Altered high-density lipoprotein composition and functions during severe COVID-19

Abstract

Coronavirus disease 2019 (COVID-19) pandemic is affecting millions of patients worldwide. The consequences of initial exposure to SARS-CoV-2 go beyond pulmonary damage, with a particular impact on lipid metabolism. Decreased levels in HDL-C were reported in COVID-19 patients. Since HDL particles display antioxidant, anti-inflammatory and potential anti-infectious properties, we aimed at characterizing HDL proteome and functionality during COVID-19 relative to healthy subjects. HDLs were isolated from plasma of 8 severe COVID-19 patients sampled at admission to intensive care unit (Day 1, D1) at D3 and D7, and from 16 sex- and age-matched healthy subjects. Proteomic analysis was performed by LC-MS/MS. The relative amounts of proteins identified in HDLs were compared between COVID-19 and controls. apolipoprotein A-I and paraoxonase 1 were confirmed by Western-blot analysis to be less abundant in COVID-19 versus controls, whereas serum amyloid A and alpha-1 antitrypsin were higher. HDLs from patients were less protective in endothelial cells stiumalted by TNFα (permeability, VE-cadherin disorganization and apoptosis). In these conditions, HDL inhibition of apoptosis was blunted in COVID-19 relative to controls. In conclusion, we show major changes in HDL proteome and decreased functionality in severe COVID-19 patients.

Proteomic Analysis Identifies Prolonged Disturbances in Pathways Related to Cholesterol Metabolism and Myocardium Function in the COVID-19 Recovery Stage

“…One study showed that HDLs from COVID-19 patients were less protective for endothelial cells stimulated with TNFα than HDLs from healthy subjects. 13 The proteins identified may be potential indicators of a prolonged cholesterol metabolism disorder. From the clinical data obtained from patient blood samples ( Figure 1 a), we found that the serum total cholesterol level and the low-density lipoprotein level were increased at disease onset and did not fully return to the original values even at the 6 month follow-up, both in moderate and severe COVID-19 patients ( Figure 3 e and Figure S3 ).…”

Clinical Performance of Paraoxonase-1-Related Variables and Novel Markers of Inflammation in Coronavirus Disease-19. A Machine Learning Approach

“…PON1 activity in the serum of COVID-19 patients may be lower for several, though not mutually exclusive, reasons. SARS-CoV-2 infected patients are known to often have low HDL levels [ 27 ], and recent studies reported that patients with severe COVID-19 had lower HDL cholesterol and higher triglyceride levels before and after the infection than patients without severe COVID-19 or the healthy population [ 28 , 29 ]. Begue et al [ 29 ] found that the HDL cholesterol concentration of COVID-19 patients admitted to the Intensive Care Unit was about half that of healthy individuals and that their HDL particles were enriched in various inflammatory proteins and depleted in PON1.…”

Higher Serum Cholesterol Levels Are Associated With Reduced Systemic Inflammation and Mortality During Tuberculosis Treatment Independent of Body Mass Index

“…Additionally, reverse cholesterol transport mediated by ATP-binding cassette transporter (ABC) and lecithin-cholesterol acyltransferase (LCAT) are decreased during inflammation, leading to decreased HDL (30). Lower serum lipid levels are also associated with greater levels of systemic inflammation in other infections (9)(10)(11)(31)(32)(33). A similar clinical scenario has been explored in patients with rheumatoid arthritis (RA).…”