SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations post recovery, 2022, Frere et al

Discussion in 'Long Covid research' started by SNT Gatchaman, Jun 11, 2022.

  1. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations post recovery
    Justin J. Frere, Randal A. Serafini, Kerri D. Pryce, Marianna Zazhytska, Kohei Oishi, Ilona Golynker, Maryline Panis, Jeffrey Zimering, Shu Horiuchi, Daisy A. Hoagland, Rasmus Møller, Anne Ruiz, Albana Kodra, Jonathan B. Overdevest, Peter D. Canoll, Alain C. Borczuk, Vasuretha Chandar, Yaron Bram, Robert Schwartz, Stavros Lomvardas, Venetia Zachariou, Benjamin R. tenOever

    The host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in prolonged pathologies collectively referred to as post-acute sequalae of COVID-19 (PASC) or long COVID.

    To better understand the mechanism underlying long COVID biology, we compared the short- and long-term systemic responses in the golden hamster following either SARS-CoV-2 or influenza A virus (IAV) infection.

    Results demonstrated that SARS-CoV-2 exceeded IAV in its capacity to cause permanent injury to the lung and kidney and uniquely impacted the olfactory bulb (OB) and epithelium (OE). Despite a lack of detectable infectious virus, the OB and OE demonstrated myeloid and T cell activation, proinflammatory cytokine production, and an interferon response that correlated with behavioral changes extending a month post viral clearance.

    These sustained transcriptional changes could also be corroborated from tissue isolated from individuals who recovered from COVID-19. These data highlight a molecular mechanism for persistent COVID-19 symptomology and provide a small animal model to explore future therapeutics.

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  2. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    They used ancestral SARS-CoV-2 so may not be as applicable to newer variants. They compared to influenza A (IAV). The paper suggests that they potentially have an animal model of Long Covid, albeit with limitations against corroboration with humans due to inability to biopsy CNS in patients with mild-moderate disease who don't succumb in the relevant timeframe.

     
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  3. Hutan

    Hutan Moderator Staff Member

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    This is an interesting paper, with a lot of analyses. But the study on anxiety/mood changes didn't seem very good.
    So, they have this test, supposedly for 'elevated compulsiveness or anxiety-like behaviours' - the number of marbles at least 60% buried by each hamster at 26 days after infection. Clearly, I'm no expert on the behaviour of hamsters, but not burying marbles doesn't sound like 'elevated compulsiveness'. Indeed this study:
    Pharmacological evaluation of the adequacy of marble burying as an animal model of compulsion and/or anxiety
    concluded
    Furthermore, the literature suggests an increase in marble-burying behaviour is regarded as a sign of increased OCD-ness; diazepam (valium) decreases marble-burying behaviour. The study that is the subject of this thread reports that the previously infected hamsters buried less marbles. Therefore, one interpretation is that they actually became less anxious.


    The text claims that the marble-burying study is evidence of behavioural changes caused by the SARS-CoV-2 infection.

    But, look at the chart:
    Screen Shot 2022-06-11 at 2.59.05 pm.png
    The differences are not statistically significant. Furthermore, the text under the chart says that they removed an outlier from the SARS-CoV-2 group. But they seem to have kept in two outliers in the mock infection group. So, it really doesn't matter whether the marble-burying test is useful or not. The results of this study do not suggest a difference in marble-burying behaviour, certainly not beyond what you might expect in animals recovering from any infection.

    The problem partly originates in the really sloppy epidemiological studies of Long Covid that claim to find increased anxiety as an intrinsic part of the post-acute Covid-19 syndrome. For example, this study's abstract says:
    But, when we look at the various studies reporting increased anxiety in humans, we find very little to support this idea. And yet, the idea prevails. And although this study found no evidence to support increased anxiety in post-infected animals, and arguably a slight trend to suggest the opposite, the authors have not said that. And so, this idea of increased anxiety (beyond what is an entirely normal response to having an illness that isn't going away and that prevents you from earning a living and doing much of what you love and that there is no cure for) continues.
     
    Last edited: Jun 11, 2022
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