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Phenotypic changes in low-density lipoprotein particles as markers of adverse clinical outcomes in COVID-19
Helison Rafael P Carmo1, Marcos Y Yoshinaga2, Alejandro Rosell Castillo1
1Cardiology Division, Unicamp Medical School, SP, Brazil.
Insights
Changes in low-density lipoprotein (LDL) particle characteristics during COVID-19 correlate with disease severity and patient outcomes. Oxidized LDL (ox-LDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels can predict mortality risk in hospitalized patients.
Area of Science:
- Biochemistry
- Immunology
- Clinical Medicine
Background:
- Low-density lipoprotein (LDL) plasma concentration decline is a recognized biomarker for acute inflammatory diseases like COVID-19.
- Phenotypic alterations in LDL during COVID-19 infection may significantly correlate with adverse clinical outcomes.
Purpose of the Study:
- To investigate the association between LDL phenotypic changes and clinical outcomes in patients hospitalized with COVID-19.
- To assess the dynamic changes in oxidized LDL (ox-LDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity during the course of COVID-19.
Main Methods:
- Enrolled 40 individuals hospitalized with COVID-19, collecting blood samples on days 0, 2, 4, 6, and 30.
- Measured serum ox-LDL and Lp-PLA2 activity; performed lipidomic analysis on isolated LDL particles from a subset of patients.
- Investigated correlations between LDL phenotypic changes and clinical outcomes, including mortality.
Main Results:
- Serum ox-LDL increased from day 0 to day 6 and decreased by day 30; elevated ox-LDL levels were associated with mortality.
- Plasma Lp-PLA2 activity increased progressively throughout the 30-day period.
- Lipidomic analysis revealed significant changes in LDL particle composition, with distinct lipid species profiles in non-survivors compared to survivors.
Conclusions:
- Phenotypic modifications in LDL particles are linked to COVID-19 disease progression.
- These LDL alterations serve as potential prognostic biomarkers for adverse clinical outcomes in COVID-19 patients.
Background And Aims:
Low-density lipoprotein (LDL) plasma concentration decline is a biomarker for acute inflammatory diseases, including coronavirus disease-2019 (COVID-19). Phenotypic changes in LDL during COVID-19 may be equally related to adverse clinical outcomes.
Methods:
Individuals hospitalized due to COVID-19 (n = 40) were enrolled. Blood samples were collected on days 0, 2, 4, 6, and 30 (D0, D2, D4, D6, and D30). Oxidized LDL (ox-LDL), and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity were measured. In a consecutive series of cases (n = 13), LDL was isolated by gradient ultracentrifugation from D0 and D6 and was quantified by lipidomic analysis. Association between clinical outcomes and LDL phenotypic changes was investigated.
Results:
In the first 30 days, 42.5% of participants died due to Covid-19. The serum ox-LDL increased from D0 to D6 (p < 0.005) and decreased at D30. Moreover, individuals who had an ox-LDL increase from D0 to D6 to over the 90th percentile died. The plasma Lp-PLA2 activity also increased progressively from D0 to D30 (p < 0.005), and the change from D0 to D6 in Lp-PLA2 and ox-LDL were positively correlated (r = 0.65, p < 0.0001). An exploratory untargeted lipidomic analysis uncovered 308 individual lipids in isolated LDL particles. Paired-test analysis from D0 and D6 revealed higher concentrations of 32 lipid species during disease progression, mainly represented by lysophosphatidyl choline and phosphatidylinositol. In addition, 69 lipid species were exclusively modulated in the LDL particles from non-survivors as compared to survivors.
Conclusions:
Phenotypic changes in LDL particles are associated with disease progression and adverse clinical outcomes in COVID-19 patients and could serve as a potential prognostic biomarker.
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