Retinal Neurovascular Coupling in Patients Previously Infected With COVID-19

• ClinicalTrials.gov Identifier: NCT05650905
• Recruitment Status: Recruiting
• First Posted: December 14, 2022
• Last Update Posted: December 16, 2022
• Sponsor: Medical University of Vienna
• Information provided by (Responsible Party): Doreen Schmidl, Medical University of Vienna

Study Description

Brief Summary:

The Study objective is to measure retinal neurovascular coupling and blood flow parameters in patients previously infected with COVID-19, long COVID-19 and healthy age- and sex- matched control subjects

Condition or disease	Intervention/treatment
COVID-19; Post-COVID-19 Syndrome	Device: Dynamic Vessel Analyzer (DVA); Device: Fourier domain optical coherence tomography (FDOCT); Device: Optical coherence tomography (OCT); Device: Laser Speckle Flowgraphy (LSFG); Diagnostic Test: Proteomics and Metabolites in Plasma, tear fluid and finger sweat

Detailed Description:

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is affecting almost all countries in the world and because of its worldwide spread has been declared as pandemic in March 2020. While respiratory symptoms are the main manifestation of acute infection, there is also increasing evidence that neurological and vascular symptoms occur, and it is unknown whether residuals remain after patients have recovered. A recent report shows that changes in the human retina are even present one month after onset of symptoms. The eye, as an extension of the brain, offers the advantage that blood vessels as well as neural tissue can be visualized non-invasively in-vivo. Neurovascular coupling is the ability of neural tissue to adapt its blood flow to its metabolic demands, a phenomenon that does not only occur in the brain, but also in the retina. In the retina, neurovascular coupling can be studied by stimulating the retina with flicker light and measuring the response of the vessels. Retinal neurovascular coupling has been found to be impaired in diseases of the central nervous system (CNS) as well as in diseases associated with endothelial dysfunction. Since COVID-19 comes with CNS manifestations as well as endothelial dysfunction, we speculate that retinal neurovascular coupling might be impaired in patients even after they have recovered from COVID-19 infection. In the current study, retinal neurovascular coupling will be measured in patients who have recovered from COVID-19 infection with and without long COVID-19 and in healthy age- and sex-matched controls with no history of COVID-19 infection. In addition, retinal oxygen saturation, vessel diameters, vessel density as well as retinal and optic nerve head blood flow will be measured. To assess structural changes, measurement of central retinal thickness as well as retinal nerve fiber layer thickness will be performed.

Study Design

• Study Type: Observational
• Estimated Enrollment: 90 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: Retinal Neurovascular Coupling in Patients Previously Infected With COVID-19
• Actual Study Start Date: July 26, 2021
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: December 31, 2023

Groups and Cohorts

Group/Cohort	Intervention/treatment
subjects previously infected with COVID-19; subjects previously infected with COVID-19	Device: Dynamic Vessel Analyzer (DVA); Retinal neurovascular coupling, Retinal vessel diameters and Retinal oxygen saturation will be assessed using the DVA; Device: Fourier domain optical coherence tomography (FDOCT); Retinal blood velocities and Retinal blood flow will be assessed using the FDOCT; Device: Optical coherence tomography (OCT); Retinal nerve fiber layer thickness, Central retinal thickness and Retinal vessel density will be assessed using the OCT; Device: Laser Speckle Flowgraphy (LSFG); Normalized blur and Relative flow volume will be assessed using the LSFG; Diagnostic Test: Proteomics and Metabolites in Plasma, tear fluid and finger sweat; Proteomics and Metabolites in Plasma, tear fluid and finger sweat will be assessed using a Blooddraw, filter paper and Schirmer-test
subjects with long COVID-19; subjects with long COVID-19 according to the WHO-guideline	Device: Dynamic Vessel Analyzer (DVA); Retinal neurovascular coupling, Retinal vessel diameters and Retinal oxygen saturation will be assessed using the DVA; Device: Fourier domain optical coherence tomography (FDOCT); Retinal blood velocities and Retinal blood flow will be assessed using the FDOCT; Device: Optical coherence tomography (OCT); Retinal nerve fiber layer thickness, Central retinal thickness and Retinal vessel density will be assessed using the OCT; Device: Laser Speckle Flowgraphy (LSFG); Normalized blur and Relative flow volume will be assessed using the LSFG; Diagnostic Test: Proteomics and Metabolites in Plasma, tear fluid and finger sweat; Proteomics and Metabolites in Plasma, tear fluid and finger sweat will be assessed using a Blooddraw, filter paper and Schirmer-test
healthy age-and sex- matched control subjects with no history of COVID-19 infection; healthy age-and sex- matched control subjects with no history of COVID-19 infection	Device: Dynamic Vessel Analyzer (DVA); Retinal neurovascular coupling, Retinal vessel diameters and Retinal oxygen saturation will be assessed using the DVA; Device: Fourier domain optical coherence tomography (FDOCT); Retinal blood velocities and Retinal blood flow will be assessed using the FDOCT; Device: Optical coherence tomography (OCT); Retinal nerve fiber layer thickness, Central retinal thickness and Retinal vessel density will be assessed using the OCT; Device: Laser Speckle Flowgraphy (LSFG); Normalized blur and Relative flow volume will be assessed using the LSFG; Diagnostic Test: Proteomics and Metabolites in Plasma, tear fluid and finger sweat; Proteomics and Metabolites in Plasma, tear fluid and finger sweat will be assessed using a Blooddraw, filter paper and Schirmer-test

