ArticleImmunity2021
Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19.
Open access · bronzeAbstract readMulticenter Study
In one paragraph
Article in Immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
157citing papers in PubMed, 1 pooled it
18.2field-weighted citation impact, top 1% of its field
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Who cites it
157 citing papers in PubMed, 1 synthesis or guideline pooled it, 251 citations in OpenAlex.
- Gut distress and interventionFrontiers in public health · 2023Pooled it
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- Dynamic single-cell transcriptomic analysis of peripheral blood mononuclear cells identifies novel biomarkers for autoimmune encephalitis.Molecular psychiatry · 2026Article
- Natural Killer Cell Assays: Clinical Applications and Future Directions.Annals of laboratory medicine · 2026Review
- Immune dysregulation in prolonged Long-COVID: lymphocytes emerge as key mediators of persistent inflammation, exhaustion and cytotoxicity.Journal of translational medicine · 2026Article
- Elevated ANG2/ACE2 and immune responses associated with Plasmodium falciparum and SARS-CoV-2 coinfection in Cameroon.PLOS global public health · 2026Article
- Dysregulated NK-cell gene expression defines the enduring symptoms of long COVID-19.Frontiers in immunology · 2026Article
- Integrating mechanical cues inFrontiers in immunology · 2026Review
- Exosomes in Cancer Biology: Emerging Biomarkers and Therapeutic Targets.Journal of Cancer · 2026Review
- Clinical and Immunological Recovery Trajectories in Severe COVID-19 Survivors: A 12-Month Prospective Follow-Up Study.Viruses · 2025Article
- Single-cell analysis unravels the role of NK cells and monocytes in the control of SARS-CoV-2 breakthrough infections in vaccinated individuals.Human vaccines & immunotherapeutics · 2025Article
- Interferon-mediated NK cell activation increases cytolytic activity against T follicular helper cells and limits antibody response to SARS-CoV-2.Nature immunology · 2025Article
- Anti-SARS-CoV-2 antibodies from severe COVID-19 individuals or S2 immunizations do not worsen disease in hamsters.Communications biology · 2025Article
- Mapping NK cell diversity in response to COVID-19 and mRNA vaccination.Scientific reports · 2025Article
- NK-derived exosomes in anti-tumor strategies.Medical oncology (Northwood, London, England) · 2025Review
- MICBG406A polymorphism reduces risk of mechanical ventilation and death during viral acute lung injury.JCI insight · 2025Article
- Deciphering state-dependent immune features from multi-layer omics data at single-cell resolution.Nature genetics · 2025Article
- Ageing and dysregulated lung immune responses in fatal COVID-19.Immunity & ageing : I & A · 2025Article
- Article
97 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
49 authors at 16 institutions in 4 countries.
Benjamin KrämerDepartment of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
Rainer KnollSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Lorenzo BonaguroSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Michael ToVinhDepartment of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
Jan RaabeDepartment of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
Rosario Astaburuaga-GarcíaCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt- Universität zu Berlin, Institute of Pathology, Berlin, Germany; IRI Life Sciences & Institute of Theoretical Biology, Humboldt-Universität zu Berlin, Berlin, Germany.
Jonas Schulte-SchreppingSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Kim Melanie KaiserDepartment of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
Gereon J RiekeDepartment of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
Jenny BischoffDepartment of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
Malte B MoninDepartment of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
Christoph HoffmeisterDepartment of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
Stefan SchlabeDepartment of Internal Medicine I, University Hospital Bonn, Bonn, Germany; German Center for Infection Research (DZIF), Germany.
Elena De DomenicoSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, and University of Bonn, Bonn, Germany.
Nico ReuschSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Kristian HändlerSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, and University of Bonn, Bonn, Germany.
Gary ReynoldsBiosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Nils BlüthgenCharité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt- Universität zu Berlin, Institute of Pathology, Berlin, Germany; IRI Life Sciences & Institute of Theoretical Biology, Humboldt-Universität zu Berlin, Berlin, Germany.
Gudrun HackDepartment of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
Claudia FinnemannDepartment of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
Hans D NischalkeDepartment of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
Christian P StrassburgDepartment of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
Emily StephensonBiosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Yapeng SuInstitute for Systems Biology, Seattle, WA 98109, USA.
