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

Research output: Contribution to journalResearch articleContributedpeer-review


  • Deutsche COVID-19 OMICS Initiative (DeCOI) - (Author)


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.


Original languageEnglish
Pages (from-to)2650-2669.e14
Issue number11
Publication statusPublished - 4 Sept 2021

External IDs

PubMed 34592166
ORCID /0000-0002-8704-4713/work/141544372


Research priority areas of TU Dresden

Sustainable Development Goals


  • antiviral, COVID-19, lung fibrosis, moderate, NK cells, proteomics, scRNA-seq, severe, TNF, type 1 IFN

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