Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19

Abstract

Background and Aims Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the sole causative agent of coronavirus infectious disease-19 (COVID-19). Methods and Results We performed a retrospective single-center study of consecutively admitted patients between March 1 st and May 15 th, 2020, with a definitive diagnosis of SARS-CoV-2 infection. The primary end-point was to evaluate the association of lipid markers with 30-days all-cause mortality in COVID-19. A total of 654 patients were enrolled, with an estimated 30-day mortality of 22.8% (149 patients). Non-survivors had lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels during the entire course of the disease. Both showed a significant inverse correlation with inflammatory markers and a positive correlation with lymphocyte count. In a multivariate analysis, LDL-c ≤ 69 mg/dl (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.14-3.31), C-reactive protein > 88 mg/dl (HR 2.44; 95% CI, 1.41-4.23) and lymphopenia < 1,000 (HR 2.68; 95% CI, 1.91-3.78) at admission were independently associated with 30-day mortality. This association was maintained 7 days after admission. Survivors presented with complete normalization of their lipid profiles on short-term follow-up. Conclusion Hypolipidemia in SARS-CoV-2 infection may be secondary to an immune-inflammatory response, with complete recovery in survivors. Low LDL-c serum levels are independently associated with higher 30-day mortality in COVID-19 patients.

Estimating causal effects of atherogenic lipid-related traits on COVID-19 susceptibility and severity using a two-sample Mendelian randomization approach

“…A systematic review and meta-analysis including 23 studies involving 10,122 COVID-19 patients showed that hospitalized patients with severe disease or non-survivor status had significantly lower serum LDL-C but not TG levels compared to patients with milder disease or survivor status; however, only a few studies of those with European ancestry were included [ 8 ]. A retrospective single-center study with 654 patients in Spain showed that LDL-C < 69 mg/dl at admission was independently associated with a greater risk of 30-day mortality from COVID-19 (hazard ratio, 1.94; 95% CI, 1.14–3.31, P = 0.014) [ 9 ]. However, a prospective single-center study with 48 COVID-19 patients in France did not detect a significant relationship between LDL-C and 28-day mortality [ 10 ].…”

“…For example, serum lipid levels might be lower as a result of poor nutrition status due to COVID-19 severity [ 8 ]. Associations between serum lipid levels and COVID-19 risks might be secondary to immune-inflammatory responses that could worsen COVID-19 outcomes [ 8 , 9 , 11 ], though the association of LDL-C with COVID-19 mortality was independent of inflammatory markers in the above Spanish study [ 9 ]. MR studies can overcome such limitations of observational studies [ 12 ].…”

Strong relationship between cholesterol, low-density lipoprotein receptor, Na+/H+ exchanger, and SARS-COV-2: this association may be the cause of death in the patient with COVID-19

“…On the other hand, LDL carries a large percentage of plasma Coenzyme Q10 (CoQ10), which has a significant antioxidant capacity and prevents peroxidative damage to cellular membranes [ 12 ]. Low LDL levels may contribute to endothelial dysfunction by causing a decrease in plasma CoQ10 levels.…”

“…Additionally, acute phase response during COVID-19 may lead to oxide-LDL formation and LDLR upregulation [ 12 ]. Oxide-LDL via lectin-like oxidized LDLR-1 (LOX-1) activation leads to ACE gene expression [ 33 ].…”

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

“…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.…”