Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
- Chair of Preclinical stem cell therapy and diabetes
- Center for Regenerative Therapies Dresden
- Biomedical Genomics (Research Group)
- Biotechnology Center
- Neuroimaging Center
- University of Bonn
- German Center for Neurodegenerative Diseases (DZNE)
- Charité – Universitätsmedizin Berlin
- Humboldt University of Berlin
- German Center for Infection Research
- Newcastle University
- Institute for Systems Biology
- Swedish Medical Center
- University of Washington
- Kiel University
- Quanterix Corporation
- Wellcome Sanger Institute
- Newcastle upon Tyne Hospitals NHS Foundation Trust
- BRANFORD
- Board of Directors of PACT Pharma
- Heinrich Heine University Düsseldorf
- German Center for Lung Research (DZL)
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.
Details
Original language | English |
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Pages (from-to) | 2650-2669.e14 |
Journal | Immunity |
Volume | 54 |
Issue number | 11 |
Publication status | Published - 4 Sept 2021 |
Peer-reviewed | Yes |
External IDs
PubMed | 34592166 |
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ORCID | /0000-0002-8704-4713/work/141544372 |
Keywords
Research priority areas of TU Dresden
Sustainable Development Goals
ASJC Scopus subject areas
Keywords
- antiviral, COVID-19, lung fibrosis, moderate, NK cells, proteomics, scRNA-seq, severe, TNF, type 1 IFN