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

Pierre Bost; Francesco De Sanctis; Stefania Canè; Stefano Ugel; Katia Donadello; Monica Castellucci; David Eyal; Alessandra Fiore; Cristina Anselmi; Roza Maria Barouni; Rosalinda Trovato; Simone Caligola; Alessia Lamolinara; Manuela Iezzi; Federica Facciotti; Annarita Mazzariol; Davide Gibellini; Pasquale De Nardo; Evelina Tacconelli; Leonardo Gottin; Enrico Polati; Benno Schwikowski; Ido Amit; Vincenzo Bronte

doi:10.1038/s41467-021-21702-6

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

Pierre Bost, Francesco De Sanctis, Stefania Canè, Stefano Ugel, Katia Donadello, Monica Castellucci, David Eyal, Alessandra Fiore, Cristina Anselmi, Roza Maria Barouni, Rosalinda Trovato, Simone Caligola, Alessia Lamolinara, Manuela Iezzi, Federica Facciotti, Annarita Mazzariol, Davide Gibellini, Pasquale De Nardo, Evelina Tacconelli, Leonardo GottinEnrico Polati, Benno Schwikowski, Ido Amit, Vincenzo Bronte

Department of Systems Immunology

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	1428
Number of pages	15
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-21702-6
State	Published Online - 5 Mar 2021

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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Bost, P., De Sanctis, F., Canè, S., Ugel, S., Donadello, K., Castellucci, M., Eyal, D., Fiore, A., Anselmi, C., Barouni, R. M., Trovato, R., Caligola, S., Lamolinara, A., Iezzi, M., Facciotti, F., Mazzariol, A., Gibellini, D., De Nardo, P., Tacconelli, E., ... Bronte, V. (2021). Deciphering the state of immune silence in fatal COVID-19 patients. Nature Communications, 12(1), Article 1428. Advance online publication. https://doi.org/10.1038/s41467-021-21702-6

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title = "Deciphering the state of immune silence in fatal COVID-19 patients",

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 na{\"i}ve 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.",

author = "Pierre Bost and \{De Sanctis\}, Francesco and Stefania Can{\`e} and Stefano Ugel and Katia Donadello and Monica Castellucci and David Eyal and Alessandra Fiore and Cristina Anselmi and Barouni, \{Roza Maria\} and Rosalinda Trovato and Simone Caligola and Alessia Lamolinara and Manuela Iezzi and Federica Facciotti and Annarita Mazzariol and Davide Gibellini and \{De Nardo\}, Pasquale and Evelina Tacconelli and Leonardo Gottin and Enrico Polati and Benno Schwikowski and Ido Amit and Vincenzo Bronte",

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Bost, P, De Sanctis, F, Canè, S, Ugel, S, Donadello, K, Castellucci, M, Eyal, D, Fiore, A, Anselmi, C, Barouni, RM, Trovato, R, Caligola, S, Lamolinara, A, Iezzi, M, Facciotti, F, Mazzariol, A, Gibellini, D, De Nardo, P, Tacconelli, E, Gottin, L, Polati, E, Schwikowski, B, Amit, I & Bronte, V 2021, 'Deciphering the state of immune silence in fatal COVID-19 patients', Nature Communications, vol. 12, no. 1, 1428. https://doi.org/10.1038/s41467-021-21702-6

TY - JOUR

T1 - Deciphering the state of immune silence in fatal COVID-19 patients

AU - Bost, Pierre

AU - De Sanctis, Francesco

AU - Canè, Stefania

AU - Ugel, Stefano

AU - Donadello, Katia

AU - Castellucci, Monica

AU - Eyal, David

AU - Fiore, Alessandra

AU - Anselmi, Cristina

AU - Barouni, Roza Maria

AU - Trovato, Rosalinda

AU - Caligola, Simone

AU - Lamolinara, Alessia

AU - Iezzi, Manuela

AU - Facciotti, Federica

AU - Mazzariol, Annarita

AU - Gibellini, Davide

AU - De Nardo, Pasquale

AU - Tacconelli, Evelina

AU - Gottin, Leonardo

AU - Polati, Enrico

AU - Schwikowski, Benno

AU - Amit, Ido

AU - Bronte, Vincenzo

N1 - Copyright: This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine

PY - 2021/3/5

Y1 - 2021/3/5

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-021-21702-6

DO - 10.1038/s41467-021-21702-6

M3 - مقالة

C2 - 33674591

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1428

ER -

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

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