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

Endothelial Dysfunction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05635552
• Other study ID #: 2022317PCS
• Status: Recruiting
• Start date: October 17, 2022
• Est. completion date: July 21, 2023

Study information

• Verified date: November 2022
• Source: Technical University of Munich
• Contact: Christoph Schmaderer, Prof. Dr.
• Phone: 089 4140 5053
• Email: christoph.schmaderer[@]mri.tum.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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?

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: July 21, 2023
• Est. primary completion date: February 21, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Endothelial Dysfunction

Intervention

Diagnostic Test:
• Dynamic retinal vessel analysis (DVA)
DVA is an established, non-invasive tool to measure the responsiveness of retinal vessels to flickering light. In addition static retinal vessel parameters are recorded.
• Optical coherence tomography (OCT)
OCT is an imaging technique which applies low-coherence light to capture high resolution images from the ocular fundus.
• Biochemistry and immune phenotyping
Blood sample collection for clinical chemistry and isolation of PBMCs for FACS analysis.
• Handgrip strength test
Measure the maximum isometric strength of the hand and forearm muscles and their fatiguability.
• Questionnaires (Patient reported outcomes)
The questionnaires evaluate anxiety, depression, chronic fatigue, quality of life, and post-covid typical symptoms

Locations

Country	Name	City	State
Germany	Klinikum rechts der Isar	München	Bavaria

Sponsors (2)

Lead Sponsor	Collaborator
Technical University of Munich	Ludwig-Maximilians - University of Munich

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Bahmer T, Borzikowsky C, Lieb W, Horn A, Krist L, Fricke J, Scheibenbogen C, Rabe KF, Maetzler W, Maetzler C, Laudien M, Frank D, Ballhausen S, Hermes A, Miljukov O, Haeusler KG, Mokhtari NEE, Witzenrath M, Vehreschild JJ, Krefting D, Pape D, Montellano FA, Kohls M, Morbach C, Stork S, Reese JP, Keil T, Heuschmann P, Krawczak M, Schreiber S; NAPKON study group. Severity, predictors and clinical correlates of Post-COVID syndrome (PCS) in Germany: A prospective, multi-centre, population-based cohort study. EClinicalMedicine. 2022 Jul 18;51:101549. doi: 10.1016/j.eclinm.2022.101549. eCollection 2022 Sep. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PCS patients show an impaired retinal vessel responsiveness when compared with fully recovered COVID-19 participants.	Static and dynamic parameters of the retinal vessel analysis.	Baseline
Secondary	PCS patients show an impaired retinal vessel responsiveness at baseline when compared with infection naïve participants.	Static and dynamic parameters of the retinal vessel analysis.	Baseline
Secondary	PCS patients with improved symptoms show a change in retinal vessel responsiveness after 6 months when compared with baseline parameters.	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.	Baseline to month 6
Secondary	Symptom severity of PCS in patients correlates with impaired retinal vessel responsiveness.	Correlation between PCS severity scores with static and dynamic parameters of the retinal vessel analysis.	Baseline
Secondary	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.	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-ß, IFN-?1,TNFa. Comparison of marker levels to the COVID-19 recovered cohort.	Baseline
Secondary	PCS patients with impaired RVA show a reactivation of EBV.	Using PCR to measure EBV reactivation in patients plasma .	Baseline
Secondary	Characterization of immune cell composition in PCS patients and comparison with COVID-19 recovered and COVID-19 infection naïve participants.	Using flow cytometry to detect different T-cell and monocyte subpopulations.	Baseline
Secondary	PCS patients show a decrease in vessel density in OCT-A when compared with COVID-19 recovered participants.	Parameters of OCT-A.	Baseline