Endothelial Damage and Angiogenesis Biomarkers During COVID-19

Association of Endothelial Damage and Angiogenesis Biomarkers With Morbidity and Mortality in SARS-CoV-2 Infection

Severe SARS-CoV-2 disease is characterized by a progressive hypoxemic respiratory failure. Autopsies from these patients show severe endothelial damage with extensive vascular thrombosis, microangiopathy, and occlusion of alveolar capillaries and, finally, evidence of new vessel growth through intussusceptive angiogenesis.

This research aims to study endothelial damage and angiogenesis biomarkers and its association with major cardiovascular events.

Study Overview

• Status: Completed
• Conditions: Covid19; Endothelial Dysfunction; Angiogenesis; Cardiovascular Morbidity
• Intervention / Treatment: Diagnostic test: Endothelial damage and angiogenic biomarkers

Detailed Description

To study the presence of endothelial damage and angiogenic biomarkers with major cardiovascular events, the investigators will perform an observational study to evaluate plasma biomarkers concentrations in Covid-19 patients hospitalized in critical care units.

After ethical review board approval, the investigators will select 40 patients admitted to intensive care units (ICU). After patient written consent or if the participants are unable to consent, after a relative subrogated acceptance, the investigators will collect blood samples in the first 24 hrs and on the 10th day of hospitalization.

Venous blood samples are collected. After obtaining all samples, serum Syndecan-1, thrombomodulin, ANG-2, FGF basic, HGF, IL-8, PDGF-BB, TIMP-1, TIMP-2, TNFα y VEGF will be determined by a researcher blinded to the patient using commercially available Elisa kits. The concentration of each biomarker at each sample time will be compared. The investigators will observe clinical outcomes after one, 3, 6, and 12 months after the hospitalization.

The investigators found no previous data of this measurement in the COVID-19 scenario. In this observational study, the investigators select a sample size on convenience for the primary outcome.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Chile
  • Santiago
    • Independencia, Santiago, Chile, 8380456
      • Hospital Clinico de la Universidad de Chile

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The investigators will include Covid 19 patients admitted to ICU with the need for oxygen and ventilatory support. Blood plasma biomarkers will be obtained on the first and 10th day of hospitalization. Information on major cardiac events will be obtained from the patient clinical file and by phone interview after hospitalization.

Description

Inclusion Criteria:

1. Patients older than 18 years
2. Patient with a diagnosis of COVID-19 confirmed by PCR
3. Patient with radiological image suggestive of COVID-19 with pending confirmation
4. Need for ventilatory support with oxygen therapy by HFNC (High-flow nasal cannula)
5. Need for invasive mechanical ventilation.

Exclusion Criteria:

1. Patient with an image suggestive of COVID-19 with negative PCR
2. Anticoagulation users before admission for any reason.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline Syndecan-1 concentration at 10th day	Elevation of plasma Syndecan-1	24 Hours, 10 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline ANG-2 concentration at 10th day	Elevation of plasma ANG-2	24 Hours, 10 Days
Change from Baseline FGF basic concentration at 10th day	Elevation of plasma FGF basic	24 Hours, 10 Days
Change from Baseline HGF concentration at 10th day	Elevation of plasma HGF	24 Hours, 10 Days
Change from Baseline IL-8 concentration at 10th day	Elevation of plasma IL-8	24 Hours, 10 Days
Change from Baseline PDGF-BB concentration at 10th day	Elevation of plasma PDGF-BB	24 Hours, 10 Days
Change from Baseline TIMP-1 concentration at 10th day	Elevation of plasma TIMP-1	24 Hours, 10 Days
Change from Baseline TIMP-2 concentration at 10th day	Elevation of plasma TIMP-2	24 Hours, 10 Days
Change from Baseline TNFα concentration at 10th day	Elevation of plasma TNFα	24 Hours, 10 Days
Change from Baseline VEGF concentration at 10th day	Elevation of plasma VEGF	24 Hours, 10 Days
Change from Baseline Thrombomodulin concentration at 10th day	Elevation of plasma Thrombomodulin	24 Hours, 10 Days
Major cardiovascular events	Acute coronary syndrome, myocardial injury, pulmonary embolism, and death.	1 month, 3 months, 6 months 12 months.

Collaborators and Investigators

• Sponsor: University of Chile
• Investigators: Principal Investigator: Felipe Maldonado, M.D., M.Sc., Hospital Clinico de la Universidad de Chile

Publications and helpful links

General Publications

• Maldonado F, Morales D, Diaz-Papapietro C, Valdes C, Fernandez C, Valls N, Lazo M, Espinoza C, Gonzalez R, Gutierrez R, Jara A, Romero C, Cerda O, Caceres M. Relationship Between Endothelial and Angiogenesis Biomarkers Envisage Mortality in a Prospective Cohort of COVID-19 Patients Requiring Respiratory Support. Front Med (Lausanne). 2022 Mar 16;9:826218. doi: 10.3389/fmed.2022.826218. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2020
• Primary Completion (Actual): September 26, 2021
• Study Completion (Actual): November 30, 2021

Study Registration Dates

• First Submitted: October 23, 2020
• First Submitted That Met QC Criteria: October 28, 2020
• First Posted (Actual): October 30, 2020

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 21, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Syndecan-1; Thrombomodulin; VEFG; ANG-2
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: OAIC 1164/20

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