A new study published on the preprint server bioRxiv* in May 2020 suggests that the strikingly increased mortality in COVID-19 patients who are either old or also have high blood pressure, diabetes, cardiovascular disease is due to high tissue cholesterol levels. It also indicates the role of a healthy diet, by showing that polyunsaturated fatty acids (PUFA) in blood oppose the effects of cholesterol and thus the risk for severe COVID-19 symptoms.
Wang et al. demonstrated that loading cells with cholesterol from blood serum using the cholesterol transport protein apolipoprotein E (apoE) enhances the endocytic entry of pseudotyped SARS-CoV-2. Super resolution imaging of the SARS-CoV-2 entry point with high cholesterol showed markedly increased apparent diameter (~10% to 100 nm) and almost twice the total number of viral entry points. The cholesterol concomitantly traffics angiotensinogen converting enzyme (ACE2) to the viral entry site where SARS-CoV-2 docks to properly exploit entry into the cell. Furthermore, we show cholesterol enhances binding of SARS-CoV-2 to the cell surface which increases association with the endocytic pathway. Decreasing cellular cholesterol by treating with methyl β-cyclodextrin has the opposite effect.
Based on these findings and known loading of cholesterol into peripheral tissue during aging and inflammation, a cholesterol dependent model for COVID19 lethality in elderly and the chronically ill was built . As cholesterol increases with age and inflammation (e.g. smoking and diabetes), the cell surface is coated with viral entry points and optimally assembled viral entry proteins. Importantly this model suggests high levels of cholesterol is most alarming in the tissue, not the blood. In fact, rapidly dropping cholesterol in the blood may indicate severe loading of cholesterol in peripheral tissue and a dangerous situation for escalated SARS-CoV-2 infectivity. Polyunsaturated fatty acids (PUFAs) oppose the effects of cholesterol and provide a molecular basis for eating healthy diets to avoid severe cases of COVID19.
Wang, H., Yuan, Z., Pavel, M.A., Hansen, S.B. (2020). Cholesterol and COVID19 lethality in elderly. bioRxiv preprint doi: https://www.biorxiv.org/content/10.1101/2020.05.09.086249v2