Volume 31, No 3, Mar 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 3, March 2021: 272-290

ORIGINAL ARTICLES

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

Els Wauters^1,2 , Pierre Van Mol^2,3,4 , Abhishek Dinkarnath Garg⁵ , Sander Jansen⁶ , Yannick Van Herck⁷ , Lore Vanderbeke⁸ , Ayse Bassez^3,4 , Bram Boeckx^3,4 , Bert Malengier-Devlies⁹ , Anna Timmerman^3,4 , Thomas Van Brussel^3,4 , Tina Van Buyten⁶ , Rogier Schepers^3,4 , Elisabeth Heylen⁶ , Dieter Dauwe¹⁰ , Christophe Dooms^1,2 , Jan Gunst¹⁰ , Greet Hermans¹⁰ , Philippe Meersseman¹¹ , Dries Testelmans^1,2 , Jonas Yserbyt^1,2 , Sabine Tejpar¹² , Walter De Wever¹³ , Patrick Matthys⁹ , CONTAGIOUS collaborators, Johan Neyts⁶ , Joost Wauters¹¹ , Junbin Qian^14,* , Diether Lambrechts^3,4,*

¹Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
²Department of Pneumology, University Hospitals Leuven, Leuven, Belgium
³Laboratory of Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium
⁴VIB Center for Cancer Biology, VIB, Leuven, Belgium
⁵Laboratory for Cell Stress & Immunity (CSI), Department of Cellular and Molecular Medicine (CMM), KU Leuven, Leuven, Belgium
⁶Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium
⁷Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven, Belgium
⁸Laboratory of Clinical Bacteriology and Mycology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
⁹Laboratory of Immunobiology, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium
¹⁰Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
¹¹Laboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
¹²Molecular Digestive Oncology, Department of Oncology, KU Leuven, Leuven, Belgium
¹³Department of Imaging & Pathology, KU Leuven, Leuven, Belgium
¹⁴Department of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China
These authors contributed equally: Els Wauters, Pierre Van Mol, Abhishek Dinkarnath Garg, Sander Jansen, Johan Neyts, Joost Wauters A list of authors and their affiliations appears at the end of the paper. Correspondence: Junbin Qian(dr_qian@zju.edu.cn)Diether Lambrechts(Diether.Lambrechts@kuleuven.vib.be)

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.

https://doi.org/10.1038/s41422-020-00455-9

FULL TEXT | PDF

Browse 948