Phenotypic changes in low-density lipoprotein particles as markers of adverse clinical outcomes in COVID-19

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Carmo, Helison Rafael P. ; Yoshinaga, Marcos Y. ; Castillo, Alejandro Rosell ; Chaves-Filho, Adriano Britto ; Bonilha, Isabella ; Barreto, Joaquim ; Muraro, Stefanie Primon ; de Souza, Gabriela Fabiano ; Davanzo, Gustavo Gastao ; Perroud Jr, Mauricio W. ; Lukhna, Kishal ; Ntsekhe, Mpiko ; Davidson, Sean ; Velloso, Licio A. ; Nadruz, Wilson ; Carvalho, Luiz Sergio F. ; Sainz-Jaspeado, Miguel ; Farias, Alessandro S. ; Proenca-Modena, Jose Luiz ; Moraes-Vieira, Pedro M. ; Karathanasis, Sotirios K. ; Yellon, Derek ; Miyamoto, Sayuri ; Remaley, Alan T. ; Sposito, Andrei C.

• Document type: Journal article
• Source: MOLECULAR GENETICS AND METABOLISM; v. 138, n. 4, p. 8-pg., 2023-03-06.

Abstract

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. Ina 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.(c) 2023 Published by Elsevier Inc. (AU)

• FAPESP's process: 20/04558-0 - Characterization of intrinsic risk factors and the development of new diagnostic and treatment alternatives for COVID-19
• Grantee: José Luiz Proença Módena
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/12649-5 - Multicenter, prospective, randomized, double-blind, placebo-controlled study to evaluate the effect of diacerein to prevent death or dysfunction of organic organs in patients with ARDS secondary to COVID-19
• Grantee: Alejandro Rosell Castillo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/00194-8 - Pathogenesis and neurovirulence of emerging viruses in Brazil
• Grantee: José Luiz Proença Módena
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 18/17792-0 - HDL-S1P against pyroptosis damage after Acute Myocardial Infarction
• Grantee: Helison Rafael Pereira Do Carmo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral