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

[forestglip]

Comparing ME/CFS following mononucleosis with Long COVID

Jason, Leonard A; Furst, Jacob; Katz, Ben Z

Objectives
Long COVID following SARS-CoV-2 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) following infectious mononucleosis (IM) are examples of post-infectious chronic illnesses. Behavioral and pathophysiological underpinnings of both ME/CFS following IM and Long COVID are not well understood.

Methods
We studied ME/CFS development following IM in a diverse group of college students who were enrolled before the onset of IM. We categorized those meeting either moderate or severe ME/CFS criteria.

We subsequently recruited a matched sample of those infected with SARS-CoV-2, some of whom recovered and others of whom developed Long COVID. We compared and contrasted ME/CFS and Long COVID following IM and SARS-CoV-2 infection in terms of somatic symptoms, coping strategies, depression and anxiety symptoms, and functional status.

Results
In general, the Long COVID group's symptom burden was less than that of the Severe ME/CFS group but more than that of the Moderate ME/CFS group.

Discussion
These findings may allow investigators a better understanding of these post-viral illness pathophysiologies.

Web | DOI | PDF | Chronic Illness | Paywall

 

[Nightsong]

This compares their previous 2014-2018 glandular fever cohort to an LC cohort who

were recruited in 2023-2024 by social media sources and from posters and recruitment efforts at local universities

The participants were given

a medical evaluation, and that, along with self-report questionnaires (see below) helped determine whether a person had recovered or not from SARS-CoV-2. Those classified as Long COVID had continuous, relapsing, and remitting symptoms affecting one or more organ symptoms for at least three months following acute SARS-CoV-2 infection.1

Matching occurred on sex, race, ethnicity, and age for those 55 with ME/CFS following IM, the 55 with Long COVID, the 62 Controls who recovered from Mono and the 62 controls who recovered from SARS-CoV-2

There are pages of data tables comparing the ME/CFS and LC groups on various metrics. They used DSQ, SF-36, Compass-31, the Perceived Stress Scale, the Modifiable Activity Questionnaire, the Fatigue Severity scale, a 'Coping Orientation to Problems Experienced' Scale, and the Beck Depression Inventory. A few brief quotes from the summary of results ("Severe ME/CFS" here means those who met >1 set of criteria):

The Long COVID group had 18 significantly higher frequency/severity of symptoms than the Moderate ME/CFS group, including post-exertional malaise, Sleep, Neurocognitive, Neuroendocrine, Pain, and Autonomic domains; only in the Immune and Gastrointestinal domains were there no significant differences. It was more difficult to differentiate patients with Long COVID symptoms from those with Severe ME/CFS, but the latter group was more impaired in the following domains: Sleep (“needing to nap”), Immune (“sore throat” and “tender lymph nodes”), and Gastrointestinal (“abdomen/stomach pain”).

Although the Long COVID group had more physical functioning limitations and worse scores on anxiety and use of denial than the moderate ME/CFS groups, for almost all the other measures in Table 3, there were no significant differences, suggesting that while symptomatology does vary across the groups, functioning, coping, autonomic dysfunction, fatigue and stress were comparable. When differences did occur, they tended to be between the Long COVID and Control groups, with fewer differences between the ME/CFS groups and the Controls, and this is particularly apparent in the areas of coping.

In summary, the Long COVID group has less symptomatology than the Severe ME/CFS group, while the Long COVID group in comparison to the Moderate ME/CFS group had more symptoms, physical functioning reductions, and were more likely to have anxiety and use of denial as a coping mechanism.

 

[ME/CFS Science Blog]

Hard to take anything useful from this paper...

Seems like all of Jason's studies are now based on that distinction between moderate ME/CFS and severe ME/CFS. But the latter is not actually severe ME/CFS, just patients that meet more than one case definition for ME/CFS.

They then conclude that the LC patients had disability and symptoms somewhere in between those two groups.

 

[InitialConditions]

In general, the Long COVID group's symptom burden was less than that of the Severe ME/CFS group but more than that of the Moderate ME/CFS group.

