1. The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome.
- Author
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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, and LYMPHONIE study group
- Subjects
COVID-19 ,GRANULOCYTE-macrophage colony-stimulating factor ,IMMUNE response ,ARTIFICIAL respiration ,ARTIFICIAL respiration equipment ,PRINCIPAL components analysis - Abstract
Background: 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.Methods: 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.Results: 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.Conclusion: 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. ClinicalTrials.gov: NCT03505281. [ABSTRACT FROM AUTHOR]- Published
- 2020
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