Risks for Developing ME/CFS in College Students Following Infectious Mononucleosis: A Prospective Cohort Study, 2020, Jason et al

Perhaps, but for a young adult, anxiety and depression would be totally appropriate if you had an infection and did not recover, could not possibly go dancing and socializing at night, and had trouble studying- the prolonged illness state is unexpected especially at this stage of their lives. Uncertainty and lingering symptoms that restrict living a full life while not getting answers in health care would generate anxiety and depression.

Unfortunately, from the facebook Long-COVID groups, patients with Long-COVID also experience anxiety and depression due to their circumstances, not being believed being one major cause, but also uncertainty in regards to their future.

 

Does anyone know when we can expect the final version, and find out what they mean by "behavioral measures"?

 

Well, I've written about Mayo multiple times, and have repeatedly blasted the CDC for avoiding its public health responsibilities in this domain. However, the UK cabal has been the primary driver of this movement in the literature and in research, along perhaps with the Dutch and the Danes--even if the use of the term CFS for the Tahoe outbreak inspired them on this front.

 

Yes, but all they did was to develop the concept of illness behaviour which was already developed in the US. All their ideas are already to be seen in the McHugh and Vallis book. I am not making a point about the US. I am sure there was a great deal of cross fertilisation of ideas; in the UK Shepherd was clearly an exponent of such opinions, but they are less well known, and it appears that before writing his 1966 paper on illness behaviour Mechanic spent time at the Maudsley and acnowledges the assistance of JK Wing.

It should also be borne in mind that in the 1995 Surawy et al paper (al including Sharpe) the advice of Beck was acknowledged. They could never have done this alone.

 

Sure, that's a reasonable perspective, although I might quibble with the phrase "all they did"--that covers a lot of damage!! The distinction between illness and disease has also been popular in medical anthropology circles in the US for decades, so it's nothing new from Michael Sharpe. But when it comes to applying general theories to this particular illness or cluster of illnesses, the UK group grabbed that and ran with it for the last 30 years.

 

S-ME/CFS also had higher perceived stress at baseline. Not by much but still...

 

I have read that Michael Sharpe was part of the group at the CDC who defined CFS and Wessley was at the original conference.

 

Iniital thoughts

Hats off to Lenny Jason and colleagues for pulling off and a huge and significant study.

This is the first truly prospective study of post-infectious ME/CFS. The importance of prospective studies is that measuring what happens before the illness starts allows researchers to identify causal factors. Most studies in ME/CFS can only find associations with illness, which can’t distinguish cause from effect.

This was a huge study. 4700 students were enrolled between March 2014 and June 2018. Most of them were in their first year and about half of each incoming class enrolled in the study. More than 95% of those who enrolled completed the surveys (nine of them, I think) and gave a blood sample.

The paper says that students were compensated fortaking part, which looks like a smart move, because these participation rates are incredible.

Out of this huge cohort of 4500 students, 238 (5%) developed infectious mononucleosis (glandular fever) by the end of June 2019. 55 of these (23%) met at least one of the criteria for ME/CFS are (CCC, Fukuda and IOM). 20 students meant at least 2 criteria and were classified as severe (@Andy no further qjustification for this was given).

157 students no longer had symptoms at six months and were classified as recovered.

Key results

Comparing those with mono who recovered with those who developed ME/CFS, there appear to be two important results from this study:
1. There are no siginficant differences between the two groups on the measured psychological factors of stress, coping, anxiety or depression at baseline. That seriously undermines psychosocial theories of the illness. If they need undermining any further.

2. "In a previous study, we identified mononucleosis severity as a risk factor for severe ME/CFS. That relationship was found in the present analysis as well (p = 0.04; data not shown)". and the P value isn't impressive but it also ties in with findings from the Dubbo study. And with Peter White's infectious mono study, which found that days of bedrest predicted CFS. They don't say how severity was measured.

Otherwise, not so much to see, I fear

Based on my first reading of the paper, there is otherwise not a huge amount here. There are some differences but I'm not sure if the authors have corrected sufficiently for the very high number of comparisons(e.g they use results from 12 different scales but use a p value of 0.01). And in any case the differences appear to be quite small even if they are significant.

I'd be very to know if @Jonathan Edwards thinks cytokine differences given in table 3 are likely to mean very much.

Some issues to discuss

This situation is disappointing. There are a few methodological issues that may or may not be relevant. I would appreciate the views of others.

1. Data and blood samples were taken "within six weeks of diagnosis". That strikes me as quite a wide window and I thought it was much shorter for both Dubbo and the Peter White study. This raises the possibility that, for at least some people, the data and blood sample were collected after the main action was over.

