Post-COVID-19 syndrome: retinal microcirculation as a potential marker for chronic fatigue, 2022, Schlick et al

Discussion in 'Long Covid research' started by SNT Gatchaman, Sep 24, 2022.

  1. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Post-COVID-19 syndrome: retinal microcirculation as a potential marker for chronic fatigue
    Sarah Schlick, Marianna Lucio, Alexander Johannes Bartsch, Adam Skornia, Jakob Hoffmanns, Charlotte Szewczykowski, Thora Schroeder, Franzi Raith, Lennart Rogge, Felix Heltmann, Michael Moritz, Lorenz Beitlich, Julia Schottenhamml, Martin Herrmann, Thomas Harrer, Marion Ganslmayer, Friedrich E. Kruse, Robert Laemmer, Christian Mardin, Bettina Hohberger

    Post-COVID-19 syndrome (PCS) summarizes persisting sequelae after infection with the severe-acute-respiratory-syndrome-Coronavirus-2 (SARS-CoV-2). PCS can affect patients of all covid-19 disease severities. As previous studies revealed impaired blood flow as a provoking factor for triggering PCS, it was the aim of the present study to investigate a potential association of self-reported chronic fatigue and retinal microcirculation in patients with PCS, potentially indicating an objective biomarker.

    A prospective study was performed, including 201 subjects: 173 patients with PCS and 28 controls. Retinal microcirculation was visualized by OCT-Angiography (OCT-A) and quantified by the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic Fatigue (CF) was assessed with the variables Bell score, age and gender. The VD in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed considering the repetitions (12 times).

    Taking in account of such repetitions a mixed model was performed to detect possible differences in the least square means between different groups of analysis. An age effect on VD was observed between patients and controls (p<0.0001). Gender analysis yielded that women with PCS showed lower VD levels in SVP compared to male patients (p=0.0015). The PCS patients showed significantly lower VD of ICP as compared to the controls (p=0.0001, [CI: 0.32; 1]). Moreover, considering PCS patients, the mixed model reveals a significant difference between chronic fatigue (CF) and without CF in VD of SVP (p=0.0033, [CI: -4.5; -0.92]). The model included age, gender and the variable Bell score, representing a subjective marker for CF.

    Consequently, the retinal microcirculation might be an objective biomarker in subjective-reported chronic fatigue of patients with PCS.

    Link | PDF (MedRxiv)

    See post #3 for link to published paper.
     
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  2. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    DCP = deep capillary plexus
    ICP = intermediate capillary plexus
    PCS = post-covid syndrome
    SCP = superficial capillary plexus
    VD = vessel density

    See also Sex-Specific Characteristics of the Microcirculation
     
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  3. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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  4. Hutan

    Hutan Moderator Staff Member

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    I want this idea of reduced retinal capillaries to be true. But the differences between the post-covid-19 syndrome results and those of the controls seems so small as a percentage of the total numbers:

    They had to adjust for age and gender. Figure 1 just doesn't look that convincing, and I'm not even sure that there really is an age effect.

    See for example Fig 1a for the superficial vascular plexus layer. What seems to be happening is that most of the people with PCS look like the healthy controls, but there are a substantial number of 'outliers' with much lower vessel densities.

    I've found this paper hard to get to grips with. I don't fully understand Figure 2. What do others think?
     
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  5. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    That figure 2 is confusing and the 95% prediction ellipse is obscured, which isn't helpful.

    As a general comment though: in comparison to the capillary decrease that can be seen in muscle, perhaps the retina is relatively protected or resilient. (Perhaps from an evolutionary perspective, if you can avoid the predator altogether you don't have to run fast). If the retinal function had been more easily compromised, that would be overt and we might have had something like a "Day of the Triffids" scenario. However, when researchers look, they find — even if the changes are not marked. The eye is the window to the vasculature (as well as the soul) but will be a clue and not be fully representative.

    From the thread Assessment of early and long-COVID related retinal neurodegeneration with optical coherence tomography (2022) —

    That paper also says —

    That last sentence references —

    Study of inner retinal neurodegeneration in Diabetes Mellitus using spectral domain optical coherence tomography (2021)
    Neurodegeneration in Patients with Type 2 Diabetes Mellitus without Diabetic Retinopathy (2019)

    See also
    Retinal vessels modifications in acute and post-COVID-19 (2021)
    The impact of acute COVID-19 on the retinal microvasculature assessed with multimodal imaging (2022)
     
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  6. duncan

    duncan Senior Member (Voting Rights)

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    Again, I am brought back to VEGF.

    Wish they were talking cognitive decline....
     
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  7. Hutan

    Hutan Moderator Staff Member

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    That study looks at acute Covid-19.
    They didn't find any difference between hospitalised patients and controls with respect to vessel density.
     
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  8. Hutan

    Hutan Moderator Staff Member

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    I don't understand @duncan, what is the link?
     
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  9. duncan

    duncan Senior Member (Voting Rights)

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    Sorry. I'm tired. This link is worrisome to me. I'm probably wrong. But who of us has tested our serum VEGF? I have over several years, off and on. What cursory searching I've found is that often it doesn't have a good outcome, at least with cognitive stuff. I test weird so of course I wonder. Sorry to hog conversation. But I've done some digging and the cognitive stuff concerns me. I apologize for commanding too much bandwidth.

    High Vegf has a bad look looking at most things. Look at low Vegf.
     
    Last edited: Feb 18, 2023
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  10. Hutan

    Hutan Moderator Staff Member

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    No need to apologise, you don't. Besides, people posting is what keeps the forum alive. I'll make a thread to discuss it, if we don't have one.

    Here: VEGF - Vascular Endothelial Growth Factor
     
    Last edited: Feb 18, 2023
  11. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    True, but I thought it was a good recent paper that shows some of the complexities of assessment and gives an overview and references prior literature —

    Yes, but I thought this point from that same paper was important (I hope it's ok to keep in this thread) —

    This last point was made in the context of experienced independent raters, with good reliability. (MAD reliability not given I think.)

     
  12. Hutan

    Hutan Moderator Staff Member

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    I've tried again, but it still does my head in a bit.

    So, for the whole sample, the controls had a mean vessel density in the SVP of 30.1. The paper makes a big thing of patients with the symptom of chronic fatigue (CF). This group (with fatigue as one of the symptoms of their post-covid illness) had a mean of 30.3, slightly higher than the controls. People without chronic fatigue but with persisting symptoms had 27.6. For example, here's the abstract:
    How can retinal microcirculation be an objective biomarker for chronic fatigue in post-Covid syndrome, if the retinal density is basically the same in people with chronic fatigue and in the controls? I don't think I've seen an analysis of how different those two groups are - the authors just compare the groups with and without chronic fatigue within the bigger group with persisting symptoms.
     
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