ME Association regular research roundup

ME/CFS and Long Covid Research: 04 – 10 April 2023 

The weekly research round-up includes recent publications about ME/CFS and Long Covid. We highlight the studies that have particularly caught our interest and follow these with the full list of publications together with their abstracts (summaries).


The ME Association maintains a comprehensive index of published research on ME/CFS and Long Covid that is free to use and updated weekly.

Audio Commentary by Dr Katrina Pears

ME/CFS Research Published 4 – 10 April 2023 

There’s been a mix of research this week, with four new ME/CFS studies but nineteen new Long Covid studies. 

None of the studies particularly caught our attention this week, therefore we have provided a snapshot of two studies which are of most interest this week.  

Paper one (1) looks at the effectiveness of Low Dose Naltrexone (LDN) mostly focusing on Fibromyalgia (FM) and looking into real-world prescribing practices. The researchers evaluated 115 patients, with 65% reporting a benefit. The study concludes that further investigation is needed in controlled trials.  

We have previously reviewed the evidence on LDN in specific research related to ME/CFS, finding mixed patient experiences and no sound evidence available yet for its use, see here

Paper four (4) reviews therapeutical interventions which have been through clinical trials, specifically those which have made it to phase four (IV). Phase IV of a trial is where a drug has already been approved for use in the general population, and this is to further study the side-effects over time.  

Unfortunately, we cannot read the full study, but unsurprisingly there were few clinical trials identified related to ME/CFS. Despite this, the most common interventions were micronutrients, sodium oxybate was the most common pharmacological intervention (commonly used to treat narcolepsy), and the interventions which had been through phase IV clinical trials involved drugs that mainly interacted with the central nervous system (CNS). 

ME/CFS Research References and Abstracts  

1. Efficacy of Low-Dose Naltrexone and Predictors of Treatment Success or Discontinuation in Fibromyalgia and Other Chronic Pain Conditions: A Fourteen-Year, Enterprise-Wide Retrospective Analysis 

Driver CN, D’Souza RS. 

Biomedicines. 2023; 11(4):1087.  


Current pharmacologic treatments may provide limited analgesia in fibromyalgia and other chronic pain disorders. Low-dose naltrexone (LDN) has emerged as a potential analgesic option that has been minimally explored.  

This study aims to describe current real-world prescribing practices of LDN, to investigate if patients have a perceived benefit of LDN in treating pain symptoms and to identify predictors associated with a perceived benefit or discontinuation of LDN.  

We evaluated all outpatient prescriptions for LDN prescribed for any pain indication in the Mayo Clinic Enterprise from 1 January 2009 to 10 September 2022. A total of 115 patients were included in the final analysis.  

The patients were 86% female, had a mean age of 48 ± 16 years, and 61% of prescriptions were for fibromyalgia-related pain. The final daily dose of oral LDN ranged from 0.8 to 9.0 mg, while the most common dose was 4.5 mg once daily.  

Of patients who reported follow-up data, 65% reported benefit in their pain symptoms while taking LDN. Adverse effects were reported in 11 (11%) patients and 36% discontinued taking LDN by the most recent follow-up.  

Concomitant analgesic medications were used by 60% of patients and were not associated with perceived benefit nor discontinuation of LDN, including concomitant opioids.  

LDN is a relatively safe pharmacologic option that may benefit patients with chronic pain conditions and warrants further investigation in a prospective, controlled, and well-powered randomized clinical trial. 

2. Psychiatric disorders and the onset of self-reported fibromyalgia and chronic fatigue syndrome: The lifelines cohort study 

Creed F.  

Front Psychiatry. 2023 Mar 24;14:1120250. 


Introduction: This study aimed to assess whether psychiatric disorders predict the onset of fibromyalgia and chronic fatigue syndrome (CFS) which develop in the presence of pre-existing muscle pain or fatigue. 

Methods: The population-based Lifelines cohort study included 148,614 adults with relevant data for the fibromyalgia study and 136,423 for the CFS study. Participants with prior self-reported fibromyalgia (or CFS) at baseline were excluded from the relevant analysis. At follow-up (mean 2.4 years), new onsets of each syndrome were identified by self-report. Logistic regression was used to identify which of the baseline variables predicted new onsets of each syndrome. The total number of psychiatric disorders (depression, anxiety, burnout, panic disorder, social phobia, agoraphobia, obsessive-compulsive, and eating disorders) was used as a predictor. Prior to the analyses the samples were divided into those with and without marked muscle pain (for fibromyalgia analysis) or persistent fatigue (for CFS). 

Results: During follow-up, there were 685/136,423 (0.5%) new onsets of self-reported FM in participants without marked muscle pain and 281/7481 (3.75%) in those with such pain; for CFS it was 292/124,223 (0.2%) for those without and 192/10,025 (1.9%) for those with baseline fatigue. In both univariate and logistic regression analyses of participants with prior persistent fatigue psychiatric disorder was clearly associated with onset of CFS. This was not so for onset of fibromyalgia in participants with prior muscle pain. 

