Comparing ME/CFS following mononucleosis with Long COVID, 2026, Jason et al

I'm in my 70s and so is Dr. Jason. We're old school manners and etiquette

I'm in my 70s too and I don't see this as an issue of old school manners, to be honest. Members here are critical of the scientific methodology, as they should be. I have seen no hostility. Not a hint of 'personal attacks'. And this forum is not 'social media'. It is a science forum. We have lots of professors and MDs and other experts hiding behind avatars! We all admire Dr Jason and his team for their commitment, but everybody in science has to be open to criticism of ideas and publications.
I get my ideas torn to pieces by members here every day and I love it. It is the life blood of science. It is what one expected of a medical Grand Round forty years ago whether in the Ether Dome, at a Gowers Round at Queen Square or wherever. That for me was the old school approach. The pity is that these days it seems to have submerged in a sea of political correctness.

It is all about loosening up really. :)
 
I didn’t perceive anything as directed at me personally. I would still suggest avoiding general statements without explicitly saying they are about social media at large, and not the specific forum or thread you’re currently on. If share your frustration with social media, but it probably isn’t very relevant for the topics here either.
Good advice, thank you.
 
I'm in my 70s too and I don't see this as an issue of old school manners, to be honest. Members here are critical of the scientific methodology, as they should be. I have seen no hostility. Not a hint of 'personal attacks'. And this forum is not 'social media'. It is a science forum. We have lots of professors and MDs and other experts hiding behind avatars! We all admire Dr Jason and his team for their commitment, but everybody in science has to be open to criticism of ideas and publications.
I get my ideas torn to pieces by members here every day and I love it. It is the life blood of science. It is what one expected of a medical Grand Round forty years ago whether in the Ether Dome, at a Gowers Round at Queen Square or wherever. That for me was the old school approach. The pity is that these days it seems to have submerged in a sea of political correctness.

It is all about loosening up really. :)
Thanks, Jonathan. Like I mentioned, I was not speaking specifically about this forum or individual comments, but rather social media in general. I have moderated several very large support groups for chronic illness and you can't have thin skin when you do that....we would get PMs with profane rants and even death threats. That's what I'm talking about. And if you are in the camp with those who have contributed to medical trauma (doctor, researcher, etc) then you are often guilty by association and considered fair game. We have to decide where to allocate our mental and physical resources and I'm more willing to put up with the negativity (and positive constructive criticism) than most professionals I know. So tear away :)

By the way, these are not "my" studies. I'm part of a large team as a patient advisor and epidemiologist but there are many people involved in different projects at any given time and I contribute where I am most needed. So I can try to explain some approaches or conclusions, but only representing myself, not the authors.
 
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I'm in my 70's too, since the subject of age has come up. I don't think manners have anything to do with age, nor do I think we need to be educated about how to behave. That's all irrelevant to this discussion. It's the quality and insight of critiques that matters, not the politeness of expression, surely. So long as posts are within forum rules, we don't tone police. Of course as a mod, I've been subjected to some abuse. PwME don't become saints by virtue of getting sick.
 
I realize I'm suddenly a proxy for your anger and frustration with researchers in general and our team in particular. And I knew that when I stepped into the conversation, but it still stings a bit.
Hi Janet, glad to have you here and appreciate the dialogue. I'm thinking about my experience in broader (not me/cfs) support groups plus my experience as a scientist as I write this. I feel part of the rebuff you received may have been the result of miscommunications, but part are also with respect to valid methodological concerns which were expressed. Assuming the former could be counterproductive. Anyway, as a fellow patient I hear you and give you the benefit of the doubt. This condition does make effective communication including conflict resolution more difficult.

In terms of technical input, in my opinion consistent terminology is foundational. If people introduce alternative interpretions to existing language without broad consensus from everyone, it's confusing for everyone. Establishing and maintaining consistent language will pay dividends for everyone including those who join the cause in the future. Alternatively, any uncertainty can be exploited by those who attempt to discredit us.
 
