Structural and functional impairments of skeletal muscle in patients with [PASC], 2023, Colosio et al.

Discussion in 'Long Covid research' started by SNT Gatchaman, Sep 7, 2023.

  1. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Structural and functional impairments of skeletal muscle in patients with post-acute sequelae of SARS-CoV-2 infection
    Marta Colosio ; Lorenza Brocca ; Marco Gatti ; Marianna Neri ; Emanuela Crea ; Francesca Cadile ; Monica Canepari ; Maria Antonietta Pellegrino ; Biagio Polla ; Simone Porcelli ; Roberto Bottinelli

    Background: Following acute COVID-19, a substantial proportion of patients showed symptoms and sequelae for several months, namely the post-acute sequelae of COVID-19 (PASC) syndrome. Major phenomena are exercise intolerance, muscle weakness and fatigue. We aimed to investigate the physiopathology of exercise intolerance in patients with PASC syndrome by structural and functional analyses of skeletal muscle.

    Methods: At least 3 months after infection, non-hospitalized patients with PASC (n=11,ys:54±11; PASC) and patients without long-term symptoms (n=12,ys:49±9; CTRL) visited the laboratory on four non-consecutive days. Spirometry, lung diffusion capacity and quality of life were assessed at rest. Cardiopulmonary incremental exercise test was performed. Oxygen consumption (VO2) kinetics were determined by moderate-intensity exercises. Muscle oxidative capacity (k) was assessed by near-infrared spectroscopy. Histochemical analysis, O2 flux (JO2) by high-resolution respirometry, and quantification of key molecular markers of mitochondrial biogenesis and dynamics were performed in vastus lateralis biopsies.

    Results: Pulmonary and cardiac functions were within normal range in all patients. VO2peak was lower in PASC than CTRL (24.7±5.0vs32.9±7.4mL*min-1*kg-1, respectively, P<.05). VO2 kinetics was slower in PASC than CTRL (41±12vs30±9s-1, P<.05). k was lower in PASC than CTRL (1.54±0.49vs2.07±0.51min-1, P<.05). Citrate synthase, PGC1alfa and JO2 for mitochondrial complex II were significantly lower in PASC vs CTRL (all P<.05).

    Conclusion: In our cohort of patients with PASC, we showed limited exercise tolerance mainly due to "peripheral" determinants. Substantial reductions were observed for biomarkers of mitochondrial function, content, and biogenesis. PASC syndrome appears to negatively impact skeletal muscle function, although the disease is an heterogenous condition.

    Link | PDF (Journal of Applied Physiology) Paywall
     
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  2. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Small numbers.

     
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  3. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    (Good to see patient reports being listened to here.)

     
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  4. Arnie Pye

    Arnie Pye Senior Member (Voting Rights)

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    I always wonder which meaning of "functional" is being used in research papers because doctors often don't use the word in the same way that normal/ordinary people do. And I know doctors create that confusion in patients deliberately which I think is appalling.
     
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  5. Hutan

    Hutan Moderator Staff Member

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    University of Pavia and University of Milan. We've been seeing a few Long Covid studies from Italy.

    As SNT says, only 11 people with Long covid, non-hospitalised, which is probably too small to find many issues, given that they didn't even stratify on the presence or absence of PEM.

    54 years +- 11 years, so, quite old on average. I think age can serve to confound ME/CFS symptoms somewhat - eventually even healthy people probably start to look a bit like a person with ME/CFS. The controls were a bit younger (49 years +- 9 years). I don't know what the +-'s are in Table 1 (actual range, 95%, SD, SE?) - I couldn't find it stated in the table, in the caption or the text. (I found it in methodology - ranges are SDs unless otherwise stated.)

    Gender mix: 50% women in controls; 64% women in PASC.

    A pretty extensive range of investigations were done.
     
    Last edited: Sep 8, 2023
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  6. Sean

    Sean Moderator Staff Member

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    the speed of adjustment of oxidative metabolism during transitions to moderate-intensity exercise (O2 kinetics)

    That is an interesting angle.
     
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  7. Hutan

    Hutan Moderator Staff Member

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    70% of PASC reported fatigue.

    I'm plodding my way through these findings incredibly slowly today.

    That's the Physical Activity Questionnaire results. Not much difference between the controls and PASC, even after PASC onset. I wouldn't necessarily be so trusting of what people report about their physical activity, but I guess we can assume that the PASC people were, on average, not abnormally active or underactive before illness onset, and that the PASC people didn't curl up in bed, desperately afraid of any sort of exertion after illness onset. I think we can also assume that the PASC people were relatively mildly affected.

    There was a big drop in average reported physical activity in both the controls and PASC after the Covid-19 infection. So, I wonder if all of the controls were as symptom free as they might have thought. Or perhaps it is harder to overestimate's one physical activity when you are thinking about last week, rather than 9 months ago.

    Lung function wasn't remarkably different between groups and suggested both groups had very good lung function.

    CPET - Part 1
    VO2max were higher in the controls (32.9) than in the PASC (24.7). That's not surprising.

    [La]b - that's lactate, sampled from a warmed ear lobe, sampled at rest and up to 7 minutes after exercise. The values weren't statistically different. I think that's important to note. A lot of people talk about lactate levels being part of ME/CFS, but I think that's based on the feeling of heaviness. I think the evidence for blood lactate levels being abnormal in people with ME/CFS is very weak.

    RPE - that's perceived exertion at the end of the exertion, the same in two groups.

    Peak Heart rate as a percentage of predicted HRpeak - 99% in CTRL, 96% PASC

    GET - no, not that GET. It's Gas Exchange Threshold. It's the same as the ventilatory threshold and roughly the same as the anaerobic threshold. Here it was calculated using the slope method. It's expressed here as a percentage of VO2max and of work rate. They found that both numbers were the same in the two groups. So, that's a bit different to what has often been reported in ME/CFS, which is that the ventilatory threshold occurs at a lower workrate. However, this was just one day of tests, and participants were told not to do strenuous exercise for 48 hours before the test. (I do find it a bit surprising that both groups would not only have the same GET expressed as a percentage of both V02max and of work rate, with the exact same standard deviations. I think they might have not reported that accurately.)

    Here's an interesting difference. From Table 2: 61%+-13 for CTRL; 45%+-9 for PASC.
    The measure relates to the relative concentrations of de-oxygenated haemoglobin and myoglobin and oxygenated haemoglobin and myoglobin in an outer thigh muscle. The measure is the peak muscle deoxygenation during the exercise test, expressed as a percentage of a value obtained by essentially constricting blood supply at rest for a few minutes until the de-oxygenated/oxygenated ratio reached a plateau. So, this value is regarded as a measure of skeletal muscle oxygen extraction.

    This seems like a useful measure - it's not invasive. It's measured using light. The PASC people had less muscle oxygenation. There's no individual data, but there does look to be good separation of the mean values for the two groups, and the standard deviations are tight.

    I want to see this measure done in lots of ME/CFS and LC studies. To me, it explains a lot of my symptoms. I've said before, my symptoms are a lot like what it's like when doing things at high altitude. And the tendency for numbness, and pins and needles, in limbs; the lack of coordination with repeated muscle use. And that makes sense if oxygen isn't making it into tissues.
     
    Last edited: Sep 8, 2023
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  8. Hutan

    Hutan Moderator Staff Member

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  9. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Note if it was truly paywalled originally, it's not now. PDF here.
     
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  10. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Letter to the editor, includes —

     
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  11. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Author reply, includes —

     
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