I'm sure there are other results and conclusions, but this is next to useless.

 

[Trish]

I'm sure there are other results and conclusions, but this is next to useless.

All this abstract and the short extracts tell us is a bunch of assorted people with and without symptoms of some sort after EBV and after Covid filled in some rather random sounding questionnaires a bit differently, and the team decided to interpret the results in their own idiosyncratic way.

 

[Janet Stone]

As a member of the research team I can assure you that it was not just some random sounding questionnaire and idiosyncratic interpretation. The primary questionnaire used (DSQ) has been scientifically validated over many years as the gold standard tool for measuring symptoms of ME/CFS. The analysis is rigorous and the authors are experts with years of experience studying ME/CFS and now Long COVID. We are trying to identify the subtle differences among various post-viral syndromes since that may give us a clue as to the risk factors and possible treatment approaches. Long COVID was given a large amount of funding versus ME/CFS, and showing the similarities between a condition with a known cause and one that is still lacking definitive cause may help secure more funding for ME/CFS research.

 

[Trish]

As a member of the research team I can assure you that it was not just some random sounding questionnaire and idiosyncratic interpretation. The primary questionnaire used (DSQ) has been scientifically validated over many years as the gold standard tool for measuring symptoms of ME/CFS. The analysis is rigorous and the authors are experts with years of experience studying ME/CFS and now Long COVID. We are trying to identify the subtle differences among various post-viral syndromes since that may give us a clue as to the risk factors and possible treatment approaches. Long COVID was given a large amount of funding versus ME/CFS, and showing the similarities between a condition with a known cause and one that is still lacking definitive cause may help secure more funding for ME/CFS research.

Welcome to the forum, @Janet Stone. Thank you for joining us.

Since it's my post you're quoting, perhaps I can explain. My comments were not just a throwaway rather rude and dismissive comment coming from nowhere. We have spent years following Jason's team's work. While I really appreciate the effort and intentions of these studies, and think there is some value in them, I cannot understand why your team persists in the strange definition of severe ME/CFS not used by any other team or patients as far as I know.

You may have read our comments on this paper:
https://www.s4me.info/threads/predi...ectious-mononucleosis-2022-jason-et-al.24902/

Now that you have joined us, perhaps you can explain to us why you think your definition is useful when no one else uses it.

As for questionnaires being validated and gold standard, I'm sorry, that cuts no ice here. We have been plagued by a plethora of so called gold standard questionnaires for decades. Validation of quesitonnaires just seems to be an exercise in statistical game playing. 'my questionnaire gets about the same answers as yours so mine must be valid' is not a good basis for creating gold standards. If the process were genuinely validating why are we lumbered with nonsense like the Chalder Fatigue questionnaire and some dreadful stuff like catastrophising scales? Why are people with physical illnesses given psychological questionnaires that identify physical symptoms as psychological? I could go on.

Finally, why use psychological questionnaires? ME/CFS is not a psychological disorder.

 

[Trish]

It's been a while since I looked at the DSQ questionnaire. I assume this is the latest version.
https://redcap.is.depaul.edu/surveys/index.php?s=8sM6kF6dIut8XrMt

It has 99 questions. I would like to understand better how the results are scored and what interpretation is placed on the scores. Is there a guide to scoring?

As far as I can see at a quick glance through, it still conflates fatigue symptoms and PEM, with no clear questions to separate PEM from fatigue. So still not gold standard, if that's even possible with any questionnaire, especially one with fluctuating, wide ranging symptoms and varying severity, and the effect of whether someone can pace.

We have discussed some of the recent changes being made to the DSQ PEM questionnaire to take into account these differences, including delay, duration, severity, symptoms and reduction in function of PEM episodes? Are these going to be integrated into the DSQ ME/CFS questionnaire.

I'm sorry I'm rather hampered in trying to comment on this paper since it's paywalled and I don't have access..