2. I am not convinced that the threshold for "substantial reduction in activities# was especially strong.

Surprisingly, the study does not use the SF36 Physical Functioning PF scale, which is the scale used by most researchers in diagnosis. Instead, the authors define substantial reduction as "scoring at or below at least two of three cut-offs on the SF 36: role physical <= 50, social functioning l<= 62.5, and vitality <= 35.

Also, this study uses the DePaul symptom questionnaire and its definition of PEM. There are reasons to question whether that actually captures PEM, with the risk that sweeps people into a diagnosis that perhaps shouldn't be there.

However, all diagnosed cases did have a medical exam and physical and psychological assessment.

Certainly, the very high proportion of people with IM developing ME/CFS at six months (23%) is surprisingly.

3. For the non-severe ME/CFS cases (i.e. meeting only one criteria, which the paper says was almost always Fukuda) the increases in fatigue and DSQ scores from baseline are modest.

DSQ symptom scores increased from 17 at baseline to 20 at six months, while the fatigue score increased from 33 to 39. The severe ME/CFS scores showed a bigger incremental increase, but it still wasn't huge. Certainly, I think these small incremental increases cast some doubt on the validity of the single-criteria-meeting standard ME/CFS group.

Okay, I am done.

Added: apologies for not quoting people's contributions; not easy on an iphone and trying to avoid triggering the next bloody migraine with too much screen use.

 

Press release

https://resources.depaul.edu/newsroom/news/press-releases/Pages/mecfs_mono_2021.aspx

 

US News
Why Does 'Mono' Sometimes Turn Into Chronic Fatigue Syndrome?

The researchers discovered that people who developed ME/CFS had more physical symptoms and immune irregularities at baseline. The participants did not start with more psychological symptoms, such as stress, depression, anxiety or abnormal coping.

"It turns out that our results suggest those more psychiatric variables were not predictors of who got mono and stayed sick and who got mono and did not stay sick," Jason said.

According to Dr. Lily Chu, vice president of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, the misconception that ME/CFS is caused by psychological reasons has persisted for decades. This study adds to the evidence that ME/CFS is not a psychiatric or psychological condition, she said.

 

Has anyone pointed out that this appears to be a direct contradiction of the "findings" of Imboden, Canter and Cluff relating to chronic brucellosis and Asian flu, and upon which the BPS model for CFS was partly based? As Fauci seems to have supported Straus over the issue who are we to believe?

 

article:
Study examines risk factors for developing ME/CFS in college students after infectious mononucleosis

https://www.news-medical.net/news/2...-students-after-infectious-mononucleosis.aspx

 

Coming back at this paper. Participants were assessed before mononucleosis (time1) during mono (time2) and 6 months after mono (time 3).

The authors reported no statistically significant result at time 1 for anxiety (BAI questionnaire) and depression (BDI-II) but I think this is because they arbitrarily split the ME/CFS group into two. I believe that if the 49 ME/CFS patients were taken as a whole and compared to the recovered control group, many of the baseline values would show a statistically significant difference as the difference are quite obvious (see calculations below).

The main finding seems to be that patients who reported more fatigue, depression, stress, anxiety and other DSQ-symptoms before getting mono were likely to be diagnosed with ME/CFS, 6 months after mono. One interpretation could be that if your baseline level of symptoms is already high, you are more likely to meet ME/CFS diagnostic criteria after getting a serious infection.

When testing for predictors of ME/CFS it might therefore be important to control for these baseline symptoms in regression analysis or exclude patients who were already fatigued. I believe this is the approach that the Lifelines cohort used and they found that anxiety and depression were not a predictor of (self-reported) ME/CFS. One can debate what is the most suitable approach because it is quite an interesting finding in itself that baseline symptoms are a predictor. A lot depends on what you put as variables in the regression analysis. It is quite unfortunately that we have so little longitudinal data and that none of the raw data is publicly available.

Calculations and estimations
Here are my calculations. For the BAI-anxiety questionnaire at timepoint 1, I calculated the weighted mean, weighted standard deviation (using this formula) and sample size of the two ME/CFS groups combined.
Mean = 8.33
Sd = 7.44
N = 49

For the control group the values are:
Mean = 3.88
Sd = 4.57
N = 60

When I did a independent t-test for this difference, I got a significant result (t = 3.65, p = 0.00047).

Similarly for the BDI-II (depression) at time 1, the combined ME/CFS groups looks like this:
Mean = 9.86
Sd = 7.71
N = 49

For the control group the values are:
Mean = 5.43
Sd = 4.50
N = 60

Here I get a t-value of 3.56 and p-value of 0.00066.

The result for the PSS-stress questionnaire gave the following data. For the combined ME/CFS group:

Mean = 6.92
Sd = 3.14
N = 49

For the control group the values are:

Mean = 5.58
Sd = 2.74
N = 60

This gave a t-value of 2.34 and a p-value of 0.021.