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

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. and Knoll, R. and Bonaguro, L. and ToVinh, M. and Raabe, J. and Astaburuaga-García, R. and Schulte-Schrepping, J. and Kaiser, K.M. and Rieke, G.J. and Bischoff, J. and Monin, M.B. and Hoffmeister, C. and Schlabe, S. and De Domenico, E. and Reusch, N. and Händler, K. and Reynolds, G. and Blüthgen, N. and Hack, G. and Finnemann, C. and Nischalke, H.D. and Strassburg, C.P. and Stephenson, E. and Su, Y. and Gardner, L. and Yuan, D. and Chen, D. and Goldman, J. and Rosenstiel, P. and Schmidt, S.V. and Latz, E. and Hrusovsky, K. and Ball, A.J. and Johnson, J.M. and Koenig, P.A. and Schmidt, F.I. and Haniffa, M. and Heath, J.R. and Kümmerer, B.M. and Keitel, V. and Jensen, B. and Stubbemann, P. and Kurth, F. and Sander, L.E. and Sawitzki, B. and Aschenbrenner, A.C. and 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.e14
Date:9 November 2021
Additional Information:Markus Landthaler and Nikolaus Rajewsky are members of the Deutsche COVID-19 OMICS Initiative (DeCOI).
Official Publication:https://doi.org/10.1016/j.immuni.2021.09.002
PubMed:View item in PubMed

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