Clinical trial NCT05113836: LIPId Profile Changes in Inflammatory Conditions Induced by SARS-CORoronavirus-2
Official title: LIPId Profile Changes in Inflammatory Conditions Induced by SARS-CORoronavirus-2 : LIPICOR Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: SARS-CoV2 Infection
Keywords: Infecious disease
Sars-CoV2
COVID-19
LDL
HDL
SAA
PON-1
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2021-11-09
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Any patient hospitalised in intensive care for a COVID-19 infection. The health emergency of this pandemic and the potential therapeutic action of HDL particles justify the choice of this population for study.

Brief summary: In late 2019, a new coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the cause of COVID-19 (COronaVIrus Disease-2019) in Hubei Province, China. COVID-19 has become a pandemic with approximately 4.1 million confirmed cases as of May 2020 resulting in 280,000 deaths worldwide. Between 5 and 20% of patients hospitalized with SARS-CoV-2 infection are admitted to the ICU with a mortality ranging from 25 to 60% depending on the series. At present, there is no effective targeted therapy against this viral infection.

High-density lipoproteins (HDL) are nanoparticles made up of apolipoproteins, mainly apoA1, associated with phospholipids whose main function is the reverse transport of cholesterol from peripheral tissues to the liver. This property gives HDL a major cardiovascular protective effect. In addition to this effect, studies have highlighted a number of properties such as anti-inflammatory, anti-apoptotic, anti-thrombotic and anti-oxidant effects of these particles. Furthermore, it has been shown that HDL is able to bind and neutralize bacterial lipopolysaccharides (LPS), promoting their elimination.

During bacterial sepsis, a rapid decrease in plasma HDL cholesterol (HDL-C) concentration has been demonstrated, but also an inverse correlation between mortality and HDL-C concentration. In addition to the quantitative decrease in HDL during sepsis, dysfunctions of these particles have been described, such as major differences in size, or a notable alteration in protein composition with, in particular, more pro-inflammatory proteins. In this context of both quantitative and qualitative alteration of HDL, authors have tested the efficacy of injection of either reconstituted HDL (apoA1 + phosphatidylcholines) or peptides structurally similar to ApoA1 in animal models of sepsis and have demonstrated a protective effect on morbidity and mortality, with in particular a decrease in the inflammatory state induced by sepsis.

Low-density lipoproteins (LDL) can also neutralize LPS and observational studies have shown a decrease in the concentration of LDL cholesterol (LDL-C) during sepsis. The authors also showed that low LDL-C was associated with a poor prognosis in patients with sepsis.

During COVID-19-induced sepsis, a few studies have demonstrated a decrease in lipoprotein (HDL and LDL) concentration. More specifically, some authors have found an association between low lipoprotein concentrations and increased disease severity. To the best of the knowledge of the investigators, no study has specifically investigated particulate dysfunction of lipoproteins and in particular HDL during severe COVID-19 infections. On the other hand, as it has been described that lipoproteins and particularly HDL can bind bacterial components (LPS or LTA) favoring their clearance, it can be envisaged that these particles can also bind SARS-CoV-2 components, and this, in a more or less strong way depending on the virus strain.

The preliminary results of the investigators show that in sepsis, serum amyloid A (SAA) protein tends to replace apolipoprotein A1, making HDL dysfunctional. In addition, paraoxonase-1, an antioxidant enzyme mainly carried by HDL, is almost absent or degraded in septic patients. The SAA/PON-1 ratio could allow to assess the severity of COVID-19 damage and to reinforce a possible therapeutic strategy based on the supplementation of severe patients with apolipoprotein A1 and PON-1 rich HDL nanoparticles.

Main objective: To evaluate the functionality of HDL as a prognostic marker of mortality in COVID-19 patients in ICU. To do so, a quantification of the SAA/PON-1 ratio at plasma level and on isolated lipoproteins will be performed by ELISA.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years.
* Patient hospitalized in surgical intensive care unit for COVID-19 infection.

Exclusion Criteria:

* Pregnant or breastfeeding women
* CHILD B or C cirrhotic patients
* Moribund patients with an estimated life expectancy of less than 48 hours on admission to the ICU
* Subject protected by law under guardianship or curatorship
* No affiliation to a social security system
* Absence of signed consent

Primary outcomes:
measure: Change of concentration of Serum Amyloid A (SAA, inflammation protein) and paroxonase-1 (PON-1, antioxidant enzyme) in plasma and lipoproteins.
timeFrame: Day 1 and Day 7.
Secondary outcomes:
measure: Assessment of structural dysfunctions by proteomic approaches to lipoproteins during severe COVID-19 infections.
timeFrame: Day 1, Day 3 and Day 7
measure: Quantification of plasma HDL-C, LDL-C and triglyceride concentrations over time in patients hospitalized in ICU for severe COVID-19 infection.
timeFrame: Day 1, Day 3 and Day 7
measure: Study of HDL and LDL particle size profiles using the Lipo-print® technique.
timeFrame: Day 1, Day 3 and Day 7
measure: Comparison of pro- and anti-inflammatory cytokines levels, such as IL-1 beta, IL-6, TNF-alpha, IL-10 or IL-18, in patients according to their particle dysfunction data.
timeFrame: Day 1, Day 3 and Day 7
measure: Comparison of particle dysfunction data to markers of endothelial dysfunction.
timeFrame: Day 1, Day 3 and Day 7
measure: Comparison of lipid profiles to the genotype of COVID-19 strains.
timeFrame: Day 1, Day 3 and Day 7
measure: Search for binding of viral proteins to lipoproteins.
timeFrame: Day 1, Day 3 and Day 7
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Bichat
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Sebastien TANAKA, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: