Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, Greece.
Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, Greece.
Med Hypotheses. 2021 Jan;146:110452. doi: 10.1016/j.mehy.2020.110452. Epub 2020 Dec 9.
Statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors interfere with several pathophysiological pathways of coronavirus disease 2019 (COVID-19). Statins may have a direct antiviral effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by inhibiting its main protease. Statin-induced up-regulation of angiotensin-converting enzyme 2 (ACE2) may also be beneficial, whereas cholesterol reduction might significantly suppress SARS-CoV-2 by either blocking its host-cell entry through the disruption of lipid rafts or by inhibiting its replication. Available human studies have shown beneficial effects of statins and PCSK9 inhibitors on pneumonia and sepsis. These drugs may act as immunomodulators in COVID-19 and protect against major complications, such as acute respiratory distress syndrome and cytokine release syndrome. Considering their antioxidative, anti-arrhythmic, antithrombotic properties and their beneficial effect on endothelial dysfunction, along with the increased risk of mortality of patients at high cardiovascular risk infected by SARS-CoV-2, statins and PCSK9 inhibitors might prove effective against the cardiovascular and thromboembolic complications of COVID-19. On the whole, randomized clinical trials are needed to establish routine use of statins and PCSK9 inhibitors in the treatment of SARS-CoV-2 infection. In the meantime, it is recommended that lipid-lowering therapy should not be discontinued in COVID-19 patients unless otherwise indicated.
他汀类药物和前蛋白转化酶枯草溶菌素 9(PCSK9)抑制剂干扰 2019 年冠状病毒病(COVID-19)的几个病理生理途径。他汀类药物可能通过抑制其主要蛋白酶对严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)具有直接的抗病毒作用。他汀类药物诱导的血管紧张素转换酶 2(ACE2)上调也可能有益,而胆固醇降低可能通过破坏脂筏阻断其宿主细胞进入或通过抑制其复制而显著抑制 SARS-CoV-2。现有的人体研究表明他汀类药物和 PCSK9 抑制剂对肺炎和败血症有有益作用。这些药物可能在 COVID-19 中作为免疫调节剂发挥作用,并预防急性呼吸窘迫综合征和细胞因子释放综合征等主要并发症。考虑到它们的抗氧化、抗心律失常、抗血栓形成特性以及对血管内皮功能障碍的有益影响,以及心血管风险高的 SARS-CoV-2 感染患者的死亡率增加,他汀类药物和 PCSK9 抑制剂可能对 COVID-19 的心血管和血栓栓塞并发症有效。总的来说,需要进行随机临床试验来确定他汀类药物和 PCSK9 抑制剂在 SARS-CoV-2 感染治疗中的常规使用。同时,建议除非另有指示,否则不应在 COVID-19 患者中停止降脂治疗。