Welcome to the 111th edition of Emerge Australia’s Research Digest. This month, we highlight studies that explore how individuals with ME/CFS adapt their technology use and investigate how physical activity-induced post-exertional malaise (PEM) reveals insights into microvascular changes and immunometabolic interactions in those living with ME/CFS and post-COVID. We also feature the largest two-day cardiopulmonary exercise test (CPET) study on ME/CFS.
Contributing Digesters: Shan, Jyothsna, Solène and Sarah.
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Good days, bad days: Understanding the trajectories of technology use during chronic fatigue syndrome
Authors: Paymal L, Homewood S (University of Copenhagen, Denmark)
Publication: Proceedings of the 2024 CHI Conference on Human Factors in Computing Systems
Link: https://doi.org/10.1145/3613904.3642553
ME/CFS is a dynamic disability with day-to-day fluctuations both in response to environmental triggers and inherent to the illness itself. This initial scoping study sought to articulate how this fluctuation influences the way people living with ME/CFS use and adapt to technology, and to improve the accessibility of the human-computer interface (HCI) for people who experience sensory sensitivities, cognitive limitations, and fatigue.
Seven people with ME/CFS (diagnostic criteria unspecified) were recruited from Denmark and Sweden for remote semi-structured interviews examining the state of their illness and their technology use in day-to-day life. The interview answers were analysed for key elements which determined major themes throughout the data.
The study found that technology use was shaped by the experience of the illness. Technology was often used to help conserve energy (such as electric adjustable beds or robot vacuum cleaners). Other technology was repurposed to meet the needs of the person living with ME/CFS (such as social media to find recipes cooked in stages, fitness trackers to keep within energy limits). For some participants, the strategy was not using technology, particularly where it couldn’t be adapted (for example, digital screens). Technology was often adapted to meet the participants’ sensory needs (such as reducing screen brightness or sound volume on devices).
Technology use also varied with illness fluctuation, with participants using less technology on good days when they would engage in other activities instead, and more on bad days when energy and activities are more limited. On very bad days, some participants described having minimal use of technology at all. The authors propose a model of Trajectories of Technology used to explain this pattern, and propose that this model can help better understand how technology is used by people living with chronic illness.
The authors believe that this research will help articulate how adopting and adapting technology allows people with chronic illness (particularly those who are isolated) to interact with the world around them and allows them to live meaningful lives, as well as the significant obstacles to adoption (such as the difficulty many with ME/CFS have, engaging with screens). They plan for future studies to involve co-designing assistive technology (especially non-screen technology) with individuals who are chronically ill, ensuring these solutions can be adapted to meet fluctuating needs.
Towards an understanding of physical activity‑induced post‑exertional malaise: Insights into microvascular alterations and immunometabolic interactions in post‑COVID condition and myalgic encephalomyelitis/chronic fatigue syndrome
Authors: Haunhorst S, Dudziak D, Scheibenbogen C, Seifert M, Sotzny F, Finke C, … Puta C (Friedrich Schiller University Jena, Germany)
Publication: Infection
Link: https://doi.org/10.1007/s15010-024-02386-8
Post-COVID condition (PCC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have similar symptoms, with post-exertional malaise (PEM) being a key feature. This review explores the possible underlying mechanisms of PEM in these two conditions.
Both PCC and ME/CFS patients show metabolic abnormalities, including reduced aerobic capacity and a shift from oxidative metabolism to anaerobic glycolysis, resulting in lactate accumulation and reduced adenosine triphosphate (ATP) production. Elevated lactate levels in ME/CFS patients are strongly associated with more severe PEM episodes, highlighting the role of metabolic disruption.
Mitochondrial dysfunction is also critical, evidenced by reduced breakdown of fatty acids and decreased mitochondrial enzyme activity during exertion. Oxygen deprivation from these metabolic shifts triggers reactive oxygen species (ROS) production and vasodilatory mediators, exacerbating oxidative stress, immune activation, and mitochondrial damage, creating a vicious cycle of declining energy production.
In addition, microcirculatory dysfunction, including endothelial damage and impaired nitric oxide (NO) production, worsens oxygen delivery to tissues, contributing to exercise intolerance. Persistent endothelial dysfunction is indicated by abnormal flow-mediated dilation (FMD) and elevated endothelial cell levels. Immunological dysregulation is significant, with chronic inflammation, reactivation of latent viruses like Epstein-Barr, and persistent viral antigens driving ongoing immune responses.
Current treatments for PCC and ME/CFS focus on symptom management, with pacing recommended to prevent overexertion. Emerging therapies targeting microcirculation (e.g., vasodilators) and addressing immunometabolic dysfunctions are being explored.
