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
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.
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
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
Medical University of Vienna, Department of Clinical Pharmacology
Vienna, Austria
Investigator: Doreen Schmidl, MD, PhD
Contact: 0043140400
klin-pharmakologie@meduniwien.ac.at
Investigator: Doreen Schmidl, MD, PhD
Not Provided