Endothelial Dysfunction in Covid-19

• Conditions: Covid19; Hypoxemic Respiratory Failure

• Registration Number: NCT04830683
• Lead Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Brief Summary

SARS-CoV-2 targets endothelial cells via the angiotensin-converting enzyme 2 receptor. The specific impact of the resulting endothelial injury is currently unknown but may contribute to the pro-coagulant state classically described during Covid-19 disease and commonly associated with an exacerbated activation of the renin-angiotensin-aldosterone system.

Detailed Description

We prospectively compared clinical and biological parameters in ICU- and non-ICU-admitted Covid-19 patients, ICU-admitted patients with septic shock unrelated to Covid-19 and matched control subjects.

Primary hemostasis and coagulation parameters and endothelial biomarkers are measured. Activation of the renin-angiotensin-aldosterone system is monitored through measurements of plasma renin, angiotensin II, aldosterone, and serum soluble angiotensin-converting enzyme 2. Vascular oxidative status is assessed by measuring plasma lipids peroxides. Neutrophilic polymorphonuclear activation is assessed by measuring plasma levels of Triggering receptor expressed on myeloid cells-1. Vascular nitric oxide bioavailability is measured by quantification of the concentration of heme-nitrosylated hemoglobin (HbNO) in venous erythrocytes using Electron Paramagnetic Resonance spectroscopy. Structural abnormalities of vascular endothelial cells were analyzed by Transmission Electron- and Scanning Electron Microscopy.

Study Timeline

• Study Start: 2020-04-27
• Primary Completion: 2021-03-25
• Study First Submitted: 2021-03-26
• Status Verified: 2021-04
• Study Completion: 2021-04-01
• Study First Submitted QC: 2021-04-02
• Study First Posted: 2021-04-05
• Last Update Submitted: 2021-04-06
• Last Update Posted: 2021-04-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 85

Inclusion Criteria

• positive result on a reverse-transcriptase-polymerase chain reaction testing performed on nasopharyngeal swab at hospital admission

Exclusion Criteria

• ICU admission more than five days after admission on a general ward,
• concomitant bacterial infection
• older than 75 years
• cirrhosis

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Vascular oxidative stress in Covid-19 versus septic shock and control patients	ICU or general ward hospital admission	HbNO (nmol/L) and NOX levels (μM/L), oxidative stress with plasma lipids peroxides (mmol/L) levels and soluble TREM-1 measurements. Blood HbNO levels directly correlate with endothelial function and inversely with major cardiovascular risk factors. The nitrite/nitrate levels (NOx) are the the stable end products of NO metabolism that also suggest NO production. Plasma lipids peroxides reflets the surrounding endovascular oxidative stress. sTREM-1 participates in the sepsis-induced ROS production through activation of NADPH oxidase (NOX)-2 during the respiratory burst of activated polymorphonuclear.

Secondary Outcome Measures

Name	Time	Method
Vascular Renin-angiotensin-aldosterone system measurements in Covid-19 versus septic shock and control patients	ICU or general ward hospital admission	Renin (pg/mL), Agiotensin II (fmol/mL), Aldosterone (pg/mL) measurements. The RAAS system is a classical activator of vascular NOX2 and ROS production.

Trial Locations

Locations (1)

Cliniques Universitaires Saint Luc; 🇧🇪 Brussels, Belgique, Belgium