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Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation, 2021, Fernandez, Monje, Nath et al

Discussion in 'Long Covid research' started by Andy, Jan 12, 2022.

  1. Andy

    Andy Committee Member

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    Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain

    Preprint Abstract

    Survivors of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection frequently experience lingering neurological symptoms, including impairment in attention, concentration, speed of information processing and memory. This long-COVID cognitive syndrome shares many features with the syndrome of cancer therapy-related cognitive impairment (CRCI). Neuroinflammation, particularly microglial reactivity and consequent dysregulation of hippocampal neurogenesis and oligodendrocyte lineage cells, is central to CRCI.
    We hypothesized that similar cellular mechanisms may contribute to the persistent neurological symptoms associated with even mild SARS-CoV-2 respiratory infection.

    Here, we explored neuroinflammation caused by mild respiratory SARS-CoV-2 infection, without neuroinvasion, and effects on hippocampal neurogenesis and the oligodendroglial lineage. Using a mouse model of mild respiratory SARS-CoV-2 infection induced by intranasal SARS-CoV-2 delivery, we found white matter-selective microglial reactivity, a pattern observed in CRCI. Human brain tissue from 9 individuals with COVID-19 or SARS-CoV-2 infection exhibits the same pattern of prominent white matter-selective microglial reactivity. In mice, pro-inflammatory CSF cytokines/chemokines were elevated for at least 7-weeks post-infection; among the chemokines demonstrating persistent elevation is CCL11, which is associated with impairments in neurogenesis and cognitive function. Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects). Impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss in subcortical white matter were evident at 1 week, and persisted until at least 7 weeks, following mild respiratory SARS-CoV-2 infection in mice.

    Taken together, the findings presented here illustrate striking similarities between neuropathophysiology after cancer therapy and after SARS-CoV-2 infection, and elucidate cellular deficits that may contribute to lasting neurological symptoms following even mild SARS-CoV-2 infection.

    https://www.biorxiv.org/content/10.1101/2022.01.07.475453v1

    Mod note: The abstract of the final version is below
     
    Last edited by a moderator: Jul 5, 2022
    merylg, Nightsong, Hutan and 14 others like this.
  2. rvallee

    rvallee Senior Member (Voting Rights)

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    How nice it would have been if brain fog hadn't been dismissed forever, we could have compared with other cohorts with brain fog. At least chemo fog seems a good proxy for it, but it's pretty amazing that something this important having been dismissed for decades is apparently of no concern to anyone but those suffering. Literally not even bothering giving this crippling symptomology a name. Still not even happening yet.

    Cognitive dysfunction is simply inadequate, frankly. Too vague. Man, does medicine need to get their language straightened up, it's embarrassing to be this dysfunctional at basic vocabulary. Imagine still being stuck at the first level for decades and not being bothered by it. I frankly can't.
     
    merylg, Chris, Amw66 and 3 others like this.
  3. Kalliope

    Kalliope Senior Member (Voting Rights)

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  4. Kalliope

    Kalliope Senior Member (Voting Rights)

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    Wyva, Chris, cfsandmore and 1 other person like this.
  5. Samuel

    Samuel Senior Member (Voting Rights)

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    what is a good definition of brain fog? my symptoms include extreme crippling versions of some aspects of executive dysfunction.

    which itself gets confusing compared to autistic inertia and non-hyperactive add.

    part of the mix is extreme problems with decsion making, planning, scheduling and for lack of a better term GETTING THINGS DONE [i wish i could make this more specific]. also initiating and completing tasks. sequencing, prioritizing, doing, doing without stress pem.

    getting things done can include a project [/listing/ desperately needed vitamins to be ordered can take years to accomplish] or merely reaching out to get food when i am hungry that i was told repeatedly is there. just reaching the arm out is for some reason not possible.

    i want a name and credible diagnosis for stuff like that. this is NOT normal. but idk if fits with paper or with brain fog definitions.

    also stm and remembering that something is there or that i need to do something at a time or at all. todo lists completely unmanageable.

    which of those things, if any, are brain fog, vs. other stuff? like from the paper.

    paper abstract> impairment in attention, concentration, speed of information processing and memory

    is this specified in detail in teh paper or in standard credible neuro tests or ugh questionnaires?
     
    Last edited: Jan 17, 2022
  6. Trish

    Trish Moderator Staff Member

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    Milo likes this.
  7. rvallee

    rvallee Senior Member (Voting Rights)

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    Merged thread

    Full title: Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation
    Authors: 17 authors including Avindra Nath, Akiko Iwasaki, David Putrino
    Published: June 12, 2022
    Journal: Cell
    Open access: https://www.cell.com/cell/fulltext/S0092-8674(22)00713-9


    COVID survivors frequently experience lingering neurological symptoms that resemble cancer therapy-related cognitive impairment, a syndrome for which white-matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared to SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis and elevated CCL11 at early timepoints, but after influenza only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.
     
    Last edited by a moderator: Jul 5, 2022
  8. rvallee

    rvallee Senior Member (Voting Rights)

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    Hutan, SNT Gatchaman, Ron and 4 others like this.
  9. leokitten

    leokitten Senior Member (Voting Rights)

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  10. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Capturing some of Dr. Monje's sub-tweets from the above thread. (My bolding)

     
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