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Yes suspect that the cohorts were simply too different. Half of the pneunomia cohort was above 70 years, compared to roughly a third for COVID-19 and only a sixth for Influenza.

I think this is the main finding of the paper but wonder if it may simply be a longer-term consequence of less extreme deconditioning. For example that the longer you remain inactive the more type 1 fibers are affected relative to others. The bed rest was a short period of extreme inactivity...

Yes, a bit. The main caveat is that past literature was mainly about head-up tilt table testing which usually show higher heart rate increases upon standing than this (NASA) lean test. In this study only 4 out of 112 had abnormal tests, including one with a heart rate increase > 30 bpm and 2...

Some more references: Bias caused by reliance on patient-reported outcome measures in non-blinded randomized trials: an in-depth look at exercise therapy for chronic fatigue syndrome: Fatigue: Biomedicine, Health & Behavior: Vol 8, No 4 Assessment of the scientific rigour of randomized...

I think Leptin (LEP in figure 2B) is also showing up again, as in the study by Beentjes et al?

The lifelines cohort is very valuable. I wonder if they could retrospectively try to make the definition of ME/CFS more stringent to get something below 1% prevalence. They could for example make the CDC symptom inventory items for PEM, unrefreshing sleep and concentration problems mandatory...

I suspect the ME/CFS prevalence in this cohort was largely based on the CDC symptom inventory. This Wiki for the Lifelines project provides some more information: https://wiki.lifelines.nl/doku.php?id=cfs_diagnostic_score https://wiki.lifelines.nl/doku.php?id=fatigue_cdc

The supplementary material states: So I suppose we have to wait until that other manuscript is published until we know more how the Fukuda criteria were assessed (my guess is through questionnaires rather than a medical examination). The paper itself does not comment on the remarkable high...

The authors clarify that they could not distinguish between genetics and shared environments. For most disorders the recurrence risk ratio was similar for first or second degree relatives and the authors argue that this suggests that the recurrent was likely not due to a shared environment...

If I understand the data correctly, having one (or more) first-degree relatives with ME/CFS makes it 2.23 times more likely that you have ME/CFS compared to the general population (which includes those with first-degree relatives with ME/CFS).

They said they evaluated the Fukuda criteria yet 4.7% of the more than 150.000 people in the cohort had ME/CFS (Table 1)? That seems an unreasonably high estimate.

I suspect it is this study: Familial coaggregation and shared familiality of functional and internalizing disorders in the Lifelines cohort, 2025, Bos et al | Science for ME

Thanks for tagging me. Interesting that cerebral blood flow and small fiber neuropathy showed no significant differences. The sample size was really small though. Almost as if the added the conclusions of a different paper, it doesn't match what the study actually found.

Interesting study. Sad that the concordance between the different ME/CFS pieces information in the UK biobank is so low. For example: 2,312 (0.46% of the 0.5 million biobank participants) self-reported a clinical diagnosis of CFS (C1). But of these, 28% also reported 'good' or 'excellent'...

Yes it would be useful to have a review on this from a researcher who can comment on the quality of measurements and possible confounders.

I think the main ones are already mentioned so do not have much to add. Perhaps NK cytotoxicity as Baraniuk tried to argue that null results were due to different handling of samples? Meta-analysis of natural killer cell cytotoxicity in myalgic encephalomyelitis/chronic fatigue syndrome - PubMed...

Seems like this study captured the main themes quite well. The struggle between becoming an adult and remaining dependent because of illness, the disbelief by doctors which cause an erosion of trust, feeling blamed for your illness, the disbelief that a young person could be so ill, trying to...

Looks like a worthwhile project. Suspect there is a great need for this. Interested to see how this will develop.

Oops, sorry for the confusion. Looked for another reference figure: in the PACE trial the GET group also increased with around 35 meters compared to the control group on the 6MWT.

Thanks for pointing that out, was indeed misinterpreting the graphs. Given that the PASC-ME/CFS cases seem to be similar to other ME/CFS cases, it indeed suggests a doubling of new cases in that period because of Long Covid. The PASC-ME/CFS cases, however, already seems to decrease from the...