High-Density Lipoprotein function is modulated by the SARS-CoV-2 spike protein in a lipid-type dependent manner, 2023, Correa et al.

[SNT Gatchaman]

High-Density Lipoprotein function is modulated by the SARS-CoV-2 spike protein in a lipid-type dependent manner
Correa; Del Giudice; Waldie; Thépaut; Micciula; Gerelli; Moulin; Delaunay; Fieschi; Pichler; Haertlein; Forsyth; Le Brun; Moir; Russell; Darwish; Brinck; Wodaje; Jansen; Martín; Cárdenas

There is a close relationship between the SARS-CoV-2 virus and lipoproteins, in particular high-density lipo- protein (HDL). The severity of the coronavirus disease 2019 (COVID-19) is inversely correlated with HDL plasma levels. It is known that the SARS-CoV-2 spike (S) protein binds the HDL particle, probably depleting it of lipids and altering HDL function.

Based on neutron reflectometry (NR) and the ability of HDL to efflux cholesterol from macrophages, we confirm these observations and further identify the preference of the S protein for specific lipids and the consequent effects on HDL function on lipid exchange ability. Moreover, the effect of the S protein on HDL function differs depending on the individuals lipid serum profile. Contrasting trends were observed for individuals presenting low triglycerides/high cholesterol serum levels (LTHC) compared to high triglycerides/ high cholesterol (HTHC) or low triglycerides/low cholesterol serum levels (LTLC).

Collectively, these results suggest that the S protein interacts with the HDL particle and, depending on the lipid profile of the infected individual, it impairs its function during COVID-19 infection, causing an imbalance in lipid metabolism.

Link | PDF (Journal of Colloid and Interface Science)

 

[SNT Gatchaman]

The hypothesis was that the HDL capacity to remove and exchange lipids is impaired in presence of the S protein and this depends on the lipid saturation of the model membrane, cholesterol, and the lipid profile of the donor. Our research suggests that the S protein from the SARS-CoV-2 virus has a stronger ability to remove cholesterol and polyunsaturated lipids compared to saturated and monounsaturated ones.

Co-incubation of the S protein and HDL samples pooled from healthy adults with a fluid, saturated phospholipid model led to impaired HDL function, but the effect could be reverted when polyunsaturated lipids were used instead. This implies that the S protein preferentially removes polyunsaturated lipids from HDL, which leads to changes in its surface properties or remodelling.

Here we show that the S protein changes HDL function in a manner that depends on the lipid serum profile. HDL samples with low triglycerides and high cholesterol serum levels (LTHC) presented an inverse trend induced by the Spike protein to that of low triglycerides/low cholesterol (LTLC) or high triglycerides/high cholesterol (HTHC) serum levels.

This could indicate that individuals with an LTHC profile have a lower tendency to have the lipid metabolism highjacked by the SARS-CoV-2 virus and could present a weaker interaction with the S protein upon COVID-19 illness or vaccination against COVID-19.

 

[Midnattsol]

Cool. Some research at University of Oslo have also found impaired cholesterol metabolism in hospital admitted patients. Focus primarily on LDL. Not sure if there is another publication, but here is a "letter to the editor" about their findings: Low-density lipoprotein particles carrying proinflammatory proteins with altered aggregation pattern detected in COVID-19 patients 3 months after hospitalization.