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
em En
| MEDLINE
| ID: mdl-34592166
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Fator de Necrose Tumoral alfa
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Interferon-alfa
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SARS-CoV-2
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COVID-19
Tipo de estudo:
Clinical_trials
Limite:
Humans
País/Região como assunto:
America do norte
/
Europa
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article