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10.1038/s41422-020-00455-9

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33473155!8027624!33473155
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suck abstract from ncbi


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pmid33473155      Cell+Res 2021 ; 31 (3): 272-290
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  • Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages #MMPMID33473155
  • Wauters E; Van Mol P; Garg AD; Jansen S; Van Herck Y; Vanderbeke L; Bassez A; Boeckx B; Malengier-Devlies B; Timmerman A; Van Brussel T; Van Buyten T; Schepers R; Heylen E; Dauwe D; Dooms C; Gunst J; Hermans G; Meersseman P; Testelmans D; Yserbyt J; Tejpar S; De Wever W; Matthys P; Neyts J; Wauters J; Qian J; Lambrechts D
  • Cell Res 2021[Mar]; 31 (3): 272-290 PMID33473155show ga
  • 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 (T(RM)) and CD4(+) T-helper-17 (T(H17)) 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 naive. Vice versa, CD4(+) T-cells with T-helper-1 characteristics (T(H1)-like) and CD8(+) T-cells expressing exhaustion markers (T(EX)-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[MESH]
  • |*Bronchoalveolar Lavage[MESH]
  • |*Immunity, Innate[MESH]
  • |*Single-Cell Analysis[MESH]
  • |Bronchoalveolar Lavage Fluid[MESH]
  • |CD4-Positive T-Lymphocytes/cytology[MESH]
  • |CD8-Positive T-Lymphocytes/cytology[MESH]
  • |COVID-19/*diagnosis/*immunology[MESH]
  • |Cell Communication[MESH]
  • |Gene Expression Profiling[MESH]
  • |Humans[MESH]
  • |Lung/virology[MESH]
  • |Macrophages, Alveolar/cytology[MESH]
  • |Monocytes/cytology[MESH]
  • |Neutrophils/cytology[MESH]
  • |Phenotype[MESH]
  • |Principal Component Analysis[MESH]
  • |RNA-Seq[MESH]


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