Outcome Measures

Primary Outcome Measures :

1. Retinal neurovascular coupling [ Time Frame: Day 0 ]
   Retinal neurovascular coupling will be assessed using the DVA

Secondary Outcome Measures :

1. Retinal vessel diameters [ Time Frame: Day 0 ]
   Retinal vessel diameters will be assessed using the DVA
2. Retinal oxygen saturation [ Time Frame: Day 0 ]
   Retinal oxygen saturation will be assessed using the DVA
3. Retinal blood velocities [ Time Frame: Day 0 ]
   Retinal blood velocities will be assessed using FDOCT
4. Retinal blood flow [ Time Frame: Day 0 ]
   Retinal blood flow will be assessed using FDOCT
5. Ocular perfusion pressure [ Time Frame: Day 0 ]
   Ocular perfusion pressure is going to be calulated
6. Retinal nerve fiber layer thickness [ Time Frame: Day 0 ]
   Retinal nerve fiber layer thickness will be assessed using OCT
7. Central retinal thickness [ Time Frame: Day 0 ]
   Central retinal thickness will be assessed using OCT
8. Retinal vessel density [ Time Frame: Day 0 ]
   Retinal vessel density will be assessed using OCT
9. Normalized blur [ Time Frame: Day 0 ]
   Normalized blur will be assessed using LSFG
10. Relative flow volume [ Time Frame: Day 0 ]
    Relative flow volume will be assessed using LSFG
11. Proteomics and Metabolites in Plasma [ Time Frame: Day -14 to -1 ]
    Proteomics and Metabolites in Plasma will be assessed through a Blood Sample
12. Proteomics and Metabolites in tear fluid [ Time Frame: Day 0 ]
    Proteomics and Metabolites in tear fluid will be assessed using Schirmer
13. Proteomics and Metabolites in finger sweat [ Time Frame: Day 0 ]
    Proteomics and Metabolites in finger sweat will be assessed using finger sweat filters

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Probability Sample

Study Population

A total of 90 subjects will be included:

30 subjects previously infected with COVID-19 30 subjects with long COVID-19 30 age-and sex- matched subjects with no history of COVID-19 infection

Criteria

Inclusion Criteria:

Inclusion criteria for healthy subjects

• Men and women aged over 18 years
• Non-smokers
• Normal findings in the medical history unless the investigator considers an abnormality to be clinically irrelevant
• No previous history of COVID-19 infection
• Negative testing for SARS-CoV-2 seroprevalence using nucleocapsid antibody tests
• Negative PCR test for SARS-CoV-2
• Normal ophthalmic findings, ametropy < 6 Dpt.

Inclusion criteria for subjects with history of COVID-19 infection

• Men and women aged over 18 years
• Non-smokers
• History of COVID-19 infection (confirmed by a positive PCR test for SARS-CoV2 in the medical history) within the last 6 months
• Positive testing for SARS-CoV-2 seroprevalence using spike protein IgG antibody tests
• Negative PCR test for SARS-CoV-2

Inclusion criteria for subjects with long COVID-19

• Men and women aged over 18 years
• Non-smokers
• History of COVID-19 infection (confirmed by a positive PCR test for SARS-CoV2 in the medical history)
• Positive testing for SARS-CoV-2 seroprevalence
• Negative PCR test for SARS-CoV-2
• Long Covid according to the latest WHO-Guidelines

Exclusion Criteria:

Any of the following will exclude a healthy control subject from the study:

• Symptoms of a clinically relevant illness in the 3 weeks before the first study day
• Presence or history of a severe medical condition as judged by the clinical investigator
• Participation in a clinical trial in the 3 weeks preceding the study
• Blood donation during the previous three weeks
• History or family history of epilepsy
• Presence of any abnormalities preventing reliable measurements in the study eye as judged by the investigator
• Best corrected visual acuity < 0.8 Snellen
• Pregnancy, planned pregnancy or lactatin
• History of epilepsia

Any of the following will exclude a subject with history of COVID-19 infection from the study:

• Blood donation during the previous three weeks
• History or family history of epilepsy
• Presence of any abnormalities preventing reliable measurements in the study eye as judged by the investigator
• Best corrected visual acuity < 0.8 Snellen
• Ametropy >6 Dpt
• Pregnancy, planned pregnancy or lactating
• History of epilepsia

Any of the following will exclude a subject with long COVID-19 from the study:

• Blood donation during the previous three weeks
• History or family history of epilepsy
• Presence of any abnormalities preventing reliable measurements in the study eye as judged by the investigator
• Best corrected visual acuity < 0.8 Snellen
• Ametropy >6 Dpt
• Pregnancy, planned pregnancy or lactating
• History of epilepsia
• Diabetes mellitus

Contacts and Locations

Locations

Austria

Medical University of Vienna, Department of Clinical Pharmacology; Recruiting

Vienna, Austria, 1090

Contact: Doreen Schmidl, MD, PhD 0043140400 ext 29810 klin-pharmakologie@meduniwien.ac.at

Principal Investigator: Doreen Schmidl, MD, PhD

Sponsors and Collaborators

Medical University of Vienna

More Information

• Responsible Party: Doreen Schmidl, Associate Professor, MD, PhD, Medical University of Vienna
• ClinicalTrials.gov Identifier: NCT05650905
• Other Study ID Numbers: OPHT-180520
• First Posted: December 14, 2022
• Last Update Posted: December 16, 2022
• Last Verified: December 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases