All Eyes on PCS - Analysis of the Retinal Microvasculature in Patients With Post-COVID-19 Syndrome

Recruiting

• Conditions: Long Covid19; Post COVID-19 Condition; Endothelial Dysfunction
• Interventions: Diagnostic Test: Dynamic retinal vessel analysis (DVA); Diagnostic Test: Optical coherence tomography (OCT); Diagnostic Test: Biochemistry and immune phenotyping; Diagnostic Test: Handgrip strength test; Diagnostic Test: Questionnaires (Patient reported outcomes)

• Registration Number: NCT05635552
• Lead Sponsor: Technical University of Munich

Brief Summary

The goal of this observational, prospective study is to in depth analyze the retinal microvasculature in patients with Post-COVID-19 Syndrome (PCS). The main questions it aims to answer is:

Do patients with PCS show a prolonged endothelial dysfunction when compared with fully COVID-19 recovered participants? Does symptom severity in PCS patients correlate with the extend of endothelial dysfunction? Do these changes correlate with improvement in symptoms in the prospective observation?

Detailed Description

The investigators will recruit patients with PCS, fully COVID-19 recovered participants and COVID-19 infection naïve participants. After comprehensive clarification and given written informed consent, measurements will take place in the Klinikum rechts der Isar. To evaluate the retinal microvasculature dynamic retinal vessel analysis (DVA) and optical coherence tomography (OCT) are used. Patient reported outcomes (PROM) of PCS typical symptoms will be collected using standardized questionnaires. To ensure data quality the investigators will use standard operating procedures (SOP) for both technical measurements and data collection. For DVA measurements all examiners will be trained by a single experienced supervisor and must reach high image accuracy and quality in at least 10 volunteers. Examiners are only involved in data acquisition.

Study Timeline

• Study Start: 2022-10-17
• Status Verified: 2022-11
• Study First Submitted: 2022-11-18
• Study First Submitted QC: 2022-11-30
• Last Update Submitted: 2022-11-30
• Study First Posted: 2022-12-02
• Last Update Posted: 2022-12-02
• Primary Completion: 2023-02-21
• Study Completion: 2023-07-21

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Patients with Post-COVID syndrome (positive PCR or positive rapid antibody test ≥3 months) with a currently existing, PCS-typical complaint complex, ongoing for at least 2 months and cannot be explained by an alternative diagnosis.
• Control group: recovered from COVID-19 infection (positive PCR or positive rapid antibody test ≥ 3 months) without residual symptoms.
• Healthy cohort: no history of COVID-19 infection

Exclusion Criteria

• Missing or incomplete consent form
• Age < 18 years
• Pregnancy
• Malignancy
• Diseases associated with a significant change in life expectancy
• Autoimmune diseases of the rheumatological type
• Cataract
• Epilepsy
• Glaucoma

