Effect of COVID-19 on Endothelial Function

COVID-19 disease (coronavirus disease 2019) primarily affects the respiratory system, using the angiotensin-converting enzyme 2 receptor. However, there is increasing evidence that COVID-19 can also affect the heart (myocardial injury, myocarditis, arrhythmias) and the vascular system, effects that may worsen the clinical outcome of patients.

The aim of this study is to assess the effect of COVID-19 on the patients' endothelial function, during the acute phase of the disease (inpatient), shortly after recovery (2 months) and in the mid-term (6 months). Evaluation of endothelial function will be performed non-invasively by the method of Peripheral Arterial Tonometry (PAT) using the EndoPAT2000 system (Itamar Medical, Israel).

This is a prospective, case-controlled, single-center clinical observational study.

The study will include adult patients who developed COVID-19 disease for whom admission for hospitalization was required, while the control group will consist of healthy volunteers matched for age, gender and cardiovascular risk factors.

Patients enrolled in the study will undergo the following visits:

• Visit 1: Hospitalization
• Visit 2: 2 months after discharge
• Visit 3: 6 months after discharge
• Visit 4: 1 year after discharge Patients will be subjected to measurement of the reactive hyperemia index with the EndoPAT2000 system in Visits 1, 2 and 3.

The aim of the study is to compare the endothelial function between the two groups (COVID-19 vs. Controls).

Study Overview

• Status: Completed
• Conditions: COVID-19; Endothelial Dysfunction

Detailed Description

1. Introduction COVID-19 disease (coronavirus disease 2019) primarily affects the respiratory system, using the angiotensin-converting enzyme 2 receptor. However, there is increasing evidence that COVID-19 can also affect the heart (myocardial injury, myocarditis, arrhythmias) and the vascular system, effects that may worsen the clinical outcome of patients.

   Regarding COVID-19, there is increasing evidence of endothelial dysfunction, both directly due to direct infection of the vascular endothelium by the SARS-COV-2 virus (endothelitis), and indirectly due to the systemic inflammatory response and cascade of cytokines.

   In the context of this study, the evaluation of endothelial function will be performed non-invasively by the method of Peripheral Arterial Tonometry (PAT) using the EndoPAT2000 system (Itamar Medical, Israel). The EndoPAT system quantifies the endothelium-dependent pulsatile arterial volume changes. During the examination, plethysmography biosensors are placed in the right and left patient's index fingers. Subsequently, arterial tone is measured in three phases:

   A. at rest (baseline) B. during ischemia caused by a cuff inflated in one of the two arms at a level above that of systolic blood pressure for a period of 5 minutes C. during the phase of reactive hyperemia after the lifting of the arterial blockade by deflating the cuff The arterial tone signals detected in the above phases of the examination by the plethysmography biosensors are converted into digital signals for each upper limb and the EndoPAT2000 system software finally calculates the hyperemic vascular response (Ln Reactive Hyperemia Index-LnRHI). Endothelial dysfunction is defined as LnRHI≤0.51.

2. Aim of the study The aim of this study is to assess the effect of COVID-19 on the patients' endothelial function, during the acute phase of the disease (inpatient), shortly after recovery (2 months) and in the mid-term (6 months).
3. Methods This is a prospective, case-controlled, single-center clinical observational study.

The study will include adult patients who developed COVID-19 disease for whom admission for hospitalization was required, while the control group will consist of healthy volunteers matched for age, gender and cardiovascular risk factors.

Based on the limited existing data, patients in the COVID group are expected to have an average LnRHI of 0.58 (SD 0.25) at 2 months after discharge versus an average LnRHI of 0.79 in the control group. By selecting α=0.05, power=90% and enrollment ratio=1, the inclusion of 30 patients in each group is required to detect the above difference (60 in total).

Patients enrolled in the study will undergo the following visits:

• Visit 1: Hospitalization
• Visit 2: 2 months after discharge
• Visit 3: 6 months after discharge
• Visit 4: 1 year after discharge Patients will be subjected to measurement of the reactive hyperemia index with the EndoPAT2000 system in Visits 1, 2 and 3.

For all participants, the following will also be recorded:

• Demographics, cardiovascular risk factors, past medical history, chronic medical treatment
• Body weight, body mass index (BMI), systolic and diastolic blood pressure, resting heart rate
• Laboratory testing: Ht, Hgb, PLT, WBC, Ur, Cr, K, Na, SGOT, SGPT, UA, total cholesterol, LDL cholesterol, small dense LDL cholesterol, HDL cholesterol, triglycerides, non-HDL cholesterol, fasting glucose, HbA1c, insulin, hsCRP, thyroid function check (TSH, T3, fT4), hs Troponin I
• ECG
• Thansthoracic ultrasound study (LVEF, GLS, parameters of diastolic function)
• Thrombotic complications, cardiovascular events, hospitalizations

• Study Type: Observational
• Enrollment (Actual): 44

Contacts and Locations

Study Locations

• Greece
  • Achaia
    • Patras, Achaia, Greece, 26504
      • University Hospital of Patras

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

The study will include adult patients who developed COVID-19 disease for which admission for hospitalization was required, while the control group will be healthy matched volunteers for age, gender and cardiovascular risk factors.

Description

Inclusion Criteria:

• Age >18 years
• Documented SARS-COV-2 infection with PCR test
• Need for hospitalization in a COVID clinic
• Informed written consent

Exclusion Criteria:

• Inability to cooperate for peripheral arterial tonometry
• Hemodynamic instability
• High probability of non-compliance with the procedures of the study
• Reduced life expectancy <1 year
• Established atherosclerotic cardiovascular disease
• Pregnancy, postpartum
• Alcoholism

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
COVID-19; Patients admitted to our hospital due to COVID-19
Controls; Healthy volunteers matched for age, sex and cardiovascular risk factors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Natural logarithm of reactive hyperemia index (Ln-RHI)	Endothelial dysfunction is defined as LnRHI≤0.51	2 months after discharge

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the Curve (AUC) of the Reactive Hyperemia index (RHI) measurements during hospitalization, at 2 months after discharge and at 6 months after discharge.	At 6 months after discharge
Natural logarithm of reactive hyperemia index (Ln-RHI)	During hospitalization (up to day 10)
Reactive Hyperemia Index (RHI)	At 6 months after discharge
Rate of endothelial dysfunction (LnRHI≤0.51)	During hospitalization (up to day 10)
Rate of endothelial dysfunction (LnRHI≤0.51)	At 2 months after discharge
Rate of endothelial dysfunction (LnRHI≤0.51)	At 6 months after discharge
Change in RHI index (ΔRHI) from hospitalization to 6 months	At 6 months after discharge
Duration (days) of hospitalization for COVID-19	Predischarge (up to 3 months)
Incidence of thrombotic events	Up to 12 months after discharge
Incidence of cardiovascular events	Up to 12 months after discharge
Mortality	Up to 12 months after discharge

Collaborators and Investigators

• Sponsor: University Hospital of Patras
• Investigators: Principal Investigator: Athanasios Moulias, MD, PhD, General University Hospital of Patras; Principal Investigator: Periklis Davlouros, MD, PhD, General University Hospital of Patras

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2022
• Primary Completion (Actual): July 20, 2023
• Study Completion (Actual): July 20, 2023

Study Registration Dates

• First Submitted: July 30, 2022
• First Submitted That Met QC Criteria: August 12, 2022
• First Posted (Actual): August 15, 2022

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 22, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• 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: 16/02-02-2022

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