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Lookup NU author(s): Dr Gary ReynoldsORCiD, Dr Emily StephensonORCiD, Dr Louis Gardner, Professor Muzlifah Haniffa
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© 2021 Elsevier Inc.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.
Author(s): Kramer B, Knoll R, Bonaguro L, ToVinh M, Raabe J, Astaburuaga-Garcia R, Schulte-Schrepping J, Kaiser KM, Rieke GJ, Bischoff J, Monin MB, Hoffmeister C, Schlabe S, De Domenico E, Reusch N, Handler K, Reynolds G, Bluthgen N, Hack G, Finnemann C, Nischalke HD, Strassburg CP, Stephenson E, Su Y, Gardner L, Yuan D, Chen D, Goldman J, Rosenstiel P, Schmidt SV, Latz E, Hrusovsky K, Ball AJ, Johnson JM, Koenig P-A, Schmidt FI, Haniffa M, Heath JR, Kummerer BM, Keitel V, Jensen B, Stubbemann P, Kurth F, Sander LE, Sawitzki B, Altmuller J, Angelov A, Aschenbrenner AC, Bals R, Bartholomaus A, Becker A, Becker M, Bezdan D, Bitzer M, Blumert C, Bonifacio E, Bork P, Boyke B, Blum H, Casadei N, Clavel T, Colome-Tatche M, Cornberg M, De La Rosa Velazquez IA, Diefenbach A, Dilthey A, Fischer N, Forstner K, Franzenburg S, Frick J-S, Gabernet G, Gagneur J, Ganzenmueller T, Gauder M, Geissert J, Goesmann A, Gopel S, Grundhoff A, Grundmann H, Hain T, Hanses F, Hehr U, Heimbach A, Hoeper M, Horn F, Hubschmann D, Hummel M, Iftner T, Iftner A, Illig T, Janssen S, Kalinowski J, Kallies R, Kehr B, Keller A, Keppler OT, Kim-Hellmuth S, Klein C, Knop M, Kohlbacher O, Kohrer K, Korbel J, Kremsner PG, Kuhnert D, Kurth I, Landthaler M, Li Y, Ludwig KU, Makarewicz O, Marini F, Marz M, McHardy AC, Mertes C, Munchhoff M, Nahnsen S, Nothen M, Ntoumi F, Nurnberg P, Ossowski S, Overmann J, Peter S, Pfeffer K, Pink I, Poetsch AR, Protzer U, Puhler A, Rajewsky N, Ralser M, Reiche K, Riess O, Ripke S, Nunes da Rocha U, Rosenstiel P, Saliba A-E, Sander LE, Scheithauer S, Schiffer P, Schmid-Burgk J, Schneider W, Schulte E-C, Schultze JL, Sczyrba A, Sharaf ML, Singh Y, Sonnabend M, Stegle O, Stoye J, Theis F, Ulas T, Vehreschild J, Velavan TP, Vogel J, Volland S, von Kleist M, Walker A, Walter J, Wieczorek D, Winkler S, Ziebuhr J, Nattermann J
Publication type: Article
Publication status: Published
Journal: Immunity
Year: 2021
Volume: 54
Issue: 11
Pages: 2650-2669.e14
Print publication date: 01/11/2021
Online publication date: 04/09/2021
Acceptance date: 31/08/2021
ISSN (print): 1074-7613
ISSN (electronic): 1097-4180
Publisher: Cell Press
URL: https://doi.org/10.1016/j.immuni.2021.09.002
DOI: 10.1016/j.immuni.2021.09.002
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