I'm lying here in bed thinking, what if I say to a doctor 'I have severe ME/CFS', and they have read this paper and seen that apparently people with severe ME/Cfs have mean SF-36 PF of 77. That implies I can walk several blocks and climb several flights of stairs with little or no difficulty, so I certainly won't need a home visit from the doctor. What if I need to reapply for disability benefits?

Decisions to redefine terms by researchers have real world consequences.
 
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Decisions to redefine terms by researchers have real world consequences.

My impression is that there is a fatal conceptual flaw in this study in that it attempts to compare severities in two populations when the way those populations have been collected is likely to heavily bias the severity of measures. The point of making an estimation of this sort is to generalise to a larger identifiable population but there is no reason to think these differences can be generalised.

'ME/CFS' as a term already implies a level of severity of functional loss. Long Covid does not. Disabling symptoms in both categories occur as part of a wider population as long as a piece of string, varying from normal to bed bound.

And, yes, it seems likely that hardly anyone in this study had severe ME/CFS as generally understood.
 
I have been reading the paper again and have a comment on the sampling methods and subdivision of the post Mono (IM) group and lack of subdivision of the LC group.

First a bit of data:
IM infected 238
6 months post IM:
Asymptomatic: 157 - some used as controls
ME/CFS Fukuda 35
ME/CFS 2 criteria met: 20
Not mentioned 26 presumably symptomatic but not meeting any ME/CFS criteria

LC 3 months post infection
Asymptomatic control group (infected recovered) 62
LC at least 1 symptom continuous or relapsing remitting 55

So the comparison of post infectious conditions between IM and Covid does not use matching groups. They are 6 and 3 months post infection, the LC group combines all 3 of the ongoing symptom groups from the IM subgrouping. Unsurprisingly the LC group therefore comes out approximately in the middle of presence and severity of symptoms and function between the IM groups.

There are hundreds of comparisons between various groups on dozens of symptoms, functions and psychological factors, all shown in tables. as scores on the questionnaires and little superscripts attached to those that showed significant differences statistically. I don't think they corrected for multiple comparisons, but I rather lost the will to live at that stage.

I can't see that taking:
  • a mixed group with at least one symptom after 3 months from one population
  • subgroups of another population that are sampled with different methodology, and who only meet specific criteria that include at least 4 symptoms
and comparing them on large numbers of symptoms and functions collected by questionnaire, tells us anything useful.

I think all we are getting here is artefacts of flawed methodology.
 
I'm lying here in bed thinking, what if I say to a doctor 'I have severe ME/CFS', and they have read this paper and seen that apparently people with severe ME/Cfs have mean SF-36 PF of 77. That implies I can walk several blocks and climb several flights of stairs with little or no difficulty, so I certainly won't need a home visit from the doctor. What if I need to reapply for disability benefits?

Decisions to redefine terms by researchers have real world consequences.
It's so frustrating for us patients (especially those with severe illness, because our days are endless and painful) that we're still dealing with these kinds of blatant errors. It's difficult for non-scientists like me to understand this kind of error after so many years of research into the disease.
 
On the question of severity definitions, you’re right that the way we evaluate “severe” using multiple case definitions doesn’t map cleanly onto how patients typically describe severity (e.g., housebound/bedbound), and I understand why that’s a sticking point. That’s an area where there’s still a lot of debate, and it’s helpful to hear how it’s being interpreted from your perspective.
In some of these studies, “severity” isn’t defined by functional status (like housebound or bedbound), but by how many case definitions a person meets at the same time. The idea is that people who meet multiple definitions tend to report a broader range and higher frequency/severity of symptoms, so they’re grouped as “more severe” within that framework.

But as you pointed out, that doesn’t necessarily line up with how patients experience severity in real life, where functional ability is usually the key distinction. So it’s a bit of a proxy measure rather than a direct one, and that mismatch is part of why it can be confusing or controversial.
It's good to hear acknowledgement that this is controversial, but the primary problem is not that it doesn't line up with patient experience. The primary problem is that it doesn't line up with how the term has been used for decades in research and clinical practice.

