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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-12-03

AUTHORS

Mathieu Blot, Jean-Baptiste Bour, Jean Pierre Quenot, Abderrahmane Bourredjem, Maxime Nguyen, Julien Guy, Serge Monier, Marjolaine Georges, Audrey Large, Auguste Dargent, Alexandre Guilhem, Suzanne Mouries-Martin, Jeremy Barben, Belaid Bouhemad, Pierre-Emmanuel Charles, Pascal Chavanet, Christine Binquet, Lionel Piroth

ABSTRACT

BackgroundAlthough 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.MethodsThirty-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.ResultsAt 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.ConclusionWe 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. More... »

PAGES

457

Journal

TITLE

Journal of Translational Medicine

ISSUE

1

VOLUME

18

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12967-020-02646-9

DOI

http://dx.doi.org/10.1186/s12967-020-02646-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1132950811

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/33272291


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29 schema:description BackgroundAlthough 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.MethodsThirty-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.ResultsAt 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.ConclusionWe 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.
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354 Geriatrics Internal Medicine Department, Dijon Bourgogne University Hospital, Dijon, France
355 Hematobiology, Dijon Bourgogne University Hospital, Dijon, France
356 Infectious Diseases Department, Dijon Bourgogne University Hospital, 14 rue Paul Gaffarel, 21079, Dijon, France
357 Laboratory of virology, Dijon Bourgogne University Hospital, Dijon, France
358 Lipness team, INSERM Research Center LNC-UMR1231 and LabEx LipSTIC, University of Burgundy, Dijon, France
359 rdf:type schema:Organization
360 grid-institutes:grid.5613.1 schema:alternateName Cytometry core facility, University of Burgundy Franche-Comté, Dijon, France
361 Lipness team, INSERM Research Center LNC-UMR1231 and LabEx LipSTIC, University of Burgundy, Dijon, France
362 schema:name Cytometry core facility, University of Burgundy Franche-Comté, Dijon, France
363 Infectious Diseases Department, Dijon Bourgogne University Hospital, 14 rue Paul Gaffarel, 21079, Dijon, France
364 Lipness team, INSERM Research Center LNC-UMR1231 and LabEx LipSTIC, University of Burgundy, Dijon, France
365 rdf:type schema:Organization
 




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