A US-based research team led by Johanna Squires, and including well-known ME/CFS researcher Dr David Systrom, has published an abstract of a study exploring the physiological similarities between people with ME/CFS and those with long COVID. The study used invasive cardiopulmonary exercise testing (iCPET), which allows for assessment of cardiovascular (blood flow and heart function), respiratory (lung efficiency), and metabolic (energy production) performance.
Methods
The study focused on five main physiological measurements:
- Peak VO₂ – a measure of aerobic capacity i.e. the maximum amount of oxygen used during exercise
- Peak cardiac (heart) output – the maximum amount of blood the heart can pump per minute.
- Peak right atrial pressure – blood pressure in the right atrium (heart chamber), indicative of how much blood is returning to the heart and how well the right side of the heart is filling and pumping.
- Peak systemic oxygen extraction – indicates the body’s ability to draw oxygen from blood into tissues during exercise.
- Ventilatory efficiency (VE/VCO₂) – how effectively the lungs expel carbon dioxide.
Between January 2019 and December 2024, 1,518 patients underwent iCPET at Brigham and Women’s Hospital in Boston. After excluding individuals with confounding conditions (such as lung disease, cancer, or elite athletic status), results from 438 individuals with ME/CFS, 73 individuals with long COVID, and 43 “symptomatic but otherwise normal controls” were analysed. The researchers describe this as “the largest cohort of ME/CFS and LC [long COVID] patients investigated with iCPET to date.”
Key Findings
In comparison to controls, both ME/CFS and long COVID groups showed significantly reduced exercise capacity compared to controls across nearly all measured parameters:
- Lower peak oxygen use
- Reduced cardiac output
- Lower right atrial pressure
- Impaired systemic oxygen extraction
Ventilatory efficiency was normal, suggesting the lungs themselves were not the limiting factor.
There were no significant differences between the ME/CFS and long COVID groups – both showed a similar pattern of physiological limitations during exercise.
Conclusions
The results show that ME/CFS and long COVID present similar physiological abnormalities during exercise. This is not surprising given that many people with long COVID meet diagnostic criteria for ME/CFS, including experiencing post-exertional malaise (PEM) – the hallmark feature of ME/CFS.
The authors concluded that the reduced aerobic capacity in both disease groups is driven by:
- Preload insufficiency – the heart is not filling with enough blood during exercise, which reduces cardiac output and oxygen delivery.
- Impaired oxygen extraction – possibly due to skeletal muscle dysfunction, or “peripheral left-to-right shunting” (terminology frequently referred to by Dr Systrom that likely means an abnormal direction/route of blood flow in the peripheral circulation i.e. outside of heart).
Note: Only the abstract of the study has been released so far, so a full analysis awaits publication of a full research paper.
The authors conclude:
“We hope these data inform the pending prospective NIH RECOVER iCPET study of LC [long COVID].”
It is understandable to question the necessity of a study that involves exercise testing individuals with ME/CFS because there is not only a risk of PEM but of worsening disease severity. It is important to weigh up the risk-benefits of such studies and ensure that there is appropriate ethics approval and informed consent.
Read more about exercise testing in ME/CFS – including ethics
