Deciphering the State of Immune Silence in Fatal COVID-19 Patients

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Mar 6

PMID 33674591

Citations 88

Authors

Pierre Bost

Francesco De Sanctis

Stefania Cane

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

Affiliations

Soon will be listed here.

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.

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