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Preprint Long COVID is associated with extensive in-vivo neuroinflammation on [18F]DPA-714 PET, 2022, Visser et al

Discussion in 'Long Covid research' started by SNT Gatchaman, Jun 5, 2022.

  1. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Long COVID is associated with extensive in-vivo neuroinflammation on [18F]DPA-714 PET (Preprint)
    Denise Visser, Sandeep S.V. Golla, Sander C.J. Verfaillie, Emma M. Coomans, Roos M. Rikken, Elsmarieke M. van de Giessen, Marijke E. den Hollander, Anouk Verveen, Maqsood Yaqub, Frederik Barkhof, Janneke Horn, Bart Koopman, Patrick Schober, Dook W. Koch, Robert C. Schuit, Albert D. Windhorst, Michael Kassiou, Ronald Boellaard, Michele van Vugt, Hans Knoop, Nelleke Tolboom, Bart N.M. van Berckel

    A significant number of COVID-19 patients develop 'long COVID', a condition defined by long-lasting debilitating, often neurological, symptoms. The pathophysiology of long COVID is unknown.

    Here we present in-vivo evidence of widespread neuroinflammation in long COVID, using a quantitative assessment, [18F]DPA-714 PET, in two long COVID patients. We reanalyzed historical data from three matched healthy control subjects, for comparison purposes. Both patients with long COVID had widespread increases in [18F]DPA-714 binding throughout the brain. Quantitative measures of binding (BPND values) were increased on average by 121% and 76%, respectively.

    This implicates profound neuroinflammation in the pathophysiology of long COVID.

    Link | PDF
     
    Hutan, RedFox, Ariel and 14 others like this.
  2. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    The radio tracer DPA-714 is a translator protein (TSPO). See here and related comments here. See also Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation (2012).

     
  3. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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  4. Braganca

    Braganca Senior Member (Voting Rights)

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  5. Forbin

    Forbin Senior Member (Voting Rights)

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    Might have been interesting to know when the patient scans were made relative to their infections. The "first patient" became ill in December 2020, while the "second patient" became ill 9 months earlier in March. If the scans were done at the same time, the stronger intensity of patient 1's scan might reflect his more recent infection. Patient 2 was female, so a sex difference might also be a factor. Regardless, the scans of both patients are obviously dramatically different from the controls.
     
  6. adambeyoncelowe

    adambeyoncelowe Senior Member (Voting Rights)

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    I'm cautious. Obviously, the Nakatomi paper used PET to find glial activation in ME, so this feels like a logical finding for LC, but this is still just two patients.
     
  7. Braganca

    Braganca Senior Member (Voting Rights)

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    The James lab also had preliminary findings as stated on the page I referenced above: “Our encouraging preliminary data shows increased [11C]DPA-713-PET signal in multiple brain regions of severe ME/CFS patients compared to healthy controls.”

    it seems that this type of TSPO imaging agent finds abnormalities in a lot of CNS disorders. This paper reviewing types of radioligands describes some of the limitations of second gen agents. I don’t understand exactly if any TSPO agents are currently commercialized or if they are all used in research setting. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650818/
     
  8. LarsSG

    LarsSG Senior Member (Voting Rights)

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    If these findings hold up in a larger cohort (or show up in ME patients), it seems like this could be pretty significant. It might also be really interesting to see if LDN or Abilify treatment would change the results in follow up scans on the same patients. Perhaps this could give us some idea if the theorized anti-inflammatory effects of these two drugs are real.

    They say in their trial registration that the actual start date was February of this year, so it seems they were at a minimum 14 and 23 months after infection. It looks like they plan to enrol 20 patients in the study, hopefully we'll see more results soon.
     
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  9. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    A related pre-print (it can have it's own thread if needed on acceptance).

    SARS-CoV-2 infection of human brain microvascular endothelial cells leads to inflammatory activation through NF-κB non-canonical pathway and mitochondrial remodeling (Pre-print, Jun 2022)

     
  10. Grigor

    Grigor Senior Member (Voting Rights)

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    Note that Hans 'CBT' Knoop is a co-author. He's trying to get the effect of CBT objectified by showing in decreased neuroinflammation.
     
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  11. Braganca

    Braganca Senior Member (Voting Rights)

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