Cholesterol in Relation to COVID-19: Should We Care about It?

Abstract

Current data suggest that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing corona virus disease-19 (COVID-19) seems to follow a more severe clinical course in patients with cardiovascular disease (CVD), hypertension, and overweight/obesity. It appears that lipid-lowering pharmacological interventions, in particular statins, might reduce the risk of cardiovascular complications caused by COVID-19 and might potentially have an additional antiviral activity. It has been shown that high cholesterol levels are associated with more lipid rafts, subdomains of the plasma membrane that can harbour angiotensin-converting enzyme 2 (ACE2) receptors for the S-protein of SARS-CoV-2. Evidence of the importance of cholesterol for viral entry into host cells could suggest a role for cholesterol-lowering therapies in reducing viral infectivity. In addition to their lipid-lowering and plaque-stabilisation effects, statins possess pleiotropic effects including anti-inflammatory, immunomodulatory, and antithrombotic activities. Lower rates of mortality and intubation have been reported in studies investigating statin therapy in influenza infection, and statin therapy was shown to increase viral clearance from the blood during chronic hepatitis C infection. Statins may also serve as potential SARS-CoV-2 main protease inhibitors, thereby contributing to the control of viral infection. In this review, we elaborate on the role of cholesterol level in the process of the coronavirus infection and provide a critical appraisal on the potential of statins in reducing the severity, duration, and complications of COVID-19.

Keywords: COVID-19; SARS-CoV-2; atherosclerosis; cholesterol; coronavirus; lipid-lowering therapy; statins.

Figure 1

Proposed mechanism of the role of cholesterol and statins in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. (A) Lipid rafts rich in cholesterol serve as docking sites for angiotensin-converting enzyme 2 (ACE2) receptors and viral attachment via the S protein of SARS-CoV-2, which is then taken into the cells by clathrin. In addition, acute infection with SARS-COV-2 and macrophages via paracrine factors can lead to plaque instability and embolization causing occlusion of distal microvasculature. (B) Statins disrupt lipid rafts and viral binding; reduce cholesterol; and have plaque stabilising, antithrombotic, and anti-inflammatory properties.