Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19.
Immunity
; 54(11): 2650-2669.e14, 2021 11 09.
Article
in English
| MEDLINE | ID: covidwho-1442406
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
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Killer Cells, Natural
/
Tumor Necrosis Factor-alpha
/
Interferon-alpha
/
SARS-CoV-2
/
COVID-19
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Topics:
Long Covid
Limits:
Humans
Country/Region as subject:
North America
/
Europa
Language:
English
Journal:
Immunity
Journal subject:
Allergy and Immunology
Year:
2021
Document Type:
Article
Affiliation country:
J.immuni.2021.09.002
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