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

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Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)272-290
Number of pages19
JournalCell Research (CR)
Volume31
Issue number3
DOIs
Publication statusPublished - Mar 2021

Keywords / Materials (for Non-textual outputs)

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

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