In December 2023, ME Research UK attended a two-day conference organised by the National Institutes of Health (NIH) and titled “Advancing ME/CFS Research: Identifying Targets for Intervention and Learning from Long COVID”.
Our reflections on the topics discussed at the conference are presented in this three-part series of articles.
1. Overview | 2. Research topics | 3. Treatment targets
The topics covered at the conference included:
- The lack of funding for ME/CFS, and the need to increase research capacity through interdisciplinary collaboration.
- Consistent evidence of biological abnormalities in people with ME/CFS and those with long COVID.
- The need for research which studies ME/CFS and long COVID over time (longitudinal research).
- The importance of listening to those with lived experience of ME/CFS and/or long COVID.
The following will consider the information presented at the conference relating to each of these topics, and summarise the key messages to take away.
Lack of funding and increasing research capacity
In an introductory talk, Walter Koroshetz MD spoke about how the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Neurological Disorders and Stroke (NINDS) have been working together to try and advance ME/CFS research.
In this talk, Dr Koroshetz mentioned the “paltry” amount of funding that has been allocated to research into the disease over the years – something that ME Research UK has also highlighted for example in a response to the DHSC interim delivery plan on ME/CFS.
Dr Koroshetz then went on to say how the NIH is working on building capacity in ME/CFS research, and gave three examples of phenotyping studies which aim to assess normal features, traits and possible abnormalities in:
- People with ME/CFS – the results of this study were published in Nature in February 2024, and have been discussed in detail by ME Research UK.
- Those with long COVID.
- Gulf War veterans.
The goal to develop ME/CFS and long COVID centres for excellence in the USA was also discussed by Dr Koroshetz, who drew attention to the importance of researchers working together and pooling expertise rather than working independently. The need for collaboration between researchers with different skill-sets (interdisciplinary collaboration) was also one of the key topics discussed at both the “Understand, Diagnose, Treat: ME/CFS Conference 2023″ and “The 15th Invest in ME Research International Conference” which took place last year. Dr Koroshetz stated that interdisciplinary collaboration is also a central pillar of the ME/CFS Research Roadmap working group, which not only includes NIH staff, but 21 individuals with lived experience of ME/CFS, alongside a research council.
Biological abnormalities in ME/CFS and long COVID
Throughout the conference, presentations included research which identified biological abnormalities relating to the immune system, viruses, energy metabolism, gene regulation, and the brain and spinal cord, in people with ME/CFS and in those with long COVID.
In fact, in a summary of the conference, Antony Kormaroff MD stated that ME/CFS and long COVID have both been found to involve multiple different biological abnormalities. Dr Kormaroff also emphasised that these abnormalities have now been seen across multiple different studies – meaning it is unlikely that the findings are due to chance. This is in agreement with an article published on 31 December 2023 which provided a clear summary of why the psychosomatic view on ME/CFS is inconsistent with current research findings.
In his presentation, Professor Kormaroff also discussed findings from his research paper, published in June 2023, which summarises the biological abnormalities that have been identified in people with ME/CFS and in those with long COVID.
These include:
- Abnormalities of the central and autonomic nervous system (neurological abnormalities) such as:
- Brain fog
- Autonomic dysfunction (dysautonomia)
- Immune system abnormalities
- Metabolic abnormalities
- Decreased energy production
- Increased levels of oxidative stress – a state in the body caused by an increased number of potentially harmful molecules known as “free radicals” or “reactive oxygen species”.
- Abnormalities in the cardiovascular and pulmonary system
- Decreased exercise capacity (the maximum amount of physical exertion that a person can do)
The presentation emphasised the need for more research considering whether these biological abnormalities are the same in males and females with ME/CFS and long COVID. A similar recommendation was also made by ME Research UK in an article discussing the differences in research findings between men and women with ME/CFS:
“Much more research is needed to better understand exactly what the differences between men and women with ME/CFS are, and what these differences mean for diagnosis and treatment.”
ME Research UK notes that this recommendation would also apply to research into long COVID.
Longitudinal research
In a talk relating to the innate immune system – the part of the immune system which responds quickly to invading pathogens – Professor Ian Lipkin stated that, to date, results from studies that look at a single point in time (cross-sectional studies) have been disappointing. Prof. Lipkin pointed out that to increase knowledge and understanding, more research looking at changes over time – longitudinal research – is needed.
