Trial By Error: DecodeME Team Describes Study Sample; The Atlantic’s Ed Yong Covers PEM; STAT Busts NIH’s Stumbling Long Covid Efforts

By David Tuller, DrPH

Update: The post indicates that more than 17,000 people had submitted the DecodeME questionnaire. Actually, as of the most recent count this month, DecodeME has now received more than 23,000 questionnaires.

DecodeME paper finds ME/CFS severity linked to being female, being older and being sick longer

DecodeME is a high-profile genome-wide association study (GWAS) that is seeking to identify DNA differences between people with ME/CFS and those without it. To date, more than 17,000 people in the UK who report having been diagnosed with ME/CFS have submitted questionnaires; many have subsequently been asked for DNA samples. In a new paper posted at NIHR Open Research, the DecodeME team, which includes patients as well as academic investigators, has described characteristics of the study sample based on these questionnaires. (The project continues to seek participants.)

An initial draft of the paper was actually posted as a pre-print on NIHR Open Research earlier this year. (The site hosts research from Britain’s National Institute for Health and Care Research, which is a funder of the DecodeME project.) The investigators did not promote the findings, however, until two experts had peer-reviewed the paper and approved the final version. That process concluded this week.

The paper is called “Typing myalgic encephalomyelitis by infection at onset: A DecodeME study.” Here are the “results” and “conclusions” sections of the abstract:

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 tend to have more comorbidities 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 infection at onset; and, (v) where the occurrence of an infection at or preceding onset is not known. Among other findings, ME/CFS onset with unknown infection status was significantly associated with active fibromyalgia.
Conclusions: DecodeME participants differ in symptoms, comorbid conditions and/or illness severity when stratified by their sex-at-birth and/or infection around the time of ME/CFS onset.”

The findings received widespread and respectful attention in the UK media, including in The Guardian, Sky News, and The Independent.

Ed Yong on fatigue and post-exertional malaise

I’m a bit late on this, but Ed Yong wrote another great piece in The Atlantic—his final one, I gather, as a staff writer for the magazine. This one, published in late July, focused on the phenomenon of post-exertional malaise—something that everyone in the ME world knows about but that is pretty much a blank for everyone else, including many physicians and other clinicians.

Ed provides an up-to-date account of the thinking and science regarding PEM, in the process distinguishing it from what most of us think of as “fatigue.” He also describes what the experience is like for patients. For those immersed in these realities, it can be hard to remember that most people know nothing about PEM and have likely never heard of it.

Here’s a key passage:

“Post-exertional malaise, or PEM, is the defining trait of ME/CFS and a common feature of long COVID. It is often portrayed as an extreme form of fatigue, but it is more correctly understood as a physiological state in which all existing symptoms burn more fiercely and new ones ignite. Beyond fatigue, people who get PEM might also feel intense radiant pain, an inflammatory burning feeling, or gastrointestinal and cognitive problems.”

And another (there are lots of them): “Where fatigue usually sets in right after exertion, PEM might strike hours or days later, and with disproportionate ferocity. Even gentle physical or mental effort might lay people out for days, weeks, months. Visiting a doctor can precipitate a crash, and so can filling out applications for disability benefits—or sensing bright lights and loud sounds, regulating body temperature on hot days, or coping with stress. And if in fatigue your batteries feel drained, in PEM they’re missing entirely. It’s the annihilation of possibility.”

The Atlantic also ran an interview with Yong about the piece.


STAT busts NIH for failures on long Covid

Two years ago, the US National Institutes of Health made headlines when it committed $1.15 billion for research into long Covid, called RECOVER. The department has been under pressure to show some results. In a sharp look at the situation for STAT earlier this month, Betsy Ladyzhets reported, as stated directly in the headline, “NIH trials fail to test meaningful long Covid treatments.”

The opening pretty much says it all: “More than 2.5 years after the National Institutes of Health received a $1 billion mandate from Congress to study and treat long Covid, the agency has finally launched clinical trials for the often-debilitating condition. But both scientists who study long Covid and patients who have struggled with it say the trials are unlikely to deliver meaningful treatments, suggesting the federal government’s landmark Covid research effort may have been wasted.”

Most of the RECOVER funding has gone to observational studies, and only around 15% to treatment trials. Now that those have been launched, there is widespread dissatisfaction at their limited reach and scope, with only a handful of drugs and behavioral treatments among the interventions. According to the article:

“One reason for the lack of promising treatments among RECOVER’s trials is the initiative’s overall failure to learn from past research in other chronic diseases that share symptoms with long Covid, said Todd Davenport, a professor and rehabilitation expert at University of the Pacific. Davenport has studied myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a condition that is now a common diagnosis for long Covid patients.

“Scientists on the RECOVER team ‘have parachuted into post-infectious illness and are now trying these things for the first time, to them,’ Davenport said. ‘But it’s clear they haven’t done the reading.’

“Davenport and other scientists outside of RECOVER have long lists of drugs that they’d like to test, most of which are not included in the NIH study.”

