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

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Item Type:	Article
Title:	Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19
Creators Name:	Krämer, B., Knoll, R., Bonaguro, L., ToVinh, M., Raabe, J., Astaburuaga-García, R., Schulte-Schrepping, J., Kaiser, K.M., Rieke, G.J., Bischoff, J., Monin, M.B., Hoffmeister, C., Schlabe, S., De Domenico, E., Reusch, N., Händler, K., Reynolds, G., Blüthgen, N., Hack, G., Finnemann, C., Nischalke, H.D., Strassburg, C.P., Stephenson, E., Su, Y., Gardner, L., Yuan, D., Chen, D., Goldman, J., Rosenstiel, P., Schmidt, S.V., Latz, E., Hrusovsky, K., Ball, A.J., Johnson, J.M., Koenig, P.A., Schmidt, F.I., Haniffa, M., Heath, J.R., Kümmerer, B.M., Keitel, V., Jensen, B., Stubbemann, P., Kurth, F., Sander, L.E., Sawitzki, B., Aschenbrenner, A.C., Schultze, J.L. and Nattermann, J.
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:	NK Cells, COVID-19, scRNA-Seq, Proteomics, Severe, Moderate, Type 1 IFN, TNF, Lung Fibrosis, Antiviral
Source:	Immunity
ISSN:	1074-7613
Publisher:	Cell Press / Elsevier
Volume:	54
Number:	11
Page Range:	2650-2669
Date:	9 November 2021
Additional Information:	Janine Altmüller, Markus Landthaler and Nikolaus Rajewsky are members of the Deutsche COVID-19 OMICS Initiative (DeCOI). Copyright © 2021 Elsevier Inc.
Official Publication:	https://doi.org/10.1016/j.immuni.2021.09.002
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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