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Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages.

Published version
Peer-reviewed

Repository DOI


Type

Article

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Authors

Wauters, Els 
Garg, Abhishek Dinkarnath  ORCID logo  https://orcid.org/0000-0002-9976-9922
Van Herck, Yannick 

Abstract

How the innate and adaptive host immune system miscommunicate to worsen COVID-19 immunopathology has not been fully elucidated. Here, we perform single-cell deep-immune profiling of bronchoalveolar lavage (BAL) samples from 5 patients with mild and 26 with critical COVID-19 in comparison to BALs from non-COVID-19 pneumonia and normal lung. We use pseudotime inference to build T-cell and monocyte-to-macrophage trajectories and model gene expression changes along them. In mild COVID-19, CD8+ resident-memory (TRM) and CD4+ T-helper-17 (TH17) cells undergo active (presumably antigen-driven) expansion towards the end of the trajectory, and are characterized by good effector functions, while in critical COVID-19 they remain more naïve. Vice versa, CD4+ T-cells with T-helper-1 characteristics (TH1-like) and CD8+ T-cells expressing exhaustion markers (TEX-like) are enriched halfway their trajectories in mild COVID-19, where they also exhibit good effector functions, while in critical COVID-19 they show evidence of inflammation-associated stress at the end of their trajectories. Monocyte-to-macrophage trajectories show that chronic hyperinflammatory monocytes are enriched in critical COVID-19, while alveolar macrophages, otherwise characterized by anti-inflammatory and antigen-presenting characteristics, are depleted. In critical COVID-19, monocytes contribute to an ATP-purinergic signaling-inflammasome footprint that could enable COVID-19 associated fibrosis and worsen disease-severity. Finally, viral RNA-tracking reveals infected lung epithelial cells, and a significant proportion of neutrophils and macrophages that are involved in viral clearance.

Description

Keywords

Adaptive Immunity, Bronchoalveolar Lavage, Bronchoalveolar Lavage Fluid, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, COVID-19, Cell Communication, Gene Expression Profiling, Humans, Immunity, Innate, Lung, Macrophages, Alveolar, Monocytes, Neutrophils, Phenotype, Principal Component Analysis, RNA-Seq, Single-Cell Analysis, Th17 Cells

Journal Title

Cell Res

Conference Name

Journal ISSN

1001-0602
1748-7838

Volume Title

31

Publisher

Springer Science and Business Media LLC