First Recombinant High-Density Lipoprotein Particles Administration in a Severe ICU COVID-19 Patient, a Multi-Omics Exploratory Investigation

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2022 Apr 23

PMID 35453504

Authors

Sebastien Tanaka

Floran Begue

Bryan Veeren

Alexy Tran-Dinh

Tiphaine Robert

Parvine Tashk

Brice Lortat-Jacob

Dorothee Faille

Luc de Chaisemartin

Nathalie Zappella

Enora Atchade

Laura Kramer

Philippe Montravers

Olivier Meilhac

Affiliations

Soon will be listed here.

Abstract

High-density lipoproteins (HDLs) have multiple endothelioprotective properties. During SARS-CoV-2 infection, HDL-cholesterol (HDL-C) concentration is markedly reduced, and studies have described severe impairment of the functionality of HDL particles. Here, we report a multi-omic investigation of the first administration of recombinant HDL (rHDL) particles in a severe COVID-19 patient in an intensive care unit. Plasma ApoA1 increased and HDL-C decreased after each recombinant HDL injection, suggesting that these particles were functional in terms of reverse cholesterol transport. The proportion of large HDL particles also increased after injection of recombinant HDL. Shotgun proteomics performed on HDLs isolated by ultracentrifugation indicated that ApoA1 was more abundant after injections whereas most of the pro-inflammatory proteins identified were less abundant. Assessment of Serum amyloid A-1, inflammatory markers, and cytokines showed a significant decrease for most of them during recombinant HDL infusion. Our results suggest that recombinant HDL infusion is feasible and a potential therapeutic strategy to be explored in COVID-19 patients.

Citing Articles

Metabolomic Characterisation of Low-Density Lipoproteins Isolated from Iodixanol and KBr-Based Density Gradient Ultracentrifugation.

Webb R, Lodge J, Scott S, Davies I Metabolites. 2025; 15(2).

PMID: 39997693 PMC: 11857088. DOI: 10.3390/metabo15020068.

HDL proteome and apolipoproteins concentrations in severe ICU COVID-19 patients.

Begue F, Veeren B, Rondeau P, Florence A, Jamard S, Montravers P Lipids Health Dis. 2025; 24(1):32.

PMID: 39891286 PMC: 11783863. DOI: 10.1186/s12944-024-02381-w.

The Pleiotropic Effects of Lipid-Modifying Interventions: Exploring Traditional and Emerging Hypolipidemic Therapies.

Kounatidis D, Tentolouris N, Vallianou N, Mourouzis I, Karampela I, Stratigou T Metabolites. 2024; 14(7).

PMID: 39057711 PMC: 11278853. DOI: 10.3390/metabo14070388.

Stadler J, Habisch H, Pruller F, Mangge H, Barnthaler T, Kargl J Antioxidants (Basel). 2023; 12(11).

PMID: 38001862 PMC: 10669705. DOI: 10.3390/antiox12112009.

Beneficial effects of recombinant CER-001 high-density lipoprotein infusion in sepsis: results from a bench to bedside translational research project.

Stasi A, Fiorentino M, Franzin R, Staffieri F, Carparelli S, Losapio R BMC Med. 2023; 21(1):392.

PMID: 37915050 PMC: 10621167. DOI: 10.1186/s12916-023-03057-5.

References

Tanaka S, de Tymowski C, Assadi M, Zappella N, Jean-Baptiste S, Robert T . Lipoprotein concentrations over time in the intensive care unit COVID-19 patients: Results from the ApoCOVID study. PLoS One. 2020; 15(9):e0239573. PMC: 7514065. DOI: 10.1371/journal.pone.0239573. View

Vaisar T, Tang C, Babenko I, Hutchins P, Wimberger J, Suffredini A . Inflammatory remodeling of the HDL proteome impairs cholesterol efflux capacity. J Lipid Res. 2015; 56(8):1519-30. PMC: 4513993. DOI: 10.1194/jlr.M059089. View

Gibson C, Kerneis M, Yee M, Daaboul Y, Korjian S, Poyan Mehr A . The CSL112-2001 trial: Safety and tolerability of multiple doses of CSL112 (apolipoprotein A-I [human]), an intravenous formulation of plasma-derived apolipoprotein A-I, among subjects with moderate renal impairment after acute myocardial infarction. Am Heart J. 2018; 208:81-90. DOI: 10.1016/j.ahj.2018.11.008. View

Tanaka S, Stern J, Bouzid D, Robert T, Dehoux M, Snauwaert A . Relationship between lipoprotein concentrations and short-term and 1-year mortality in intensive care unit septic patients: results from the HIGHSEPS study. Ann Intensive Care. 2021; 11(1):11. PMC: 7815878. DOI: 10.1186/s13613-021-00800-0. View

