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Impaired exercise capacity in post-COVID syndrome: the role of VWF-ADAMTS13 axis, 2022, Prasannan et al

Discussion in 'Long Covid research' started by LarsSG, May 11, 2022.

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  1. LarsSG

    LarsSG Senior Member (Voting Rights)

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    370
    Key Points
    • VWF(Ag):ADAMTS13 ratio ≥1.5 was evident in 28% of PCS cohort
    • 55% of patients with impaired exercise capacity had a raised VWF(Ag):ADAMTS13 ratio ≥1.5 (OR 4)
    Post-COVID syndrome (PCS) or Long-COVID is an increasingly recognised complication of acute SARS-CoV-2 infection, characterised by persistent fatigue, reduced exercise tolerance chest pain, shortness of breath and cognitive slowing. Acute COVID-19 is strongly linked with increased risk of thrombosis; a prothrombotic state, quantified by elevated Von Willebrand Factor (VWF) Antigen (Ag):ADAMTS13 ratio, and is associated with severity of acute COVID-19 infection. We investigated if patients with PCS also had evidence of a pro-thrombotic state associating with symptom severity. In a large cohort of patients referred to a dedicated post-COVID-19 clinic, thrombotic risk including VWF(Ag):ADAMTS13 ratio, was investigated.

    An elevated VWF(Ag):ADAMTS13 ratio (≥1.5) was raised in nearly one-third of the cohort and four times more likely in patients with impaired exercise capacity as evidenced by desaturation ≥3% and/or rise in lactate level more than 1 from baseline on 1-minute sit to stand test and/or 6-minute walk test (p<0.0001). 20% (56/276) had impaired exercise capacity, of which 55% (31/56) had a raised VWF(Ag):ADAMTS13 ratio ≥1.5 (p<0.0001). FVIII and VWF(Ag) were elevated in 26% and 18% respectively and support a hypercoagulable state in some patients with PCS. These findings suggest possible ongoing microvascular/endothelial dysfunction in the pathogenesis of PCS and highlight a potential role for antithrombotic therapy in the management of these patients.

    Link with full text PDF
     
    LarsSG, May 11, 2022
    #1
    Mij, Grigor, DokaGirl and 7 others like this.
  2. Hutan

    Hutan Moderator Staff Member

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    ADAMTS13 regulates VWF. In acute Covid, an increase in VWF:Ag(antigen) and a decrease in ADAMTS13 has been reported.
    50 healthy controls were used to determine the healthy VWF(Ag)/ADAMTS13 ratio. They don't say whether some/all the healthy controls had recovered from Covid-19, or the age or sex ratio of the controls.
    72% of the patients reported fatigue - overall this was a mixed patient group reporting a range of symptoms including chest discomfort. 3% of the patient group are reported as being asymptomatic.


    So, median VWF(Ag)/ADAMTS13 ratio in controls was 0.98 (interquartile range 0.76 to 1.34). The ratio in patients was 1.2 (0.9-1.5). I think it is a bit of a stretch to say these are different if we take into account confounding factors like age.
    Execise test:
    I don't think the exercise test measure is a very sensitive test of exercise capacity in ME/CFS. Below, the chart comparing the ratios of those patients with normal and abnormal exercise test performance. The y axis is 0,1,2,3,4. Perhaps there is something there, bearing in mind the median of the healthy controls was approximately 1. I think we'd need to see the analysis repeated with just people reporting fatigue to begin to get an idea as to whether this is relevant to people with ME/CFS-like symptoms.

    Screen Shot 2023-07-11 at 5.20.14 am.png

    The chart is only for the subset who completed the test - not all patients did the exercise test, and some attempting it did not complete it.
    It's of note that older people had higher ratios - perhaps this accounts for the difference with the controls?
     
    Last edited: Jul 10, 2023
    Hutan, Jul 10, 2023
    #2
    SNT Gatchaman likes this.
  3. Hutan

    Hutan Moderator Staff Member

    Messages:
    27,828
    Location:
    Aotearoa New Zealand
    I had thought that the older people might have been more likely to have severe disease, and so the higher ratio might just have been a result of lung or heart damage, or of their treatments. It doesn't look as though hospitalisation/severe acute disease alone accounts for higher ratios here.

    But it looks as though a previous study did find a relationship between severe acute disease and the ratio; perhaps that is mediated by age?

    It's not clear to me what the basis of the authors saying that the ratio was not correlated with fatigue presence. The report is a bit patchy.

    I'm not finding the VWF(Ag): ADAMSTS13 ratio very compelling as a reason for ME/CFS-like symptoms.
     
    Last edited: Jul 10, 2023
    Hutan, Jul 10, 2023
    #3
    SNT Gatchaman likes this.

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