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
de 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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Cellules tueuses naturelles
/
Facteur de nécrose tumorale alpha
/
Interféron alpha
/
SARS-CoV-2
/
COVID-19
Type d'étude:
Clinical_trials
Limites:
Humans
Pays/Région comme sujet:
America do norte
/
Europa
Langue:
En
Journal:
Immunity
Sujet du journal:
ALERGIA E IMUNOLOGIA
Année:
2021
Type de document:
Article
Pays d'affiliation:
Allemagne