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Reduced Muscle Strength in Patients with Long-COVID-19 Syndrome Is Mediated by Limb Muscle Mass 2022 Ramírez-Vélez et al

Discussion in 'Long Covid research' started by Andy, Dec 1, 2022.

  1. Andy

    Andy Committee Member

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    Abstract

    Understanding the impact of COVID-19 on muscle strength may help to elucidate the organ systems that contribute to acute and chronic COVID-19 sequelae. We questioned whether patients with postdischarge symptoms after COVID-19 had compromised muscle strength compared with a control group, and if this potential relationship was mediated by the lower appendicular lean mass index (ALMI).

    A total of 99 patients with long-COVID-19 and 97 control participants were screened. Maximal grip strength was assessed with a TKK 5101 digital dynamometer, and leg extension 1RM was measured using EGYM Smart Strength machines. Body composition (fat mass percentage, lean mass, visceral fat and appendicular lean mass index) was determined using a whole-body dual-energy X-ray densitometer. Results showed that grip strength and leg extension strength were significantly higher in controls than in COVID-19 survivors (mean [SD], 32.82 [10.01] vs. 26.94 [10.33] kg; difference, 5.87 kg; P < 0.001) and (mean [SD], 93.98 [33.73] vs. 71.59 [33.70] kg; difference, 22.38 kg; P < 0.001), respectively). The relationship between long-COVID syndrome and grip/leg strength levels was partly mediated by ALMI, which explained 52% of the association for grip strength and 39% for leg extension.

    Our findings provide novel insights into the mechanisms underlying the relationship between long-COVID syndrome and grip/leg strength levels, supporting the negative effects of long-COVID syndrome on muscle function.

    Open access, https://journals.physiology.org/doi/abs/10.1152/japplphysiol.00599.2022
     
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  2. Mij

    Mij Senior Member (Voting Rights)

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    Is this the same as testing for muscle weakness or muscle fatigue? I was tested for muscle weakness by an M.E doc early on during PVFS and it was determined that I didn't have muscle weakness. Later in the years I experience get both, but the weakness is transient.
     
  3. CRG

    CRG Senior Member (Voting Rights)

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    The conclusion is based on a statistical correlation of the lean muscle mass of the limbs of patients with PASC compared to a control group who were COVID negative - the authors seem to be saying that having a low lean muscle mass of the limbs is indicative of a predisposition to having PASC:

    "In conclusion, patients with long-COVID-19 syndrome have lower absolute and relative muscle strength than control participants, and this relationship may be mostly mediated by ALMI. These findings provide novel insights into the mechanisms underlying the relationship between long-COVID-19 syndrome and grip/leg strength levels. As the effects of long-COVID-19 syndrome on muscle function are striking future studies investigating the mechanisms of dysfunction will help accelerate the development of therapies to improve the functional status of these patients."
     
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  4. Trish

    Trish Moderator Staff Member

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    I don't read that from the abstract. I think they are saying low muscle mass leads to low muscle strength, but not what caused the low muscle mass. I had assumed they meant the PASC led to reduced muscle mass, and their suggestion of therapies gives me an uneasy feeling they are talking about deconditioning and GET.
     
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  5. rvallee

    rvallee Senior Member (Voting Rights)

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    I really don't understand the utility of measuring strength when strength is so massively different between individuals. Even with a prior test it's pretty much meaningless, as being ill for months will obviously reduce muscle strength whether the illness has any direct impact on ability to apply strength or not.

    I really don't get how it can be of any use here. We have the same issue with cognitive testing, this is not a solved problem, we just don't have baseline values to compare to and even then we don't have objective assessments anyway. With strength come many other factors like neuropathy or current energy levels.
     
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  6. Hutan

    Hutan Moderator Staff Member

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    I haven't read the paper, but on the basis of the abstract I agree with @Trish - the paper says nothing about muscle mass being a risk factor for developing Long Covid.

    And yes, the obvious conclusion from the title is that people with Long Covid have muscle weakness because they are sitting around doing nothing - so the treatment should be getting people moving again. But even the information in the abstract raises a question about this. The title would more accurately be 'Reduced Muscle Strength in Patients with Long-COVID-19 Syndrome Is Partially Mediated by Limb Muscle Mass'. And really, as @rvallee said, that people who cannot be as active as they once were have lower muscle mass is hardly surprising or revelatory. It's the fact that muscle mass doesn't wholly explain reduced strength that I find intriguing, and much more worthy of a title.

