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Glial activation among individuals with Neurological [PASC]: A Brain Fog Positron Emission Tomography Study of [18F]-FEPPA, 2025, Clouston+

Discussion in 'Long Covid research' started by Nightsong, Jan 17, 2025 at 1:51 AM.

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  1. Nightsong

    Nightsong Senior Member (Voting Rights)

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    Abstract
    Background: This study examined the regional distribution of glial activation in essential workers with neurological post-acute sequelae of coronavirus disease 2019 (COVID-19) infections (N-PASC).

    Methods: We injected ≤185 MBq of [18F]-FEPPA as an intravenous bolus and positron-emission tomography over two hours. To measure distribution volume (VT) we acquired an arterial input function in 24 essential workers (14 N-PASC, 10 Never-COVID-19 Controls, of whom eight successfully placed arterial lines). Individuals with low binding affinity were excluded from this study, and VT was adjusted for translocator protein genotype. Analyses that passed the false discovery rate are reported.

    Results: Participants at midlife survived mild to moderate COVID-19 without hospitalization but reported onset of post-acute sequelae for, on average, 22 months before undergoing neuroimaging. Hippocampal VT was higher (VT=1.70, 95% C.I. = [1.30-2.21], p=0.001) in participants with persistent brain fog after COVID-19, reflecting an increase of 10.58 ml/cm3 in VT (area under the receiver-operating curve, AUC= 0.95 [0.85-1.00]). At a cutoff of 10.6, sensitivity/specificity/accuracy were 0.88/0.93/0.91.

    Conclusion: The results from this study imply that neuroimmune response is a distinct and identifiable characteristic of brain fog after COVID-19. Results suggest that [18F]-FEPPA could be used to support PASC diagnosis.

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    Nightsong, Jan 17, 2025 at 1:51 AM
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  2. forestglip

    forestglip Senior Member (Voting Rights)

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    As far as I can tell, this is only comparing a group of people who had COVID and continue to have brain fog many months later, with a group who got scans before the pandemic. Seems premature to connect the difference in scans to brain fog specifically, but maybe there's some justification in the paper.
     
    forestglip, Jan 17, 2025 at 2:08 AM
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  3. Hutan

    Hutan Moderator Staff Member

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    Could be worth checking out those STROBE guidelines some time.

    N-PASC cohort: Non-hospitalised Covid-19 infection; lasting neurological symptoms including brain fog for at least 6 months and still present at teh time of scanning.
    Controls: people from the same monitoring program, prior to the pandemic, healthy at the time of scanning.

    Just by the way, on the use of TSPO scanning:
     
    Hutan, Jan 17, 2025 at 2:29 AM
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  4. Hutan

    Hutan Moderator Staff Member

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    So, a radioactive molecule that binds with TSPO, which is a marker of macrophage and microglia activation. The scanning then allowed 3D modelling of where in the brain the radioactive molecule showed up.

    The researchers also took samples of arterial blood to measure the uptake of the radioactive molecule. I'm not yet sure why they did that. I assume that if there was microglial activation, the radioactive molecule would have been pulled out of the blood quicker and bound to the TSPO. Maybe there was some adjustment based on the levels of the radioactive molecule in the blood. Anyway.
     
    Last edited: Jan 17, 2025 at 2:43 AM
    Hutan, Jan 17, 2025 at 2:36 AM
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  5. Hutan

    Hutan Moderator Staff Member

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    Although the abstract says 14, there were only 10 PASC participants.
    Edit: I think there is an error in the abstract. Table 1 suggests that there were 10 PASC participants and 14 controls.




    They then note that they weren't able to place an arterial line in 2 of the 10 people, so they only got scanning results for 8 people, but reported the demographic characteristics for 10 people.

    A study of 8 PASC people, for whom we don't know the demographic characteristics compared to the healthy controls is a bit thin. The 10 PASC people were already older on average compared to the healthy controls (61 years compared to 56).

    There do seem to be real differences between the two groups in the volume of brain found to express the radioactive ligand though, significantly higher in the PASC group.
     
    Last edited: Jan 17, 2025 at 3:46 AM
    Hutan, Jan 17, 2025 at 3:02 AM
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  6. Hutan

    Hutan Moderator Staff Member

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    Here's Figure 2. Top two rows are the PASC group; bottom two are the controls. Red indicates more radioactive ligand binding to the TSPO. As I said, there look to be real differences that differentiate the two groups but I've only skimmed the paper quickly and haven't understood all of it. I think it's worth a closer look, and following the research group's next move.


    Screen Shot 2025-01-17 at 4.05.28 pm.png

    It would be good to understand better what the symptoms of the PASC group are, to assess if they match with ME/CFS. They do some assessment of correlations between marker binding and cognitive symptoms within groups, but I don't think they found much. In fact they seemed to find that the people with more putative neuroinflammation were thinking better.
     
    Last edited: Jan 17, 2025 at 3:22 AM
    Hutan, Jan 17, 2025 at 3:16 AM
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  7. Hutan

    Hutan Moderator Staff Member

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    From the discussion:

    They suggest others have found evidence of what they describe as neuroinflammation (glial activation)
    They tried hard to think of explanations for the finding that more TSPO was related to better cognitive performance in the PASC group, suggesting that the glial activation is adaptive. But I think, when they are working with data from 8 people, hypothesising is a bit premature.
    They seem to be questioning if the TSPO binding really does indicate inflammation....
     
    Hutan, Jan 17, 2025 at 3:28 AM
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  8. EndME

    EndME Senior Member (Voting Rights)

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    From what I recall there was also a study by Hellemonds that tagged TSPO (the molecule used was a different one). They published a preprint that made it all over the news with 2 LC patients, but from what I've heard the full study actually had very mixed results (and hasn't been published yet even though it's been a few years). There have also been several other TSPO tagging studies in LC.

    Edit: This is the study I meant (Hellemonds wasn't actually part of it as it was other dutch researchers).
     
    Last edited: Jan 17, 2025 at 5:15 PM
    EndME, Jan 17, 2025 at 5:10 PM
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