Clinical trial NCT05650905: Retinal Neurovascular Coupling in Patients Previously Infected With COVID-19
Official title: Retinal Neurovascular Coupling in Patients Previously Infected With COVID-19
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: COVID-19
Post-COVID-19 Syndrome
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2022-12-14
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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

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

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.

Eligibility 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

Primary outcomes:
measure: Retinal neurovascular coupling
timeFrame: Day 0
Secondary outcomes:
measure: Retinal vessel diameters
timeFrame: Day 0
measure: Retinal oxygen saturation
timeFrame: Day 0
measure: Retinal blood velocities
timeFrame: Day 0
measure: Retinal blood flow
timeFrame: Day 0
measure: Ocular perfusion pressure
timeFrame: Day 0
measure: Retinal nerve fiber layer thickness
timeFrame: Day 0
measure: Central retinal thickness
timeFrame: Day 0
measure: Retinal vessel density
timeFrame: Day 0
measure: Normalized blur
timeFrame: Day 0
measure: Relative flow volume
timeFrame: Day 0
measure: Proteomics and Metabolites in Plasma
timeFrame: Day -14 to -1
measure: Proteomics and Metabolites in tear fluid
timeFrame: Day 0
measure: Proteomics and Metabolites in finger sweat
timeFrame: Day 0
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna, Department of Clinical Pharmacology
Study officials:
References: