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

I'm putting together a few comments on the paper. I will submit to the journal but they prefer comments to come from people with an affiliation, so they may not publish. But I noted the CMRC/MERC + its PAG are not thanked in the Acknowledgements. They should be. Stephen did a lot behind the scenes, but in the early stages of DecodeME (before it was even called that) so did other members and PAG'ers.

 

Thanks for everyone who worked on this. Some findings I found interesting:

• 83% of patients were female
• The majority, around 60%, described their illness as fluctuating. This group was much larger than those who indicated improving, getting worse, no difference of relapsing/remitting.
  
• Age was one one of the factors that best predicted symptom severity.
• Participants who had an infection at onset were more likely to have had ME/CFS symptoms for over 10y despite their similar
  ages as those with no infectious onset.
• There seems to be an under-representation of non-white, male patients with ME/CFS onset less than 3 years ago. The group of patients with ME/CFS following COVID was also very small (only 380 out of 170.000).

 

Anybody is welcome to submit any comments direct to the team via info@decodeme.org.uk - please help us by using "Comments on the questionnaire analysis preprint" as the subject line.

 

That's good. I will post on the open respository and if they're not published I will send to that email address.

 

Thanks team DecodeME!

Do we have a thread for discussing the DecodeME questionnaire? My search strategy is failing me

 

No, we don't.

 

The preprint links to a copy of the questionnaire and specifies the particular questions which appear in the image, so no, I wouldn't have thought we would intend to do that.

 

All study documents, including the questionnaire, that we are currently able to make available can be found here, https://www.decodeme.org.uk/documents/

Anticipating questions, what is not available is the algorithm used to determine whether or not we ask people for a DNA sample.

 

i haven't read this properly yet so I'm maybe getting it wrong - but is subtyping based on the assumption that respondents don't have certain conditions (whether they are truly comorbidities or intrinsic parts of ME) if they don't have a formal diagnosis. I have the symptoms of PoTS, MCAS, IBS, Fibromyalgia & Migraine, but I've never been diagnosed with any of these.

I've forgotten what the questions were exactly, but I think participants could only claim to have these comorbidities if they had been given a formal diagnosis. So although this of interest in delineating our progression through the health service, a negative response doesn't exclude having these comorbidities. But maybe the symptoms questions clarify possible comorbidities?

I haven't expressed this well. I hope it's understandable.

 

The sub-typing is simply by onset,

"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."

with further analysis of the questionnaire answers, including reported comorbidities, within and between the different types,

"These onset types reveal differences amongst those with ME/CFS regarding their symptoms and comorbidities (Figure 4). However, these distinctions are not absolute. For example, those reporting no infection at onset (Type 4, above) are not cleanly distinguished from all others by active clinical depression. Rather, they were the only onset type that was more likely to report this diagnosis (25.4%) than all other participants were (19.6%). Similarly, Type 3 contains a higher proportion (9.4%) of those who report inactive shingles, than all other participants (7.3%)."

And yes, participants were asked to report comorbidities only if they have received an official diagnosis.

 

Thanks, Andy.

 

Here are some (mostly minor) comments from me. I will also send these to the lead author.

 

I find it disappointing that enteroviruses are lumped in with "other infections" with enteroviral infection being the infection type that led to ME being defined as a disease and EBV shown to not be significant in the Tahoe outbreak.

My symptoms were overwhelmingly neurological in the early days but matched those of many people who had been ill for many years including the Royal Free outbreak. I wonder if that is because of enteroviral damage to the brain.

Feels like a lost opportunity.

 

One of my comments is on this topic. The answers to infection type are 'baked-in' to the questionnaire, so now you can't subset by e.g., enteroviruses. Having said that, glandular fever is relatively easier to confirm in the clinic.

 

Primary progressive M.E might be distinct from other M.E subtypes which has been shown to be the case in MS.

https://academic.oup.com/brain/article/146/5/1979/7024973?login=false

 

Does the "more likely to report clinical depression" group differ in other ways?

Is this clinical depression being confused with ME/CFS, or is it ME/CFS that is misdiagnosed as depression because the lack of infection makes clinicians think depression instead of ME/CFS, or does this group simply have more severe depression for some obscure reason?

The last scenario seems to suggest differences in pathophysiology.