CXCL10 could drive longer duration of mechanical ventilation during COVID-19 ARDS.
Adult
Aged
COVID-19
Case-Control Studies
Chemokine CXCL10
/ metabolism
Coronavirus Infections
/ complications
Female
Humans
Male
Middle Aged
Pandemics
Pneumonia, Viral
/ complications
Prospective Studies
Respiration, Artificial
/ statistics & numerical data
Respiratory Distress Syndrome
/ etiology
Time Factors
Acute respiratory distress syndrome
Biomarker
Bronchoalveolar lavage
COVID-19
CXCL10
Immune response
Mechanical ventilation
Mitochondrial DNA
SARS-CoV-2
Journal
Critical care (London, England)
ISSN: 1466-609X
Titre abrégé: Crit Care
Pays: England
ID NLM: 9801902
Informations de publication
Date de publication:
02 11 2020
02 11 2020
Historique:
received:
04
08
2020
accepted:
05
10
2020
entrez:
3
11
2020
pubmed:
4
11
2020
medline:
6
11
2020
Statut:
epublish
Résumé
COVID-19-related ARDS has unique features when compared with ARDS from other origins, suggesting a distinctive inflammatory pathogenesis. Data regarding the host response within the lung are sparse. The objective is to compare alveolar and systemic inflammation response patterns, mitochondrial alarmin release, and outcomes according to ARDS etiology (i.e., COVID-19 vs. non-COVID-19). Bronchoalveolar lavage fluid and plasma were obtained from 7 control, 7 non-COVID-19 ARDS, and 14 COVID-19 ARDS patients. Clinical data, plasma, and epithelial lining fluid (ELF) concentrations of 45 inflammatory mediators and cell-free mitochondrial DNA were measured and compared. COVID-19 ARDS patients required mechanical ventilation (MV) for significantly longer, even after adjustment for potential confounders. There was a trend toward higher concentrations of plasma CCL5, CXCL2, CXCL10, CD40 ligand, IL-10, and GM-CSF, and ELF concentrations of CXCL1, CXCL10, granzyme B, TRAIL, and EGF in the COVID-19 ARDS group compared with the non-COVID-19 ARDS group. Plasma and ELF CXCL10 concentrations were independently associated with the number of ventilator-free days, without correlation between ELF CXCL-10 and viral load. Mitochondrial DNA plasma and ELF concentrations were elevated in all ARDS patients, with no differences between the two groups. ELF concentrations of mitochondrial DNA were correlated with alveolar cell counts, as well as IL-8 and IL-1β concentrations. CXCL10 could be one key mediator involved in the dysregulated immune response. It should be evaluated as a candidate biomarker that may predict the duration of MV in COVID-19 ARDS patients. Targeting the CXCL10-CXCR3 axis could also be considered as a new therapeutic approach. ClinicalTrials.gov, NCT03955887.
Sections du résumé
BACKGROUND
COVID-19-related ARDS has unique features when compared with ARDS from other origins, suggesting a distinctive inflammatory pathogenesis. Data regarding the host response within the lung are sparse. The objective is to compare alveolar and systemic inflammation response patterns, mitochondrial alarmin release, and outcomes according to ARDS etiology (i.e., COVID-19 vs. non-COVID-19).
METHODS
Bronchoalveolar lavage fluid and plasma were obtained from 7 control, 7 non-COVID-19 ARDS, and 14 COVID-19 ARDS patients. Clinical data, plasma, and epithelial lining fluid (ELF) concentrations of 45 inflammatory mediators and cell-free mitochondrial DNA were measured and compared.
RESULTS
COVID-19 ARDS patients required mechanical ventilation (MV) for significantly longer, even after adjustment for potential confounders. There was a trend toward higher concentrations of plasma CCL5, CXCL2, CXCL10, CD40 ligand, IL-10, and GM-CSF, and ELF concentrations of CXCL1, CXCL10, granzyme B, TRAIL, and EGF in the COVID-19 ARDS group compared with the non-COVID-19 ARDS group. Plasma and ELF CXCL10 concentrations were independently associated with the number of ventilator-free days, without correlation between ELF CXCL-10 and viral load. Mitochondrial DNA plasma and ELF concentrations were elevated in all ARDS patients, with no differences between the two groups. ELF concentrations of mitochondrial DNA were correlated with alveolar cell counts, as well as IL-8 and IL-1β concentrations.
CONCLUSION
CXCL10 could be one key mediator involved in the dysregulated immune response. It should be evaluated as a candidate biomarker that may predict the duration of MV in COVID-19 ARDS patients. Targeting the CXCL10-CXCR3 axis could also be considered as a new therapeutic approach.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03955887.
Identifiants
pubmed: 33138839
doi: 10.1186/s13054-020-03328-0
pii: 10.1186/s13054-020-03328-0
pmc: PMC7604548
doi:
Substances chimiques
CXCL10 protein, human
0
Chemokine CXCL10
0
Banques de données
ClinicalTrials.gov
['NCT03955887']
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
632Investigateurs
François Aptel
(F)
Auguste Dargent
(A)
Marjolaine Georges
(M)
Marie Labruyère
(M)
Laurent Lagrost
(L)
Audrey Large
(A)
Serge Monier
(S)
Jean-Baptiste Roudaut
(JB)
Charles Thomas
(C)
Commentaires et corrections
Type : ErratumIn
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