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Multi-omics provide evidence for an anti-inflammatory immune signature and metabolic alterations in ... Long COVID Syndrome, 2022, Kovarik et al

Discussion in 'Long Covid research' started by marcjr, Jul 18, 2022.

  1. marcjr

    marcjr Established Member

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    6
    ABSTRACT

    Despite the increasing prevalence of patients with Long Covid Syndrome (LCS), to date the pathophysiology of the disease is still unclear, and therefore diagnosis and therapy are a complex effort without any standardization. To address these issues, we performed a broad exploratory screening study applying state-of-the-art post-genomic profiling methods to blood plasma derived from three groups: 1) healthy individuals vaccinated against SARS-CoV-2 without exposure to the full virus, 2) asymptomatic fully recovered patients at least three months after SARS-CoV-2 infection, 3) symptomatic patients at least 3 months after a SARS-CoV-2 infection, here designated as Long Covid Syndrome (LCS) patients.

    Multiplex cytokine profiling indicated slightly elevated cytokine levels in recovered individuals in contrast to LCS patients, who displayed lowest levels of cytokines. Label-free proteome profiling corroborated an anti-inflammatory status in LCS characterized by low acute phase protein levels and a uniform down-regulation of macrophage-derived secreted proteins, a pattern also characteristic for chronic fatigue syndrome (CFS). Along those lines, eicosanoid and docosanoid analysis revealed high levels of omega-3 fatty acids and a prevalence of anti-inflammatory oxylipins in LCS patients compared to the other study groups. Targeted metabolic profiling indicated low amino acid and triglyceride levels and deregulated acylcarnithines, characteristic for CFS and indicating mitochondrial stress in LCS patients. The anti-inflammatory osmolytes taurine and hypaphorine were significantly up-regulated in LCS patients. In summary, here we present evidence for a specific anti-inflammatory and highly characteristic metabolic signature in LCS which could serve for future diagnostic purposes and help to establish rational therapeutic interventions in these patients.

    https://www.medrxiv.org/content/10.1101/2022.07.11.22277499v1

    Not sure if we are allowed to post images from the paper, but the last one summarizes well their findings.
     
    Last edited by a moderator: Jul 19, 2022
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  2. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Will read shortly, but: multi-omics in healthy/vaccinated vs Covid-recovered vs long Covid - Hallelujah!
     
  3. LarsSG

    LarsSG Senior Member (Voting Rights)

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    "Targeted metabolic profiling indicated low amino acid and triglyceride levels and deregulated acylcarnithines, characteristic for CFS and indicating mitochondrial stress in LCS patients."

    Oddly, these are only low in the LC group relative to the Covid recovered group, not low relative to the healthy controls (with the exception of one amino acid, valine). Other aminos were higher in LC than controls. Some of it could just be random since the groups only have 13 people in each (e.g. triglyceride could just happen to have been higher in a few members of the recovered group, which the intervals given suggest). It's certainly interesting, but lower levels relative to recovered patients seems kind of different from lower levels relative to healthy controls.
     
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  4. dreampop

    dreampop Senior Member (Voting Rights)

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    Iirc Ron Davis said he found higher omega3s in me/cfs patients but postulated it was due to supplementation. Think it was in a video.
     
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  5. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    (EPA is eicosapentaenoic acid and DHA is docosahexaenoic acid).
     
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  6. Midnattsol

    Midnattsol Moderator Staff Member

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    One week is not nearly enough to compare omega-3 levels to someone who has been supplementing regularly, blood levels can increase for weeks after starting supplementation. I would have given them supplementation at least a month, and might even have increased the dose to 3 g/day not a bit under 2 g/day.

    Edit: There are also obviously individual differences and 10 people isn't a lot.
     
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  7. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    A few points from a recent review article: Vitamin D Binding Protein: A Historic Overview (2020)

    It developed early in evolution and is conserved.

    Two major functions —

    Its plasma concentration is stable and independent of many factors, including vitamin D levels.

    Concentration is increased in females.

    Concentration is increased with infection.

    It binds extracellular actin and is involved in clearance of fibrillar actin.

    May effect macrophage function.

