Statins and PCSK9 inhibitors: What is their role in coronavirus disease 2019?

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.

Statin use and mortality in COVID-19 patients: Updated systematic review and meta-analysis

“…It should be noted that statin-treated individuals are more likely to be older and to have cardiovascular risk factors or disease, and thereby more likely to have severe COVID-19 [ 3 ]. Statins seem to up-regulate angiotensin-converting enzyme 2, which could possibly enhance COVID-19 transmissibility [ 4 ]; on the other hand, these drugs present anti-oxidative, anti-inflammatory, anti-arrhythmic, anti-thrombotic properties and have beneficial effects on endothelial dysfunction, which could be proved protective against fatal respiratory, cardiovascular and thromboembolic complications in COVID-19 [ 5 , 6 ].…”

Sodium-glucose cotransporter inhibitors may reduce the risk of pneumonia: an updated meta-analysis of cardiovascular outcome trials

“…The reasons for the differential association of SGLT2i with the risk of pneumonia versus upper or lower respiratory infection are unknown [ 2 ]. Considering the inflammatory pathways involved in the pathophysiology of pneumonia, the anti-inflammatory properties of SGLT2i may be more relevant [ 14 ]. Furthermore, pneumonia is a more objective endpoint since its diagnosis is established with imaging criteria.…”

Endothelial Dysfunction and SARS-CoV-2 Infection: Association and Therapeutic Strategies

“…The available data indicate that the use of RAAS inhibitors did not increase the risk of SARS-CoV-2 infection or cause adverse outcomes [ 40 , 81 , 83 , 84 , 85 ]. On the contrary, due to an increase in the production of angiotensin 1–7 and the catabolism of angiotensin II, ACE2 upregulation may be more helpful than harmful for patients infected with SARS-CoV-2 [ 86 , 87 ]. Evidence from cardiology showed that RAAS inhibitors such as ACEIs and ARBs can reduce the risk of thrombus formation [ 88 ].…”