Trial Report Bulk RNA sequencing for analysis of post COVID-19 condition in adolescents and young adults, 2024, Sommen

Discussion in 'Long Covid research' started by Dolphin, Mar 28, 2024.

  1. Dolphin

    Dolphin Senior Member (Voting Rights)

    Messages:
    5,141
    Free fulltext:
    https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-05117-7
    Bulk RNA sequencing for analysis of post COVID-19 condition in adolescents and young adults
    Journal of Translational Medicine volume 22, Article number: 312 (2024) Cite this article

    Abstract
    Background
    Post COVID-19 condition (PCC) is a complication of SARS-COV-2 infection and can lead to long-term disability.

    Methods
    The present study was designed to analyse the gene expression patterns of PCC through bulk RNA sequencing of whole blood and to explore the potential molecular mechanisms of PCC. Whole blood was collected from 80 participants enrolled in a prospective cohort study following SARS-CoV-2 infected and non-infected individuals for 6 months after recruitment and was used for bulk RNA sequencing. Identification of differentially expressed genes (DEG), pathway enrichment and immune cell deconvolution was performed to explore potential biological pathways involved in PCC.

    Results
    We have found 13 differentially expressed genes associated with PCC. Enriched pathways were related to interferon-signalling and anti-viral immune processes.

    Conclusion
    The PCC transcriptome is characterized by a modest overexpression of interferon-stimulated genes, pointing to a subtle ongoing inflammatory response.

     
    Last edited: Mar 28, 2024
    Hutan and Kitty like this.
  2. Dolphin

    Dolphin Senior Member (Voting Rights)

    Messages:
    5,141
    I noticed that biopsychosocial proponent Vegard Bruun Bratholm Wyller is one of the co-authors though in the least important position.

    Another co-author is Joel Selvakumar.
    That's not a name that is familiar to me but here is his Twitter profile:
    Paediatrician. PhD student @UniOslo. ‘Long COVID’, child health, overdiagnosis. Father of
     
    Hutan and Kitty like this.
  3. Dolphin

    Dolphin Senior Member (Voting Rights)

    Messages:
    5,141
  4. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

    Messages:
    4,514
    Location:
    Aotearoa New Zealand
    Last edited: Mar 30, 2024
    Hutan and Kitty like this.
  5. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

    Messages:
    4,514
    Location:
    Aotearoa New Zealand
    Hutan, Kitty, Amw66 and 1 other person like this.
  6. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

    Messages:
    4,514
    Location:
    Aotearoa New Zealand
     
    Hutan and Kitty like this.
  7. Eleanor

    Eleanor Established Member (Voting Rights)

    Messages:
    68
    "The biological factors in PCC, such as immune activation, might be the result of a conditioning mechanism by chronic stress"

    ... if we ignore all the cases in which there was no chronic stress. No need to even think about them. Just stick our fingers in our ears and sing la la la and they'll go away.
     
    Hutan, Kitty, Sean and 1 other person like this.
  8. Midnattsol

    Midnattsol Moderator Staff Member

    Messages:
    3,613
    Selvkuumar has multiple times on twitter defended the notion that children have symptoms of long covid due to "long lockdown" and being scared. Explaining what stress can to do the body to the children (and their parents) they will feel empowered and complaints will reduce.
     
    Grigor, SNT Gatchaman, Sean and 4 others like this.
  9. rvallee

    rvallee Senior Member (Voting Rights)

    Messages:
    12,552
    Location:
    Canada
    Given this, how does it even make sense to do RNA analysis? What possible relevance could this possibly have in a "long lockdown" model?

    Or I guess the philosopher's stone of psychosomatic ideologues everywhere is finding evidence of psychology influencing biology, nevermind that in all cases they are overlooking the actual biological cause. In the sense that it's just a myth and they'll never find it. But it still seems obvious that this person's biases make them useless contributors to this kind of research at best.
     
    Last edited by a moderator: Apr 1, 2024
    Sean and Kitty like this.
  10. Midnattsol

    Midnattsol Moderator Staff Member

    Messages:
    3,613
    Not the first time BPS throws in som biomedical stuff they can then point to and say "see, we look at that too".
     
    Sean, Kitty, Trish and 3 others like this.
  11. Hutan

    Hutan Moderator Staff Member

    Messages:
    27,121
    Location:
    Aotearoa New Zealand
    So
    SARS+F+: 20 participants SARS-CoV-2 positive; high fatigue (numerical CFQ>=21); meeting WHO PCC and Fukuda criteria
    SARS+F-: 20 participants SARS-CoV-2 positive; low fatigue (numerical CFQ<=11); not meeting WHO PCC and Fukuda criteria
    SARS-F+: 20 participants SARS-CoV-2 negative; high fatigue (bimodal CFQ>=4)
    SARS-F-: 20 participants SARS-CoV-2 negative; low fatigue ('not reporting fatigue'), not meeting WHO PCC and Fukuda criteria

    That's already looking a bit odd - they used a different method to identify SARS-CoV-2-negative participants with high fatigue. Figure 1 shows that the SARS-F+ group did not all meet WHO PCC and did not all meet Fukuda criteria

    They don't say how they selected the 20 participants for each group from the larger numbers qualifying.
    All participants female.
     
    SNT Gatchaman, Sean and Kitty like this.
  12. Hutan

    Hutan Moderator Staff Member

    Messages:
    27,121
    Location:
    Aotearoa New Zealand
    The 13 differentially expressed genes are between the SARS+F+ group and the SARS+F- group. That's good. Although 20 people is not a big sample.
     
    SNT Gatchaman, Sean and Kitty like this.
  13. Hutan

    Hutan Moderator Staff Member

    Messages:
    27,121
    Location:
    Aotearoa New Zealand
    PCA analysis
    The PCA is in Figure 2 - there's no separation of any of the groups, despite the axes accounting for a lot of the variation in gene expression. I guess there's just so much individual variation.

    Screen Shot 2024-04-02 at 3.15.25 pm.png

    I guess PCA probably isn't appropriate with such a small number of samples relative to the massive number of gene expression features.

    Maybe the blood sample needs to be stratified, to get smaller samples of features, to zero in on what is different? Or there could be prior decisions to only look at certain gene expressions, such as those for viral defense genes.
     
    Sean and SNT Gatchaman like this.
  14. Hutan

    Hutan Moderator Staff Member

    Messages:
    27,121
    Location:
    Aotearoa New Zealand
    Top differentially expressed genes

    Screen Shot 2024-04-02 at 3.20.42 pm.png

    Fig 4 looks a bit more exciting. The heat map is the difference between each group versus the mean of the other three groups. They say that the only significant differences were the 13 gene expressions different between the SARS+F+ and the rest.

    And the upregulated gene expressions do tell a pretty coherent story about an immune response to viral infection.

    We just have to remember that these are the most different gene expressions found out of about 59,000. And also , it looks as though about 4 individuals in the 20 people in the SARS+F+ group are doing the heavy lifting in terms of the upregulation. Most of the others look quite a lot like the rest of the people in the other groups. (Each individual is represented by a column in the heat map - see the red coloured columns.)
     
    Sean likes this.

Share This Page