%A Iftner, Thomas
%A Iftner, Angelika
%A Illig, Thomas
%A Janssen, Stefan
%A Kalinowski, Jörn
%A Kallies, René
%A Kehr, Birte
%A Keller, Andreas
%A Keppler, Oliver T
%A Kim-Hellmuth, Sarah
%A Klein, Christoph
%A Knop, Michael
%A Kohlbacher, Oliver
%A Köhrer, Karl
%A Korbel, Jan
%A Kremsner, Peter G
%A Kühnert, Denise
%A Kurth, Ingo
%A Landthaler, Markus
%A Li, Yang
%A Ludwig, Kerstin U
%A Makarewicz, Oliwia
%A Marini, Federico
%A Marz, Manja
%A McHardy, Alice C
%A Mertes, Christian
%A Münchhoff, Maximilian
%A Nahnsen, Sven
%A Nöthen, Markus M.
%A Ntoumi, Francine
%A Nürnberg, Peter
%A Ossowski, Stephan
%A Overmann, Jörg
%A Peter, Silke
%A Pfeffer, Klaus
%A Pink, Isabell
%A Poetsch, Anna R
%A Protzer, Ulrike
%A Pühler, Alfred
%A Rajewsky, Nikolaus
%A Ralser, Markus
%A Reiche, Kristin
%A Rieß, Olaf
%A Ripke, Stephan
%A Nunes da Rocha, Ulisses
%A Rosenstiel, Philip
%A Saliba, Antoine-Emmanuel
%A Sander, Leif Erik
%A Sawitzki, Birgit
%A Scheithauer, Simone
%A Schiffer, Philipp
%A Schmid-Burgk, Jonathan
%A Schneider, Wulf
%A Schulte, Eva-Christina
%A Schultze, Joachim
%A Sczyrba, Alexander
%A Sharaf, Mariam
%A Singh, Yogesh
%A Sonnabend, Michael
%A Stegle, Oliver
%A Stoye, Jens
%A Theis, Fabian
%A Ulas, Thomas
%A Vehreschild, Janne
%A Velavan, Thirumalaisamy P
%A Vogel, Jörg
%A Volland, Sonja
%A von Kleist, Max
%A Walker, Andreas
%A Walter, Jörn
%A Wieczorek, Dagmar
%A Winkler, Sylke
%A Ziebuhr, John
%T Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19.
%J Immunity
%V 54
%N 11
%@ 1074-7613
%C New York, NY
%I Elsevier
%M DZNE-2021-01569
%P 2650 - 2669.e14
%D 2021
%X 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.
%K Base Sequence
%K COVID-19: immunology
%K Humans
%K Immunity, Innate: immunology
%K Inflammation: immunology
%K Interferon-alpha: blood
%K Interferon-alpha: immunology
%K Killer Cells, Natural: immunology
%K Pulmonary Fibrosis: pathology
%K RNA-Seq
%K SARS-CoV-2: immunology
%K Severity of Illness Index
%K Transcriptome: genetics
%K Tumor Necrosis Factor-alpha: metabolism
%K United Kingdom
%K United States
%K COVID-19 (Other)
%K NK cells (Other)
%K TNF (Other)
%K antiviral (Other)
%K lung fibrosis (Other)
%K moderate (Other)
%K proteomics (Other)
%K scRNA-seq (Other)
%K severe (Other)
%K type 1 IFN (Other)
%K IFNA1 protein, human (NLM Chemicals)
%K Interferon-alpha (NLM Chemicals)
%K Tumor Necrosis Factor-alpha (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34592166
%2 pmc:PMC8416549
%R 10.1016/j.immuni.2021.09.002
%U https://pub.dzne.de/record/162916