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Galectin-9, a Player in Cytokine Release Syndrome and a Surrogate Diagnostic Biomarker in SARS-CoV-2 Infection.
Bozorgmehr, Najmeh; Mashhouri, Siavash; Perez Rosero, Eliana; Xu, Lai; Shahbaz, Shima; Sligl, Wendy; Osman, Mohammed; Kutsogiannis, Demetrios J; MacIntyre, Erika; O'Neil, Conar R; Elahi, Shokrollah.
  • Bozorgmehr N; School of Dentistry, Division of Foundational Sciences, University of Alberta, Edmonton, Alberta, Canada.
  • Mashhouri S; School of Dentistry, Division of Foundational Sciences, University of Alberta, Edmonton, Alberta, Canada.
  • Perez Rosero E; School of Dentistry, Division of Foundational Sciences, University of Alberta, Edmonton, Alberta, Canada.
  • Xu L; School of Dentistry, Division of Foundational Sciences, University of Alberta, Edmonton, Alberta, Canada.
  • Shahbaz S; School of Dentistry, Division of Foundational Sciences, University of Alberta, Edmonton, Alberta, Canada.
  • Sligl W; Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
  • Osman M; Department of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada.
  • Kutsogiannis DJ; Division of Infectious Diseases, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
  • MacIntyre E; Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
  • O'Neil CR; Department of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada.
  • Elahi S; Misericordia Community Hospital, Edmonton, Alberta, Canada.
mBio ; 12(3)2021 05 04.
Article in English | MEDLINE | ID: covidwho-1216782
ABSTRACT
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-α), IP-10, MIP-1α, and MCP-1 but an inverse correlation with transforming growth factor ß (TGF-ß) in COVID-19 patients. In agreement, we found enhanced production of IL-6 and TNF-α 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Biomarkers / Sex Factors / Galectins / Cytokine Release Syndrome / COVID-19 Type of study: Diagnostic study / Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Year: 2021 Document Type: Article Affiliation country: MBio.00384-21

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Biomarkers / Sex Factors / Galectins / Cytokine Release Syndrome / COVID-19 Type of study: Diagnostic study / Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Year: 2021 Document Type: Article Affiliation country: MBio.00384-21