Repository logo

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

Published version

Repository DOI



Change log


Wauters, Els 
Garg, Abhishek Dinkarnath  ORCID logo
Van Herck, Yannick 


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.



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


Volume Title



Springer Science and Business Media LLC