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

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Abstract BackgroundEvaluation of biomarkers in the context of ARDS is used to detect the presence of endothelial and/or alveolar epithelial injuries. 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 aim of this study was to evaluate whether the trends in plasma concentration of the biomarkers mentioned above were different in survivors and non-survivors of COVID-19-related ARDS. Furthermore, we compared the expression of biomarkers of vascular and endothelial injury in patients with COVID-19-related ARDS and classical ARDS. MethodsThis 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 10 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.ResultsIn 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).ConclusionsCOVID-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

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