Welcome to the 121st edition of the Research Digest. In this issue, we explore new research into the neurological and genetic underpinnings of ME/CFS and long COVID, including links to neurodegeneration and neuropsychiatric conditions. We also share findings on the effectiveness of telehealth for homebound individuals, and an Australian study highlighting the profound impact of long COVID on disability, daily functioning, and quality of life. Together, these articles underscore the urgent need for continued research, better care strategies, and recognition of the serious, long-term effects of these conditions.
Contributing Digesters: Lauren, Jyothsna and Simone.
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How pandemics reshape our brain: Common links and targets between long‐haul COVID‐19, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), oxidative stress, and neurodegeneration
Authors: Herman M (Building Global Research Competency, Guatemala)
Publication: Neuroprotection (May 2025)
Link: https://onlinelibrary.wiley.com/doi/10.1002/nep3.70007
Easy Read Overview: This article explains how long-COVID and ME/CFS can cause long-term problems in the brain. Scientists suggest these illnesses may be caused by a stressed immune system and damage inside cells, that could even resemble early stages of brain diseases. The article also highlights that ME/CFS has been overlooked for many years, but COVI-19 has brought more attention to it. The article stresses the urgent need for more research and better treatments to support people living with these serious, long-term conditions.
This article examines the neurological consequences of pandemics, focusing on the overlap between long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Both conditions are characterised by disabling fatigue, cognitive impairment, sleep disruption, and autonomic dysfunction, and are increasingly recognised as neurodegenerative disorders driven by immune dysregulation and oxidative stress. The aim was to highlight ME/CFS as a research model for understanding the long-term impact of viral infections on brain health.
The study reviewed published literature, epidemiological data, and recent clinical trial findings. It analysed historical patterns of pandemic-related immune selection, biological mechanisms such as oxidative stress and energy metabolism, and parallels between ME/CFS, long-COVID, and other neurodegenerative diseases.
Research has shown that approximately half of long-COVID cases meet diagnostic criteria for ME/CFS, substantially raising prevalence estimates. Both conditions demonstrate persistent immune hyperactivity, high oxidative stress, impaired cellular energy conversion, and neuroinflammatory changes. EEG studies of long-COVID patients reveal abnormalities resembling early neurodegenerative disease. Recovery is rare, with only ~5% of ME/CFS patients achieving remission.
The discussion emphasises that ME/CFS has long been underdiagnosed and underfunded, with research hampered by the absence of biomarkers and limited awareness among clinicians. However, increased post-COVID funding offers new opportunities. The author argues that ME/CFS and long-COVID should not be dismissed as functional disorders, but recognised as conditions with degenerative features and shared mechanisms with established neurodegenerative diseases.
ME/CFS and long-COVID provide valuable models for studying the neurological effects of prolonged oxidative stress. Their recognition as neurodegenerative conditions is essential for developing neuroprotective strategies. Expanded research, clinical trials of targeted therapies, and better use of health data and tissue banks are urgently needed to improve outcomes for this underserved population.
Neurodevelopment genes encoding Olduvai domains link myalgic encephalomyelitis to neuropsychiatric disorders
Authors: Arcos-Burgos M, Arcos-Holzinger A, Mastronardi C, Isaza-Ruget MA, Vélez JI, Lewis DP, … Lidbury BA (The Australian National University, Australia)
Publication: Diagnostics (June 2025)
Link: https://www.mdpi.com/2075-4418/15/12/1542
Easy Read Overview: Scientists studied whether certain brain-related genes might increase the risk of developing ME/CFS. They looked at 77 ME/CFS patients and compared their genes to those of people from a large genetic database. The study focused on genes with Olduvai (DUF1220) domains, which are important for brain growth. They found strong links to three genes—NBPF1, NBPF10, and NBPF16—that help with brain development. Other gene changes, like ATR and NTRK2, were also more common in people with ME/CFS. Similar results were found in a separate group of ME/CFS patients from the U.S.
Previous studies have found genetic links to infection, autoimmunity, and neuropsychiatric comorbidities in ME/CFS, though consensus on genetic factors has not been found. The current study investigates whether variations in neurodevelopmental genes, specifically those encoding Olduvai (DUF1220) domains, may contribute to ME/CFS susceptibility.
Seventy-seven ME/CFS patients (International Consensus Criteria) were recruited for the study. Blood samples were taken, and whole-exome sequencing was conducted. After stringent quality control, variants were compared with European-ancestry data from the 1000 Genomes Project, which served as population controls. Network and pathway analysis was undertaken to determine if specific functional pathways were over-represented in the ME/CFS variants identified, and correction for multiple comparisons was conducted.
The strongest associations were observed in Neuroblastoma Breakpoint Family encoding Olduvai (DUF1220) domains, namely NBPF1, NBPF10, and NBPF16, all of which are implicated in cortical neurogenesis and human brain evolution.
