Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
Department of Internal Medicine, Radboud university medical center, Nijmegen, The Netherlands.
EBioMedicine. 2020 Sep;59:102969. doi: 10.1016/j.ebiom.2020.102969. Epub 2020 Aug 25.
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.
新型冠状病毒病（COVID-19）主要与肺部和肾脏的严重炎症有关。有报道称，肝素/低分子量肝素（LMWH）的使用对 COVID-19 患者的死亡率有有益影响。部分原因是肝素/LMWH 的抗凝特性。在这里，我们总结了肝素/LMWH 治疗 COVID-19 患者的潜在有益的非抗凝机制，包括：（i）抑制负责血管内皮渗漏的肝素酶活性；（ii）中和趋化因子和细胞因子；（iii）干扰白细胞迁移；（iv）减少病毒细胞进入；以及（v）中和细胞外细胞毒性组蛋白。考虑到肝素/LMWH 靶向的多种炎症和致病机制，有必要进行临床研究，评估 COVID-19 患者的肝素/LMWH 治疗剂量。此外，鉴定具有针对非抗凝机制的功能的特定肝素衍生序列，可能对 COVID-19 患者以及患有其他炎症性疾病的患者具有更高的治疗潜力。
