Plasma Endothelial and Oxidative Stress Biomarkers Associated with Late Mortality in Hospitalized COVID-19 Patients

Abstract

Background: Coronavirus infectious disease 2019 (COVID-19) is a significant public health problem worldwide. COVID-19 increases the risk of non-pulmonary complications such as acute myocardial injury, renal failure, thromboembolic events, and multi-organic damage. Several studies have documented increased inflammation molecules, endothelial dysfunction biomarkers, and dysregulation of coagulation factors in COVID-19 patients. In addition, endothelium dysfunction is exacerbated by the oxidative stress (OxS) promoted by endocrine and cardiovascular molecules. Our objective was to evaluate whether endothelial and OxS biomarkers were associated with mortality in hospitalized COVID-19 patients. Methods: A prospective cohort study was performed. Patients ≥18 years old with confirmed COVID-19 that required hospitalization were included in a prospective cohort study. Endothelium and oxidative stress biomarkers were collected between 3 and 5 days after admission. Results: A total of 165 patients were evaluated; 56 patients succumbed. The median follow-up was 71 days [23–129]. Regarding endothelial dysfunction and OxS biomarkers, patients who did not survive had higher levels of nitrates (0.4564 [0.1817–0.6761] vs. 0.2817 [0.0517–0.5], p = 0.014), total nitrates (0.0507 [−0.0342–0.1809] vs. −0.0041 [−0.0887–0.0909], p = 0.016), sE-Selectin (1.095 [0.86–1.495] vs. 0.94 [0.71–1.19], p = 0.004), and malondialdehyde (MDA) (0.50 [0.26–0.72] vs. 0.36 [0.23–0.52], p = 0.010) compared to patients who survived. Endothelial and OxS biomarkers independently associated with mortality were sE-selectin (HR:2.54, CI95%; from 1.11 to 5.81, p = 0.027), nitrates (HR:4.92, CI95%; from 1.23 to 19.63, p = 0.024), and MDA (HR: 3.05, CI95%; from 1.14 to 8.15, p = 0.025). Conclusions: Endothelial dysfunction (sE-selectin and nitrates) and OxS (MDA) are independent indicators of a worse prognosis in COVID-19 patients requiring hospitalization.

Biomarkers of endothelial dysfunction are associated with poor outcome in COVID‐19 patients: A systematic review and meta‐analysis

“…Ten studies 9,11,29,41,45,[71][72][73][74][75] for E-selectin and 11 studies for Pselectin 10,11,32,36,45,52,71,72,[76][77][78] were reviewed with a total of 896 (351 with poor outcome vs. 545 with good outcome) and 1042 patients (353 with poor outcome vs. 689 with good outcome) for Eselectin and P-selectin respectively. The pooled standard mean difference among the two groups showed a significant increase in Eselectin and P-selectin levels among patients with poor outcome relative to those with good outcome (SMD: 1.09 (0.55, 1.63), p < 0.0001 for E-selectin and SMD: 0.59 (0.24, 0.94), p = 0.001 for Pselectin) (Figure 5, panel A and B respectively).…”

“…74 Lastly, Orea-Tejada et al stated in their study that E-selectin was independently associated with a greater risk of death in hospitalised COVID-19 patients. 75 The substantial variation between studies in terms of E-selectin values, could be explained by different treatment strategies. High tidal volume ventilation and high dosages of cortisone would cause an increase in GL degradation and therefore increase in E-selectin levels.…”

Longitudinal Assessment of Plasma Syndecan-1 Predicts 60-Day Mortality in Patients with COVID-19

“…Once the endothelial layer is disrupted following infection [ 3 ], released toxin [ 4 ], trauma [ 5 ], irradiation [ 6 ], ischemia [ 7 ], etc., an endotheliopathy develops. Endotheliopathy is marked by an increased level of plasma von Willebrand factor (VWF), E-selectin, plasminogen activator inhibitor-1 (PAI-1), soluble thrombomodulin (sTM), and syndecan-1 [ 8 ], which is strongly associated with a poor outcome in patients with severe COVID-19 [ 9 , 10 ].…”

Longitudinal Assessment of Plasma Syndecan-1 Predicts 60-Day Mortality in Patients with COVID-19

“…Once endothelial layer is disrupted following infection 3 , released toxin 4 , trauma 5 , irradiation 6 , and ischemia 7 , etc., an endotheliopathy develops. Endotheliopathy is marked by an increased level of plasma von Willebrand factor (VWF), E-selectin, plasminogen activator inhibitor-1 (PAI-1), soluble thrombomodulin (sTM), and syndecan-1 8 , which is strongly associated with a poor outcome in patients with severe COVID-19 9,10 .…”