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Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19

2021; Cell Press; Volume: 54; Issue: 11 Linguagem: Inglês

10.1016/j.immuni.2021.09.002

1097-4180

Benjamin Krämer, Rainer Knoll, Lorenzo Bonaguro, Michael ToVinh, Jan Raabe, Rosario Astaburuaga-García, Jonas Schulte-Schrepping, Kim M Kaiser, Gereon Rieke, Jenny Bischoff, Malte B. Monin, Christoph Hoffmeister, Stefan Schlabe, Elena De Domenico, Nico Reusch, Kristian Händler, Gary Reynolds, Nils Blüthgen, Gudrun Hack, Claudia Finnemann, Hans Dieter Nischalke, Christian P. Strassburg, Emily Stephenson, Yapeng Su, Louis Gardner, Dan Yuan, Daniel Chen, Jason D. Goldman, Philip Rosenstiel, Susanne V. Schmidt, Eicke Latz, Kevin Hrusovsky, Andrew J. Ball, Joseph M. Johnson, Paul-Albert Koenig, Florian I. Schmidt, Muzlifah Haniffa, James R. Heath, Beate M. Kümmerer, Verena Keitel, Björn‐Erik Ole Jensen, Paula Stubbemann, Florian Kurth, Leif Erik Sander, Birgit Sawitzki, Anna C. Aschenbrenner, Joachim L. Schultze, Jacob Nattermann, Janine Altmüller, Angel Angelov, Anna C. Aschenbrenner, Robert Bals, Alexander Bartholomäus, Anke Becker, Matthias Becker, Daniela Bezdan, Michael Bitzer, Conny Blumert, Ezio Bonifacio, Peer Bork, Boyke Bunk, Helmut Blum, Nicolas Casadei, Thomas Clavel, Maria Colomé‐Tatché, Markus Cornberg, Inti Alberto De La Rosa Velázquez, Andreas Diefenbach, Alexander Dilthey, Nicole Fischer, Konrad U. Förstner, Sören Franzenburg, Julia-Stefanie Frick, Gisela Gabernet, Julien Gagneur, Tina Ganzenmueller, Marie Gauder, Janina Geißert, Alexander Goesmann, Siri Göpel, Adam Grundhoff, Hajo Grundmann, Torsten Hain, Frank Hanses, Ute Hehr, André Heimbach, Marius M. Hoeper, Friedemann Horn, Daniel Hübschmann, Michael Hummel, Thomas Iftner, Angelika Iftner, Thomas Illig, Stefan Janssen, Jörn Kalinowski, René Kallies, Birte Kehr, Andreas Keller, Oliver T. Keppler, Sarah Kim-Hellmuth, Christoph Klein, Michael Knop, Oliver Kohlbacher, Karl Köhrer, Jan O. Korbel, Peter G. Kremsner, Denise Kühnert, Ingo Kurth, Markus Landthaler, Yang Li, Kerstin U. Ludwig, Oliwia Makarewicz, Fédérico Marini, Manja Marz, Alice C. McHardy, Christian Mertes, Maximilian Münchhoff, Sven Nahnsen, Markus M. Nöthen, Francine Ntoumi, Peter Nürnberg, Stephan Ossowski, Jörg Overmann, Silke Peter, Klaus Pfeffer, Isabell Pink, Anna R. Poetsch, Ulrike Protzer, Alfred Pühler, Nikolaus Rajewsky, Markus Ralser, Kristin Reiche, Olaf Rieß, Stephan Ripke, Ulisses Nunes da Rocha, Philip Rosenstiel, Antoine‐Emmanuel Saliba, Leif Erik Sander, Birgit Sawitzki, Simone Scheithauer, Philipp H. Schiffer, Jonathan L. Schmid‐Burgk, Wulf Schneider, Eva C. Schulte, Joachim L. Schultze, Alexander Sczyrba, Mariam L. Sharaf, Yogesh Preet Singh, Michael Sonnabend, Oliver Stegle, Jens Stoye, Fabian J. Theis, Thomas Ulas, Jörg Janne Vehreschild, Thirumalaisamy P. Velavan, Jörg Vogel, Sonja Volland, Max von Kleist, Andreas Walker, Jörn Walter, Dagmar Wieczorek, Sylke Winkler, John Ziebuhr,

Long-Term Effects of COVID-19

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.