Further to the reference I provided above, here are some more study cohorts' SF36 PF scores to illustrate why a group with a mean SF36 PF of 77 cannot be described as severe. I'm mindful that (a) a prospective study would be expected to pick up more mild and marginal cases, which would raise the mean SF36PF scores, and (b) the Jason cohort is much earlier in the illness than most other studies.

The median SF36PF of 345 people with ME/CFS attending eleven specialist NHS clinics in the UK 2014-2016 and providing follow-up data was 40 (interquartile range 25-60), and they had been sick for a median 26 months (IQR 12-80), see Collin & Crawley 2017 Appendix.

Rekeland et al. 2022 has a nice table showing SF36 PF scores of various study cohorts. Now some of these deliberately excluded milder patients, so that will reduce average scores, but it still gives an idea of the physical function of people who want intervention:

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And finally, this is table 3 from van Campen et al. 2020:
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There's one other study I've come across that labelled their cohort as severe when that was not warranted: Friedberg et al. 2016 "Efficacy of two delivery modes of behavioral self-management in severe chronic fatigue syndrome". In that study, baseline SF36 PF was 38, so, pretty average, not severe, though some with severe ME/CFS were included.. 37% of the sample was working (21 were working full-time, 12 half-time and 17 part-time). Again, just not a severe batch of patients. But Friedberg et al. defended it in the paper (perhaps in response to a reviewer?) as follows:
Illness-related fatigue and functional limitations in the study sample appeared to be severe based on the fact that the vast majority of participants presented baseline FSS scores equal to or higher than 5.0 (98.5%), considered to be ‘high fatigue’ severity, that is, two SDs above healthy controls.[41,42] In addition, the mean FSS score at baseline, 6.52 (SD = .49), was about two SDs higher than that found in a primary care sample of combined unexplained chronic fatigue and CFS patients that underwent a similar cognitivebehavioral self-management intervention.[20] Also, on the baseline web diary, the mean seven-day numerical fatigue rating (0–10) was 6.92 (SD = 1.28) which was about 1 SD higher than that reported in a previous CFS study sample recruited from the local community.[43] Finally, the mean SF-36 PF score of 37 was 2.0 SDs below the US population mean, [44] and 1.0 SD below SF-36 PF scores averaged over five published CFS self-management studies (Discussion). Based on population data, only 16% of individuals with SF-36 PF scores in the 30–39 range can walk one block or more.[23] These statistics suggest that our sample was severely ill.

If the goal is to get more funding and recognition as indicated above, then severity labels should not have been invoked in this series of papers on the prospective IM study. It looks more like crying wolf, and could be counterproductive. A solution? Call the groups what they are. Label them by the criteria they fulfilled e.g. Fukuda only, IOM only, CCC only, Fukuda/CCC, Fukuda/IOM, Fukuda/CCC/IOM. And then conflate them into fewer groups in whatever way the data leads e.g. Fukuda only vs ≥2 criteria or Fukuda +CCC/IOM. I would love to see an analysis where we see this at baseline, 6 months and 7 years, so we learn which criteria do a better job of picking out the people who remain ill.

If future studies want to focus on more severe patients, then assess severity. Decode ME did a nice job of this (#27 in questionnaire 1):
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I'm borderline moderate severe, depending which description is used. I scored myself currently on SF36 PF at 5. Anyone with very severe ME/CFS would score zero.

I have been trying out some of the other questionnaires used.

Beck Depression Inventory I scored 23 which is classed as moderate depression

Beck Anxiety Inventory I scored 22 which is classed as moderate anxiety

I am neither depressed nor anxious, apart from situational anxiety when I need to do something that is likely to set me back.

The questions include ones about physical symptoms and functional capacity. These questionnaires should not be used on people with physical illnesses such as ME/CFS and LC, as they will falsely diagnose people with anxiety and depression.

