Higher HDL Cholesterol Levels Decrease Susceptibility to COVID-19 Infection

Introduction: Host cell-membrane cholesterol, an important player in viral infections, is in constant interaction with serum high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C). Low serum lipid levels during hospital admission are associated with COVID-19 severity. However, the effect of antecedent serum lipid levels on COVID-19 infection risk has not been explored. Methods: From our retrospective cohort from the Arkansas Clinical Data-Repository, we used log-binomial regression to assess the risk of COVID-19 infection among the trajectories of lipid levels during the 2 years antecedent to COVID-19 testing, identified using group-based-trajectory modeling. We used mixed-effects linear regression to assess the serum lipid level trends followed up to the time of, and 2-months following COVID-19 testing. Results: Among the 11001 individuals with a median age of 59 years (IQR 46-70), 1340 (12.2%) tested positive for COVID-19. The highest trajectory for antecedent serum HDL-C was associated with the lowest COVID-19 infection risk (RR 0.63, 95%CI 0.46-0.86). Antecedent serum LDL-C, total cholesterol (TC), and triglycerides (TG) were not independently associated with COVID-19 infection risk. In COVID-19 patients, serum HDL-C (-7.7, 95%CI -9.8 to -5.5 mg/dL), and LDL-C (-6.29, 95%CI -12.2 to -0.37 mg/dL), but not TG levels, decreased transiently at the time of testing. Conclusions: Higher antecedent serum HDL-C, but not LDL-C, TC, or TG, levels were associated with a lower COVID-19 infection risk. Serum HDL-C, and LDL-C levels declined transiently at the time of infection. Further studies are needed to determine the potential role of lipid-modulating therapies in the prevention and management of COVID-19. Funding: Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1 TR003107.