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10.1186/s12964-021-00754-7

http://scihub22266oqcxt.onion/10.1186/s12964-021-00754-7
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suck abstract from ncbi


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pmid34238338      Cell+Commun+Signal 2021 ; 19 (1): 73
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  • Single-cell analysis reveals cell communication triggered by macrophages associated with the reduction and exhaustion of CD8(+) T cells in COVID-19 #MMPMID34238338
  • He L; Zhang Q; Zhang Y; Fan Y; Yuan F; Li S
  • Cell Commun Signal 2021[Jul]; 19 (1): 73 PMID34238338show ga
  • BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has become an ongoing pandemic. Understanding the respiratory immune microenvironment which is composed of multiple cell types, together with cell communication based on ligand-receptor interactions is important for developing vaccines, probing COVID-19 pathogenesis, and improving pandemic control measures. METHODS: A total of 102 consecutive hospitalized patients with confirmed COVID-19 were enrolled in this study. Clinical information, routine laboratory tests, and flow cytometry analysis data with different conditions were collected and assessed for predictive value in COVID-19 patients. Next, we analyzed public single-cell RNA-sequencing (scRNA-seq) data from bronchoalveolar lavage fluid, which offers the closest available view of immune cell heterogeneity as encountered in patients with varying severity of COVID-19. A weighting algorithm was used to calculate ligand-receptor interactions, revealing the communication potentially associated with outcomes across cell types. Finally, serum cytokines including IL6, IL1beta, IL10, CXCL10, TNFalpha, GALECTIN-1, and IGF1 derived from patients were measured. RESULTS: Of the 102 COVID-19 patients, 42 cases (41.2%) were categorized as severe. Multivariate logistic regression analysis demonstrated that AST, D-dimer, BUN, and WBC were considered as independent risk factors for the severity of COVID-19. T cell numbers including total T cells, CD4(+) and CD8(+) T cells in the severe disease group were significantly lower than those in the moderate disease group. The risk model containing the above mentioned inflammatory damage parameters, and the counts of T cells, with AUROCs ranged from 0.78 to 0.87. To investigate the molecular mechanism at the cellular level, we analyzed the published scRNA-seq data and found that macrophages displayed specific functional diversity after SARS-Cov-2 infection, and the metabolic pathway activities in the identified macrophage subtypes were influenced by hypoxia status. Importantly, we described ligand-receptor interactions that are related to COVID-19 serverity involving macrophages and T cell subsets by communication analysis. CONCLUSIONS: Our study showed that macrophages driving ligand-receptor crosstalk contributed to the reduction and exhaustion of CD8(+) T cells. The identified crucial cytokine panel, including IL6, IL1beta, IL10, CXCL10, IGF1, and GALECTIN-1, may offer the selective targets to improve the efficacy of COVID-19 therapy. TRIAL REGISTRATION: This is a retrospective observational study without a trial registration number. Video Abstract.
  • |*Cell Communication[MESH]
  • |*Single-Cell Analysis[MESH]
  • |Aged[MESH]
  • |Bronchoalveolar Lavage Fluid/immunology[MESH]
  • |CD8-Positive T-Lymphocytes/immunology/pathology[MESH]
  • |COVID-19/epidemiology/*immunology/*pathology/physiopathology[MESH]
  • |China/epidemiology[MESH]
  • |Cytokines/blood/immunology[MESH]
  • |Female[MESH]
  • |Humans[MESH]
  • |Macrophages/*immunology/pathology[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Receptors, Cytokine[MESH]
  • |Retrospective Studies[MESH]
  • |Sequence Analysis, RNA[MESH]


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