tetano
Editor, Senior Moderator
J Transl Med
. 2020 Dec 3;18(1):457.
doi: 10.1186/s12967-020-02646-9.
The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome
Mathieu Blot[SUP] 1 2 [/SUP], Jean-Baptiste Bour[SUP] 3 [/SUP], Jean Pierre Quenot[SUP] 4 5 6 7 [/SUP], Abderrahmane Bourredjem[SUP] 6 7 [/SUP], Maxime Nguyen[SUP] 4 8 [/SUP], Julien Guy[SUP] 9 [/SUP], Serge Monier[SUP] 4 10 [/SUP], Marjolaine Georges[SUP] 11 [/SUP], Audrey Large[SUP] 5 [/SUP], Auguste Dargent[SUP] 4 5 [/SUP], Alexandre Guilhem[SUP] 12 [/SUP], Suzanne Mouries-Martin[SUP] 13 [/SUP], Jeremy Barben[SUP] 14 [/SUP], Belaid Bouhemad[SUP] 4 8 [/SUP], Pierre-Emmanuel Charles[SUP] 4 5 [/SUP], Pascal Chavanet[SUP] 15 6 7 [/SUP], Christine Binquet[SUP] 4 6 7 [/SUP], Lionel Piroth[SUP] 15 6 7 [/SUP], LYMPHONIE study group
Affiliations
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.
Keywords: Acute respiratory distress syndrome; COVID-19; CXCL10; GM-CSF; Immune response; Mechanical ventilation; Pneumonia.
. 2020 Dec 3;18(1):457.
doi: 10.1186/s12967-020-02646-9.
The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome
Mathieu Blot[SUP] 1 2 [/SUP], Jean-Baptiste Bour[SUP] 3 [/SUP], Jean Pierre Quenot[SUP] 4 5 6 7 [/SUP], Abderrahmane Bourredjem[SUP] 6 7 [/SUP], Maxime Nguyen[SUP] 4 8 [/SUP], Julien Guy[SUP] 9 [/SUP], Serge Monier[SUP] 4 10 [/SUP], Marjolaine Georges[SUP] 11 [/SUP], Audrey Large[SUP] 5 [/SUP], Auguste Dargent[SUP] 4 5 [/SUP], Alexandre Guilhem[SUP] 12 [/SUP], Suzanne Mouries-Martin[SUP] 13 [/SUP], Jeremy Barben[SUP] 14 [/SUP], Belaid Bouhemad[SUP] 4 8 [/SUP], Pierre-Emmanuel Charles[SUP] 4 5 [/SUP], Pascal Chavanet[SUP] 15 6 7 [/SUP], Christine Binquet[SUP] 4 6 7 [/SUP], Lionel Piroth[SUP] 15 6 7 [/SUP], LYMPHONIE study group
Affiliations
- PMID: 33272291
- DOI: 10.1186/s12967-020-02646-9
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.
Keywords: Acute respiratory distress syndrome; COVID-19; CXCL10; GM-CSF; Immune response; Mechanical ventilation; Pneumonia.