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
PCS patients	Handgrip strength test	Patients with a COVID-19 infection at least 3 months ago (positive PCR or rapid antibody test) and PCS typical symptoms (e.g. fatigue, breast pain, heart palpitations, cognitive impairment) ongoing for at least 2 months and which cannot be explained by an alternative diagnosis.
PCS patients	Questionnaires (Patient reported outcomes)	Patients with a COVID-19 infection at least 3 months ago (positive PCR or rapid antibody test) and PCS typical symptoms (e.g. fatigue, breast pain, heart palpitations, cognitive impairment) ongoing for at least 2 months and which cannot be explained by an alternative diagnosis.
COVID-19 recovered participants	Biochemistry and immune phenotyping	Participants with Sars-CoV-2 infection at least 3 months ago (positive PCR or positive rapid antibody test) which are fully recovered.
PCS patients	Biochemistry and immune phenotyping	Patients with a COVID-19 infection at least 3 months ago (positive PCR or rapid antibody test) and PCS typical symptoms (e.g. fatigue, breast pain, heart palpitations, cognitive impairment) ongoing for at least 2 months and which cannot be explained by an alternative diagnosis.
COVID-19 recovered participants	Dynamic retinal vessel analysis (DVA)	Participants with Sars-CoV-2 infection at least 3 months ago (positive PCR or positive rapid antibody test) which are fully recovered.
COVID-19 infection naïve	Biochemistry and immune phenotyping	No history of COVID-19 infection (exclusion via measurement of specific antibodies). Consists of an already established, pre-pandemic healthy cohort and a cohort recruited during the pandemic.
PCS patients	Optical coherence tomography (OCT)	Patients with a COVID-19 infection at least 3 months ago (positive PCR or rapid antibody test) and PCS typical symptoms (e.g. fatigue, breast pain, heart palpitations, cognitive impairment) ongoing for at least 2 months and which cannot be explained by an alternative diagnosis.
COVID-19 infection naïve	Optical coherence tomography (OCT)	No history of COVID-19 infection (exclusion via measurement of specific antibodies). Consists of an already established, pre-pandemic healthy cohort and a cohort recruited during the pandemic.
COVID-19 infection naïve	Dynamic retinal vessel analysis (DVA)	No history of COVID-19 infection (exclusion via measurement of specific antibodies). Consists of an already established, pre-pandemic healthy cohort and a cohort recruited during the pandemic.
PCS patients	Dynamic retinal vessel analysis (DVA)	Patients with a COVID-19 infection at least 3 months ago (positive PCR or rapid antibody test) and PCS typical symptoms (e.g. fatigue, breast pain, heart palpitations, cognitive impairment) ongoing for at least 2 months and which cannot be explained by an alternative diagnosis.
COVID-19 recovered participants	Optical coherence tomography (OCT)	Participants with Sars-CoV-2 infection at least 3 months ago (positive PCR or positive rapid antibody test) which are fully recovered.
COVID-19 recovered participants	Handgrip strength test	Participants with Sars-CoV-2 infection at least 3 months ago (positive PCR or positive rapid antibody test) which are fully recovered.
COVID-19 recovered participants	Questionnaires (Patient reported outcomes)	Participants with Sars-CoV-2 infection at least 3 months ago (positive PCR or positive rapid antibody test) which are fully recovered.

Primary Outcome Measures

Name	Time	Method
PCS patients show an impaired retinal vessel responsiveness when compared with fully recovered COVID-19 participants.	Baseline	Static and dynamic parameters of the retinal vessel analysis.

Secondary Outcome Measures

Name	Time	Method
PCS patients with improved symptoms show a change in retinal vessel responsiveness after 6 months when compared with baseline parameters.	Baseline to month 6	Static and dynamic parameters of the retinal vessel analysis. Test items of the The COVID-19 Yorkshire Rehabilitation Scale (C19-YRS) and PCS questionnaire. Calculation of PCS severity scores (Bahmer, 2022) in each patient with a range of score values from zero (better outcome) to 59 (worse outcome). Comparison of retinal vessel parameters and PCS scores between Baseline and month 6.
PCS patients show a decrease in vessel density in OCT-A when compared with COVID-19 recovered participants.	Baseline	Parameters of OCT-A.
Symptom severity of PCS in patients correlates with impaired retinal vessel responsiveness.	Baseline	Correlation between PCS severity scores with static and dynamic parameters of the retinal vessel analysis.
PCS patients show an impaired retinal vessel responsiveness at baseline when compared with infection naïve participants.	Baseline	Static and dynamic parameters of the retinal vessel analysis.
PCS patients with impaired RVA analysis show elevated levels of markers of endothelial dysfunction and of chronic inflammation when compared with COVID-19 recovered cohort.	Baseline	Measurement of markers of endothelial dysfunction: Concentration of: sICAM, sVCAM, Thrombomodulin, P-Selectin,E-Selectin, ADMA, SADMA, Endothelin-1, ACE-1, ACE-2, ANG-2, GDF-15.; Measurement of markers of chronic inflammation Concentration of IFN-β, IFN-λ1,TNFa. Comparison of marker levels to the COVID-19 recovered cohort.
PCS patients with impaired RVA show a reactivation of EBV.	Baseline	Using PCR to measure EBV reactivation in patients plasma .
Characterization of immune cell composition in PCS patients and comparison with COVID-19 recovered and COVID-19 infection naïve participants.	Baseline	Using flow cytometry to detect different T-cell and monocyte subpopulations.

Trial Locations

Locations (1)

Klinikum rechts der Isar; 🇩🇪 München, Bavaria, Germany