LIPId Profile Changes in Inflammatory Conditions Induced by SARS-CORoronavirus-2

NCT ID: NCT05113836

Last Updated: 2021-11-09

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 135 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-12-19
• Study Completion Date: 2022-07-01

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.

Conditions

SARS-CoV2 Infection

Keywords

Infecious disease; Sars-CoV2; COVID-19; LDL; HDL; SAA; PON-1

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Any patient hospitalised in intensive care for a COVID-19 infection.

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.

Deep nasopharyngeal swab

Intervention Type: BIOLOGICAL

On admission in ICU, a deep nasopharyngeal swab will be performed (15mL).

Blood sample at D1, D3 and D7

Intervention Type: BIOLOGICAL

Specific samples for research and lipid analysis will be performed at D1, D3 and D7:

Assessments will be carried out on the same blood tube as the blood ionogram carried out as part of the usual management.

This means a 5 ml tube of blood on EDTA medium will be taken at the same time as the blood ionogram for the treatment at D1, D3 and D7 (15mL in total).

Interventions

Deep nasopharyngeal swab

On admission in ICU, a deep nasopharyngeal swab will be performed (15mL).

Intervention Type: BIOLOGICAL

Blood sample at D1, D3 and D7

Specific samples for research and lipid analysis will be performed at D1, D3 and D7:

Assessments will be carried out on the same blood tube as the blood ionogram carried out as part of the usual management.

This means a 5 ml tube of blood on EDTA medium will be taken at the same time as the blood ionogram for the treatment at D1, D3 and D7 (15mL in total).

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sebastien TANAKA, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Hôpital Bichat

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Sebastien TANAKA, MD, PhD

Role: CONTACT

Phone: 01 40 25 79 10

Email: sebastien.tanaka@aphp.fr

Facility Contacts

Sebastien TANAKA, MD, PhD

Role: primary

References

Andrei S, Meilhac O, De Tymowski C, Snauwaert A, Stern J, Robert T, Lortat-Jacob B, Atchade E, Kantor E, Begue F, Montravers P, Tanaka S. Relationship between high-density lipoprotein cholesterol (HDL-C) concentration and ventilator-associated pneumonia in ICU COVID-19 patients. Anaesth Crit Care Pain Med. 2025 Aug;44(4):101535. doi: 10.1016/j.accpm.2025.101535. Epub 2025 May 1.

Reference Type: DERIVED

PMID: 40318849 (View on PubMed)

Other Identifiers

2020-A02638-3

Identifier Type: REGISTRY

Identifier Source: secondary_id

APHP20128

Identifier Type: -

Identifier Source: org_study_id