The recent National Institutes of Health (NIH) ME/CFS Deep Phenotyping Study was not intended as a standalone project, but as the first phase of a three-part NIH initiative to investigate post-infectious ME/CFS. Whilst the first phase had its shortcomings, it also yielded numerous significant findings that could have been further explored. However, the study’s principal investigator, Dr Avindra Nath, is now redirecting his research efforts to focus specifically on long COVID.
Last month, a quote from a resurfaced interview with Dr Nath, shared on X/Twitter, left many in the ME/CFS community frustrated and disappointed. Explaining his shift in research focus, Dr Nath stated:
“…the population affected by long COVID is so much larger and the symptoms are so much more severe compared to ME/CFS that we decided that what we should do is focus on long COVID.”
The remark about severity suggests a lack of understanding of the debilitating nature of ME/CFS. It also indicates a lack of awareness that an estimated one-quarter of individuals with ME/CFS suffer from a severe form of the disease, often leaving them house- or bedbound and requiring significant care. Such a comment is especially perplexing when stated by someone who led a major study on ME/CFS. It would be helpful if Dr Nath clarified whether his statement was misconstrued – for example, whether his reference to severity pertained to the acute organ damage sometimes caused by COVID-19.
This statement risks creating division between the ME/CFS and long COVID communities, causing each to justify why their condition is more severe than the other. Moreover, Dr Nath should be aware that there are individuals with long COVID who have been diagnosed with ME/CFS or meet ME/CFS diagnostic criteria. Consequently, a substantial proportion of those with “severe” long COVID may, in fact, have ME/CFS triggered by COVID-19.
The statement within context
To provide a fair and balanced response, it is important to examine statements within their broader context. Below, we have provided a transcript of the relevant segment from the “COVID On The Brain” podcast, along with further commentary. The segment begins around 24 minutes in –
Interviewer: “…Will you be returning to your focus on [ME/CFS]?”
Avindra Nath: “…We did a lot of research on ME/CFS and we have a paper that should soon be published…The thing is that there is so much overlap between that and long COVID, and the population affected by long COVID is so much larger and the symptoms are so much more severe compared to ME/CFS that we decided that what we should do is focus on long COVID. And all the experience that we gain from ME/CFS, we will apply to this population. The advantage of studying long COVID is that you know what the starting pathogen was. In ME/CFS there is the same thing people say ‘well we had an infection of some sort’ and now they develop these symptoms but they have no way of going back to try and find out what infection they had because you’re seeing several years after the initial event. So, I think whatever we learn from long COVID would be applicable to ME/CFS but … will be a lot easier to sort it out here than in those other patients.”
Interviewer: “Absolutely, and we briefly discussed the subcategories of long COVID – are they particularly defined? Can you comment a little more on that?”
Avindra Nath: “…Yes, we are starting to realise there are subcategories, but they may not be entirely distinct. So, there is a fair bit of overlap between them. But by and large what I do is I divide them into a subgroup of individuals who are complaining of predominantly exercise intolerance, so that means that every time they exercise or take a flight of stairs or whatever, they just get exhausted either physically or mentally, or both. And then there is a category that has largely cognitive problems, so they have difficulty with concentration, with sleep, and they can also develop depression or anxiety – so I put them as one category together. And then there’s a third category – complains of POTS-like syndrome which is every time they stand up they get dizzy, and their heart rate goes up, their blood pressure falls… and they also develop symptoms of peripheral neuropathy, so they can develop pain or numbness in their extremities at the same time – so that’s predominantly a peripheral nerve problem, so that is why I put it together in a separate category. And then the fourth category is pain syndromes … so you can get fibromyalgia, or headaches…within the pain syndromes headaches should form a separate category because sometimes you can find causes for the headaches that are treatable. So, I think those are the four major categories. …There is … [a] set of patients who develop tinnitus and hearing problems – and I never quite figure out where to put them in this thing, but they are a smaller subgroup there… That’s the way I look at it.”
Further thoughts
The shift away from explicitly studying ME/CFS will likely disappoint many individuals with ME/CFS, a condition that is already under-researched and often stigmatised. This shift may even feel like yet another abandonment of the ME/CFS community.
However, it is important to recognise that Dr Nath, aside from his contentious comment about severity, does provide a rationale for his shift in focus – the fact that with long COVID, researchers know the starting pathogen/triggering event. ME/CFS can have multiple triggers, both viral (including COVID) and non-viral. Thus, focusing solely on long COVID might be an attempt to ensure a more homogenous study population, reducing confounding variables and allowing for clearer interpretation of results. Moreover, Dr Nath seems to imply that he would use the long COVID study findings to benefit individuals with ME/CFS.
Nevertheless, it is not entirely safe to assume that disease triggered by COVID-19 is identical at a pathophysiological level to disease triggered by other agents. This might explain why ME/CFS, known for having diverse triggers, is such a heterogeneous disease, where individuals share core features but have a variety of symptoms and responses to ‘treatments’. Therefore, waiting for long COVID study results is not a viable option for the broader ME/CFS community. Continued advocacy for ME/CFS research funding remains crucial.
The latter part of the interview segment highlights that studying long COVID is not straightforward and suggests that it is likely an umbrella term encompassing different diseases. For example, Dr Nath describes a subgroup of long COVID patients who may be experiencing post-exertional malaise (the cardinal feature of ME/CFS) and lists symptoms frequently reported by individuals with ME/CFS, such as cognitive and sleep issues, as well as common ME/CFS comorbidities.
Thus, it is worth considering whether shifting the research focus from ME/CFS to long COVID might actually introduce new challenges.