    Maybe there's a clue there, if the relationship between muscle mass and muscle strength is not what would be expected in people with Long Covid. Maybe something is causing the muscle mass that is still there to not work as well, and maybe that something relates directly to the Long Covid pathology.

    So, if I was reading this paper, that's the question that I would have in mind as I read. I'd also want to know more about the actual measurement - did it involve sustained muscle activity (e.g. a single long grip) and/or repeated use?
     
    Last edited: Dec 1, 2022
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  7. Hutan

    Hutan Moderator Staff Member

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    This 2013 paper is relevant:
    Relationship between muscle mass and muscle strength, and the impact of comorbidities: a population-based, cross-sectional study of older adults in the United States
    It compared the ALMI (appendicular lean mass index) with quadriceps strength - that might be comparable with the leg strength measure in this study. The 2022 study found that ALMI explained 39% of the variation in leg muscle strength. If I'm reading it right, the 2013 study found that ALMI explained 36.5% of the variation. So, that's actually looking pretty normal.


    This is from the 2022 study:
    Screen Shot 2022-12-02 at 12.44.53 pm.png
    "Limb muscle wasting common to patients with COVID-19 limits daily activities and exercise". They provide no proof that it is limb muscle wasting that limits daily activities and exercise. I seriously doubt that that is true.



    Oh my goodness. This is also from the 2022 study:
    Screen Shot 2022-12-02 at 12.59.17 pm.png

    Spot the issue? The controls weren't matched. The Long Covid cohort had 71% females, the controls just had 53%. It is therefore not at all surprising that body fat percentage was higher and lean muscle tissue and muscle strength parameters were lower.

    The authors write 'the prevalence of muscle mass loss estimated based on ALMI' and muscle strength were significantly lower in Long Covid compared to the controls. But, there's no way that they can know what muscle mass was actually lost - there were no measurements taken prior to getting Covid-19.

    Here's Table 1 with the data:
    Screen Shot 2022-12-02 at 1.05.58 pm.png
    See how they haven't reported most of the data separately for men and women? For example, there's just a mean percentage of body fat given for the entire cohort, and a mean appendicular lean mass index.

    They do report the percentage of people with low muscle mass, checking each participant against a cut off specific for their gender (6.0 kg/m3 for women and 7.0 kg/m3 for men. 12% of the Long Covid group had low muscle mass, higher than the 3% in the controls. But that means that 88% of the Long Covid group did not have low muscle mass.

    Also, the difference in the percentage of females in each group could be affecting the percentage of people reported as having low muscle mass. To explain what I mean there, have a look at Figure 1 from the 2013 study I mentioned above, specifically the bars for the 50-54 age group which is similar to the mean ages in the 2022 study. Look how a cutoff of 6 for women would suggest a fairly large percentage of women in this population-based sample would be regarded as having low muscle mass. Now look at what a cutoff of 7 does for the men - that would suggest a much lower percentage of men would be regarded as having low muscle mass. The cutoffs for each gender aren't equivalent. Age also confounds things. So, when the 2022 study authors apply these cutoffs and one group has a much higher percentage of females than the other, the results are not comparable.

    Screen Shot 2022-12-02 at 1.19.19 pm.png


    The 2022 study really is not very good. Their suggestion that limb muscle wasting limits activity levels of people with Long Covid is not even remotely supported by their data.
     
    Last edited: Dec 2, 2022
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  8. Peter Trewhitt

    Peter Trewhitt Senior Member (Voting Rights)

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    I have not read any of the original Ramsey ME papers, but didn’t he regard muscle related issues as a defining characteristic of ME? Was this based on research data or clinical observation?
     
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  9. rvallee

    rvallee Senior Member (Voting Rights)

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    This is especially relevant considering how massive the strength imbalance between sexes is. It's something like the average male is stronger than 99% of females, this completely skews any cohort that isn't completely matched far above any statistical significance, let alone a clinical one.

    In addition to so many factors, from genetics to employment and hobbies. Obviously someone who is a lifelong climber will have different strength from someone who basically hates sweating. A professional dancer will have different leg strengths. So so many confounding factors.
     

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