Journal Article

Markers of endothelial and epithelial pulmonary injury in mechanically ventilated COVID-19 ICU patients

Contoli, Marco, Tunstall, Tanushree, Vieceli Dalla Sega, Francesco, Volta, Carlo Alberto, Ottaviani, Irene, Grasso, Salvatore, Papi, Alberto, Campo, Gianluca, Marangoni, Elisabetta, Rizzo, Paola, Fortini, Francesca, Zucchetti, Ottavio, Verri, Marco, Pavasini, Rita, Fogagnolo, Alberto, Spadaro, Savino, Ferrari, Roberto, Murgolo, Francesco, Scaramuzzo, Valentina

2021

Overview

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

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Acute respiratory distress syndrome / Aged / Angiopoietin-2 / Antigens, Neoplasm - analysis / Antigens, Neoplasm - blood / Area Under Curve / Biological markers / Biomarkers / Biomarkers - analysis / Cohort Studies / Complications and side effects / COVID-19 / COVID-19 - blood / COVID-19 - prevention & control / Critical Care Medicine / Diagnosis / E-Selectin - analysis / E-Selectin - blood / Emergency Medicine / Female / Humans / Intensive / Intensive Care Units - organization & administration / Intensive Care Units - statistics & numerical data / Intercellular adhesion molecule-1 / Intercellular Adhesion Molecule-1 - analysis / Intercellular Adhesion Molecule-1 - blood / Lung Injury - blood / Lung Injury - diagnosis / Lung Injury - physiopathology / Male / Medicine / Medicine & Public Health / Middle Aged / Mitogen-Activated Protein Kinases - analysis / Mitogen-Activated Protein Kinases - blood / Observations / P-Selectin - analysis / P-Selectin - blood / Prospective Studies / Respiration, Artificial - adverse effects / Respiration, Artificial - standards / Respiration, Artificial - statistics & numerical data / Respiratory Distress Syndrome - blood / Respiratory Distress Syndrome - physiopathology / ROC Curve / Vascular cell adhesion protein 1 / Versicans - analysis / Versicans - blood / Vesicular Transport Proteins - analysis / Vesicular Transport Proteins - blood