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@ARTICLE{Krmer:162916,
author = {Krämer, Benjamin and Knoll, Rainer and Bonaguro, Lorenzo
and ToVinh, Michael and Raabe, Jan and Astaburuaga-García,
Rosario and Schulte-Schrepping, Jonas and Kaiser, Kim
Melanie and Rieke, Gereon J and Bischoff, Jenny and Monin,
Malte B and Hoffmeister, Christoph and Schlabe, Stefan and
De Domenico, Elena and Reusch, Nico and Händler, Kristian
and Reynolds, Gary and Blüthgen, Nils and Hack, Gudrun and
Finnemann, Claudia and Nischalke, Hans D and Strassburg,
Christian P and Stephenson, Emily and Su, Yapeng and
Gardner, Louis and Yuan, Dan and Chen, Daniel and Goldman,
Jason and Rosenstiel, Philipp and Schmidt, Susanne V and
Latz, Eicke and Hrusovsky, Kevin and Ball, Andrew J and
Johnson, Joe M and Koenig, Paul-Albert and Schmidt, Florian
I and Haniffa, Muzlifah and Heath, James R and Kümmerer,
Beate M and Keitel, Verena and Jensen, Björn and
Stubbemann, Paula and Kurth, Florian and Sander, Leif E and
Sawitzki, Birgit and Aschenbrenner, Anna C and Schultze,
Joachim and Nattermann, Jacob and Altmüller, Janine and
Angelov, Angel and Aschenbrenner, Anna C and Bals, Robert
and Bartholomäus, Alexander and Becker, Anke and Becker,
Matthias Kai Holger and Bezdan, Daniela and Bitzer, Michael
and Blumert, Conny and Bonifacio, Ezio and Bork, Peer and
Boyke, Bunk and Blum, Helmut and Casadei, Nicolas and
Clavel, Thomas and Colome-Tatche, Maria and Cornberg, Markus
and De La Rosa Velázquez, Inti Alberto and Diefenbach,
Andreas and Dilthey, Alexander and Fischer, Nicole and
Förstner, Konrad and Franzenburg, Sören and Frick,
Julia-Stefanie and Gabernet, Gisela and Gagneur, Julien and
Ganzenmueller, Tina and Gauder, Marie and Geißert, Janina
and Goesmann, Alexander and Göpel, Siri and Grundhoff, Adam
and Grundmann, Hajo and Hain, Torsten and Hanses, Frank and
Hehr, Ute and Heimbach, André and Hoeper, Marius and Horn,
Friedemann and Hübschmann, Daniel and Hummel, Michael and
Iftner, Thomas and Iftner, Angelika and Illig, Thomas and
Janssen, Stefan and Kalinowski, Jörn and Kallies, René and
Kehr, Birte and Keller, Andreas and Keppler, Oliver T and
Kim-Hellmuth, Sarah and Klein, Christoph and Knop, Michael
and Kohlbacher, Oliver and Köhrer, Karl and Korbel, Jan and
Kremsner, Peter G and Kühnert, Denise and Kurth, Ingo and
Landthaler, Markus and Li, Yang and Ludwig, Kerstin U and
Makarewicz, Oliwia and Marini, Federico and Marz, Manja and
McHardy, Alice C and Mertes, Christian and Münchhoff,
Maximilian and Nahnsen, Sven and Nöthen, Markus M. and
Ntoumi, Francine and Nürnberg, Peter and Ossowski, Stephan
and Overmann, Jörg and Peter, Silke and Pfeffer, Klaus and
Pink, Isabell and Poetsch, Anna R and Protzer, Ulrike and
Pühler, Alfred and Rajewsky, Nikolaus and Ralser, Markus
and Reiche, Kristin and Rieß, Olaf and Ripke, Stephan and
Nunes da Rocha, Ulisses and Rosenstiel, Philip and Saliba,
Antoine-Emmanuel and Sander, Leif Erik and Sawitzki, Birgit
and Scheithauer, Simone and Schiffer, Philipp and
Schmid-Burgk, Jonathan and Schneider, Wulf and Schulte,
Eva-Christina and Schultze, Joachim and Sczyrba, Alexander
and Sharaf, Mariam and Singh, Yogesh and Sonnabend, Michael
and Stegle, Oliver and Stoye, Jens and Theis, Fabian and
Ulas, Thomas and Vehreschild, Janne and Velavan,
Thirumalaisamy P and Vogel, Jörg and Volland, Sonja and von
Kleist, Max and Walker, Andreas and Walter, Jörn and
Wieczorek, Dagmar and Winkler, Sylke and Ziebuhr, John},
collaboration = {Initiative, Deutsche COVID-19 OMICS},
title = {{E}arly {IFN}-α signatures and persistent dysfunction are
distinguishing features of {NK} cells in severe {COVID}-19.},
journal = {Immunity},
volume = {54},
number = {11},
issn = {1074-7613},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DZNE-2021-01569},
pages = {2650 - 2669.e14},
year = {2021},
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.},
keywords = {Base Sequence / COVID-19: immunology / Humans / Immunity,
Innate: immunology / Inflammation: immunology /
Interferon-alpha: blood / Interferon-alpha: immunology /
Killer Cells, Natural: immunology / Pulmonary Fibrosis:
pathology / RNA-Seq / SARS-CoV-2: immunology / Severity of
Illness Index / Transcriptome: genetics / Tumor Necrosis
Factor-alpha: metabolism / United Kingdom / United States /
COVID-19 (Other) / NK cells (Other) / TNF (Other) /
antiviral (Other) / lung fibrosis (Other) / moderate (Other)
/ proteomics (Other) / scRNA-seq (Other) / severe (Other) /
type 1 IFN (Other) / IFNA1 protein, human (NLM Chemicals) /
Interferon-alpha (NLM Chemicals) / Tumor Necrosis
Factor-alpha (NLM Chemicals)},
cin = {Schultze - PRECISE / $R\&D$ PRECISE},
ddc = {610},
cid = {I:(DE-2719)1013031 / I:(DE-2719)5000031},
pnm = {354 - Disease Prevention and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-354},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34592166},
pmc = {pmc:PMC8416549},
doi = {10.1016/j.immuni.2021.09.002},
url = {https://pub.dzne.de/record/162916},
}