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.

HDL cholesterol levels and susceptibility to COVID-19.

BACKGROUND: 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 SARS-CoV-2 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 SARS-CoV-2 infection among the trajectories of lipid levels during the 2 years antecedent to COVID-19 testing, identified using group-based-trajectory modelling. 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. FINDINGS: 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 SARS-CoV-2 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 SARS-CoV-2 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. INTERPRETATION: Higher antecedent serum HDL-C, but not LDL-C, TC, or TG, levels were associated with a lower SARS-CoV-2 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.

Association of Lipid Levels With COVID-19 Infection, Disease Severity and Mortality: A Systematic Review and Meta-Analysis.

Background: Coronavirus disease 2019 (COVID-19) ranges from asymptomatic infection to severe illness. Cholesterol in the host cell plasma membrane plays an important role in the SARS-CoV-2 virus entry into cells. Serum lipids, especially low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), are in constant interaction with the lipid rafts in the host cell membranes and can modify the interaction of virus with host cells and the resultant disease severity. Recent studies on serum lipid levels and COVID-19 disease severity lack consistency. Objectives: Our systematic review and meta-analysis compared the serum levels of total cholesterol (TC), LDL-C, HDL-C, and triglycerides (TG) between (1) COVID-19 patients vs. healthy controls; (2) severe vs. non-severe COVID-19 disease; (3) deceased vs. surviving COVID-19 patients. Methods: PRISMA guidelines were followed. We included peer-reviewed articles on observational (case-control and cohort) studies from PubMed and Embase published from the database inception until September 1, 2021. We used random-effects meta-analysis for pooled mean-differences (pMD) in lipid levels (mg/dL) for the above groups. Results: Among 441 articles identified, 29 articles (26 retrospective and 3 prospective cohorts), with an aggregate of 256,721 participants, were included. COVID-19 patients had lower TC (pMD-14.9, 95%CI-21.6 to -8.3) and HDL-C (pMD-6.9, 95%CI -10.2 to -3.7) levels (mg/dL). Severe COVID-19 patients had lower TC (pMD-10.4, 95%CI -18.7 to -2.2), LDL-C (pMD-4.4, 95%CI -8.4 to -0.42), and HDL-C (pMD-4.4, 95%CI -6.9 to -1.8) at admission compared to patients with non-severe disease. Deceased patients had lower TC (pMD-14.9, 95%CI -21.6 to -8.3), LDL-C (pMD-10.6, 95%CI -16.5 to -4.6) and HDL-C (pMD-2.5, 95%CI -3.9 to -1.0) at admission. TG levels did not differ based on COVID-19 severity or mortality. No publication bias was noted. Conclusion: We demonstrated lower lipid levels in patients with COVID-19 infection and an association with disease severity and mortality. Their potential role in COVID-19 pathogenesis and their utility as prognostic factors require further investigation.