 

[Janet Stone]

This page lists the versions of the DePaul Symptom Questionnaires that are available. They are used worldwide and the PEM questionnaire has been especially useful to clinicians because it helps them separate ME/CFS from other conditions involving fatigue.

Measures

csh.depaul.edu

To give a little background, I developed ME/CFS in my teens after a combination of mono and a toxic chemical exposure. I've lived with it over 50 years in varying intensities from fairly functional to bed bound. Viruses are my kryptonite and I have focused on post-viral syndromes in particular. When I started treating MCAS several years ago I saw a significant change in my symptoms and I went back to school to achieve my lifelong goal of becoming an epidemiologist and participating in ME/CFS research. I was invited to become a member of Dr. Jason's team which includes several professors, an MD, and students working on various related projects.

Seeing the research process from the inside was eye-opening and gave me a sense of what kind of hurdles researchers face when they are truly trying to advocate for ME/CFS patients including politics, funding, and criticism from the researchers and doctors who insist we just need to get out of bed and exercise more. Sadly, we also get a lot of criticism from the people we are trying to help, usually because they don't have all the facts. As a psychologist, Dr. Jason has spent the majority of his career validating patients and using his expertise to show that ME/CFS is not a psychological disorder. He is an expert in methodology and requires meticulous statistical analysis which is why his work is so well respected in the field.

One of our goals is to influence policy by providing accurate research, and economic burden is a major driver of policy change. While ME/CFS is a spectrum, focusing on the more severe population and helping lawmakers realize how serious this condition is for a significant portion of people can be a motivating factor for funding research and supporting proper diagnosis and treatment to avoid letting someone deteriorate to that level of need in the first place. It's an uphill battle fighting the GET and CBT crowd...that's what lawmakers would like to hear to ease their conscience, but it's not reality.

As to the scoring, yes, we use both frequency and severity of symptoms as measures when considering a score (scale of 1-4). Most questionnaires do not employ both so a symptom may be severe, but only for one day out of the month so it can be misrepresented. We also use a combination of criteria in studies and that is noted. Dr. Jason wants to see a worldwide consensus for research criteria and has been on many committees to try to make that happen, but there is much resistance. This study explains the revised DSQ-2 and what went into the validation process.

The DePaul Symptom Questionnaire-2: A Validation Study - PMC

The DePaul Symptom Questionnaire (DSQ) was developed to assess the symptomatology and case definition fulfillment of individuals with myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). The questionnaire was recently revised to ...

pmc.ncbi.nlm.nih.gov

Feedback is constantly evaluated and our team meets weekly to discuss the various projects and get input from other members so that we are considering all the different points of view. We do not take the responsibility lightly or try to impose some pet idealogy. Dr. Jason is committed to doing every study and project with the highest level of integrity. It's such an honor to be part of a team like that and I wish you all could see behind the scenes and know how committed we are to representing the ME/CFS community with the best data collection and publications.

 

[SNT Gatchaman]

Welcome @Janet Stone. With the data collection from 2014-18 this and related studies predate FUNCAP (Website | S4ME tag). Has the team discussed using it for future studies, to demarcate severity?

 

[Andy]

Sadly, we also get a lot of criticism from the people we are trying to help, usually because they don't have all the facts.

Wow, well you lost me there. 'Don't criticse us because you don't know everything we do!' Whose fault is it if we mere patients don't have all the facts, especially when publications from your group are behind a paywall?

Your group is responsibe for establishing a distorted concept of PEM in the literature which in many ways is unrecogniseable to patients; perhaps your group should take some responsibility for creating the frustration that many of us feel at that.

 

[Evergreen]

Great to have you here @Janet Stone. Very glad to hear you improved enough to train and work with Jason’s team – that must be so gratifying. I look forward to reading this paper when it is available, as I do to all papers from Jason’s team.

We have discussed many of Jason’s team’s papers here, for example, the Risks paper (Jason et al. 2020) and the 7-year follow-up paper (Jason et al. 2026). There is a lot of interest in this series of papers because a prospective study of ME/CFS after IM could give us a lot of valuable information. Members here have also raised a number of concerns.

