HDL cholesterol levels and susceptibility to COVID-19

Abstract

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.

Keywords: LDL; Risk; SARS-CoV-2; Total cholesterol; Triglycerides.

Figure 1

Flow chart of the individuals included in the study.

Figure 2

Trajectories of LDL-C, HDL-C, TC and TG levels during the two years antecedent to COVID-19 testing using group-based trajectory modelling (GBTM) and COVID-19 related outcomes. The first row (a, e) corresponds to LDL-C; second row (b, f) to HDL-C; third row (c, g) to TC, and fourth row (d, h) to TG. Low, medium, and high trajectories are represented by numbers 1,2, and 3, respectively. The left panel (a-d) presents the trajectories of lipid levels during the past two years over the eight 3-month time periods before COVID-19 testing (X-axis). The right panel (e-h) presents the outcomes in patients in each of the trajectories: the five outcomes represented are i) not infected (COVID-19 negative), ii) infected (COVID-19 positive) but not requiring admission, iii) admitted with non-severe COVID-19, iv) admitted with severe COVID-19 but survived and v) in-hospital death. Patients in the trajectories 2 and 3 of HDL-C had higher proportion of patients with negative COVID-19 tests.

Figure 3

Coefficient plot for the association of antecedent lipid levels with the probability of testing positive for COVID-19. There is an inverse relationship between antecedent HDL-C levels and the probability of testing positive for COVID-19 (panel b). LDL-C (panel a) and TG (panel c) did not have a relationship with the probability of testing positive for SARS-CoV-2 infection [Pr (COVID test=1)]. The solid lines (—) represent the coefficient plot and the dashed lines (- -) represent the 95% confidence intervals. The p-values are calculated based on log-binomial regression.

Figure 4

Serum lipid levels before, at the time of, and after COVID-19 testing with trends assessed using mixed-effects linear regression analysis. Antecedent to COVID-19 testing (N=9202) (730 days to 14 days prior to COVID-19 testing), HDL-C was significantly lower in the COVID-19 positive group, while antecedent LDL-C and TG were not different. At the time of testing (N=1886) (within 14 days before or after COVID-19 testing), LDL-C (panel a), and HDL-C levels (panel b) were significantly lower in COVID-19 positive patients while TG levels (panel c) were similar across the two groups. The median duration of follow-up subsequent to COVID testing is 261 (IQR 115 to 395) days. After 60 days follow-up post testing (N=2198), LDL-C, HDL-C and TG levels returned to nearly pre-infection levels among COVID-19 patients who survived.

Figure 5

Summary of Results. The top panel - association of antecedent lipid levels with the risk of COVID-19. The middle panel - subgroup analysis of the risk of SARS-CoV-2 infection for the 3 trajectories of HDL-C among the 3 trajectories of LDL-C. The bottom panel shows the trends in lipid levels during and after COVID-19.