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Research Digest | Issue 104

Greetings and welcome to the 104th edition of Emerge Australia’s Research Digest. In this edition, besides showcasing the latest research in the realms of ME/CFS and Long COVID, we are experimenting with the integration of ‘text-to-speech’ technology. This enhancement allows subscribers not only to read the summaries, but also to listen to them. Just click the button pertaining to the summary below, to have the research summaries read to you. We trust that you will find this to be a welcomed addition, to Emerge Australia’s Research Digest.

Contributing Digesters: Jyothsna, Solène, Sarah and Simone.

Digest Editor: Simone Eyssens.

You can also join our community and choose to have the Digest delivered straight to your inbox at the end of every month, by signing up to our mailing list here. We appreciate the support of everyone who reads the Digest – we encourage regular subscribers to support us with a monthly suggested donation of $2.

Investigating the human intestinal DNA virome and predicting disease-associated virus–host interactions in severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Authors: Hsieh S-Y, Savva GM, Telatin A, Tiwari SK, Tariq MA, Newberry F … Carding SR (University of East Anglia, United Kingdom)
International Journal of Molecular Sciences

Viral infection is a common trigger for ME/CFS, and gastrointestinal (GI) viral infections may contribute to the pathology seen in ME/CFS. This study aimed to explore the potential contribution of the human GI virome to severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), by combining DNA virome from isolated virus-like particles (VLPs) and whole metagenomes (WMS) from faecal samples.

The cohort of the study included nine female ME/CFS patients (diagnosed according to the Canadian Consensus Criteria and NICE 2007 criteria) and eight healthy individuals from the same households as the ME/CFS patients, (three male and five female). Same-household controls (SHHC) were used to account for environmental factors and minimize their impact on the microbiome. Participants provided a faecal sample, which was collected from their homes. Faecal VLP and VLP DNA were isolated, and WMS was sequenced. DNA viromes from isolated VLPs and WMS were combined for analysis.

The enriched virome datasets from VLPs and WMSs had overlapping but distinct components. Most of the viral clusters (VCs) identified consisted of communal viruses shared by ME/CFS and SHHC samples, though there were some which were unique to ME/CFS or SHHC samples.

Analysis revealed a core virome consisting mainly of tailed phages of the Caudoviricetes class, alongside a greater diversity of DNA viruses, including extracellular phages and integrated prophages. The investigation of the bacterial hosts revealed associations between ME/CFS-unique viruses and genera such as Bacteroides, Ruminococcus, Clostridium, Anaerotruncus, and Eubacterium. Particularly, the Anaerotruncus genus, known for its potential anti-inflammatory properties, showed increased abundance in ME/CFS, suggesting a possible link to the disease pathology.

The authors conclude that the disease-associated viruses may play a role in modulating bacterial hosts, contributing to dysbiosis symptoms in ME/CFS patients. Despite the limitations of the study’s sample size, the results provide a foundation for future research involving larger patient cohorts to validate and extend these observed associations.

A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial.

Authors: Lau RI, Su Q, Lau ISF, Ching JYL, Wong MCS, Lau LHS,   …  Ng SC (The Chinese University of Hong Kong, China).
The Lancet Infectious Diseases. 

Patients with post-acute COVID-19 syndrome (PACS) have significant alterations in gut microbiota (both in richness and diversity with depletion of beneficial bacteria). The authors hypothesised that microbiome modulation with probiotics or prebiotics may alleviate PACS. This randomised, double-blind, placebo-controlled trial assessed the efficacy of the synbiotic preparation SIM01 in alleviating PACS. SIM01 is a micro-encapsulated lyophilised powder containing three bacterial strains along with prebiotic compounds.

Participants were aged 18 years and older and had a COVID-19 initial infection followed by four weeks or more, of at least one symptom from the 14 referenced in the PACSQ-14 questionnaire. The 463 participants were randomly assigned to two groups: 232 individuals received the oral synbiotic preparation (SIM01), while 231 were given a placebo (vitamin C). The trial ran for six months. Participants were followed up at three and six months to assess compliance and adverse events. At six months, faecal and blood samples were collected for metagenomic analyses of their gut microbiome, complete blood count, liver and renal functions assessment, and inflammatory cytokine profiling. The primary outcome was the alleviation of PACS symptoms at six months. Secondary outcomes included quality of life; changes in the faecal microbiota, microbiome resistome and functions, and inflammatory profile; and rates of adverse events.