    See also Vitamin D-binding protein as a biomarker to confirm specific clinical diagnoses (2019)
     
  8. Hutan

    Hutan Moderator Staff Member

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    Location:
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    A team entirely from Vienna, Austria:
    There's acknowledgement that LC isn't just anxiety and stress. There's a good list of symptoms, although 'lack of physical fitness' would have been better replaced with 'post exertion malaise and easy fatiguability'. The severity of the disease is noted. Although LC is described as 'novel', they go on to recognise the similarity with CFS in general and MERS and SARS in particular. This is not the first paper to suggest that long term symptoms following SARS1 has been observed 'for up to two years'. I'm sure that the persistence of symptoms from MERS and SARS have been much longer than that - there must surely be a reference that records that. But, overall, I thought it was a really good start.

     
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  9. Hutan

    Hutan Moderator Staff Member

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    There are four groups:
    H - healthy, vaccinated at least 3 months ago, no covid 19 infection - 13 people

    HL - healthy, no covid 19 infection, given tablets containing 870mg Omega-3 (420 mg EPA and 330 mg DHA) twice a day for one week - 10 people

    R - recovered from a Covid-19 infection at least 3 months ago - 13 people

    LCS - had a Covid-19 infection at least 3 months ago and have lingering symptoms (notably fatigue (9/13) and/or cognitive difficulties (10/13), dyspnoea (9/13)) - 13 people

    They describe this study as an exploratory study - the sample sizes are small at 13 people in each group. From the listed symptoms of the LCS group, I don't think they would all qualify for an ME/CFS diagnosis, although perhaps if they were assessed by a clinician who routinely diagnoses ME/CFS, the description of symptoms would be different.

    The samples look fairly well matched in terms of gender and age, although the inclusion of people with significant health conditions is a bit odd (e.g. the LCS group includes a person with multiple sclerosis and a person with autoimmune thyroiditis).
     
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  10. Hutan

    Hutan Moderator Staff Member

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    They make quite a lot of IL-18 levels being lower in the LCS group, but there's a lot of overlap with the other two groups- I'm not convinced there is a real difference in IL-18.

    Screen Shot 2022-07-24 at 3.10.23 pm.png

    But, some of the the LCS group do look different from the healthy groups - look at the PCA and volcano plot. They just aren't presenting as a particularly well-characterised group - individuals in the LCS group seems to be fairly different from each other as well as different from the healthy groups, which isn't very helpful.

    Screen Shot 2022-07-24 at 3.13.38 pm.png

    Serpina5 looks really interesting - the LCS are nicely clustered with lower levels. The clustering of BTD (biotinidase) in the LCS is nice, but there's a lot of overlap with the healthy groups, so, not so interesting. GC (inexplicably to me at the moment, 'GC' is actually Vitamin D binding protein) levels are statistically different between the recovered and Long Covid groups, but there is plenty of overlap between the Long Covid group and the healthy groups, so it's not looking very important to me.

    Screen Shot 2022-07-24 at 3.16.21 pm.png
     

    Attached Files:

  11. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    GC was its old name ("group-specific component") which reflected —

    (from the review article linked above)
     
  12. Hutan

    Hutan Moderator Staff Member

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    Here's something about Serpina 5 - I'm posting it at least partly because I like the title:
    Cell penetrating SERPINA5 (Protein C inhibitor, PCI): More questions than answers
    A 2016 paper, perhaps coincidentally by two people also based in Vienna.

    SERPINA5 binds glycosaminoglycans, phospholipids, and retinoic acid. Glycosaminoglycans and certain phospholipids can modulate its inhibitory activity and specificity. Studies suggest that SERPINA5 may play a role in hemostasis*, in male reproduction, in host defense, and as a tumor suppressor. However, its biological role has not yet been defined. So far SERPINA5 deficiency has not been described in man.

    SERPINA5 can be internalized by cells and translocated to the nucleus. The internalization is dependent on the phospholipidphosphatidylethanolamine and on the intact N-terminus of SERPINA5, which functions as a cell penetrating peptide. Further functional analysis of intracellular SERPINA5 will contribute to our understanding of the biological role of this molecule.

    *hemostasis:
    Hemostasis is a complex network of cellular and humoral systems, involving the platelet system, the coagulation process, the anticoagulant, and the fibrinolytic pathways)

    Edited to add: the authors of the paper that is the subject of this thread had this to say about SERPINA5:
     
    Last edited: Jul 24, 2022

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