The authors noted that no single cause of the disease has been conclusively identified, suggesting that the observed pathophysiological features may not always coexist. The authors recommend that future research explore connections between these mechanisms, particularly immunometabolic signatures linked to post-exertional malaise (PEM). Investigating these links further could inform better activity management strategies for PCC and ME/CFS, helping to reduce the risk of triggering PEM.
Persistent autonomic and immunologic abnormalities in neurologic post-acute sequelae of SARS-CoV2 Infection
Authors: Goldstein DS, Mina Y, Walitt B, Sullivan P, Enose-Akahata Y, Jacobson S… Nath A (National Institutes of Health, USA)
Publication: Neurology
Link: https://doi.org/10.1212/wnl.0000000000209742
The post-acute sequelae of SARS-CoV-2 (PASC) is posing an increasing challenge to public health, often manifesting as cognitive dysfunction, fatigue, and other central neurological symptoms, collectively referred to as Neuro-PASC. An initial observational study involved a dozen Neuro-PASC patients who underwent tests categorised into central, autonomic, neuroendocrine, and immune/inflammatory domains. Results highlighted various immune/inflammatory and autonomic abnormalities in some patients. The goal of this study was to determine whether these previously detected autonomic and immunologic abnormalities persist after one year.
Seven participants previously studied (six women, age range 42–63 years) returned for follow-up testing at least one year after the initial evaluation. Follow-up testing included all the tests of the original study.
The frequencies and types of abnormalities observed in participants varied significantly between individuals. However, within each participant, most test results—whether normal, elevated, or reduced—remained consistent at follow-up compared to the initial evaluation.
On average, 69% of test results among the participants remained persistently abnormal. Across various domains, 71% of the abnormalities identified during the initial evaluation were still present at follow-up testing (for example, cerebral spinal fluid (CSF) indices of central catecholamine deficiency, baroreflex-cardiovagal dysfunction, tilt-evoked sudden hypotension, white matter hyper-intensities on MRI, and adaptive responses in CSF).
The authors acknowledge several limitations of their study. The sample was very small, and its generalisation to the broader Neuro-PASC population is unknown. Additionally, there was no comparison group of fully recovered individuals. Some data were incomplete, and prescribed medications that could have influenced the results were not discontinued.
This study found that most abnormalities initially observed in patients with Neuro-PASC persisted for at least a year. These findings reinforce concerns that the public health burden of post-COVID-19 neurological impairments is likely to persist.
Cardiopulmonary and metabolic responses during a 2-day CPET in myalgic encephalomyelitis/chronic fatigue syndrome: translating reduced oxygen consumption to impairment status to treatment considerations
Authors: Keller B, Receno CN, Franconi CJ, Harenberg S, Stevens J, Mao X … & Hanson MR (Cornell University, New York)
Publication: Journal of Translational Medicine
Link: https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-05410-5
Post-exertional malaise (PEM) represents a variety of abnormal responses to exertion (physical, cognitive or emotional) and is the hallmark characteristic of ME/CFS. Completing cardiopulmonary exercise tests (CPET) two days in a row objectively demonstrates this abnormal response, but has only been validated in studies utilising small sample sizes. This study sought to add to the existing evidence with a larger sample size.
Participants were recruited through a multi-site initiative via Cornell University. Eighty-four participants with ME/CFS (Canadian Consensus Criteria) and 71 sedentary controls completed two CPETs on a cycle ergometer, 24 hours apart. A range of measures were taken at rest, at ventilatory/anaerobic threshold (VAT), and at peak exertion. Identical CPET protocols were used on both days.
The authors found that the ME/CFS participants were unable to reproduce their performance from CPET-1 in CPET-2, with lower measurements observed across many parameters. In contrast, the sedentary controls demonstrated greater stability in CPET variables across the two tests. The CPET-2 results in ME/CFS participants showed a more severe impairment status (none-mild, mild-moderate, moderate-severe, severe) compared to the sedentary controls.
This study represented the largest two-day CPET study of ME/CFS. The result contributed to the evidence demonstrating substantially impaired recovery in ME/CFS following an exertional stressor, through the drop-off in results in CPET-2 compared to CPET-1. The ongoing post-exertional CPET responses in the ME/CFS group, when compared to the sedentary controls, indicate that fitness level is not responsible for the exertion intolerance seen in ME/CFS. The authors propose that autonomic nervous system dysregulation and observable reduction in post-exertional energy metabolism may be responsible for the abnormal ME/CFS responses and worsening of impairment status. The authors propose that further research should be completed into treatments that focus on re-regulating autonomic nervous system signalling in order to improve oxygen delivery.
