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

Abstract

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

Distinct temporal characteristics of circulating alveolar epithelial and endothelial injury markers in ARDS with COVID-19

“…The increase in the circulating surfactant protein concentration indicates alveolar barrier disruption in ARDS cases [ 5 ]. Recently, Spadaro et al reported that COVID-19 ARDS is characterised by increase in the circulating endothelial injury markers [ 6 ]. However, the detailed temporal characteristics of these markers remain unclear.…”

Management of Intraoperative Mechanical Ventilation to Prevent Postoperative Complications after General Anesthesia: A Narrative Review

“…Notably, studies focused on RMs during GA do not take into account the recruitability of the lung, which may significantly differ in accordance with patient’s baseline comorbidities and surgical position [ 54 ]. In addition, RMs are usually well tolerated hemodynamically but seem to be not free from the risk of overdistention, as described also in critically ill patients [ 37 ]; a recent RCT, indeed, found higher levels of receptor for advanced glycation end-products, a marker of lung epithelial injury [ 55 ], in patients receiving intraoperative RMs [ 56 ]. Further studies are needed to elucidate which patients should receive intraoperative RM and how.…”

Cardiovascular Imaging Evaluation in COVID-19 Heart and Vascular Non-Ischaemic Involvement

“…COVID-19 gives severe lung involvement and hemodynamic alterations that therefore induce commonly cardiovascular complications showing a wide spectrum of severity [136]. Clinical studies and several evidences show that patients with severe COVID19, as critically ill patient, generally are affected by the "cytokine storm" which plays a crucial role in the disease progression and severity, and in influencing the COVID-19-associated acute respiratory distress syndrome (ARDS) and multiorgan dysfunction syndrome [137,138]. Cardiac involvement may occur in critically ill patients, either as a consequence of mechanical ventilation and a direct effect of SARS-CoV2 virus [138][139][140].…”