Low HDL Cholesterol Efflux Capacity Indicates a Fatal Course of COVID-19

Abstract

Plasma membrane cholesterol is required for proper trafficking and localization of receptors that facilitate severe acute respiratory syndrome coronavirus 2 infection. High-density lipoproteins (HDL) mobilize plasma membrane cholesterol, and HDL-cholesterol levels are associated with the severity of COVID-19 disease and mortality. However, HDL-cholesterol levels poorly reflect the function of this complex family of particles, and a detailed assessment of COVID-19-associated changes in HDL functionality and its prognostic value is lacking. In the present study, we assessed HDL cholesterol efflux capacity, HDL anti-inflammatory and antioxidant properties, and changes in HDL composition and metabolism in COVID-19 (n = 48) and non-COVID pneumonia patients (n = 32). COVID-19 infection markedly reduced the activity of lecithin-cholesteryl-acyltransferase and functional parameters of HDL, such as the cholesterol efflux capacity, arylesterase activity of paraoxonase 1, and anti-oxidative capacity of apoB-depleted serum when compared to non-COVID pneumonia at baseline, paralleled by markedly reduced levels of HDL-cholesterol. Of particular interest, low HDL cholesterol efflux capacity was associated with increased mortality risk in COVID-19 patients, independent of HDL-C levels. Our results highlight profound effects of COVID-19 infection on HDL function, metabolism, and composition. Low HDL cholesterol efflux capacity indicates a fatal course of COVID-19, independent of HDL-cholesterol levels.

High-Density Lipoprotein function is modulated by the SARS-CoV-2 spike protein in a lipid-type dependent manner

“…The data show that, while the S protein is responsible for only a low amount of cholesterol efflux (2% of the total cholesterol), the incubation of cells with the mixture of HDL and S protein decreased the cholesterol efflux capacity of HDL by a factor of 2 (from 12 to 6%). Our results are in agreement with recent cholesterol efflux capacity experiments of HDL that were found to significantly decrease in COVID-19 patients [37] . Together, these results strongly suggest that the presence of the S protein interferes with the efflux process mediated by HDL.…”

COVID-19 Biomarkers Comparison: Children, Adults and Elders

“…Cholesterol can indirectly increase the susceptibility of patients to SARS-CoV-2 and increase the risk of death. Significantly decreased HDL levels in patients with COVID-19 were correlated with both disease severity and mortality [ 11 , 20 , 21 ]. A study from Turkey even considers it a good predictor of one-year mortality in patients with COVID-19 [ 22 ].…”

Lipid metabolism indicators in patients with SARS-CoV-2 infection

“…Как и при других инфекционных заболеваниях, состав ЛПВП изменяется при COVID-19 со снижением титров Апо A-I, A-II, параоксоназы, белка B, взаимосвязанного с легочным сурфактантом, и увеличением содержания сывороточного амилоида A и альфа-1 антитрипсина [11]. У пациентов с COVID-19 также снижены элиминация холестерина и антиоксидантная способность аполипопротеина B сыворотки [12].…”