Cholesterol, lipoproteins, and COVID-19: Basic concepts and clinical applications.

Cholesterol is being recognized as a molecule involved in regulating the entry of the SARS-CoV-2 virus into the host cell. However, the data about the possible role of cholesterol carrying lipoproteins and their receptors in relation to infection are scarce and the connection of lipid-associated pathologies with COVID-19 disease is in its infancy. Herein we provide an overview of lipids and lipid metabolism in relation to COVID-19, with special attention on different forms of cholesterol. Cholesterol enriched lipid rafts represent a platform for viruses to enter the host cell by endocytosis. Generally, higher membrane cholesterol coincides with higher efficiency of COVID-19 entry. Inversely, patients with COVID-19 show lowered levels of blood cholesterol, high-density lipoproteins (HDL) and low-density lipoproteins. The modulated efficiency of viral entry can be explained by availability of SR-B1 receptor. HDL seems to have a variety of roles, from being itself a scavenger for viruses, an immune modulator and mediator of viral entry. Due to inverse roles of membrane cholesterol and lipoprotein cholesterol in COVID-19 infected patients, treatment of these patients with cholesterol lowering statins needs more attention. In conclusion, cholesterol and lipoproteins are potential markers for monitoring the viral infection status, while the lipid metabolic pathways and the composition of membranes could be targeted to selectively inhibit the life cycle of the virus as a basis for antiviral therapy.

Polyunsaturated fatty acid biosynthesis pathway and genetics. implications for interindividual variability in prothrombotic, inflammatory conditions such as COVID-19✰,✰✰,☠,☠☠.

COVID-19 symptoms vary from silence to rapid death, the latter mediated by both a cytokine storm and a thrombotic storm. SARS-CoV (2003) induces Cox-2, catalyzing the synthesis, from highly unsaturated fatty acids (HUFA), of eicosanoids and docosanoids that mediate both inflammation and thrombosis. HUFA balance between arachidonic acid (AA) and other HUFA is a likely determinant of net signaling to induce a healthy or runaway physiological response. AA levels are determined by a non-protein coding regulatory polymorphisms that mostly affect the expression of FADS1, located in the FADS gene cluster on chromosome 11. Major and minor haplotypes in Europeans, and a specific functional insertion-deletion (Indel), rs66698963, consistently show major differences in circulating AA (>50%) and in the balance between AA and other HUFA (47-84%) in free living humans; the indel is evolutionarily selective, probably based on diet. The pattern of fatty acid responses is fully consistent with specific genetic modulation of desaturation at the FADS1-mediated 20:3→20:4 step. Well established principles of net tissue HUFA levels indicate that the high linoleic acid and low alpha-linoleic acid in populations drive the net balance of HUFA for any individual. We predict that fast desaturators (insertion allele at rs66698963; major haplotype in Europeans) are predisposed to higher risk and pathological responses to SARS-CoV-2 could be reduced with high dose omega-3 HUFA.