Тема - темы
COVID-19/complications , Endothelial Cells/virology , Endothelium, Vascular/virology , Pandemics , SARS-CoV-2/pathogenicity , Vasculitis/etiology , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/physiopathology , Anticoagulants/therapeutic use , Apoptosis , Bone Marrow Transplantation/adverse effects , COVID-19/epidemiology , Endothelial Cells/pathology , Glucuronidase/antagonists & inhibitors , Graft vs Host Disease/etiology , Graft vs Host Disease/physiopathology , Heparin/therapeutic use , Hepatic Veno-Occlusive Disease/etiology , Hepatic Veno-Occlusive Disease/physiopathology , Humans , Idiopathic Interstitial Pneumonias/etiology , Idiopathic Interstitial Pneumonias/physiopathology , Interleukin-6/physiology , Multiple Organ Failure/etiology , Multiple Organ Failure/physiopathology , Organ Specificity , Polydeoxyribonucleotides/therapeutic use , SARS-CoV-2/isolation & purification , Stem Cell Transplantation/adverse effects , Thrombophilia/drug therapy , Thrombophilia/etiology , Thrombotic Microangiopathies/etiology , Thrombotic Microangiopathies/physiopathology , Vasculitis/drug therapy , Vasculitis/virology , Viral TropismРеферат
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.
Тема - темы
Endothelium/pathology , Glucuronidase/antagonists & inhibitors , Glucuronidase/blood , Heparin Antagonists/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Tight Junctions/pathology , Aged , Betacoronavirus , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Creatinine/blood , Critical Care , Cross-Sectional Studies , Female , Glucuronidase/metabolism , Heparitin Sulfate/blood , Humans , Interleukin-6/blood , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , SARS-CoV-2Реферат
Coronavirus disease-2019 (COVID-19) is associated with severe inflammation in mainly the lung, and kidney. Reports suggest a beneficial effect of the use of heparin/low molecular weight heparin (LMWH) on mortality in COVID-19. In part, this beneficial effect could be explained by the anticoagulant properties of heparin/LMWH. Here, we summarise potential beneficial, non-anticoagulant mechanisms underlying treatment of COVID-19 patients with heparin/LMWH, which include: (i) Inhibition of heparanase activity, responsible for endothelial leakage; (ii) Neutralisation of chemokines, and cytokines; (iii) Interference with leukocyte trafficking; (iv) Reducing viral cellular entry, and (v) Neutralisation of extracellular cytotoxic histones. Considering the multiple inflammatory and pathogenic mechanisms targeted by heparin/LMWH, it is warranted to conduct clinical studies that evaluate therapeutic doses of heparin/LMWH in COVID-19 patients. In addition, identification of specific heparin-derived sequences that are functional in targeting non-anticoagulant mechanisms may have even higher therapeutic potential for COVID-19 patients, and patients suffering from other inflammatory diseases.