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SARS-CoV-2 is associated with changes in brain structure in UK Biobank, 2022, Douaud et al

Discussion in 'Epidemics (including Covid-19, not Long Covid)' started by Andy, Jun 17, 2021.

  1. Andy

    Andy Committee Member

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    Hampshire, UK
    Abstract from 2021 preprint

    There is strong evidence for brain-related pathologies in COVID-19, some of which could be a consequence of viral neurotropism. The vast majority of brain imaging studies so far have focused on qualitative, gross pathology of moderate to severe cases, often carried out on hospitalised patients. It remains unknown however whether the impact of COVID-19 can be detected in milder cases, in a quantitative and automated manner, and whether this can reveal a possible mechanism for the spread of the disease. UK Biobank scanned over 40,000 participants before the start of the COVID-19 pandemic, making it possible to invite back in 2021 hundreds of previously-imaged participants for a second imaging visit.

    Here, we studied the effects of the disease in the brain using multimodal data from 782 participants from the UK Biobank COVID-19 re-imaging study, with 394 participants having tested positive for SARS-CoV-2 infection between their two scans.

    We used structural and functional brain scans from before and after infection, to compare longitudinal brain changes between these 394 COVID-19 patients and 388 controls who were matched for age, sex, ethnicity and interval between scans.

    We identified significant effects of COVID-19 in the brain with a loss of grey matter in the left parahippocampal gyrus, the left lateral orbitofrontal cortex and the left insula. When looking over the entire cortical surface, these results extended to the anterior cingulate cortex, supramarginal gyrus and temporal pole.

    We further compared COVID-19 patients who had been hospitalised (n=15) with those who had not (n=379), and while results were not significant, we found comparatively similar findings to the COVID-19 vs control group comparison, with, in addition, a greater loss of grey matter in the cingulate cortex, central nucleus of the amygdala and hippocampal cornu ammonis (all |Z|>3).

    Our findings thus consistently relate to loss of grey matter in limbic cortical areas directly linked to the primary olfactory and gustatory system. Unlike in post hoc disease studies, the availability of pre-infection imaging data helps avoid the danger of pre-existing risk factors or clinical conditions being mis-interpreted as disease effects.

    Since a possible entry point of the virus to the central nervous system might be via the olfactory mucosa and the olfactory bulb, these brain imaging results might be the in vivo hallmark of the spread of the disease (or the virus itself) via olfactory and gustatory pathways.

    https://www.medrxiv.org/content/10.1101/2021.06.11.21258690v1.full-text (June 15 2021 version - 'Brain imaging before and after COVID-19 in UK Biobank')


    Link to final paper
    here; 2022 abstract below:
    Abstract from 2022 published paper

    There is strong evidence for brain-related abnormalities in COVID-191–13. It remains unknown however whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here, we investigated brain changes in 785 UK Biobank participants (aged 51–81) imaged twice, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans, with 141 days on average separating their diagnosis and second scan, and 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects.

    We identified significant longitudinal effects when comparing the two groups, including: (i) greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, (ii) greater changes in markers of tissue damage in regions functionally-connected to the primary olfactory cortex, and (iii) greater reduction in global brain size. The infected participants also showed on average larger cognitive decline between the two timepoints. Importantly, these imaging and cognitive longitudinal effects were still seen after excluding the 15 cases who had been hospitalised.

    These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease via olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious impact can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow up.
     
    Last edited by a moderator: Mar 7, 2022
  2. Hutan

    Hutan Moderator Staff Member

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    Location:
    Aotearoa New Zealand
    Excellent to see the use of biobanks for longitudinal research. It seems like a nice study.

    I thought this was interesting.
    They compared nearly 400 people who had had Covid-19 with nearly 400 who had not - that's a big sample. But, if they just relied on the comparison at that single time-point, they would have concluded that there was a particular difference in the brains of the two groups. But, because they had the scans of these people before the pandemic, they could see that that difference was there before some got the disease - so the difference was not due to the disease process.

    It puts the findings of brain-imaging studies of 5 or even 20 people with ME/CFS and matched healthy controls into perspective.

    It sounds as though there will be more imaging done, and hopefully some analysis of scans of people who have me/cfs-like Long Covid symptoms vs those that do not.
     
  3. Andy

    Andy Committee Member

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    20,360
    Location:
    Hampshire, UK
    Possibly worth noting that there are a certain number of people in the UK Biobank who self-report a diagnosis of ME/CFS, although I'm not sure if it would be possible to see if any of those are among the cohort discussed in this paper.
     
  4. Cheshire

    Cheshire Moderator Staff Member

    Messages:
    4,674
    Now published

    SARS-CoV-2 is associated with changes in brain structure in UK Biobank

    There is strong evidence for brain-related abnormalities in COVID-191–13. It remains unknown however whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here, we investigated brain changes in 785 UK Biobank participants (aged 51–81) imaged twice, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans, with 141 days on average separating their diagnosis and second scan, and 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects.

    We identified significant longitudinal effects when comparing the two groups, including: (i) greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, (ii) greater changes in markers of tissue damage in regions functionally-connected to the primary olfactory cortex, and (iii) greater reduction in global brain size. The infected participants also showed on average larger cognitive decline between the two timepoints.

    Importantly, these imaging and cognitive longitudinal effects were still seen after excluding the 15 cases who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease via olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious impact can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow up.

    https://www.nature.com/articles/s41586-022-04569-5
     
    Last edited: Mar 7, 2022
    Simon M, Andy, Hutan and 4 others like this.
  5. Hutan

    Hutan Moderator Staff Member

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    Location:
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    I note the change in the title of the paper:

    June 2021: Brain imaging before and after COVID-19 in UK Biobank

    March 2022: SARS-CoV-2 is associated with changes in brain structure in UK Biobank

    I've added the new abstract (which also materially differs) to the first post.
     
    Last edited: Mar 7, 2022
  6. NelliePledge

    NelliePledge Moderator Staff Member

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    This was covered on the main BBC TV news tonight so quite a big reach.
     
    Grigor, MEMarge, Wonko and 1 other person like this.
  7. Milo

    Milo Senior Member (Voting Rights)

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    Last edited by a moderator: Dec 12, 2022

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