Plasma Endostatin Correlates with Hypoxia and Mortality in Covid-19-Associated Acute Respiratory Failure

Abstract

Background: The contribution of endothelial injury in the pathogenesis of COVID-19-associated acute respiratory distress syndrome (ARDS) and resulting respiratory failure remains unclear. Plasma endostatin, an endogenous inhibitor of angiogenesis and endothelial dysfunction is upregulated during hypoxia, inflammation and progress of pulmonary disease. Aim: To investigate if plasma endostatin is associated to hypoxia, inflammation and 30-day mortality in patients with severe COVID-19 infection. Method: Samples for blood analysis and plasma endostatin quantification were collected from adult patients with ongoing COVID-19 (n = 109) on admission to intensive care unit (day 1). Demographic characteristics and 30-day mortality data were extracted from medical records. The ability of endostatin to predict mortality was analyzed using receiving operating characteristics and Kaplan–Meier analysis with a cutoff at 46.2 ng/ml was used to analyze the association to survival. Results: Plasma endostatin levels correlated with; PaO2/FiO2 (r = -0.3, p < 0.001), arterial oxygen tension (r = -0.2, p = 0.01), lactate (r = 0.2, p = 0.04), C-reactive protein (r = 0.2, p = 0.04), ferritin (r = 0.2, p = 0.09), D-dimer (r = 0.2, p = 0.08) and IL-6 (r = 0.4, p < 0.001). Nonsurvivors at 30 days had higher plasma endostatin levels than survivors (72 ± 26 vs 56 ± 16 ng/ml, p = 0.01). Receiving operating characteristic curve (area under the curve 0.7) showed that plasma endostatin >46.2 ng/ml predicts mortality with a sensitivity of 92% and specificity of 71%. In patients with plasma endostatin >46.2 ng/ml probability of survival was lower (p = 0.02) in comparison to those with endostatin <46.2 ng/ml. Conclusion: Our results suggest that plasma endostatin is an early biomarker for disease severity in COVID-19.

Basement membrane product, endostatin, as a link between inflammation, coagulation and vascular permeability in COVID-19 and non-COVID-19 acute respiratory distress syndrome

“…Basement membrane damage and fragmentation are key pathological features observed in various types of ARDS. In line, elevated plasma levels of endostatin, the matrikine of collagen XVIIIα1, have been reported for COVID-19 and non-COVID-19 ARDS patients ( 6 , 7 ). However, whether endostatin is more than a mere biomarker associated with disease severity is currently unknown.…”

“…Exposure of the BM during injury and concomitant increased protease activity can lead to the release of BM fragments, with a novel biological function distinct from their parent molecules; these molecules are known as matrikines. Endostatin is a matrikine of collagen XVIIIα1 (encoded by COL18A1) and is currently suggested to be an early biomarker for non-COVID-19 and COVID-19 associated ARDS ( 6 , 7 ). However, whether endostatin is a mere biomarker or whether it also functionally contributes to disease pathogenesis in ARDS has not been investigated so far.…”

Association of lactate/albumin ratio with in-hospital mortality in ICU patients with acute respiratory failure: A retrospective analysis based on MIMIC-IV database

“…The same trend was observed when LAR was treated as a categorical variable. However, the results obtained Despite numerous studies evaluating the prognosis of patients with ARF, including galectin-3, [30] growth differentiation factor-15, [31] and plasma endostatin, [32] none of these biomarkers are perfect. While these biomarkers demonstrate a positive predictive effect on ARF prognosis, their inherent drawbacks include limited accessibility, high cost, and regional or technological constraints, preventing widespread implementation within a short timeframe.…”

Plasma endostatin is an early creatinine independent predictor of acute kidney injury and need for renal replacement therapy in critical care

“…Endostatin has been shown to predict renal recovery and mortality in AKI 11,23 . Furthermore, endostatin has been associated with acute respiratory distress syndrome (ARDS) pathology and disease severity in COVID-19 24,25 . In the general intensive care population, a prospective study from 2017 concluded that endostatin has limited value as a predictor of mortality, while a more recent study showed that endostatin combined with age was useful in mortality prediction.…”