8 thoughts on “Trial By Error: DecodeME Team Describes Study Sample; The Atlantic’s Ed Yong Covers PEM; STAT Busts NIH’s Stumbling Long Covid Efforts”

  1. With regards to the DecodeME study, I wonder – could the people with fibromyalgia but no apparent infection trigger/cause have a different illness instead? It looks to me like there’s quite a difference between those who report that their problems started with infection and those who don’t.
    It would be nice to able to see raw symptom data for each of the onset types to see how their symptom profiles compare.

    It looks like those with glandular fever type onset tend to be younger. Does that suggest that patients with this type of onset (overall) have a better chance of recovery as time goes on?

  2. I see that for glandular fever type onset, the DecodeME data suggest that older people getting glandular fever are more likely to develop ME/CFS. Putting that together with the data showing that the onset type due to glandular fever tends to be younger (than other types) , wouldn’t that point to sufferers with glandular fever type onset having a better chance of recovery? I mean, if that trend isn’t due to younger people being more likely to get ME/CFS then it’s possibly down to more people recovering?

  3. In the Decode ME Study I can’t quite unpack the stats on men – vested interest, man with ME/CFS.

    Is being male a significant factor in risk of deterioration into severity or not? Is it ‘just’ more likely that women will get more severe with age? But do men get worse over time too? Or is there hope that men don’t deteriorate and is there something in the male that could help women not deteriorate so fast or so far?

    Do men get more severe the longer they’ve had ME/CFS or is it only women? If not, how?

    Are the comorbidities that affect older women, with ME/CFS for over ten years, gender-specific? I.e. men cannot have them (menopause comes to mind)? Would they affect older women anyway, but the effects are always worse for those with ME/CFS? Similarly, do men with ME/CFS with, e.g. prostate issues, experience them similarly or worse or less severely than men without ME/CFS?

    If they are shared comorbidities but of lower incidence in men, then there’s a more genuine gender disparity – what can be learned here? Should men with ME/CFS be researched separately to women because it affects each gender differently, to statistically and clinically relevant levels? Is there something that can be learned from one gender’s lived experience and responses to treatments that could assist the other?

    The effect of ME/CFS on women is horrid, the gaslighting, negative gender stereotyping, accusations of hysteria, mental illness, disbelief and spurious treatments needs constant challenge.

    However, the social stigma on the flip side is that for men with ME/CFS, they are lumped in with being told “it’s a women’s condition”, which is seen horribly as pejorative. The concepts of “Man up, push through, etc” compound on men disproportionately as toxic mentalities and tropes.

    It’s overall a truly emasculating experience to read multiple studies and media articles inferring that somehow because women’s comorbidities are more numerous, men must be suffering less. In the doctor’s office this equates to men must be suffering to such a lesser degree that they are not really suffering and must be making it up, or making out that it’s worse than it is, a trope reinforced in so many circles by the ‘lazy, good-for-nothing, fat, pathetic, uncaring, etc’ labels of memes, sitcoms and more.

    Given that suicide rates are higher amongst men in general, I wonder if the stats on male/female prevalence are skewed, because more men can’t stand the additional shame and humiliation of being unable to work, unable to be effective husbands, fathers, bread-winners, etc. Yes, that’s stereotyping, but we’re in denial if we think that isn’t the prevailing expectation and conceptualisation of male roles and intrinsic worth in Western societies.

    I would be very interested in a deeper exploration of the findings that goes into the male/female dividing factors…

    On the plus side, great research and I’m glad to have both filled out the questionnaire and provided my DNA.

    Keep up the good work!

  4. I think Trevor has raised some very important questions and points here. Men with ME/CFS should not be stigmatized or side-lined because the gender bias of this disease is so much towards women.

  5. What are the reasons for rejection of male applicants compared with female applicants, I wonder?

  6. I am pleased to see the questions being asked as to why such things as the menopause did not rule out female replies? Surely, knowing many women going through that if very similar symptoms should have seen them rejected.

    Likewise, the failure to concentrate any effort for conclusion on male suffering showed to me a lack of need to do so.

    Entities such as the ME Association and DecodeME survive on funding and publicity. That the initial very seriously flawed findings claimed a female dominance of ME, they were not so keen to show just how close the stats were with men. They are there but not in the press releases or interviews. Likewise, the level of female participation with a broader cross section of ages was not mentioned.

    This lot need to be stopped before they do some (more) seriously lifelong damage to the thousands of male sufferers.

    Mine started in 2014, diagnosed 2017. It’s very serious and aged me loads. From a fit 51 year old to a very poorly disabled 60 year old fighting to stop myself becoming the most severe group which, for me personally, I feel is a choice and one I am not going to make as I still in my mind at least, have a lot of life to try and live and now, apparently, I am a minority sufferer. I am in the wrong clique!

    They have no idea how their stupid publicity stunt has damaged the reputations of male sufferers.

    For years I have been in one minority group after another.

    I am a gay man who raised his 4 children when the mother left.
    Two of those children have SEN mental and physical
    I have been an unpaid carer.
    All the support groups want me to be in with the male support groups, I have no interest in boobs and football.
    I am short, I wear hearing aids and need strong glasses.

    Effectively, I don’t fit into any group and now, I am not as important as women with exactly the same condition as me!

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