Louis GardnerBiosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Dan YuanInstitute for Systems Biology, Seattle, WA 98109, USA.
Daniel ChenInstitute for Systems Biology, Seattle, WA 98109, USA.
Jason GoldmanInstitute for Systems Biology, Seattle, WA 98109, USA; Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA 98109, USA; Providence St. Joseph Health, Renton, WA 98057, USA; Division of Allergy & Infectious Diseases, University of Washington, Seattle, WA 98109, USA.
Philipp RosenstielInstitute of Clinical Molecular Biology, Kiel University and University Medical Center Schleswig-Holstein, Kiel, Germany.
Susanne V SchmidtInstitute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany.
Eicke LatzInstitute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany.
Kevin HrusovskyQuanterix Corporation, Billerica, MA, USA.
Andrew J BallQuanterix Corporation, Billerica, MA, USA.
Joe M JohnsonQuanterix Corporation, Billerica, MA, USA.
Paul-Albert KoenigInstitute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany; Core Facility Nanobodies, Medical Faculty, University of Bonn, Bonn, Germany.
Florian I SchmidtInstitute of Innate Immunity, Medical Faculty, University of Bonn, Bonn, Germany; Core Facility Nanobodies, Medical Faculty, University of Bonn, Bonn, Germany.
Muzlifah HaniffaBiosciences Institute, Newcastle University, Newcastle upon Tyne, UK; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK; NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Department of Dermatology, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
James R HeathInstitute for Systems Biology, Seattle, WA 98109, USA; Board of Directors of Isoplexis, Branford, CT 06405, USA; Department of Bioengineering, University of Washington, Seattle, WA 98105, USA; Board of Directors of PACT Pharma, South San Francisco, CA 94080, USA.
Beate M KümmererGerman Center for Infection Research (DZIF), Germany; Institute of Virology, Medical Faculty, University of Bonn, Bonn, Germany.
Verena KeitelDepartment of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Björn JensenDepartment of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Paula StubbemannDepartment of Infectious Diseases and Respiratory Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.
Florian KurthDepartment of Infectious Diseases and Respiratory Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany; German Center for Lung Research (DZL), Germany.
Leif E SanderDepartment of Infectious Diseases and Respiratory Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany; German Center for Lung Research (DZL), Germany.
Birgit SawitzkiInstitute of Medical Immunology, Charité, Universitätsmedizin Berlin, Berlin, Germany.
Deutsche COVID-19 OMICS Initiative (DeCOI)
Anna C AschenbrennerSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, and University of Bonn, Bonn, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands.
Joachim L SchultzeSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany; Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, and University of Bonn, Bonn, Germany.
Jacob NattermannDepartment of Internal Medicine I, University Hospital Bonn, Bonn, Germany; German Center for Infection Research (DZIF), Germany. Electronic address: jacob.nattermann@ukbonn.de.
University Hospital Bonn · DEUniversity of Bonn · DECharité - Universitätsmedizin Berlin · DEDüsseldorf University Hospital · DEChristian-Albrechts-Universität zu Kiel · DEGerman Center for Lung Research · DEInstitute for Systems Biology · USQuanterix (United States) · USNewcastle University · GBGerman Center for Neurodegenerative Diseases · DEHumboldt-Universität zu Berlin · DENewcastle upon Tyne Hospitals NHS Foundation Trust · GBRadboud University Nijmegen · NLGerman Center for Infection Research · DEProvidence College · USUniversity of Washington · US
Funding
No grant is acknowledged in the PubMed record.
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.
Indexed as
Base SequenceCOVID-19HumansImmunity, InnateInflammationInterferon-alphaKiller Cells, NaturalPulmonary FibrosisRNA-SeqSARS-CoV-2Severity of Illness IndexTranscriptomeTumor Necrosis Factor-alphaUnited KingdomUnited StatesIFNA1 protein, humanInterferon-alphaTumor Necrosis Factor-alphaantiviralCOVID-19lung fibrosismoderateNK cellsproteomicsscRNA-seqsevereTNFtype 1 IFN
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