Med Hypotheses146:110452. Statins and PCSK9 inhibitors: What is their role in coronavirus disease 2019? Fotios Barkas 1, Haralampos Milionis 1, Georgia Anastasiou 1, Evangelos Liberopoulos 2 Abstract 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. Keywords: Coronavirus; Infection; PCSK9 inhibitors; SARS-CoV-2; Sepsis; Statin. Copyright © 2020 Elsevier Ltd. All rights reserved. View Full-Text
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