Begue F, Tanaka S, Mouktadi Z, Rondeau P, Veeren B, Diotel N . Altered high-density lipoprotein composition and functions during severe COVID-19. Sci Rep. 2021; 11(1):2291. PMC: 7841145. DOI: 10.1038/s41598-021-81638-1. View

Guo L, Ai J, Zheng Z, Howatt D, Daugherty A, Huang B . High density lipoprotein protects against polymicrobe-induced sepsis in mice. J Biol Chem. 2013; 288(25):17947-53. PMC: 3689940. DOI: 10.1074/jbc.M112.442699. View

Wurfel M, Kunitake S, Lichenstein H, Kane J, Wright S . Lipopolysaccharide (LPS)-binding protein is carried on lipoproteins and acts as a cofactor in the neutralization of LPS. J Exp Med. 1994; 180(3):1025-35. PMC: 2191628. DOI: 10.1084/jem.180.3.1025. View

Kootte R, Smits L, van der Valk F, Dasseux J, Keyserling C, Barbaras R . Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients with FHA. J Lipid Res. 2015; 56(3):703-712. PMC: 4340317. DOI: 10.1194/jlr.M055665. View

Masana L, Correig E, Ibarretxe D, Anoro E, Arroyo J, Jerico C . Low HDL and high triglycerides predict COVID-19 severity. Sci Rep. 2021; 11(1):7217. PMC: 8010012. DOI: 10.1038/s41598-021-86747-5. View

10.

Cockerill G, Rye K, Gamble J, Vadas M, Barter P . High-density lipoproteins inhibit cytokine-induced expression of endothelial cell adhesion molecules. Arterioscler Thromb Vasc Biol. 1995; 15(11):1987-94. DOI: 10.1161/01.atv.15.11.1987. View

11.

Drew B, Duffy S, Formosa M, Natoli A, Henstridge D, Penfold S . High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus. Circulation. 2009; 119(15):2103-11. DOI: 10.1161/CIRCULATIONAHA.108.843219. View

12.

van Leeuwen H, Heezius E, Dallinga G, van Strijp J, Verhoef J, van Kessel K . Lipoprotein metabolism in patients with severe sepsis. Crit Care Med. 2003; 31(5):1359-66. DOI: 10.1097/01.CCM.0000059724.08290.51. View

13.

Didichenko S, Navdaev A, Cukier A, Gille A, Schuetz P, Spycher M . Enhanced HDL Functionality in Small HDL Species Produced Upon Remodeling of HDL by Reconstituted HDL, CSL112: Effects on Cholesterol Efflux, Anti-Inflammatory and Antioxidative Activity. Circ Res. 2016; 119(6):751-63. PMC: 5006797. DOI: 10.1161/CIRCRESAHA.116.308685. View

14.

Pavanello C, Turri M, Strazzella A, Tulissi P, Pizzolitto S, De Maglio G . The HDL mimetic CER-001 remodels plasma lipoproteins and reduces kidney lipid deposits in inherited lecithin:cholesterol acyltransferase deficiency. J Intern Med. 2021; 291(3):364-370. PMC: 9299003. DOI: 10.1111/joim.13404. View

15.

Ulevitch R, Johnston A, Weinstein D . New function for high density lipoproteins. Isolation and characterization of a bacterial lipopolysaccharide-high density lipoprotein complex formed in rabbit plasma. J Clin Invest. 1981; 67(3):827-37. PMC: 370634. DOI: 10.1172/JCI110100. View

16.

Vesy C, Kitchens R, Wolfbauer G, Albers J, MUNFORD R . Lipopolysaccharide-binding protein and phospholipid transfer protein release lipopolysaccharides from gram-negative bacterial membranes. Infect Immun. 2000; 68(5):2410-7. PMC: 97439. DOI: 10.1128/IAI.68.5.2410-2417.2000. View

17.

Watson A, Berliner J, Hama S, La Du B, Faull K, Fogelman A . Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest. 1995; 96(6):2882-91. PMC: 185999. DOI: 10.1172/JCI118359. View

18.

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J . A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020; 382(8):727-733. PMC: 7092803. DOI: 10.1056/NEJMoa2001017. View

19.

Ballout R, Kong H, Sampson M, Otvos J, Cox A, Agbor-Enoh S . The NIH Lipo-COVID Study: A Pilot NMR Investigation of Lipoprotein Subfractions and Other Metabolites in Patients with Severe COVID-19. Biomedicines. 2021; 9(9). PMC: 8471250. DOI: 10.3390/biomedicines9091090. View

20.

Mineo C, Shaul P . HDL stimulation of endothelial nitric oxide synthase: a novel mechanism of HDL action. Trends Cardiovasc Med. 2003; 13(6):226-31. DOI: 10.1016/s1050-1738(03)00098-7. View