Markers of endothelial and epithelial pulmonary injury in mechanically ventilated COVID-19 ICU patients.
Aged
Antigens, Neoplasm
/ analysis
Area Under Curve
Biomarkers
/ analysis
COVID-19
/ blood
Cohort Studies
E-Selectin
/ analysis
Female
Humans
Intensive Care Units
/ organization & administration
Intercellular Adhesion Molecule-1
/ analysis
Lung Injury
/ blood
Male
Middle Aged
Mitogen-Activated Protein Kinases
/ analysis
P-Selectin
/ analysis
Prospective Studies
ROC Curve
Respiration, Artificial
/ adverse effects
Respiratory Distress Syndrome
/ blood
Versicans
/ analysis
Vesicular Transport Proteins
/ analysis
Acute respiratory distress syndrome
Angiopoietin-2
Biomarkers
COVID-19
Intercellular adhesion molecule-1
Receptor for advanced glycation end-products
Selectin
Vascular cell adhesion protein 1
Journal
Critical care (London, England)
ISSN: 1466-609X
Titre abrégé: Crit Care
Pays: England
ID NLM: 9801902
Informations de publication
Date de publication:
19 02 2021
19 02 2021
Historique:
received:
19
10
2020
accepted:
10
02
2021
entrez:
20
2
2021
pubmed:
21
2
2021
medline:
4
3
2021
Statut:
epublish
Résumé
Biomarkers can be used to detect the presence of endothelial and/or alveolar epithelial injuries in case of ARDS. Angiopoietin-2 (Ang-2), soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), P-selectin and E-selectin are biomarkers of endothelial injury, whereas the receptor for advanced glycation end-products (RAGE) reflects alveolar epithelial injury. The aims of this study were to evaluate whether the plasma concentration of the above-mentioned biomarkers was different 1) in survivors and non-survivors of COVID-19-related ARDS and 2) in COVID-19-related and classical ARDS. This prospective study was performed in two COVID-19-dedicated Intensive Care Units (ICU) and one non-COVID-19 ICU at Ferrara University Hospital. A cohort of 31 mechanically ventilated patients with COVID-19 ARDS and a cohort of 11 patients with classical ARDS were enrolled. Ang-2, ICAM-1, VCAM-1, P-selectin, E-selectin and RAGE were determined with a bead-based multiplex immunoassay at three time points: inclusion in the study (T1), after 7 ± 2 days (T2) and 14 ± 2 days (T3). The primary outcome was to evaluate the plasma trend of the biomarker levels in survivors and non-survivors. The secondary outcome was to evaluate the differences in respiratory mechanics variables and gas exchanges between survivors and non-survivors. Furthermore, we compared the plasma levels of the biomarkers at T1 in patients with COVID-19-related ARDS and classical ARDS. In COVID-19-related ARDS, the plasma levels of Ang-2 and ICAM-1 at T1 were statistically higher in non-survivors than survivors, (p = 0.04 and p = 0.03, respectively), whereas those of P-selectin, E-selectin and RAGE did not differ. Ang-2 and ICAM-1 at T1 were predictors of mortality (AUROC 0.650 and 0.717, respectively). At T1, RAGE and P-selectin levels were higher in classical ARDS than in COVID-19-related ARDS. Ang-2, ICAM-1 and E-selectin were lower in classical ARDS than in COVID-19-related ARDS (all p < 0.001). COVID-19 ARDS is characterized by an early pulmonary endothelial injury, as detected by Ang-2 and ICAM-1. COVID-19 ARDS and classical ARDS exhibited a different expression of biomarkers, suggesting different pathological pathways. Trial registration NCT04343053 , Date of registration: April 13, 2020.
Sections du résumé
BACKGROUND
Biomarkers can be used to detect the presence of endothelial and/or alveolar epithelial injuries in case of ARDS. Angiopoietin-2 (Ang-2), soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), P-selectin and E-selectin are biomarkers of endothelial injury, whereas the receptor for advanced glycation end-products (RAGE) reflects alveolar epithelial injury. The aims of this study were to evaluate whether the plasma concentration of the above-mentioned biomarkers was different 1) in survivors and non-survivors of COVID-19-related ARDS and 2) in COVID-19-related and classical ARDS.
METHODS
This prospective study was performed in two COVID-19-dedicated Intensive Care Units (ICU) and one non-COVID-19 ICU at Ferrara University Hospital. A cohort of 31 mechanically ventilated patients with COVID-19 ARDS and a cohort of 11 patients with classical ARDS were enrolled. Ang-2, ICAM-1, VCAM-1, P-selectin, E-selectin and RAGE were determined with a bead-based multiplex immunoassay at three time points: inclusion in the study (T1), after 7 ± 2 days (T2) and 14 ± 2 days (T3). The primary outcome was to evaluate the plasma trend of the biomarker levels in survivors and non-survivors. The secondary outcome was to evaluate the differences in respiratory mechanics variables and gas exchanges between survivors and non-survivors. Furthermore, we compared the plasma levels of the biomarkers at T1 in patients with COVID-19-related ARDS and classical ARDS.
RESULTS
In COVID-19-related ARDS, the plasma levels of Ang-2 and ICAM-1 at T1 were statistically higher in non-survivors than survivors, (p = 0.04 and p = 0.03, respectively), whereas those of P-selectin, E-selectin and RAGE did not differ. Ang-2 and ICAM-1 at T1 were predictors of mortality (AUROC 0.650 and 0.717, respectively). At T1, RAGE and P-selectin levels were higher in classical ARDS than in COVID-19-related ARDS. Ang-2, ICAM-1 and E-selectin were lower in classical ARDS than in COVID-19-related ARDS (all p < 0.001).
CONCLUSIONS
COVID-19 ARDS is characterized by an early pulmonary endothelial injury, as detected by Ang-2 and ICAM-1. COVID-19 ARDS and classical ARDS exhibited a different expression of biomarkers, suggesting different pathological pathways. Trial registration NCT04343053 , Date of registration: April 13, 2020.
Identifiants
pubmed: 33608030
doi: 10.1186/s13054-021-03499-4
pii: 10.1186/s13054-021-03499-4
pmc: PMC7894238
doi:
Substances chimiques
Antigens, Neoplasm
0
Biomarkers
0
E-Selectin
0
ICAM1 protein, human
0
P-Selectin
0
SELE protein, human
0
VCAN protein, human
0
VPS51 protein, human
0
Vesicular Transport Proteins
0
Intercellular Adhesion Molecule-1
126547-89-5
Versicans
126968-45-4
MOK protein, human
EC 2.7.11.22
Mitogen-Activated Protein Kinases
EC 2.7.11.24
Banques de données
ClinicalTrials.gov
['NCT04343053']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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