Baseline characteristics of patients were similar between SIM01 and placebo groups. At six months, a significantly higher proportion of individuals who received SIM01 reported reduced fatigue, memory loss, difficulty in concentration, gastrointestinal upset, and general unwellness compared with the placebo group (after adjusting for multiple comparisons). The faecal microbiota showed a significantly higher richness (as observed by the number of bacteria species), and distinct composition in the SIM01 group compared with the placebo group. The authors found that (1) alleviation in fatigue, gastrointestinal upset, and memory loss correlated with B. adolescentis, (2) alleviation in fatigue, and general unwellness correlated with B. bifiduma, while (3) alleviation in concentration difficulty correlated with B. longum abundance. There were no significant differences in either quality of life scores or adverse events between the groups.

The authors noted that persistent fatigue after COVID-19 is like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and that metagenomic analyses of ME/CFS faecal samples have shown significant gut dysbiosis with similar depletion of butyrate-producing bacterial species seen in PACS patients. These authors have elsewhere reported that SIM01 was associated with an increase of butyrate-producing species and hypothesise that butyrate-producing species may be a mechanism explaining the alleviation of fatigue observed in this study.

The authors conclude that this study highlights the potential of therapies targeting the gut microbiome in the management of PACS, and suggest further studies are warranted.

Muscle abnormalities worsen after post-exertional malaise in long COVID

Authors: Appelman B, Charlton BT, Goulding RP, Kerkhoff TJ, Breedveld EA, Noort W, … Wust RCI (Vrije Universiteit Amsterdam, the Netherlands)
Publication: Nature Communications

Post-exertional malaise, the worsening of symptoms after physical or mental activity, is a distinctive symptom of Long COVID. This study sought to explore the pathophysiology of post-exertional malaise in Long COVID patients.

This study used a longitudinal case-control study design. Twenty- five patients with Long COVID and 21 controls who had fully recovered from mild SARS-CoV2 infection were included in this study. Blood and skeletal muscle biopsies were obtained before and after a maximal exercise test was completed. Fatigue questionnaires and accelerometer data were also used to confirm activity levels.

The authors found that Long COVID patients had a lower exercise capacity, with lower maximal ventilation and poorer ventilatory function during exercise. All Long COVID patients reported experiencing post-exertional malaise following the exercise test, with muscle pain, greater fatigue and cognitive symptoms most commonly reported up to seven days post-test. Long COVID patients were found to have metabolic disturbances of reduced maximal mitochondrial respiration and decreased mitochondrial content compared to the controls one day after exercise. Long COVID patients were also found to have exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in their skeletal muscle after induction of post-exertional malaise from the maximal test. No correlation was found between the presence of viral remnants in skeletal muscle and the limited exercise capacity and post-exertional malaise seen in the Long COVID group.

The authors conclude that this study highlights that local and systemic metabolic disturbances, exercise-induced myopathy, the infiltration of amyloid-containing deposits and the presence of immune cells in skeletal muscle are key components in the symptomology of post-exertional malaise in Long COVID. Further study is recommended to determine the molecular pathways contributing to these alterations in Long COVID patients.

Parents of son with myalgic encephalomyelitis/chronic fatigue syndrome want more research into disease

Lynne Harris described the plight of her son, Dan, who has been bedbound with ME/CFS for more than four years. Dan is unable to speak, and Lynne is unable to touch or hug him because it will trigger post-exertional malaise. “It’s horrendous, it’s horrible and it’s heartbreaking to see someone that you love suffer so much,” Lynne says. “He has lost so much.”

CEO of Emerge Australia, Anne Wilson, said, “We have desperate calls from patients every day who can’t find a doctor to treat them, and they need help. People like Lynne Harris and her son, they’re just being ignored completely. There’s grief and loss — these people suffer as a result of losing everything and no one understands they’ve lost their lives.”

'It's a matter of urgency': The push for more chronic fatigue support

“The ME/CFS community’s suffering is being compounded on all levels with persistent cost of living pressures adding financial stresses to patients’ daily bio-psycho-social struggles,” Emerge Australia CEO Anne Wilson said. “It is a matter of urgency for Australia to update its clinical guidelines for ME/CFS, to ensure Australian ME/CFS patients have access to the best possible care, based on current understanding of the disease and latest evidence.”

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