Discussion: Although psychiatric disorders did not predict self-reported fibromyalgia or CFS in participants free of pain or fatigue at baseline, in this study psychiatric disorder did predict self-reported CFS in the presence of pre-existing fatigue. Progress in understanding the etiology of these disorders may require studying separately onsets with and without pre-existing key symptoms. 

3. The Role of Psychotherapy in the Care of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome 

Grande T, Grande B, Gerner P, Hammer S, Stingl M, Vink M, Hughes BM.  

Medicina. 2023; 59(4):719. 


Myalgic encephalomyelitis/chronic fatigue (ME/CFS) is a post-infectious, chronic disease that can lead to severe impairment and, even, total disability. Although the disease has been known for a long time, and has been coded in the ICD since 1969 (G93.3), medical research has not yet been able to reach a consensus regarding its physiological basis and how best to treat it.  

Against the background of these shortcomings, psychosomatic disease models have been developed and psychotherapeutic treatments have been derived from them, but their empirical testing has led to sobering results. According to the current state of research, psychotherapy and psychosomatic rehabilitation have no curative effect in the treatment of ME/CFS.  

Nevertheless, we see numerous patients in practices and outpatient clinics who suffer severely as a result of their illness and whose mental well-being and coping strategies would benefit from psychotherapeutic help.  

In this article, we outline a psychotherapeutic approach that serves this need, taking into account two basic characteristics of ME/CFS: firstly, the fact that ME/CFS is a physical illness and that curative treatment must therefore be physical; and secondly, the fact that post exertional malaise (PEM) is a cardinal symptom of ME/CFS and thus warrants tailored psychotherapeutic attention. 

4. Therapeutical interventions for myalgic encephalomyelitis/chronic fatigue syndrome; A review of phase IV Clinical trials 

Alorfi NM. 

Bulletin of Pharmaceutical Sciences. Assiut, (), pp. Articles in Press, Accepted Manuscript. Available Online from 06 April 2023 


Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling and complex illness with multifactorial etiology. Current clinical trials were examined to understand the characteristics of ME/CFS as well as possible therapeutical interventions. 
Aim: To identify features of clinical trials related to ME/CFS registered at, specifically, the therapeutical interventions used to manage the syndrome in phase IV.  

Method: Analysis of all clinical trials registered at for ME/CFS. Those clinical trials that employed a targeted therapy were included. The analysis identified a selection of clinical trials examining a targeted therapy for ME/CFS, providing a platform for further exploration of potential treatments.  

Results: By November 19th, 2022, 151 clinical trials related to ME/CFS had been found. Interventional studies were the most prevalent type. However, the trials were restricted to specific continents and were not extensively conducted in pediatric patients. Micronutrients were the most commonly used intervention. Phase IV studies had fewer clinical trials with limited interventional measures. Only three out of nine studies completed pharmacological interventional studies, and of these, sodium oxybate was being used most frequently.  

Conclusion: Among the clinical trials identified through this paper, there were few related to ME/CFS treatment. The interventions in the completed phase IV studies involved drugs that mainly interacted with the CNS, and more rarely that had an effect on blood vessels and blood perfusion. The limited number of phase IV clinical trials meant that the results were inconclusive. 

Long-COVID Research References  

  1. Immunological dysfunction and mast cell activation syndrome in long COVID 
  1. Long COVID symptoms, pathophysiology and possible mechanisms: Still, we are learning! 
  1. Long COVID symptoms: Basic aspects of cardio-pulmonary and neurological pathways! 
  1. Long COVID: Cognitive and FDG PET evolutions in six patients 
  1. Post-COVID-19 condition and persisting symptoms in English schoolchildren: repeated surveys to March 2022 
  1. Fatigue, sleepiness and sleep quality are SARS-CoV-2 variant independent in patients with long COVID symptoms 
  1. A comprehensive systematic scoping review for physiotherapy interventions for people living with long COVID 
  1. Gut Microbiota Dysbiosis Correlates With Long COVID-19 at One-Year After Discharge 
  1. High levels of pro-inflammatory SARS-CoV-2-specific biomarkers revealed by in vitro whole blood cytokine release assay (CRA) in recovered and long-COVID-19 patients 
  1. Prevalence and Characterization of Long Covid-19 Symptoms in Health Care Professionals- A Need of the Hour 
  1. Data-driven analysis to understand long COVID using electronic health records from the RECOVER initiative 
  1. Five cluster classifications of long COVID and their background factors: A cross-sectional study in Japan 
  1. Risk factors for psychiatric symptoms in patients with long COVID: A systematic review 
  1. Cardiovascular Considerations in the Management of People with Suspected Long COVID 
  1. Mouse Adapted SARS-CoV-2 Model Induces “Long-COVID” Neuropathology in BALB/c Mice 
  1. Treatment of Long COVID symptoms with triple anticoagulant therapy 
  1. Cellular and molecular biomarkers of long COVID: a scoping review 
  1. The Breadth of the Neutralizing Antibody Response to Original SARS-CoV-2 Infection is Linked to the Presence of Long COVID Symptoms 

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent
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