Since the beginning of the SARS-CoV-2 pandemic, COVID-19 appeared as a unique disease with unconventional tissue and systemic immune features. Here we show a COVID-19 immune signature associated with severity by integrating single-cell RNA-seq analysis from blood samples and broncho-alveolar lavage fluids with clinical, immunological and functional ex vivo data. This signature is characterized by lung accumulation of naïve lymphoid cells associated with a systemic expansion and activation of myeloid cells. Myeloid-driven immune suppression is a hallmark of COVID-19 evolution, highlighting arginase-1 expression with immune regulatory features of monocytes. Monocyte-dependent and neutrophil-dependent immune suppression loss is associated with fatal clinical outcome in severe patients. Additionally, our analysis shows a lung CXCR6+ effector memory T cell subset is associated with better prognosis in patients with severe COVID-19. In summary, COVID-19-induced myeloid dysregulation and lymphoid impairment establish a condition of ‘immune silence’ in patients with critical COVID-19.

Bost, P., De Sanctis, F., Cane, S., Ugel, S., Donadello, K., Castellucci, M., et al. (2021). Deciphering the state of immune silence in fatal COVID-19 patients. NATURE COMMUNICATIONS, 12(1) [10.1038/s41467-021-21702-6].

Deciphering the state of immune silence in fatal COVID-19 patients

Facciotti F.;
2021

Abstract

Since the beginning of the SARS-CoV-2 pandemic, COVID-19 appeared as a unique disease with unconventional tissue and systemic immune features. Here we show a COVID-19 immune signature associated with severity by integrating single-cell RNA-seq analysis from blood samples and broncho-alveolar lavage fluids with clinical, immunological and functional ex vivo data. This signature is characterized by lung accumulation of naïve lymphoid cells associated with a systemic expansion and activation of myeloid cells. Myeloid-driven immune suppression is a hallmark of COVID-19 evolution, highlighting arginase-1 expression with immune regulatory features of monocytes. Monocyte-dependent and neutrophil-dependent immune suppression loss is associated with fatal clinical outcome in severe patients. Additionally, our analysis shows a lung CXCR6+ effector memory T cell subset is associated with better prognosis in patients with severe COVID-19. In summary, COVID-19-induced myeloid dysregulation and lymphoid impairment establish a condition of ‘immune silence’ in patients with critical COVID-19.
Articolo in rivista - Articolo scientifico
Aged; Aged, 80 and over; CD8-Positive T-Lymphocytes; COVID-19; Case-Control Studies; Cytokines; Female; Humans; Male; Middle Aged; Monocytes; Myeloid Cells; Neutrophils; SARS-CoV-2; T-Lymphocytes;
English
2021
12
1
1428
open
Bost, P., De Sanctis, F., Cane, S., Ugel, S., Donadello, K., Castellucci, M., et al. (2021). Deciphering the state of immune silence in fatal COVID-19 patients. NATURE COMMUNICATIONS, 12(1) [10.1038/s41467-021-21702-6].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/344558
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