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

Area of Science:

• Cardiovascular Biology
• Infectious Diseases
• Proteomics

Background:

• The COVID-19 pandemic, caused by SARS-CoV-2, has widespread effects beyond pulmonary damage, notably impacting lipid metabolism.
• Reduced high-density lipoprotein cholesterol (HDL-C) levels are observed in COVID-19 patients.
• HDL particles possess antioxidant, anti-inflammatory, and potential anti-infectious properties.

Purpose of the Study:

• To characterize the proteome and functionality of HDL particles in severe COVID-19 patients compared to healthy individuals.
• To investigate how SARS-CoV-2 infection alters HDL composition and its biological activities.

Main Methods:

• Isolation of HDL particles from plasma of severe COVID-19 patients (ICU admission, D3, D7) and healthy controls.
• Proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
• Validation of protein levels using Western blot analysis and assessment of HDL functionality in endothelial cells.

Main Results:

• Significant alterations in HDL proteome were identified in COVID-19 patients compared to controls.
• Key proteins like apolipoprotein A-I and paraoxonase 1 were decreased, while serum amyloid A and alpha-1 antitrypsin were increased.
• HDLs from COVID-19 patients exhibited reduced protective capacity against TNFα-induced endothelial cell damage, including blunted inhibition of apoptosis.

Conclusions:

• Severe COVID-19 profoundly impacts HDL proteome, leading to significant changes in its protein composition.
• The functionality of HDL particles is markedly decreased in severe COVID-19 patients, compromising their antioxidant and anti-inflammatory roles.
• These findings highlight the detrimental effects of SARS-CoV-2 on HDL function, potentially contributing to disease severity and complications.