Typing myalgic encephalomyelitis by infection at onset: A DecodeME study, 2023, Bretherick et al

Abstract

Background: People with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) daily experience core symptoms of post-exertional malaise, unrefreshing sleep, and cognitive impairment or brain fog. Despite numbering 0.2-0.4% of the population, no laboratory test is available for their diagnosis, no effective therapy exists for their treatment, and no scientific breakthrough regarding their pathogenesis has been made. It remains unknown, despite decades of small-scale studies, whether individuals experience different types of ME/CFS separated by onset-type, sex or age.

Methods: DecodeME is a large population-based study of ME/CFS that recruited 17,074 participants in the first 3 months following full launch. Their detailed questionnaire responses provided an unparalleled opportunity to investigate illness severity, onset, course and duration.

Results: The well-established sex-bias among ME/CFS patients is evident in the initial DecodeME cohort: 83.5% of participants were females. What was not known previously was that females’ comorbidities and symptoms tend to be more numerous than males’. Moreover, being female, being older and being over 10 years from ME/CFS onset are significantly associated with greater severity. Five different ME/CFS onset types were examined in the self-reported data: those with ME/CFS onset (i) after glandular fever (infectious mononucleosis); (ii) after COVID-19 infection; (iii) after other infections; (iv) without an identified infectious onset; and, (v) where the occurrence of an infection at or preceding onset is not known.

Conclusions: This revealed that people with a ME/CFS diagnosis are not a homogeneous group, as clear differences exist in symptomatology and comorbidity.

https://openresearch.nihr.ac.uk/articles/3-20/v1

[As the DecodeME team are waiting until peer review has been passed before we promote this or make any official comment, I won't be joining in the conversation below until then but will definitely follow it with interest.]

Edit to add: Final, peer reviewed version can be found here, https://openresearch.nihr.ac.uk/articles/3-20/v4

 

This study has funding to analyse the DNA of 5000 people with ME/#CFS following Covid. At the time of this analysis, only 380 had completed the questionnaire. Hopefully more people with #LongCovid can be reached to take part in this important research.

 

@Andy Can you say where this is submitted, or not? I do hope you're going for a leading / high-impact journal.

 

Damn, that's so disappointing. Such an easy goal to meet, all it would have taken is the tiniest bit of support and messaging. The LC clinics alone could have easily met that goal. The continued forced separation is really screwing everyone over.

 

I didn't realise there were so few questionnaires from people diagnosed after Covid. I wonder whether they're getting diagnosed with long Covid rather than ME, regardless of their symptom profile? The number of online support groups would suggest that at least some of these folk are proactive, engaged, and networked, and it'd be surprising if they aren't taking part simply because they don't want to.

 

Woah.
I have waited so long to see work like this and it's starting. I actually cried I was so relieved to see this pre-print paper and genuinely surprised by some of the findings. Well written and important. The beginnings of fundamental work that is so badly needed.

Thank you DecodeME team.

...and hello and welcome to the nice dose of Epidemiology

 

The team are wasting no time putting valuable work out there. Impressed.

 

@rvallee @Kitty

The other moderator I have in my ME/CFS FB group is a covid long hauler who lives in the UK. She really wanted to participate but she said only long haulers with a diagnosis of ME/CFS can, which she doesn't have. Not everyone gets this diagnosis even if their symptoms are similar to ours (I mean she wouldn't be my moderator in an ME/CFS group if she had some totally different presentation of the post-covid sequelae but these are the rules).

Actually, this is also what the DecodeME FAQ says:

I have Long Covid, can I take part?
We think many people with Long Covid will meet the criteria for ME/CFS, but not everyone. If a health professional has given you an ME/CFS diagnosis, then you can take part.​

 

One of the things that surprised me was the percentage that said they had IBS being as low as it was. I was personally actually ok about that separations at this time @Trish because more in-depth work on the cohort can happen with questionnaires. They can look further into the things your talking about which are really good questions and information that is needed which I also agree with.

 

I think most data of this sort coming from an online patient trawl will be affected by various biases and problematic interpretations. But as long as everyone knows this, and the team clearly will, it is likely that internal comparisons will throw up genuinely useful information. I think it is creditable that the team are getting this out now. As @Kitty, @NelliePledge and @Aimossy point out, the mix of expected and unexpected is intriguing.

It is interesting that longer duration is associated with severity. One obvious possibility is that this is skewed because those who have stabilised or improved a bit may have decided to 'put their ME behind them' as a way of coping and if I remember rightly people who have got better enough to feel they are no longer ill cannot take part. I do slightly wonder, if numbers are below target, whether it would be legitimate to ask for 'people who once diagnosed with ME' samples. I can think of one or two. It would have to be a separate cohort but it might be an interesting comparator, looking both for common features and differences.

 

Yes, that's what I wondered. In some respects I can understand why some GPs wouldn't take the diagnosis further than long Covid. They might think it's unlikely to help the patient or their doctors to call it by another name if there's a strong link to a Covid infection and the symptoms haven't changed.

