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.

Thyroid-Stimulating Hormone Predicts Total Cholesterol and Low-Density Lipoprotein Cholesterol Reduction during the Acute Phase of COVID-19

“…In conclusion, the results of the present study confirm that hypocholesterolemia is a clinical feature of COVID-19 and suggest an intriguing pathophysiological connection between lower TSH levels, even in the range of euthyroidism, and cholesterol metabolism derangement during the acute phase of COVID-19. Based on literature data showing a significant association between either thyroid dysfunction or hypocholesterolemia and worse COVID-19 prognosis [ 8 , 9 , 10 , 17 , 18 ], it might be speculated that the coexistence of low TSH and cholesterol levels may further worsen the prognosis of patients hospitalized due to COVID-19. However, whether these combined metabolic abnormalities might represent a possible target for therapeutic intervention should be weighed against the debated evidence on this topic.…”

“…Some reports have shown that reduced levels of plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) may represent a laboratory signature of COVID-19 and that a progressive restoration of their preinfection levels may occur over COVID-19 clinical course up to recovery [ 7 , 8 ]. Moreover, reductions of TC, LDL-C, and HDL-C have been reported with increasing COVID-19 severity and uncontrolled inflammatory response [ 8 , 9 , 10 ], suggesting a possible bidirectional link between hypocholesterolemia and COVID-19 progression towards its worst clinical forms.…”

Noncommunicable diseases risk factors and the risk of COVID-19 among university employees in Indonesia

“…However, COVID-19 patients have generally shown reduced total cholesterol, HDL, and LDL-cholesterol levels which are associated with disease severity [ 41 ]. A systematic review confirmed that lower total, HDL- and LDL-cholesterol levels were significantly associated with COVID-19 severity and mortality but not triglyceride level [ 42 ].…”

Transcriptional Effects of Candidate COVID-19 Treatments on Cardiac Myocytes

“…Nevertheless, CQ or HCQ may lead to lower levels of cholesterol, as HCQ was recently found to lower total cholesterol in a large study of patients with systemic lupus erythematosus and rheumatoid arthritis, where CQ and HCQ are common treatment options ( 45 ). In contrast, low cholesterol concentrations in COVID-19 patients have recently been linked to more severe outcomes ( 46 , 47 ). However, due to the short duration of treatment of acute COVID-19 patients compared to long term patients with rheumatoid arthritis treated with CQ or HCQ, the cholesterol-lowering effects might not play a role in progression of COVID-19 in these patients.…”