Cholesterol and Triglyceride Concentrations, COVID-19 Severity, and Mortality: A Systematic Review and Meta-Analysis With Meta-Regression

Abstract

Lipid profile alterations have been observed in patients with coronavirus disease 2019 (COVID-19) in relation to disease severity and mortality. We conducted a systematic review and meta-analysis with meta-regression of studies reporting total, HDL, and LDL-cholesterol, and triglyceride concentrations in hospitalized patients with COVID-19. We searched PubMed, Web of Science and Scopus, between January 2020 and January 2021, for studies describing lipid concentrations, COVID-19 severity, and survival status (PROSPERO registration number: CRD42021253401). Twenty-two studies in 10,122 COVID-19 patients were included in the meta-analysis. Pooled results showed that hospitalized patients with severe disease or non-survivor status had significantly lower total cholesterol (standardized mean difference, SMD = -0.29, 95% CI -0.41 to -0.16, p < 0.001), LDL-cholesterol (SMD = -0.30, 95% CI -0.41 to -0.18, p < 0.001), and HDL-cholesterol (SMD = -0.44, 95% CI -0.62 to -0.26, p < 0.001), but not triglyceride (SMD = 0.04, 95% CI -0.10 to -0.19, p = 0.57), concentrations compared to patients with milder disease or survivor status during follow up. Between-study heterogeneity was large-to-extreme. In sensitivity analysis, the effect size of different lipid fractions was not affected when each study was in turn removed. The Begg's and Egger's t-tests did not show evidence of publication bias, except for studies investigating LDL-cholesterol. In meta-regression, significant associations were observed between the SMD of LDL-cholesterol and age and hypertension, and between the SMD of triglycerides and study endpoint and aspartate aminotransferase. In our systematic review and meta-analysis, lower total, HDL, and LDL-cholesterol, but not triglyceride, concentrations were significantly associated with COVID-19 severity and mortality. Cholesterol concentrations might be useful, in combination with other clinical and demographic variables, for risk stratification and monitoring in this group. Systematic Review Registration: PROSPERO registration number: CRD42021253401.

Keywords: COVID-19; cholesterol; disease severity; mortality; triglycerides.

Figure 1

Flow chart of study selection.

Figure 2

Forest plot of studies examining total cholesterol concentrations in COVID-19.

Figure 3

(A) Sensitivity analysis of the association between total cholesterol and COVID-19. The influence of individual studies on the overall standardized mean difference (SMD) is shown. The middle vertical axis indicates the overall SMD and the two vertical axes indicate the 95% confidence intervals (CIs). The hollow circles represent the pooled SMD when the remaining study is omitted from the meta-analysis. The two ends of each broken line represent the 95% CIs. (B) Funnel plot of studies investigating low vs. high severity or surviving vs. non-surviving status after trimming and filling. Dummy studies and genuine studies are represented by enclosed circles and free circles, respectively.

Figure 4

Forest plot of studies examining LDL-cholesterol concentrations in COVID-19.

Figure 5

(A) Sensitivity analysis of the association between LDL-cholesterol and COVID-19. The influence of individual studies on the overall standardized mean difference (SMD) is shown. The middle vertical axis indicates the overall SMD and the two vertical axes indicate the 95% confidence intervals (CIs). The hollow circles represent the pooled SMD when the remaining study is omitted from the meta-analysis. The two ends of each broken line represent the 95% CIs. (B) Funnel plot of studies investigating low vs. high severity or surviving vs. non-surviving status after trimming and filling. Dummy studies and genuine studies are represented by enclosed circles and free circles, respectively.

Figure 6

Forest plot of studies examining HDL-cholesterol concentrations in COVID-19.

Figure 7

(A) Sensitivity analysis of the association between HDL-cholesterol and COVID-19. The influence of individual studies on the overall standardized mean difference (SMD) is shown. The middle vertical axis indicates the overall SMD and the two vertical axes indicate the 95% confidence intervals (CIs). The hollow circles represent the pooled SMD when the remaining study is omitted from the meta-analysis. The two ends of each broken line represent the 95% CIs. (B) Funnel plot of studies investigating low vs. high severity or surviving vs. non-surviving status after trimming and filling. Dummy studies and genuine studies are represented by enclosed circles and free circles, respectively.

Figure 8

Forest plot of studies examining the concentrations of triglycerides in COVID-19.

Figure 9

(A) Sensitivity analysis of the association between serum triglycerides and COVID-19. The influence of individual studies on the overall standardized mean difference (SMD) is shown. The middle vertical axis indicates the overall SMD and the two vertical axes indicate the 95% confidence intervals (CIs). The hollow circles represent the pooled SMD when the remaining study is omitted from the meta-analysis. Two ends of each broken line represent the 95% CIs. (B) Funnel plot of studies investigating low vs. high severity or surviving vs. non-surviving status after trimming and filling. Dummy studies and genuine studies are represented by enclosed circles and free circles, respectively.