Endothelial Dysfunction in Covid-19 (ENDOCOVID)

Endothelial Dysfunction and Oxidative Stress in ICU and Non-ICU Covid-19 Patients With Hypoxemic Respiratory Failure

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.

Study Overview

• Status: Recruiting
• Conditions: Covid19; Hypoxemic Respiratory Failure

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 Type: Observational
• Enrollment (Anticipated): 85

Contacts and Locations

• Study Contact: Name: VIRGINIE MONTIEL, MD, PhD; Phone Number: 0032496503912; Email: virginie.montiel@uclouvain.be

Study Locations

• Belgium
  • Belgique
    • Brussels, Belgique, Belgium, 1040
      • Recruiting
      • Cliniques Universitaires Saint Luc
      • Contact: VIRGINIE MONTIEL; Phone Number: 0032496503912; Email: virginie.montiel@uclouvain.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Hospitalized patients for SARS-Cov-2 infection

Description

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 Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
ICU Covid-19 patients; Covid-19 patients admitted for refractory respiratory failure despite conventional oxygen therapy requiring Intensive Care Unit (ICU) admission and oxygenation through either High Flow Nasal Cannula (HFNC) therapy or endotracheal intubation with mechanical ventilation
non-ICU Covid-19 patients; Covid-19 patients admitted at hospital requiring conventional oxygen or continuous positive airways pressure (cpap)
matched control subjects; Healthy subjects matched for similar cardiovascular risk factors than ICU Covid-19 patients
ICU septic shock patients; Septic shock patients corresponded to refractory hypotension in response to an infection, in non Covid-19 patients, requiring ICU hospitalisation for vasopressors to maintain mean arterial pressure (MAP) > 65mm Hg despite adequate volume resuscitation according to the Surviving Sepsis Campaign

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vascular oxidative stress in Covid-19 versus septic shock and control patients	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.	ICU or general ward hospital admission

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Investigators: Principal Investigator: VIRGINIE MONTIEL, MD,PhD, Cliniques Universitaires Saint-Luc

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2020
• Primary Completion (Actual): March 25, 2021
• Study Completion (Anticipated): April 1, 2021

Study Registration Dates

• First Submitted: March 26, 2021
• First Submitted That Met QC Criteria: April 2, 2021
• First Posted (Actual): April 5, 2021

Study Record Updates

• Last Update Posted (Actual): April 9, 2021
• Last Update Submitted That Met QC Criteria: April 6, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Covid19; Endothelial Dysfunction
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Respiratory Insufficiency
• Other Study ID Numbers: 2020/27AVR/247

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No