MEA Research Roundup

ME/CFS and Long Covid Research: 15 – 21 November 2022

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 15 – 21 November 2022 

It’s been another quiet week for ME/CFS research and there have only been three new ME/CFS studies but a busy week for Long Covid research with nineteen new studies. 

Similar to last week, two of the papers in the ME/CFS reference section focus on ME/CFS that has developed following Covid-19 infection (papers one (1) and two (2)), where participants fulfil the diagnostic criteria. Therefore, these are of a slightly different nature as there is a known cause, but it shows the increasing recognition for the similarities between ME/CFS and Long Covid.  

Unfortunately, few of the studies caught our eyes this week, so we have highlighted one study from the ME/CFS reference section and included snippets of two of the studies in the Long Covid reference section this week. 

Paper one (1) is a protocol for the first international study which aims to investigate the long-term effects of Covid-19 including symptoms, diagnosis and treatments, from this the prevalence of chronic fatigue syndrome/ myalgic encephalomyelitis worldwide can be gained. The study looks to involve 200 researchers in 28 countries, therefore, there are no results at this stage. 

The aims of this study are huge, especially to get an insight into less developed countries, for example, to name a few Bangladesh, Ecuador, Yemen are all listed by the authors. There are a few things that stand out making the protocol questionable: 

  1. If this study involves huge international collaboration why are there only two authors listed? 
  1. The time scale for the study is for it to be conducted between September 2021 to September 2022, however, ethics approval was only obtained in November 2021 in only a few of the countries listed, after the study was set to commence. With a number of the countries cited having not gained ethics approval yet (at the time of publishing this protocol). 
  1. This is very ambitious to coordinate and complete in the timescales quoted. 
  1. This study will also rely heavily on DePaul Questionnaires (specifically DSQ-2) which is often criticised by the ME/CFS community. For example: it only gives a snapshot of symptoms, doesn’t represent post-exertional malaise (PEM) (which is poorly described by DSQ-2) overtime accurately, doesn’t measure the effect of pacing, often too complex and lengthy to complete and has strong psychometric content. 

I also find the title of this published research protocol interesting, as the link between ME/CFS and Long Covid is recognised with the word “myalgic encephalomyelitis” being placed in brackets. To date all studies I have come across in this domain have referred to Long Covid Chronic Fatigue Syndrome. It will be interesting to see how the name changes overtime, and if in the future the two will not be distinguished between and grouped just under ME/CFS. Lastly, if this study is successful, it probably will not be long until we see results. 

In the Long Covid reference section, you may also be interested in reading: 

Paper two (2) is a comprehensive review of Long Covid focusing on what we know so far and brings many different aspects together. The review covers several topics, such as: mechanisms, epidemiology, pathophysiology, Long Covid in the physically active, the use of cardiopulmonary exercise testing (CPET), dysautonomia and POTS (postural-orthostatic tachycardia syndrome), neurological contributions, microclots and endothelial dysfunction, mitochondrial dysfunction, and the links to ME/CFS.  

One of the authors on this review is Dr Karl Morten, whose other research has been funded by the ME Associations Ramsay Research Fund, and his research group actively focuses on understanding the role of mitochondria in health and disease. Dr Karl Morten’s latest study focused on finding a diagnostic test with plasma components present in the patients with severe ME/CFS and healthy controls differing, see here

Paper three (3) is a feasibility study looking at the use of a heart rate variability biofeedback (HRV-B) technique via a standardised slow diaphragmatic breathing programme for patients with Long Covid. This study will employ wearable technology for those undertaking the programme, in which the polar chest strap device is linked to the Elite HRV phone application while undertaking the breathing exercise technique for two 10 min periods every day for at least 5 days in a week (over a 4-week period) as well as a wrist worn fitbit device.  

Currently, this is only a published protocol, so there is no data, but I look forward to seeing the outcomes of this study as I feel that a lot can be gained from wearable devices in the home to monitor vital signs. For example, we also recently saw a study where activity levels were monitored in patients with ME/CFS using Fitbits, see here.    

ME/CFS Research References and Abstracts  

1. Long-term sequelae of COVID-19 (myalgic encephalomyelitis): An international cross-sectional study 

Shaheen, Nour; Shaheen, Ahmed 

Medicine: November 11, 2022 – Volume 101 – Issue 45 – p e31819 


Background: As a result of prolonged effects on multiple organs, recovery from COVID-19 caused by SARS-CoV-2 cannot be verified. This study seeks to understand chronic and acute long-term symptoms of COVID-19 lasting from a few weeks after diagnosis. The study also aims to gain insight into prevalence of chronic fatigue syndrome/myalgic encephalomyelitis, a potentially comorbid condition for several months after the infection, in addition to taking a broad perspective on rare symptoms that may have developed during or after the infection. 

