HIGHER HDL CHOLESTEROL LEVELS DECREASE SUSCEPTIBILITY TO COVID-19 INFECTION

THERAPEUTIC AREA: ASCVD/CVD Risk Factors BACKGROUND: Host cell-membrane cholesterol, an important player in viral infections, is in constant interaction with serum lipids, such as high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Recent meta-analyses have shown an association between low serum lipid levels at hospital admission and COVID-19 severity. However, the effect of antecedent serum lipid levels on the risk of COVID-19 infection has not been explored previously. METHODS: Our retrospective cohort from the Arkansas Clinical Data Repository included all adults with lipid levels available within the 2 years antecedent to COVID-19 testing. We assessed the association of trajectories of lipid levels antecedent to COVID-19 testing, identified using group-based-trajectory-modeling with the risk of COVID-19 infection using multivariable log-binomial regression. We used mixed-effects linear regression to assess the trends in serum lipid levels followed up to the time of, and 2-months after COVID-19 testing. RESULTS: Among the 11001 individuals, 1340 (12.2%) tested positive for COVID-19. The median age was 59 years (IQR 46-70) and 40.8% were males. Log-binomial regression showed that the highest trajectory for antecedent serum HDL-C level was associated with a lower risk for COVID-19 infection (RR 0.63, 95% CI 0.46-0.86). Antecedent serum LDL-C, total cholesterol (TC), and triglycerides (TG) levels showed no independent association with COVID-19 infection risk. But the COVID-19 infection risk was the highest in the subgroup with lower HDL-C (Trajectory 1) and higher LDL-C or higher TG (Trajectory 3). In COVID-19 patients, at the time of testing, serum HDL-C (-7.7, 95% CI -9.8 to -5.5 mg/dL), LDL-C (-6.29, 95% CI -12.2 to -0.37 mg/dL) and TC (-11.71, 95%CI -18.9 to -4.5 mg/dL), but not TG levels, were lower. These returned to pre-infection values by 2-months following COVID-19 testing. CONCLUSION: Higher antecedent serum HDL-C, but not LDL-C, TC, and TG levels, were associated with a lower COVID-19 infection risk. Serum HDL-C, LDL-C, and TC levels declined transiently at the time of diagnosis, returning to pre-infection levels during follow-up. The results of our study could provide the impetus for clinical trials aimed at increasing HDL-C, such as CETP inhibitors, in the prevention and amelioration of COVID-19 infection or infections in general.