On the 15th and 16th of May this year, ME Research UK attended the first Unite To Fight conference – “The biggest community-driven ME/CFS and Long COVID conference ever”, which was held online.
Organised by those with ME/CFS, and those with long COVID, the crowd-funded conference included over 40 speakers who provided “a special mix of expert insights, personal stories, and cutting-edge research”.
Speakers at the conference included ME Research UK-funded researchers past and present; Prof. Carmen Scheibenbogen, Dr. Rob Wüst, Dr Amy Proal, and Prof. Bupesh Prusty.
During the conference, many areas of ME/CFS and long COVID research were discussed – within which, ME Research UK highlights five key topics:
- ME/CFS as a part of long COVID.
- The importance of appropriate involvement of those with lived experience in ME/CFS, and in long COVID research.
- Research – and lived experience, shows that post-exertional malaise is not a result of deconditioning.
- Stop saying “long COVID and ME/CFS are a mystery” – more specific research methods are needed.
- Long COVID research does not appear to be learning from ME/CFS research mistakes.
ME/CFS as a part of long COVID.
Professor Carmen Scheibenbogen started by presenting the findings from a small study including 19 people with ME/CFS (diagnosed using the Canadian Consensus Criteria (CCC)), and 23 with long COVID – around 50% of the people with long COVID met the CCC for ME/CFS.
The main reason why half of the individuals with long COVID did not meet the CCC was because they had less severe post-exertional malaise (PEM) which did not last until the next day, and for some of these people, brain fog was only minor. Interestingly, those with long COVID not meeting the CCC were found to have less fatigue, and their functional ability – a measure of disability, was better (indicating a lower level of disability) compared to those who did meet the criteria for ME/CFS.
According to Prof. Scheibenbogen, “regarding other symptoms which are typical, like headache, muscle pain, sleep disturbance” there was “no big difference” between the groups. However, “sensitivity to light and noise was much more pronounced in the ME/CFS cohort”.
Prof. Scheibenbogen went on to highlight the results from a paper published in eClinicalMedicine, which looked at the severity of symptoms over time for 106 people with long COVID, and compared those who met the CCC for ME/CFS (55 participants) with those who did not (51 participants).
Findings suggested that:
- For participants with long COVID who did not meet the CCC for ME/CFS, symptoms continuously improved.
- Those with long COVID who did meet the CCC for ME/CFS reported persistently high severity of symptoms.
- This group also displayed a correlation between a specific type of autoantibody – GPCR autoantibodies, and symptom severity – something not seen for those with long COVID who did not meet the CCC for ME/CFS.
Notably, the authors of this paper concluded that it may be useful to subclassify long COVID patients according to whether or not they meet the CCC for ME/CFS “due to their persistently higher symptom severity”. In the talk at the conference, Prof. Scheibenbogen concluded that “ME/CFS is a severe and chronic form of Post-COVID Syndrome”.
The importance of appropriate involvement of those with lived experience in research investigating ME/CFS, and long COVID.
Oonagh Cousins – a former Great Britain rower forced to retire with long COVID – shared her experience of becoming ill with the condition at the “peak of her physical fitness”. Oonagh now works at the University of Oxford as a patient representative on a study exploring how methods from social science – the scientific study of human society and social relationships, can be used to support and engage with people with long COVID.
In her talk, Oonagh highlighted ways in which including people with lived experience in research can lead to benefits, these included:
- Increased relevance of the research to participants.
- Improved acceptability of research methods used.
- Ensuring that information for participants is presented in a way that makes sense and considers accessibility needs.
- Providing participants with a better experience of research.
- Better communication of results at the end of the study.
ME Research UK adds that careful consideration should be given to the process of appropriate involvement of those with lived experience –patient and public involvement (PPI) in research. It is essential that researchers follow relevant guidelines – such as the UK Standards for Public Involvement, and that adequate reimbursement for PPI is costed into grant applications. Importantly, for research into ME/CFS – and into long COVID, this should reflect the time for both PPI activity itself, such as a focus group or interview, for the preparation, and for the impact the activity may have – such as symptom exacerbation, and PEM. Where carers are involved, researchers may also need to consider the impact of their absence during the PPI activity, and the cost of any additional support they may have needed to put in place.
Research – and lived experience, shows that post-exertional malaise is not a result of deconditioning.
Dr. Rob Wüst presented findings – which he also discussed at the recent Invest in ME Research conference, showing that muscle changes seen in healthy participants who undergo bed rest to induce deconditioning are not the same as those observed in studies looking at muscle samples from people with ME/CFS who experience PEM – indicating that deconditioning alone does not explain PEM.
This was also supported by Oonagh Cousins’ lived experience; Oonagh described how her symptoms of long COVID – which include PEM, cannot be explained by deconditioning as she was at the peak of her physical fitness when she became ill.
Stop saying “long COVID and ME/CFS are a mystery” – more specific research methods are needed.
Dr. Amy Proal clearly stated that “we need to stop saying that long COVID or ME/CFS are a mystery”. In her presentation on pathogen persistence, Dr Proal highlighted that there are now “really clear leads on disease mechanisms” which include pathogen persistence. Dr. Proal explained:
“over time there’s a tendency for pathogens to leave the blood where the immune system is often the most robust, and move – in simple terms, to ‘hide’ in tissues where they are better protected.”
This means that studying samples of body fluids – such as blood and urine, is not enough. Rather, it is essential to additionally examine tissue samples from areas of the body such as the gut, muscles, bone marrow, and lymph nodes.
Long COVID research is not learning from ME/CFS research mistakes.
David Tuller’s presentation considered how “long COVID researchers are repeating the ME/CFS biopsychosocial playbook” – stating that there have been many long COVID studies of exercise and cognitive behavioral therapy (CBT) with “lots of positive headlines and news coverage about exercise/CBT for long COVID”.
Also noted were the “problematic research/reporting strategies” that are being used by long COVID researchers, including:
- Interpreting associations as causal in the favored direction using cross-sectional study designs.
- Cross-sectional studies – which look at a snapshot in time, cannot assess causality as they are unable to determine the direction of effect between variables.
- Reporting statistically significant, but not clinically significant findings
- Here, the results observed are unlikely to be due to chance but are also not likely to make a difference in clinical practice.
- Often seen where a dataset is large and has the statistical power to detect very small associations that would not be considered significant outside of statistical testing.
- Here, the results observed are unlikely to be due to chance but are also not likely to make a difference in clinical practice.
- Reliance on poorly designed control groups – or lack of a control group entirely.
- Here researchers are unable to investigate whether there are differences between the group with the disease of interest – here, ME/CFS or long COVID, and a carefully selected control group (or groups).
Regrettably, these strategies have also been used in ME/CFS research over the years – and in many other areas of research.
Conclusion
A wide range of complex research areas were discussed at the Unite to Fight conference, alongside essential insights from those with lived experience of both ME/CFS, and of long COVID. Speakers highlighted the importance of using extremely thorough and careful research methods; for example, the use of carefully defined control groups, consideration of the clinical significance of results – in addition to the statistical significance, appropriate subgrouping of participants to account for population – and disease, diversity, and the use of tests which study tissues of the body – in addition to those which examine fluids such as blood and saliva. The importance of appropriately including people with lived experience in research was also clearly evident at Unite To Fight – something also noted at the NIH conference held in December 2023.
