The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome.
Aged
Aged, 80 and over
COVID-19
/ diagnosis
Critical Care
Female
France
/ epidemiology
Humans
Immunity, Innate
/ physiology
Immunophenotyping
Lymphocyte Activation
/ physiology
Male
Middle Aged
Pneumonia, Viral
/ diagnosis
Prognosis
Respiration, Artificial
SARS-CoV-2
/ physiology
Severity of Illness Index
Acute respiratory distress syndrome
COVID-19
CXCL10
GM-CSF
Immune response
Mechanical ventilation
Pneumonia
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
03 12 2020
03 12 2020
Historique:
received:
20
10
2020
accepted:
27
11
2020
entrez:
4
12
2020
pubmed:
5
12
2020
medline:
22
12
2020
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 33272291
doi: 10.1186/s12967-020-02646-9
pii: 10.1186/s12967-020-02646-9
pmc: PMC7711269
doi:
Banques de données
ClinicalTrials.gov
['NCT03505281']
Types de publication
Controlled Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
457Investigateurs
Pascal Andreu
(P)
François Aptel
(F)
Marie Labruyère
(M)
Sébastien Prin
(S)
Guillaume Beltramo
(G)
Philippe Bonniaud
(P)
Philip Bielefeld
(P)
Hervé Devilliers
(H)
Bernard Bonnotte
(B)
Marielle Buisson
(M)
Alain Putot
(A)
Commentaires et corrections
Type : ErratumIn
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