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

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Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19. / Krämer, Benjamin; Knoll, Rainer; Bonaguro, Lorenzo; ToVinh, Michael; Raabe, Jan; Astaburuaga-García, Rosario; Schulte-Schrepping, Jonas; Kaiser, Kim Melanie; Rieke, Gereon J; Bischoff, Jenny; Monin, Malte B; Hoffmeister, Christoph; Schlabe, Stefan; De Domenico, Elena; Reusch, Nico; Händler, Kristian; Reynolds, Gary; Blüthgen, Nils; Hack, Gudrun; Finnemann, Claudia; Nischalke, Hans D; Strassburg, Christian P; Stephenson, Emily; Su, Yapeng; Gardner, Louis; Yuan, Dan; Chen, Daniel; Goldman, Jason; Rosenstiel, Philipp; Schmidt, Susanne V; Latz, Eicke; Hrusovsky, Kevin; Ball, Andrew J; Johnson, Joe M; Koenig, Paul-Albert; Schmidt, Florian I; Haniffa, Muzlifah; Heath, James R; Kümmerer, Beate M; Keitel, Verena; Jensen, Björn; Stubbemann, Paula; Kurth, Florian; Sander, Leif E; Sawitzki, Birgit; Aschenbrenner, Anna C; Schultze, Joachim L; Nattermann, Jacob; Deutsche COVID-19 OMICS Initiative (DeCOI).

in: IMMUNITY, Jahrgang 54, Nr. 11, 09.11.2021, S. 2650-2669.e14.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Krämer, B, Knoll, R, Bonaguro, L, ToVinh, M, Raabe, J, Astaburuaga-García, R, Schulte-Schrepping, J, Kaiser, KM, Rieke, GJ, Bischoff, J, Monin, MB, Hoffmeister, C, Schlabe, S, De Domenico, E, Reusch, N, Händler, K, Reynolds, G, Blüthgen, 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, Kümmerer, BM, Keitel, V, Jensen, B, Stubbemann, P, Kurth, F, Sander, LE, Sawitzki, B, Aschenbrenner, AC, Schultze, JL, Nattermann, J & Deutsche COVID-19 OMICS Initiative (DeCOI) 2021, 'Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19', IMMUNITY, Jg. 54, Nr. 11, S. 2650-2669.e14. https://doi.org/10.1016/j.immuni.2021.09.002

APA

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., ... Deutsche COVID-19 OMICS Initiative (DeCOI) (2021). Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19. IMMUNITY, 54(11), 2650-2669.e14. https://doi.org/10.1016/j.immuni.2021.09.002

Vancouver

Krämer B, Knoll R, Bonaguro L, ToVinh M, Raabe J, Astaburuaga-García R et al. Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19. IMMUNITY. 2021 Nov 9;54(11):2650-2669.e14. https://doi.org/10.1016/j.immuni.2021.09.002

Bibtex

@article{98bc86fef3c9481db4986dfaea6da176,
title = "Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19",
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, 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",
author = "Benjamin Kr{\"a}mer and Rainer Knoll and Lorenzo Bonaguro and Michael ToVinh and Jan Raabe and Rosario Astaburuaga-Garc{\'i}a and Jonas Schulte-Schrepping and Kaiser, {Kim Melanie} and Rieke, {Gereon J} and Jenny Bischoff and Monin, {Malte B} and Christoph Hoffmeister and Stefan Schlabe and {De Domenico}, Elena and Nico Reusch and Kristian H{\"a}ndler and Gary Reynolds and Nils Bl{\"u}thgen and Gudrun Hack and Claudia Finnemann and Nischalke, {Hans D} and Strassburg, {Christian P} and Emily Stephenson and Yapeng Su and Louis Gardner and Dan Yuan and Daniel Chen and Jason Goldman and Philipp Rosenstiel and Schmidt, {Susanne V} and Eicke Latz and Kevin Hrusovsky and Ball, {Andrew J} and Johnson, {Joe M} and Paul-Albert Koenig and Schmidt, {Florian I} and Muzlifah Haniffa and Heath, {James R} and K{\"u}mmerer, {Beate M} and Verena Keitel and Bj{\"o}rn Jensen and Paula Stubbemann and Florian Kurth and Sander, {Leif E} and Birgit Sawitzki and Aschenbrenner, {Anna C} and Schultze, {Joachim L} and Jacob Nattermann and {Deutsche COVID-19 OMICS Initiative (DeCOI)}",
note = "Copyright {\textcopyright} 2021 Elsevier Inc. All rights reserved.",
year = "2021",
month = nov,
day = "9",
doi = "10.1016/j.immuni.2021.09.002",
language = "English",
volume = "54",
pages = "2650--2669.e14",
journal = "IMMUNITY",
issn = "1074-7613",
publisher = "Cell Press",
number = "11",

}

RIS

TY - JOUR

T1 - Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19

AU - Krämer, Benjamin

AU - Knoll, Rainer

AU - Bonaguro, Lorenzo

AU - ToVinh, Michael

AU - Raabe, Jan

AU - Astaburuaga-García, Rosario

AU - Schulte-Schrepping, Jonas

AU - Kaiser, Kim Melanie

AU - Rieke, Gereon J

AU - Bischoff, Jenny

AU - Monin, Malte B

AU - Hoffmeister, Christoph

AU - Schlabe, Stefan

AU - De Domenico, Elena

AU - Reusch, Nico

AU - Händler, Kristian

AU - Reynolds, Gary

AU - Blüthgen, Nils

AU - Hack, Gudrun

AU - Finnemann, Claudia

AU - Nischalke, Hans D

AU - Strassburg, Christian P

AU - Stephenson, Emily

AU - Su, Yapeng

AU - Gardner, Louis

AU - Yuan, Dan

AU - Chen, Daniel

AU - Goldman, Jason

AU - Rosenstiel, Philipp

AU - Schmidt, Susanne V

AU - Latz, Eicke

AU - Hrusovsky, Kevin

AU - Ball, Andrew J

AU - Johnson, Joe M

AU - Koenig, Paul-Albert

AU - Schmidt, Florian I

AU - Haniffa, Muzlifah

AU - Heath, James R

AU - Kümmerer, Beate M

AU - Keitel, Verena

AU - Jensen, Björn

AU - Stubbemann, Paula

AU - Kurth, Florian

AU - Sander, Leif E

AU - Sawitzki, Birgit

AU - Aschenbrenner, Anna C

AU - Schultze, Joachim L

AU - Nattermann, Jacob

AU - Deutsche COVID-19 OMICS Initiative (DeCOI)

N1 - Copyright © 2021 Elsevier Inc. All rights reserved.

PY - 2021/11/9

Y1 - 2021/11/9

N2 - 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.

AB - 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.

KW - Base Sequence

KW - COVID-19/immunology

KW - Humans

KW - Immunity, Innate/immunology

KW - Inflammation/immunology

KW - Interferon-alpha/blood

KW - Killer Cells, Natural/immunology

KW - Pulmonary Fibrosis/pathology

KW - RNA-Seq

KW - SARS-CoV-2/immunology

KW - Severity of Illness Index

KW - Transcriptome/genetics

KW - Tumor Necrosis Factor-alpha/metabolism

KW - United Kingdom

KW - United States

U2 - 10.1016/j.immuni.2021.09.002

DO - 10.1016/j.immuni.2021.09.002

M3 - SCORING: Journal article

C2 - 34592166

VL - 54

SP - 2650-2669.e14

JO - IMMUNITY

JF - IMMUNITY

SN - 1074-7613

IS - 11

ER -