IACFS/ME Conference (5): Keynote: Pathophysiology of exercise intolerance in ME/CFS & long COVID  

The 3rd Virtual Scientific Conference for the International Association for Chronic Fatigue Syndrome/ Myalgia Encephalomyelitis was held on the 27th-30th July 2022. The conference promoted unpublished data and included both clinicians and biomedical researchers. 

This year the conference committee utilised the virtual platform “Gather”, which allowed more interaction between attendees and for researchers to engage with one another, allowing questions to be asked. Essentially this gave the appearance of an online virtual reality conference (see image), from entering the conference room in the virtual setup, the talks were then hosted through zoom. 

The talks were grouped into different sections, including: immunology, metabolism, infectious diseases, treatment as well as several sessions on Covid. 

A few of the talks this year, were familiar to us from our weekly research roundup, so we have not covered them in this conference report. These were: 

  • Pre-Illness metabolomics data among college students following mononucleosis and ME/CFS reveals differences in multiple metabolites and metabolic pathways by Leonard A. Jason, DePaul University, USA. 
  • How to ensure the voice of the severely affected ME/CFS patient is heard in research by Helen Baxter, 25% ME Group, United Kingdom. 
  • Oxaloacetate improves physical and mental fatigue in ME/CFS and long-COVID by David Kaufman, Centre for Complex Diseases, USA. (Dr Charles Shephard has also provided a comment on this talk, available here.) 

Several of the talks have also been documented by Miriam E Tucker from Medscape News and are also available to read on our website, these are: 

  1. Treatments Explored to Ease Post-Viral Symptoms of ME/CFS and Long Covid- available here 
  1. Increasing Data Link ME/CFS, Long COVID, and Dysautonomia- available here 
  1. ME/CFS and Long COVID “Frighteningly Similar, if Not Identical”- available here 
  1. Clinicians Can Help People With Severe ME/CFS, Even Unseen- available here 

Due to the format of the conference and the focus on unpublished data, no direct recordings or pictures are available freely as this may jeopardise publication. The full conference programme can be found on the IACFS/ME website here, where recorded presentations may be purchased. Other summaries produced by attendees of the IACFS/ME may also be read on the IASCFS/ME website. 

Audio commentary by Dr Katrina Pears

5. Keynote: Pathophysiology of exercise intolerance in ME/CFS & long COVID  

David Systrom, MD  

Harvard Medical  

Dr David Systrom’s keynote talk covered several different topics which were all related to acute exercise intolerance: preload failure, small nerve fibre neuropathy, skeletal muscle mitochondrial dysfunction, Long Covid and potential treatment.  Data presented was a mixture of published and unpublished studies. 

The basis of Dr Systrom’s research and work is based on using invasive cardiopulmonary exercise testing which was first used in heart and lung disease, however, not all patients were seen to fit this diagnosis, and led him to investigate ME/CFS. These patients were seen to have “preload failure”– where a consistently reduced max oxygen consumption (VO2) alongside reduced right atrial pressure (RAP), this means that there is poor oxygen extraction. It is this preload failure that contributes to post-exertional malaise (PEM). 

Dr Systrom’s research has also looked into small Nerve Fibre Neuropathy, which has been found in a subset (around 50% of patients), and he expects this might be related to exercise intolerance in ME/CFS. Similar findings have also been seen in POTS and fibromyalgia. As part of this branch of research, the immune response “TRAIL” which is a cytokine that is produced and secreted by most normal tissue cells, responsible for apoptosis (the death of cells). 

Another part of Dr Systrom’s talk also covered impaired oxygen extraction, which may be causing the depression in VO2 max. For this part of the research muscle biopsies were examined which suggests this might be linked to muscle mitochondrial dysfunction

Dr Systrom has also investigated exercise intolerance in Long Covid, which appears to be the same as ME/CFS with preload failure presence. Ventilatory inefficiency (VE/VCO2) is also present in Long Covid, which is due to hyperventilation (seen in a subset of patients). These findings are thought to be related to dyspnea. Furthermore, using upright tilt table testing for POTS and Long Covid patients verus controls has shown hyperventilation similar to that when performing exercise with depression of cerebral blood flow. 

Dr Systrom presented some unpublished data for ME/CFS, POTS and small Nerve Fibre Neuropathy showing that preload failure is present in all. 

Finally, the talk was concluded by a small introduction to treatment, using a small dose of pyridostigmine to treat preload failure. Results currently suggest in a subset of patients this treatment may be useful. 

Published studies from this talk: 

Joseph P et al. (2021) Insights From Invasive Cardiopulmonary Exercise Testing of Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Chest 160(2):642-651. Link

Joseph P et al. (2022) Neurovascular Dysregulation and Acute Exercise Intolerance in ME/CFS: A Randomized, Placebo-Controlled Trial of Pyridostigmine. Chest: S0012-3692(22)00890-X. Link

Melamed KH et al. (2019) Unexplained exertional intolerance associated with impaired systemic oxygen extraction. Eur J Appl Physiol 119, 2375–2389. Link

Novak P et al. (2022) Multisystem Involvement in Post-Acute Sequelae of Coronavirus Disease 19. Ann Neurol 91(3):367-379. Link

Singh I et al. (2022) Persistent Exertional Intolerance After COVID-19: Insights From Invasive Cardiopulmonary Exercise Testing. Chest 161(1):54-63. Link

Tooba R et al. (2021) Dyspnea in Chronic Low Ventricular Preload States. Ann Am Thorac Soc 18(4):573-581.

Oldham WM et al. (2016) Unexplained exertional dyspnea caused by low ventricular filling pressures: results from clinical invasive cardiopulmonary exercise testing. Pulm Circ 6(1):55-62. Link

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