 

Yeah, makes sense. How was it mentioned recently, "we don't like to give ME/CFS diagnoses"? They still don't. To work out would have required the system to fix itself beforehand. So we have studies on ME hindered by the refusal to acknowledge it, which makes it far more difficult to do because the system is too obstructionist and invested in the tradition.

A kind of "we'll give you the right to vote if you can pass a law for it, and you can't vote on laws, or the people who vote on laws, and we'll fight you the whole way". Good old Catch-22 disease. It's the only catch we got.

 

Problem with that is that there is no actual term for the feeling sick every day that most of us have, no matter what you do. Fatigue ain't it. There is no term for this other than "malaise" which is also awful because it can be used to mean anything. To me it's a sort of mix between being typically ill, though not as bad as full-on flu with fever, and some sort of TBI/concussion "poisoned" feeling. And then some, because ME is rarely ever just ME, there are so many less typical symptoms.

So the lack of that term kind of forces to use PEM, since it's not actually possible to exist without exertion. Only coma meets that. So there is some baseline sickness feeling, but medicine is unable to work with the concept of feeling ill without a cause they accept. That's how we got fatigue, and it's caused so much problems.

And it's still causing problems, with us and LC, because everything is made about some magical level of exertion that people can somehow find and continue indefinitely, then grow like magical beans.

So I don't see an alternative term that could be used here. Even a better term would need years of spreading the word around, since it would be impossible to get any consensus from the medical community, they categorically reject the very notion that there can be illness when they dispute any disease at all. And even worse, now the standard is that it's happening even with respected diseases. It's not about to get any better, at least until AI medicine gets under way. This is a people problem, a problem of empathy, of being unable to understand other people's subjective experience.

I've actually seen some dudebros psychosomatizers discuss Selma Blair's denunciation of how long it took for her MS to be taken seriously, and asserting that most of the symptoms look more like conversion disorder. We are still in the golden age of medical pseudoscience, it's growing in every nook and cranny of the profession, spreading like a cancer, or maybe more appropriately like a zombifying fungus.

 

There's another thing they could do with taking into account: Those that have been ill for a long time and particularly those who were very sick throughout their childhood, often say they have recovered when they are adults. However, they do not actually realise how sick they actually still are. Their functional capacity is way below average for their age, they just don't know it. Pressumably, they do not actually remember or even know what it feels like to be well, so to them a substantial improvement feels like recovery.

Here are some musings from Dr. David Bell on the topic:

"My greatest concern is for the years from 35 to old age in persons who became ill as teens. In our first study of teens who became ill in 1985, we concentrated on risk factors and epidemiology rather than on the progression of symptoms5. At thirteen years after onset, we studied the same patients, now young adults, and we noticed a discrepancy between how they rated their overall health and their activity level6. Some of the young adults rated their health as “good,” while the amount of activity they could perform was minimal. They had become so used to their performance level, they accepted it as their new normal. Unfortunately, many of them, while they described their health as good, they were unable to work full time or carry on other duties.

This same group of young adults was studied again at twenty five years after onset, and this pattern became more pronounced7. In this latter study, only five subjects said that they still carried the diagnosis of ME / CFS, despite their activity being limited and the symptom pattern persisting. All studies employed the Rand-36 (SF-36), a questionnaire is common use. The first question of this instrument is ’how would you rate your health?’ Many of the patients rated their health as ‘good’, while the rest of the questionnaire demonstrated how poorly they were actually functioning.

... Forty year old adults who had an acute onset during their teenage years have the activity of seventy year old adults."
1. https://www.omf.ngo/prognosis-of-mecfs/
2. https://www.massmecfs.org/more-reso...in-chronic-fatigue-syndrome-rising-incapacity

 

From my experience, i have seen the exact opposite. The most severe patients tend to be young males, or just young in general. I am fairly confident that this is the case. As you say, an explanation might be that the severe young patients eventually get a lot better and put their past behind them. I have noticed this trend too, actually. It may be that the severe young patients who remain severe for their whole life are in fact very rare.

This could also explain why doctors do not take ME seriously. For an old person complaining about fatigue and pain, and on the "moderate to severe" part of the scale, it could be very easy for doctors to erroneously assume those symptoms are simply a combination of burnout, old age and a sprinkle of depression and mid-life crysis - in the case of women, perhaps the stress of dealing with their kids. For a young mild patient, you can just say it's a psychological issue and that it doesn't concern you because the patient is still able to function at a decent level.

On the other hand, severe young patients in their 20s or even teenage years are a lot harder to ignore.

I have been severely ill since my teenage years and have not been able to finish my studies or work a single day in my life. It is hard for a doctor to ignore that. I have seen about 50 doctors and most of them told me they had never seen a patient like me - and that includes psychiatrists.

I am concerned because i have been severely ill for so long and show zero signs of improving (i only get worse), which is clearly against the trend of young severe patients improving and disappearing from ME circles to carry on with their life. I had a suspicion that I am in fact a very rare patient, and the data seems to confirm that.