In addition to the NBPF genes, the researchers also found other additional variants, such as ATR, RSPH10B, ADGRE5-CD97, and NTRK2 genes, which were more common in ME/CFS. These findings were replicated in a cross-cohort comparison group of ME/CFS patients from the US, where associations were also observed with variants in genes such as PTPRD, CSMD3, RAPGEF5, and DCC.
The convergence of these signals in Olduvai-domain-containing genes points toward a potential genetic mechanism linking ME/CFS to neurodevelopmental and neuropsychiatric disorders, including autism and schizophrenia. These findings are consistent with previous evidence that Olduvai copy number variation contributes to both brain size variation and disease susceptibility.
The authors acknowledge several limitations to their study: modest sample size, its reliance on population controls that didn’t match the local ones, and the absence of functional assays. They emphasise the need for replication of the study in larger, diverse cohorts and better laboratory studies to confirm the biological impact on ME/CFS.
Emerge Australia acknowledges the contribution of Australian GP Dr Don Lewis, co-author of this paper, who provided expert care to many ME/CFS patients in Australia, and who passed away in 2019.
Telehealth as a care solution for homebound people: systematic review and meta-analysis of healthcare utilization, quality of life, and well-being outcomes
Authors: Pinero de Plaza MA, Gulyani A, Bulto LN, Allande-Cussó R, Pearson V, Lange B, … McMillan P, … Hendriks JM (Flinders University, Australia)
Publication: Health & Social Care in the Community (July 2025)
Link: https://onlinelibrary.wiley.com/doi/full/10.1155/hsc/7224151
Easy Read Overview: Telehealth uses technology to help people get healthcare without going to a clinic. It became more popular during the COVID-19 pandemic, and many patients liked it. This review looked at how telehealth helps people who can’t leave their homes. It found that telehealth reduced trips to the emergency room and helped improve mental health and well-being. The study suggests telehealth is a good option for homebound people and should be designed to fit their specific needs.
Telehealth is defined as the use of digital technologies to deliver healthcare remotely. Telehealth can be vital for homebound people who have difficulty attending a medical clinic to access healthcare. The COVID-19 pandemic accelerated the uptake of telehealth services, which have generally been well-received by patients. However, there is limited research on how effective these services are for homebound individuals. This review examined the effectiveness of telehealth services in reducing healthcare utilisation (such as hospital visits) and in improving quality of life and well-being for homebound individuals.
From an initial yield of 3,289 articles, ten studies met the inclusion criteria and eight were eligible for meta-analysis, encompassing data from 2,245 participants. The studies included interventions delivered via video, telephone, or other digital platforms. A meta-analysis was conducted, and the quality of studies evaluated using the GRADE method.
The analysis found that telehealth interventions significantly reduced healthcare utilisation, with a reduction in emergency department visits. In addition, telehealth services led to an increase in health-related quality of life, especially a reduction in pain and improvement in mental health, and a reduction in depression, isolation and loneliness.
The authors conclude that these results suggest that telehealth can be a viable alternative to in-person healthcare and can be utilised to ease the burden on the healthcare system. While telehealth services can be useful for homebound individuals, regardless of the reason they are homebound, they should be co-designed to meet the specific needs of different patient groups.
Impacts of long COVID on disability, function and quality of life for adults living in Australia
Authors: Hitch D, Botha T, Tesfay F, Holton S, Said CM, Hensher M, … Nicola-Richmond K (Deakin University, Australia)
Publication: Australian Journal of Primary Health (August, 2025)
Link: https://www.publish.csiro.au/py/pdf/PY25033
Easy Read Overview: This study looked at how long COVID affects people in Australia. It found that many people with long COVID have serious problems doing everyday activities and feel much worse than the general population. Researchers also found that their quality of life was much lower, especially in energy and social life. The study showed some connection between how recovered people felt and how well they could function. Overall, long COVID caused major health issues, and more research is needed to understand its long-term effects.
The aim of this study was to describe the level of disability, function and quality of life of people living with long COVID in Australia. The study also aimed to explore the relationship between these three factors, and to examine the impact of age, vaccination status, comorbidities and recovery status on them.
The study included 121 adults who had rapid-antigen test-confirmed COVID-19 and met the World Health Organization definition of long COVID. Participants completed surveys which included demographics, self-reported recovery status, comorbidities, disability (WHODAS 2.0) and quality of life (SF-36). Most of the participants (86%) had not been hospitalised when they had COVID-19.
The average level of disability among participants was higher than that of 98% of the general population. Most of the participants (86%) reported clinically significant disability, compared with just 9% in the general population. On average, participants experienced difficulty with daily activities 26.7 days per month, reduced participation on 19.7 days per month, and were unable to complete daily activities on 17.95 days per month. Quality of life was also significantly worse than in the general population, with vitality and social functioning most affected.
There was a moderate correlation between self-rated recovery and vitality, physical function and community participation. Disability and quality of life were weakly correlated. There was no significant relationship between comorbidities and disability, function or quality of life.
The authors conclude that long COVID is associated with a significant reduction in function and quality of life, and that further longitudinal research is needed to better understand its long-term impact.