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Blot, Mathieu; Bour, Jean-Baptiste; Quenot, Jean Pierre; Bourredjem, Abderrahmane; Nguyen, Maxime; Guy, Julien; Monier, Serge; Georges, Marjolaine; Large, Audrey; Dargent, Auguste; Guilhem, Alexandre; Mouries-Martin, Suzanne; Barben, Jeremy; Bouhemad, Belaid; Charles, Pierre-Emmanuel; Chavanet, Pascal; Binquet, Christine; Piroth, Lionel; Andreu, Pascal; Aptel, François; Labruyère, Marie; Prin, Sébastien; Beltramo, Guillaume; Bonniaud, Philippe; [...]

The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome

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  • Medientyp: E-Artikel
  • Titel: The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome
  • Beteiligte: Blot, Mathieu; Bour, Jean-Baptiste; Quenot, Jean Pierre; Bourredjem, Abderrahmane; Nguyen, Maxime; Guy, Julien; Monier, Serge; Georges, Marjolaine; Large, Audrey; Dargent, Auguste; Guilhem, Alexandre; Mouries-Martin, Suzanne; Barben, Jeremy; Bouhemad, Belaid; Charles, Pierre-Emmanuel; Chavanet, Pascal; Binquet, Christine; Piroth, Lionel; Andreu, Pascal; Aptel, François; Labruyère, Marie; Prin, Sébastien; Beltramo, Guillaume; Bonniaud, Philippe; [...]
  • Erschienen: Springer Science and Business Media LLC, 2020
  • Erschienen in: Journal of Translational Medicine
  • Sprache: Englisch
  • DOI: 10.1186/s12967-020-02646-9
  • ISSN: 1479-5876
  • Schlagwörter: General Biochemistry, Genetics and Molecular Biology ; General Medicine
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Although immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID-19), the most relevant targets remain to be found. COVID-19 has peculiar characteristics and outcomes, suggesting a unique immunopathogenesis.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Thirty-six immunocompetent non-COVID-19 and 27 COVID-19 patients with severe pneumonia were prospectively enrolled in a single center, most requiring intensive care. Clinical and biological characteristics (including T cell phenotype and function and plasma concentrations of 30 cytokines) and outcomes were compared.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>At similar baseline respiratory severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (15 [7–22] vs. 4 (0–15) days; p = 0.0049). COVID-19 patients had lower levels of most classical inflammatory cytokines (G-CSF, CCL20, IL-1β, IL-2, IL-6, IL-8, IL-15, TNF-α, TGF-β), but higher plasma concentrations of CXCL10, GM-CSF and CCL5, compared to non-COVID-19 patients. COVID-19 patients displayed similar T-cell exhaustion to non-COVID-19 patients, but with a more unbalanced inflammatory/anti-inflammatory cytokine response (IL-6/IL-10 and TNF-α/IL-10 ratios). Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariate regression analysis confirmed that GM-CSF, CXCL10 and IL-10 levels were independently associated with the duration of mechanical ventilation.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>We identified a unique cytokine response, with higher plasma GM-CSF and CXCL10 in COVID-19 patients that were independently associated with the longer duration of mechanical ventilation. These cytokines could represent the dysregulated immune response in severe COVID-19, as well as promising therapeutic targets.</jats:p> <jats:p>ClinicalTrials.gov: NCT03505281.</jats:p> </jats:sec>
  • Zugangsstatus: Freier Zugang