Journal
IMMUNITY
Volume 54, Issue 11, Pages 2650-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2021.09.002
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Funding
- German Research Foundation (DFG) [SFB TR57, SPP1937, KR 4521/1-1, INST 37/1049-1, INST 216/981-1, INST 257/605-1, INST 269/768-1, INST 217/988-1, INST 217/577-1, EXC2151 - 390873048, SFB1454 - 432325352]
- DZIF, Germany [TTU 04.816, 04.817]
- Hector Foun-dation [M89]
- Helmholtz-Gemeinschaft Deutscher Forschungszentren, Germany
- EU [733100, 00160389, 847422]
- Federal Ministry of Education and Research (BMBF) [COVIMMUNE 01KI20343]
- Medical Faculty of the University of Bonn
- Emmy Noether Programme [322568668]
- Biomedical Advanced Research and Development Authority [HHSO10201600031C]
- Mary Gates Research Fellowship
- Mahan Fellowship in the Herbold Computational Biology Program of the Fred Hutch Cancer Research Center
- Department of Genomics & Immunoreg-ulation at the LIMES Institute
- Parker Institute for Cancer Immunotherapy
- Washington State Andy Hill CARE Fund
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The study revealed differences in IFN-α and TNF responses between severe and moderate COVID-19 cases, with NK cells playing a role in anti-SARS-CoV-2 activity but being functionally impaired in severe patients, and NK cell dysfunction potentially impacting disease outcome in severe COVID-19 patients.
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)-a plasma levels in early severe COVD-19 alongside increased NK cell expression of IFN-stimulated genes (ISGs) and genes involved in IFN-a signaling, while up regulation 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-a and TNF responses in severe and moderate COVID-19, respectively, and associates a prolonged IFNa-induced NK cell response with poorer disease outcome.
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