Closed All eyes on PCS: analysis of the retinal microvasculature in patients with post-COVID syndrome—study protocol of 1 year prospective case–control study

[SNT Gatchaman]

All eyes on PCS: analysis of the retinal microvasculature in patients with post-COVID syndrome—study protocol of a 1 year prospective case–control study
Kuchler, Timon; Hausinger, Renate; Braunisch, Matthias C.; Günthner, Roman; Wicklein, Rebecca; Knier, Benjamin; Bleidißel, Nathalie; Maier, Matthias; Ribero, Andrea; Lech, Maciej; Adorjan, Kristina; Stubbe, Hans; Kotilar, Konstantin; Heemann, Uwe; Schmaderer, Christoph

Since widespread vaccination against COVID-19, the development of effective antiviral drugs, and the decreasing number of patients with COVID-19 in intensive care, the risk from SARS-CoV-2 infection appears less threatening. However, studies show that a significant number of patients suffer from long-term sequelae, even months after SARS-CoV-2 infection. The so-called post-COVID syndrome (PCS) often presents a diagnostic and treatment challenge for physicians.

This study protocol describes the “All Eyes on PCS” study, which aims to investigate the retinal microvasculature in PCS patients and COVID-19-recovered patients to provide new insights into the pathophysiology of PCS. “All Eyes on PCS” is a prospective, case–control study with the primary objective of detecting endothelial dysfunction (ED) in patients with PCS. Therefore, we intend to recruit patients with PCS, fully SARS-CoV-2-infection-recovered (CR) participants, and SARS-CoV-2-infection-naive (CN) participants. Baseline measurements will include: (1) patient-specific characteristics, (2) biochemistry, (3) retinal vessel analysis (RVA), (4) survey questionnaires as patient-reported outcomes measurements (PROMs), (5) optical coherence tomography (OCT), OCT angiography (OCTA), and adaptive optics (AO), (6) blood pressure recordings, (7) handgrip strength test.

After 6 months, baseline measurements will be repeated in the PCS cohort, and after 1 year, a telephone query will be conducted to assess residual symptoms and treatment needs. The aim of this study is to gain insight into the pathophysiology of PCS and to provide an objective biomarker for diagnosis and treatment, while also creating a comprehensive clinical database of PCS patients.

ClinicalTrials.gov Identifier: NCT05635552; Date: 2.12.2022.

Link | PDF (European Archives of Psychiatry and Clinical Neuroscience)

 

[Hutan]

While most of SARS-CoV-2-infected individuals fully recover after several weeks, symptoms such as shortness of breath, chest pain, cognitive dysfunction, fatigue, and palpitations persist for months in several patients, as do psychosocial symptoms such as depression, sleep disturbances, and agitation [15].

Agitation - really? Or just warranted concern that your whole life has been turned upside down and the medical profession and everyone you know keep wittering on about 'looking on the bright side', 'going for a walk' and 'sleep hygiene'?

One common symptom in patients with PCS is persistent fatigue, which often fulfills diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [23, 24]. Patients with ME/CFS also show ED which affects both small and large vessels [25].

Yeah, nah. ME/CFS does not equal fatigue.
Ref 25 is from the Fluge and Mella team - not in the retina I think.
Sørland K et al (2021) Reduced endothelial function in myalgic encephalomyelitis/chronic fatigue syndrome-results from open-label cyclophosphamide intervention study.

There is evidence suggesting that persistent ED is an independent marker of developing PCS and preliminary findings suggest that the retinal microcirculation may also be affected following severe SARS-CoV-2 infection [30, 31]. However, to our knowledge, until now retinal vessel analysis (RVA) has not been used in PCS patients to characterize ED.

I'm pretty sure we have seen a study looking at retinal vessels in Long Covid just the other day - ah yes - here. There was a problem with that study just looking at top layers of the retina though. In this study they will be looking at the deep layer as well as the superficial layer.

At baseline, mean values of retinal vessel densities of the superficial and deep vascular complex as well as size of the foveal avascular zone in both eyes will be measured for each cohort, respectively.

To examine the responsiveness of retinal vessels to flickering light as a surrogate for ED, we will use RVA and to further characterize the retinal microcirculation, we will include OCT angiography (OCTA) and adaptive optics (AO) measurements.

The primary objective of our study is to quantify retinal vessel responsiveness and vessel morphology using the Retinal Vessel Analyzer (RVA) in patients with PCS and compare these parameters to those of the CR and CN cohort.

The retinal vessel responsiveness is an interesting addition.

An impaired retinal microcirculation might prove as a strong and independent predictor of PCS, and therefore serve as an objective biomarker in diagnosis and therapy monitoring. Our objective is to establish a comprehensive biobank comprising individuals with PCS and those who have recovered from COVID-19, with the aim of investigating the pathophysiological mechanisms underlying PCS. The biobank will serve as a valuable resource aimed at understanding the molecular, cellular, and immunological aspects of PCS and help identify potential targets for intervention.

These people sound as though they may be committing to a substantial effort with the aim of understanding the disease. Which is fantastic.
The list of secondary objectives is long.

(1)To collect patient-reported symptoms (PROMs), assess PCS symptom severity, and then correlate these findings with RVA parameters at baseline.

(2)To monitor the development of symptom severity of PCS and endothelial function after 6 months in the PCS cohort.

(3)To conduct an in-depth study of the retina microcirculation using OCTA and AO.

(4)To classify patients based on the different organ systems affected by PCS and compare RVA parameters between these groups.

(5)To quantify fatigue in patients using the handgrip strength test as a measure of excessive fatiguability.

(6)To use cell culture experiments on retinal epithelial and endothelial cells to explain a possible phenotype of ED in PCS patients.

(7)To characterize the immune phenotype of T cell and monocyte subpopulations in PCS patients
.
(8)To investigate the potential contribution of virus reactivation, specifically Epstein–Barr virus (EBV), to ED in PCS patients.

(9)To establish a possible link between ED and the development of autonomic dysfunction by measuring basal cortisol levels in PCS patients.

Of course, cortisol is there ... such a red herring, in my view.

 

[Hutan]

I'm not clear on whether at least the first part of the study this protocol is for has been completed and published. I think maybe it has.

 

[EndME]

I'm not clear on whether at least the first part of the study this protocol is for has been completed and published. I think maybe it has.

Indeed. Some parts of the study have been published and discussed here
Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation.

 

[Andy]

The protocol says that recruitment will last until end of Q2 2023 so I doubt that this is still open.

 

[SNT Gatchaman]

Hard to know: says "recruiting" but last updated a year ago. I've changed the prefix to closed in case it's more useful to track the overall landscape.