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Persistence of SARS CoV-2 S1 Protein in CD16+ Monocytes in Post-Acute Sequelae of COVID-19 (PASC) ..., 2021, Patterson et al (in prep)

Discussion in 'BioMedical ME/CFS Research' started by Jaybee00, Jul 21, 2021.

  1. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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    https://www.biorxiv.org/content/10.1101/2021.06.25.449905v2


    The recent COVID-19 pandemic is a treatment challenge in the acute infection stage but the recognition of chronic COVID-19 symptoms termed post-acute sequelae SARS-CoV-2 infection (PASC) may affect up to 30% of all infected individuals. The underlying mechanism and source of this distinct immunologic condition three months or more after initial infection remains elusive. Here, we investigated the presence of SARS-CoV-2 S1 protein in 46 individuals. We analyzed T-cell, B-cell, and monocytic subsets in both severe COVID-19 patients and in patients with post-acute sequelae of COVID-19 (PASC). The levels of both intermediate (CD14+, CD16+) and non-classical monocyte (CD14Lo, CD16+) were significantly elevated in PASC patients up to 15 months post-acute infection compared to healthy controls (P=0.002 and P=0.01, respectively). A statistically significant number of non-classical monocytes contained SARS-CoV-2 S1 protein in both severe (P=0.004) and PASC patients (P=0.02) out to 15 months post-infection. Non-classical monocytes were sorted from PASC patients using flow cytometric sorting and the SARS-CoV-2 S1 protein was confirmed by mass spectrometry. Cells from 4 out of 11 severe COVID-19 patients and 1 out of 26 PASC patients contained ddPCR+ peripheral blood mononuclear cells, however, only fragmented SARS-CoV-2 RNA was found in PASC patients. No full length sequences were identified, and no sequences that could account for the observed S1 protein were identified in any patient. Non-classical monocytes are capable of causing inflammation throughout the body in response to fractalkine/CX3CL1 and RANTES/CCR5.
     
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  2. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    This reads like someone who has read an immunology textbook but not understood it. I may be getting old but in the days when I was in immunology an abstract like this would get a straight rejection. The sentences aren't even in a sensible order.

    'monocytes were sorted from PASC patients using flow cytometric sorting'. This is a bit like saying I opened the door by opening it. I don't understand how fifteen co-authors did not pick that up.
     
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  3. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    The authors claim the presence of spike protein fragments in CD16+ Monocytes is due to continued presence of viral genetic material up to 16 months later.

    Unfortunately, they don't provide data for each of the patients (for the test of spike protein containing monocytes). They claim:

    They claim they double checked the findings with six patient samples using chromatography. (no discussion about how those samples were selected out of the overall group)

    In addition, they sequenced samples from five patients (no discussion about how those samples were selected out of the overall group) and they state:

    So there was unlikely to be replication competent virus persisting in patients.

    There were issues:
    I don't want to speculate about this too much since I am not an expert in the methodology, but could there be a risk of contamination leading to these results?

    Some additional speculation by the authors:

     
    Last edited: Jul 22, 2021
  4. Hutan

    Hutan Moderator Staff Member

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    https://www.healthrising.org/blog/2021/07/21/patterson-cracked-long-covid/
    Cort's analysis 'Has Bruce Patterson cracked Long Covid?'
     
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  5. Hutan

    Hutan Moderator Staff Member

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  6. Hutan

    Hutan Moderator Staff Member

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    Having watched a video: Dr Patterson seems to be connected with a network of labs testing Long Covid patients, and clinicians treating them according to his protocol. Even Cort showed skepticism in his write-up, including a question-mark in his article's title. Patterson certainly has attracted a lot of attention.

    I'm a bit concerned by Patterson's suggestion that they can fix the immune system and that is what they are primarily aiming to do - rather then eliminating symptoms. Those patients with ongoing symptoms after treatment are waved away as just suffering the effects of having been sedentary for a long time. So, there's talk of slowly ramping up their activity levels after treatment. With a paradigm like that, it is hard to know if the supposed success of the treatment (i.e. the return of the 'immune system' to something that looks normal) is just the markers of infection declining over time. It sounds as though the patients who don't recover will be assured that the treatment was successful in fixing the immune system and so any failure to recover will be either their fault for not becoming active again, or perhaps will be due to some permanent damage done to the body.
     
    Last edited: Jul 22, 2021
  7. Hutan

    Hutan Moderator Staff Member

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    Figure 1

    So there are three types of monocytes: classical, intermediate and non-classical. The paper shows three charts (below) relating to each of those subsets, in that order. One key finding from the paper was that populations of intermediate and non-classical monocytes were increased in the long-haulers. Actually, the populations of the monocyte subsets looked quite similar in both of the non-healthy groups.

    Screen Shot 2021-07-22 at 3.23.50 PM.png

    This isn't particularly surprising, given that the intermediate and non-classical monocytes are involved in antigen-presentation. Increases in these two monocyte populations seems to be associated with infections. The healthy participants didn't have an infection, so, yeah... The chart does not show the level of monocyte subsets in people who have had Covid-19 but don't have Long Covid - we need to see that in order to evaluate the idea that levels of monocytes subsets are part of the story of Long Covid pathology.
     
    Last edited: Jul 22, 2021
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  8. Hutan

    Hutan Moderator Staff Member

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    Figure 3
    (as best I can work out - the charts in Figure 2 are just leading up to the conclusion presented in Figure 3)

    So, here again, there are three charts, with classical monocytes (defined as CD14++ CD16-) on the left;
    intermediate monocytes (defined as CD14+ CD16+) in the middle; and
    non-classical monocytes (defined as CD14lo CD16+) on the right.

    The y axis is a measure of the expression of the CoV-2 S1 protein on the monocyte cells. The three columns in each chart on the x-axis are for healthy controls (HC); patients with severe Covid-19 (severe); and patients with Long Covid (LH).

    Screen Shot 2021-07-22 at 3.35.39 PM.png

    So, it doesn't feel as though we have got to anything ground-breaking yet, as the people who are having or have recently had Covid-19 are the ones whose antigen-presenting monocytes are presenting a CoV-2 antigen. Again, there is no data for people who have had Covid-19 and recovered, or any examination of the effect of time since the illness.
     
    Last edited: Jul 22, 2021
  9. Nightsong

    Nightsong Senior Member (Voting Rights)

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    Patterson also seems to have been involved in a group called FLCCC, which produced this "treatment protocol" - he is listed as one of the co-authors - which is full of unevidenced claims about MCAS and ivermectin.
     
  10. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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  11. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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