The main thing that gives me pause is that people are being classified as having “severe ME/CFS” by virtue of fulfilling more than one set of criteria, when the term “severe ME/CFS” already has a meaning in the field – it has been used for decades to describe those who are completely housebound or bedbound. Introducing an alternative meaning for a phrase already in use is unhelpful. People with severe and very severe ME/CFS – and I am one of them - have a tough time getting the extent to which they are disabled by the illness across. It does not help if people who are not completely housebound or bedbound start getting that label. That would mean doctors think severe ME/CFS is not actually that severe, because they will see some with moderate and mild ME/CFS who fulfil more than one set of criteria.

There is some indication that people who are not severe may be getting classified as severe. In the 2020 Risks paper, 36.7% fulfilled more than one set of criteria, so are classified as “severe” at 6 months in that paper. That proportion is higher than the often-quoted 25% severe/very severe estimate for patients of all durations, where severe/very severe is defined in the usual way – completely housebound/bedbound. The problem is that we have no idea of the actual severity of that 36.7%. And we might expect a lower proportion with severe or very severe ME/CFS at the very early stage these patients are at compared to other cohorts where the disease has progressed, and comorbidities and ageing have added to the picture.

There's always the chance that a higher proportion of younger people are severe or very severe in the early stages. But people who are severe and very severe need care. That would generally mean withdrawing from university and returning home to be cared for, or at the very least, people needing to be seen in their dorms/housing. There is no mention of that in the 2020 Risks paper (unless I missed it). We would expect those with severe and very severe ME/CFS to drop out of studies like this – again, we’d expect a lower proportion with severe or very severe ME/CFS as a result, not higher.

It would have been very interesting to know the severity breakdown of people with post-IM ME/CFS at 6 months and 7 years, but these studies do not provide that. Perhaps something future studies could do.

I worry that this noble goal:

While ME/CFS is a spectrum, focusing on the more severe population and helping lawmakers realize how serious this condition is for a significant portion of people can be a motivating factor for funding research and supporting proper diagnosis and treatment to avoid letting someone deteriorate to that level of need in the first place.

is leading to methodological decisions that could inflate the proportion of those who develop post-IM ME/CFS and the proportion with severe/very severe ME/CFS by scooping up more of those who do not have ME/CFS and more who have mild/moderate ME/CFS respectively. Ultimately I think that will reduce credibility, not increase it.

Feedback is constantly evaluated and our team meets weekly to discuss the various projects and get input from other members so that we are considering all the different points of view.

Maybe some of the substantive issues raised by members here could be considered by the team?

For example, in a careful series of posts starting here, @Simon M ponders the higher prevalence found in these studies, and asks whether the “moderate” group in these studies might contain people who do not have ME/CFS.

And here, @ME/CFS Science Blog queries the methods behind the finding that baseline depression and anxiety do not predict ME/CFS:

Hope to see you here more, @Janet Stone.

 

[Utsikt]

There are many examples of the questionnaires creating false positives. That should cause some concern, but it doesn’t seem like the team is particularly worried about it. I haven’t understood why yet, I hope you can clarify.

Please don’t assume that criticism stems from ignorance. It’s insulting, and the antithesis of science.

He is an expert in methodology and requires meticulous statistical analysis which is why his work is so well respected in the field.

As others have tried to point out: statistics doesn’t lead to usefulness by itself. A questionnaire without content or construct validity has no use, and often cause harm. The test-retest validity etc. is irrelevant if it the data doesn’t give a useful representation of reality.

Appealing to authority or consensus won’t get you anywhere.

 

[Trish]

Hi again, @Janet Stone. Thank you for sharing your personal story of how you came to be involved with the Jason team. It helps to understand a person's context. I absolutely accept that Lenny Jason and his colleagues are dedicated workers with unimpeachable integrity and dedication to the cause of better lives for pwME. I have never questioned that.