Here are the scores on the Beck inventories for the 5 groups in the study:

Depression
Severe ME/CFS 21.1
Moderate ME/CFS 13.9
Long Covid 17.9
IM control 4.0
LC control 9.0

Anxiety
Severe ME/CFS 17.7
Moderate ME/CFS 10.0
Long Covid 16.9
IM control 3.5
LC controlv7.0
 
This graph is from Wilshire, Kindlon, Matthees & McGrath 2016, many of whom are members of this forum e.g. @Simon M. It shows the SF36 PF scores of healthy people aged 18-59 in the UK, with most scoring 100. (The various thresholds relate to the PACE trial.)

It demonstrates well that a score of 77 (as in Jason et al.'s group that met more than one set of criteria) is well below the norm - those people are disabled to an extent similar to Class I congestive heart failure. But they're still operating within striking distance of healthy people.

You can imagine severe as 0-29, moderate as 30-59 and mild as 60-100 as per van Campen 2020 (see above).



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I also want to acknowledge that my earlier reply came across as defensive. That wasn’t my intention, and I can see how some of my wording didn’t engage directly with the concerns being raised here. I realize I'm suddenly a proxy for your anger and frustration with researchers in general and our team in particular. And I knew that when I stepped into the conversation, but it still stings a bit.
It's a lot more complicated than that, though there is some of it. What we want more than anything is to simply ignore the personal and work on solving problems. It's actually not limited to ME/CFS, we see this elsewhere, substantial criticism of problematic research is usually pushed back as personal attacks by academics. Which is really weird for us, to be honest. It's super personal for us, our lives entirely depend on it, and yet we set it aside entirely because we don't have a choice.

All the seemingly 'personal' problems we appear to have with some researchers have exactly zero to do with them as people. It's their work that we criticize, and we do the same for everyone. It's the only way things will move forward, and it sure seems to make a lot of people oddly uncomfortable. Believe me, when we see work that is garbage, we plainly say it, and no one is saying that about Jason and his team. It just needs improvements, like all research does, and we've seen it all. We are a rare place of complete honesty and no bullshit politics.

No one is a proxy for anything. We just want good research, and we absolutely emphasize and recognize it when it happens, but meaningful research is rare, and not just in this field. Most academics will make no contributions throughout their whole career, and that's just the way science works. What matters most is to focus on the substance, on improving on what exists. This is technically how science and academia are supposed to work, and it's often that, but we're a rare place that just doesn't care about niceties, we've found that being too polite and deferential will get us nowhere. It's where we are, right now: nowhere. We'd like to get out of this awful place.
 
It's good to hear acknowledgement that this is controversial, but the primary problem is not that it doesn't line up with patient experience. The primary problem is that it doesn't line up with how the term has been used for decades in research and clinical practice.
What is very frustrating to me as an ME/CFS patient when I fill out a questionnaire is the interpretation of a question. I find myself talking back to it and saying things like, "Well, do you mean on a good day or a bad day?" Saying "in the last 6 months" doesn't begin to touch on the variability. I have talked to my team about this and they recognize it is a challenge because with quantitative statistics you're trying to categorize something as an absolute that is really a moving target for many of us.

Sigmund Olafsen from Norway had a blog post yesterday saying that qualitative analysis is also crucial for understanding the complexity and the true burden of living with ME/CFS. Qualitative data analysis is one of my focuses and I hope to to more interview-based studies in the future. Narratives are very powerful and while you can find many on the support groups, it won't be accepted in the medical profession unless it is done using strict methodology, IRB guidelines, and peer-reviewed publications.
 
My impression is that there is a fatal conceptual flaw in this study in that it attempts to compare severities in two populations when the way those populations have been collected is likely to heavily bias the severity of measures. The point of making an estimation of this sort is to generalise to a larger identifiable population but there is no reason to think these differences can be generalised.

'ME/CFS' as a term already implies a level of severity of functional loss. Long Covid does not. Disabling symptoms in both categories occur as part of a wider population as long as a piece of string, varying from normal to bed bound.

And, yes, it seems likely that hardly anyone in this study had severe ME/CFS as generally understood.
Exactly
Reminds me of a post recently where another forum member explained that Long Covid has a severity scale of its own, but Severe in Long Covid is only similar to mild ME.
These concepts are already well-established.
 
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