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10.1128/mBio.00384-21

http://scihub22266oqcxt.onion/10.1128/mBio.00384-21
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33947753!8262904!33947753
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suck abstract from ncbi


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pmid33947753      mBio 2021 ; 12 (3): ä
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  • Galectin-9, a Player in Cytokine Release Syndrome and a Surrogate Diagnostic Biomarker in SARS-CoV-2 Infection #MMPMID33947753
  • Bozorgmehr N; Mashhouri S; Perez Rosero E; Xu L; Shahbaz S; Sligl W; Osman M; Kutsogiannis DJ; MacIntyre E; O'Neil CR; Elahi S
  • mBio 2021[May]; 12 (3): ä PMID33947753show ga
  • The outbreak of SARS-CoV-2 infection has enormously impacted our lives. Clinical evidence has implicated the emergence of cytokine release syndrome as the prominent cause of mortality in COVID-19 patients. In this study, we observed massive elevation of plasma Galectin-9 (Gal-9) in COVID-19 patients compared to healthy controls (HCs). By using the receiver operating characteristic (ROC) curve, we found that a baseline of 2,042 pg/ml plasma Gal-9 can differentiate SARS-CoV-2-infected from noninfected individuals with high specificity/sensitivity (95%). Analysis of 30 cytokines and chemokines detected a positive correlation of the plasma Gal-9 with C-reactive protein (CRP) and proinflammatory cytokines/chemokines such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), IP-10, MIP-1alpha, and MCP-1 but an inverse correlation with transforming growth factor beta (TGF-beta) in COVID-19 patients. In agreement, we found enhanced production of IL-6 and TNF-alpha by monocytes and NK cells of COVID-19 patients once treated with the recombinant human Gal-9 in vitro Also, we observed that although the cell-membrane expression of Gal-9 on monocytes does not change in COVID-19 patients, those with higher Gal-9 expression exhibit an activated phenotype. Furthermore, we noted significant downregulation of surface Gal-9 in neutrophils from COVID-19 patients compared to HCs. Our further investigations indicated that immune activation following SARS-CoV-2 infection results in Gal-9 shedding from neutrophils. The strong correlation of Gal-9 with proinflammatory mediators suggests that inhibition of Gal-9 may severe as a therapeutic approach in COVID-19 infection. Besides, the plasma Gal-9 measurement may be used as a surrogate diagnostic biomarker in COVID-19 patients.IMPORTANCE The outbreak of SARS-CoV-2 infection has enormously impacted our lives. Clinical evidence has implicated the emergence of cytokine release syndrome as the prominent cause of mortality in COVID-19 patients. We observed substantial elevation of the plasma Galectin-9 (Gal-9) in COVID-19 patients compared to healthy controls. Gal-9 is an abundant protein in many immune and nonimmune cells. We found that Gal-9 detection assay can differentiate SARS-CoV-2-infected from noninfected individuals with a specificity/sensitivity of 95%. Importantly, we found a positive correlation of the plasma Gal-9 with a wide range of proinflammatory biomarkers in COVID-19 patients. In agreement, we found enhanced expression and production of such proinflammatory molecules by immune cells of COVID-19 patients once treated with Gal-9 in vitro Our results propose Gal-9 as an important contributing factor in cytokine release syndrome; therefore, Gal-9 inhibition may serve as a beneficial therapeutic approach by suppressing the hyperimmune activation in COVID-19 patients.
  • |*Sex Factors[MESH]
  • |Adult[MESH]
  • |Age Factors[MESH]
  • |Aged[MESH]
  • |Aged, 80 and over[MESH]
  • |Biomarkers/*blood[MESH]
  • |COVID-19/*blood/*diagnosis[MESH]
  • |Cytokine Release Syndrome/*blood/*physiopathology[MESH]
  • |Female[MESH]
  • |Galectins/*blood[MESH]
  • |Healthy Volunteers[MESH]
  • |Humans[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |ROC Curve[MESH]


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