However that doesn't mean they are always right, or always receptive to criticism and constructive feedback. Nor does it justify you criticising pwME who dare to question any of the team's work.

As others have said repeatedly over the years, the misrepresentation of PEM as an increase in fatigue related symptoms after exertion by Jason for many years has in my view muddied the water rather than bringing clarity. I have been pleased to see some effort being made recently to try to remedy that, though there is in my view more work to be done.

My particular concern with the current study under discussion here is the continued use of Fukuda criteria which doesn't require PEM, and the bizarre definition of severe ME/CFS as anyone fulfilling 2 of the main ME/CFS diagnostic criteria, regardless of actual illness severity. As far as I know no clinicians or guidelines use that definition of severe ME/CFS. Can you explain the rationale for these choices?

Thank you for the links. I'll take a look. I have also been given access privately to this paywalled paper, so will try to find energy to read it.

 

[Trish]

Over the years my ME/CFS has ranged from mild and able to work part time, through moderate and able to go out a bit, to severe and housebound and mostly in bed. The number of criteria I have met has not changed.

Until the Jason team recognise they have got their definitions of ME/CFS and severity levels badly wrong, they will continue to do harm. Misleading clinicians and patients does harm. I won't apologise for saying that.

 

[Trish]

Gosh, I have started reading the paper and looking at the data.

This line of data stands out as a demonstration of the problems of the definiton of moderate and severe ME/CFS:

SF-36 Physical functioning, mean (standard deviation)

Severe ME/CFS 77.7 (18.9)
Moderate ME/CFS 90.4(11.1)
Long Covid 73.2 (21.5)
Mono controls 98.6 (3.9)
LC controls 93.6 (11.6)

Compare those figures with the PACE trial with means around 40 to 60 across the trial, and they were all able to attend clinics so would be classed on most severity scales as mild to moderate. To enter the PACE trial you had to score 65 or less.

What on earth is going on here?

 

[Evergreen]

Thought it would be useful to park this here. These are Cox & Findley's descriptors of severity in Chronic Fatigue Syndrome from their 2000 paper. This is the paper I find researchers refer to most when talking about severity:

The patients in the mild category are mobile and self caring and able to manage light domestic and work tasks with extreme difficulty. The majority will still be working. However, in order to remain in work they will have stopped all leisure and social pursuits, often taking days off. Most will use the weekend to rest in order to cope with the week.

The patients in the moderate category will have reduced mobility and be extremely restricted in all activities of daily living, often having peaks and troughs of ability, dependent on the degree of symptoms. This group of patients have usually stopped work and require many rest periods, often sleeping in the afternoon for one to two hours. Sleep quality at night is generally poor and disturbed. This level appears to be the group most cited in the description of studies and CFS services (4-8).

The patients in the severe category will be able to carry out minimal daily tasks only; face washing, cleaning teeth, have severe
cognitive difficulties and be wheelchair dependent for mobility. These patients are often unable to leave the house except on rare occasions with severe prolonged after effect from effort.

The patients in the very severe category will be unable to mobilise or carry out any daily task for themselves and are in bed for
the majority of the time. These patients are often unable to tolerate any noise, and are generally extremely sensitive to light.

 

[MrMagoo]

Sadly, we also get a lot of criticism from the people we are trying to help,

Feedback is constantly evaluated

Sadly, we get a lot of help we didn’t ask for, don't value, didn’t want and then are blamed by the people who cannot take any criticism.

You can’t please all of the people all of the time. That’s part of life.

Just as you are not “just” a researcher and scientist - you also have ME, in this forum there are not “just” people who have ME, they also are researchers and scientists.

So let’s discuss the matter and review the science as peers, without the personal.

 

[Kitty]

It's striking that "criticism from the people we are trying to help" is paired with the word "sadly".

This is the most valuable criticism any scientist could hope to receive. It worries me when it's not recognised as such.

 

[Concentric_Spiral]

I'm new to the forum and don't know much about ME/CFS, but that feels like an extension of the 'pwME are troublesome, hysterical people' trope.