Abstract
Reports suggest a role of endothelial dysfunction and loss of endothelial barrier function in COVID-19. It is well established that the endothelial glycocalyx-degrading enzyme heparanase contributes to vascular leakage and inflammation. Low molecular weight heparins (LMWH) serve as an inhibitor of heparanase. We hypothesize that heparanase contributes to the pathogenesis of COVID-19, and that heparanase may be inhibited by LMWH. To test this hypothesis, heparanase activity and heparan sulfate levels were measured in plasma of healthy controls (n = 10) and COVID-19 patients (n = 48). Plasma heparanase activity and heparan sulfate levels were significantly elevated in COVID-19 patients. Heparanase activity was associated with disease severity including the need for intensive care, lactate dehydrogenase levels, and creatinine levels. Use of prophylactic LMWH in non-ICU patients was associated with a reduced heparanase activity. Since there is no other clinically applied heparanase inhibitor currently available, therapeutic treatment of COVID-19 patients with low molecular weight heparins should be explored.
Highlights
The coronavirus disease-2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) [1]
The non-ICU patients were further aggregated in those receiving prophylactic low molecular weight heparins (LMWH) (LMWH+) (n = 17) and those receiving either alternative anticoagulation (n = 8; vitamin K antagonist n = 6, direct oral anticoagulant n = 2) or patients for whom the sample collection was performed before initiation of any standard medical intervention (LMWH−) (n = 9)
COVID-19 appears to be a disease that leads to endothelial dysfunction and disruption of the endothelial barrier, which may underly development of acute respiratory distress syndrome (ARDS) and proteinuria/acute kidney injury (AKI) [11, 30]
Summary
The coronavirus disease-2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) [1]. Severe COVID-19 usually manifests as pneumonitis or acute respiratory distress syndrome (ARDS) [2, 3]. Studies showed that upon hospital admission 59% of COVID-19 patients had proteinuria [4], and 22% of the non-ventilated patients and 90% of the ventilated patients developed acute kidney injury (AKI) [5, 6]. As pulmonary edema occurs when fluid leaks into alveoli, dysfunction of the endothelium is likely to contribute to pulmonary edema in COVID-19. It has been well established that proteinuria occurs when the endothelial barrier function in the glomerulus is compromised [9, 10, 13]
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