In his talk, he gave two examples of ongoing longitudinal projects:
- One which aims to look at changes in molecules in the body over time, and how these changes correlate with severity of symptoms measured using a mobile phone app.
- Another which hopes to look at whether there are changes in immune system molecules (antibodies) over time, and, if so, whether these changes are linked to specific pathogens in people who meet the medical code for “chronic fatigue, unspecified” (ICD-10-CM R53.82) – regrettably the relevant information is not available for the ICD code applicable to “Chronic fatigue syndrome, ME/CFS and Myalgic encephalomyelitis” (ICD-10-CM G93.32).
- While the researchers will not be able to look at ME/CFS directly within this project, it still provides opportunities to discriminate between infections with related viruses and possibly find evidence of viral reactivation in people with “chronic fatigue, unspecified”.
- Importantly, only records between 2007 and 2020 will be assessed in this project, which will eliminate the inclusion of long COVID cases.
ME Research UK notes that in a paper by Luis Nacul and colleagues, published in 2020, relating to the course ME/CFS takes in individual people (the natural history of ME/CFS), limitations in understanding were attributed to the “the paucity of longitudinal studies” – alongside “problems in case definition”. The discussion section of this paper ended by stating:
“Well-designed longitudinal studies, with strict protocols, would help refine this attempted description of the natural course of the ME/CFS, and the interpretation of the findings”
In the four years since this paper was published, there is still a need for more longitudinal studies in ME/CFS – and now long COVID.
It is also worth highlighting that there have been some longitudinal studies published. For example, one study in 2011 investigated fatigue severity over time, and another in 2021 considered the impact of life stressors on ME/CFS symptoms. However, these studies focused predominantly on self-reported symptoms of the disease, rather than investigating whether there are changes in the body over time and how these changes may relate to symptoms and severity of disease.
Lived experience
During the conference, attendees heard from four speakers with lived experience of ME/CFS and long COVID, who shared essential insights from their own experiences.
Many important areas were highlighted within these presentations including:
- The stigma associated with ME/CFS.
- This included stigma around what severe ME/CFS “looks like”, and the need to recognise that disease severity is not “one size fits all”.
- The misconception that ME/CFS is a psychosomatic disease is ongoing.
- This is harmful for both those with ME/CFS and, due to the overlap in symptoms, for those with long COVID.
- The physical, emotional and financial impact of ME/CFS and long COVID.
- That there are inequalities among those with ME/CFS and long COVID.
- Inequalities were centered around access to care, and the additional stigma faced by black and minority ethnic groups stemming from “structural racism”.
- The need for treatment options for people with ME/CFS and long COVID.
One of the speakers with ME/CFS, Terri Wilder, gave a real-life example of when she asked her social media followers, “What would you want early career scientists, medical providers and medical students to know if you had the opportunity?”
Within the responses, of which there were over 100, issues relating to post-exertional malaise (PEM) were most common.
Important areas presented were:
- The critical importance of recognising and studying PEM.
- The urgent need for research on treatments.
- A paradigm shift amongst health professionals – although the exact paradigms were not specified, ME Research UK notes that this is likely the need for a shift from the psychological/psychosocial model to biological/biomedical model in line with current evidence.
- Involvement of people with ME/CFS and long COVID in research and development of care.
- A fresh perspective on how health professionals approach the disease.
ME Research UK observes that the powerful messages shared during the conference act as a reminder to researchers to ensure that the voices of those with lived experiences of ME/CFS and long COVID are represented appropriately in research.
Summary
The topics from the conference discussed in this article do not highlight anything new. Rather, they emphasise previously identified areas including:
- The ongoing lack of funding in ME/CFS research and how this needs to change.
- The need for interdisciplinary collaboration.
- Clear evidence of biological abnormalities in people with ME/CFS and those with long COVID.
- Differences between males and females – this is observed for both ME/CFS and long COVID.
- An apparent overlap in abnormalities between ME/CFS and long COVID.
- More longitudinal ME/CFS and long COVID research is needed.
- The importance of representing the voices of those with lived experiences of ME/CFS and long COVID in research.
1. Overview | 2. Research topics | 3. Treatment targets
