Welcome to the 80th Emerge Australia Research Digest, where you will find summaries of some of the latest research and information about ME/CFS, with links to the complete articles.

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Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Authors: Pereira G, Gillies H, Chanda S, Corbett M, Vernon SD, Milani T and Bateman L (Bateman Horne Center United States)
Publication: Frontiers in Systems Neuroscience 
Link: https://www.frontiersin.org/articles/10.3389/fnsys.2021.698240/full

The authors of this article propose that the abnormalities seen in ME/CFS could involve the corticotropin-releasing factor system and its regulation of serotonin (5HT) in the limbic system, which controls the response to homeostatic threat. They hypothesise that ME/CFS results from corticotropin-releasing factor receptor type 2 (CRFR2) upregulation in specific neurons of the raphé nuclei and limbic system, leading to a loss of homeostatic control over the functions mediated by those neurons. This study is an open-label trial of CT38s, a CRFR2 agonist, to downregulate this system.
The authors tested the safety, tolerability and efficacy of an acute dose of CT38s (a short-lived, CRFR2-selective agonist, with no known off-target activity) in 14 patients meeting the Fukuda criteria, Canadian Consensus Criteria, and National Academy of Medicine criteria for ME/CFS. CT38s was delivered subcutaneously three times. Patients were divided into four groups to test different infusion rates. Efficacy was determined by comparing symptoms in the 28-day pre-treatment assessment period and the 28-day post-treatment assessment period.
Compared to healthy people (data from Phase 1 trial), ME/CFS patients are more sensitive to the haemodynamic effects of CRFR2 stimulation. CT38s treatment was significantly associated with symptom improvement, however this was only the case for the two lowest infusion rates. The highest infusion rate worsened symptoms. Notably, the authors report 157 treatment-emergent adverse events that were classified as severe (4), mild (124) or moderate (29).
This trial showed that a CRFR2-selective agonist may provide therapeutic benefit in ME/CFS patients. However, the benefit is dose dependent. More specifically, low doses were associated with symptom improvement whereas high doses worsened symptoms. Additional research into the benefits of CT38s treatment is thus needed to optimise the dose before its efficacy can be determined in a larger group of patients.

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Impact of Life Stressors on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Symptoms: An Australian Longitudinal Study

Authors: Balinas C, Eaton-Fitch N, Maksoud R, Staines D, and Marshall-Gradisnik S.
Publication: International Journal of Environmental Research and Public Health
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535742/pdf/ijerph-18-10614.pdf

The impact of stress on many chronic conditions is well known, including in ME/CFS where stress has been linked to illness onset and symptom exacerbation. In many conditions, symptom severity can be reduced with improved stress management. This study investigated the impact of life stressors and access to professional or family support on ME/CFS symptom severity.
Thirty-six Australians aged 18-65 years with a ME/CFS diagnosis from a health practitioner and who met the Fukuda criteria, Canadian Consensus Criteria or International Consensus Criteria, completed fortnightly questionnaires over a five-month period. Questions were focussed on life stressors, including family dynamics, work changes and income loss. Other surveys recorded symptom severity, access to healthcare and support, and lifestyle factors.
Only 50% of participants were employed during the study, many of these experiencing work disruptions during the study period. Over 40% of all participants reported an unsustainable income. There were strong positive associations between access to support (healthcare, professional or volunteer) and improved symptom scores. There were also negative correlations between financial and work-related parameters and symptom scores. General Practitioners were the health service most frequently accessed, but more than 80% of participants reported having no access to paid professional support services, instead relying on family and friends for additional assistance. Assistance was most required for household chores, meal preparation and grocery shopping. 
This study highlighted that low income and unemployment are stressors which negatively impact on ME/CFS symptom severity. It also highlighted the need for access to, and delivery of, support resources, particularly to those unable to work, and the importance of stress minimisation in ME/CFS.

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The impact of COVID-19 critical illness on new disability, functional outcomes and return to work at 6 months: a prospective cohort study

Authors: Hodgson CL, Higgins AM and The COVID-Recovery Study Investigators and the ANZICS Clinical Trials Group
Publication: Critical Care
Link: https://ccforum.biomedcentral.com/articles/10.1186/s13054-021-03794-0

There are increasing numbers of patients reporting ongoing symptoms following infection with COVID-19, with significant overlap with other post-viral syndromes. This study was designed to investigate the incidence of death or new disability, functional impairment, and changes in health-related quality of life of patients 6 months after critical illness with COVID-19.
212 participants were included in this study, who were recruited from 30 intensive care units in hospitals across Australia. The median age was 61, and 58.5% were male. Outcomes of mortality, new disability and return to work were measured at 6 months via a series of questionnaires including the World Health Organization Disability Assessment Schedule 2.0 (WHODAS) and EQ5D-5L.
The authors found that at 6 months 26.9% of participants had died, and 38.9% reported a new disability. When compared to pre-illness, survivors reported WHODAS scores had worsened by a mean of 10.4% (indicating worsened functioning), 11.4% had not returned to work due to health reasons, and 71.3% reported persistent symptoms (most frequently reporting shortness of breath, loss of strength and fatigue). Reduced health-related quality of life was reported, especially in relation to mobility, usual activities and pain. Independent predictors of death or new disability were found to include higher severity of illness and increased frailty.
The authors conclude that at 6 months post critical COVID-19 illness, death (26.9%) and new disability (38.9%) rates were substantial, with new disability reported across all areas of functioning. While the long-term effects of critical illness are well-known, the authors suggest that these findings indicate that the burden of new disability post COVID-19 infection may be greater than is currently understood and represents an urgent public health problem to be addressed.

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From scientific papers to a national newspaper

Authors: Emerge Australia
Publication: Australian Financial Review
Link: https://www.emerge.org.au/australian-financial-review

Emerge Australia is pleased to have launched the latest element of our awareness campaign with a full-page advert in the Australian Financial Review on November 25 to give ME/CFS a voice in the national Long COVID conversation.
Emerge Australia is determined to seize this moment to help transform the lives of the estimated 250,000 Australians living with ME/CFS and other post-viral fatigue conditions. Please support our campaign, by sharing it amongst your networks to keep the conversation flowing.