Study design: Cross-sectional questionnaire\descriptive study. 

Methods: The questionnaire was developed to assess the long-term effects of the global pandemic of COVID-19 using DePaul Symptom Questionnaire-2. The DePaul Symptom Questionnaire, Patient Health Questionnaire, and other symptoms that have been introduced by literature review. 

Discussion: A large cohort of people from all over the world will be examined to understand the differential effects of people who have experienced COVID-19, as well as the potential occurrence of ME. In total, 20,000 COVID patients are expected to be included in the study by Sep 1, 2022. Patients who have experienced COVID-19 will be asked about their persistent symptoms from 1 week up to more than 6 months after catching or recovery from the infection. 

2. Efficacy of traditional Chinese exercises in patients with post-COVID-19 chronic fatigue syndrome: A protocol for systematic review and meta-analysis 

Liu Z, Lv Z, Zhou X, Shi J, Hong S, Huang H, Lv L.  

Medicine (Baltimore). 2022 Nov 18;101(46): e31450.  


Background: Some patients develop long-term symptoms after Corona virus disease 2019 (COVID-19), and chronic fatigue syndrome (CFS) is one of the main symptoms.  

CFS is characterized by fatigue lasting for more than 6 months accompanied by sleep disorders, anxiety, and depression, which causes a certain degree of harm to both physiological and psychological aspects of the individual.  

Traditional Chinese exercises (TCEs) are an ancient Chinese therapy and has recently been reported to be effective for CFS. Therefore, we will conduct a systematic review and meta-analysis aiming to accurately evaluate the efficacy of TCEs on post-COVID-19 CFS and provide an alternative treatment for post-COVID-19 CFS. 

Methods: Seven databases (PubMed, Ovid Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), and Wanfang) will be searched from establishment to August 2022, and we will only include randomized controlled trials of TCEs for post-COVID-19 CFS.  

Two reviews will independently include the research according to the inclusion and exclusion criteria. Review Manager 5.2 software will be used to analyze the accepted literature, and the relative risk ratio (RR) and 95% confidence interval (CI) will be used as effect indicators for the outcome indicator dichotomous variables. For continuous variables, weighted mean difference (MD) and 95% CI will be used as effect indicators. The heterogeneity test will be assessed using the I2 statistic and Q statistic.  

The PEDro scale was used to evaluate the methodological quality of the included studies. Subgroup analysis was performed according to different TCEs, age, gender, and duration of CFS. 

Results: This systematic review and meta-analysis will evaluate the efficacy of TCEs in post-COVID-19 CFS. 

Conclusion: The results of this study will provide reliable evidence for the effects of TCEs for post-COVID-19 CFS on patients' fatigue, anxiety, depression, sleep, and quality of life. 

3. Effect of electroacupuncture at back-shu points of five zang on fatigue status and cortical excitability in chronic fatigue syndrome 

Li ZX, Zhang Y, Yan LD, Lai MQ, Xu HY, Wu T, Chen RM, Shi GA, Zhou P 

Zhongguo Zhen jiu = Chinese Acupuncture & Moxibustion, 01 Nov 2022, 42(11):1205-1210. [Article in Chinese]  


Objective: To observe the effect of electroacupuncture (EA) at back-shu points of five zang on fatigue status, quality of life and motor cortical excitability in patients with chronic fatigue syndrome (CFS), so as to explore the possible mechanism of EA for CFS. 

Methods: A total of 72 patients with CFS were randomized into an EA group (36 cases, 4 cases dropped off) and a sham EA group (36 cases, 3 cases dropped off). In the EA group, EA at Ganshu (BL 18), Xinshu (BL 15), Pishu (BL 20), Feishu (BL 13) and Shenshu (BL 23) was adopted, with continuous wave, 2 Hz in frequency.  

In the sham EA group, sham EA at non-acupoints (1.5-2.0 cm lateral to back-shu points of five zang) was applied, with shallow needling, and no current was connected. The treatment in the both groups was 20 min each time, once every other day, 2 weeks as one course, 3 courses were required.  

Before and after treatment, the scores of fatigue scale-14 (FS-14) and the MOS 36-item short form health survey (SF-36) were observed, and cortical excitability (the resting motor threshold [RMT], amplitude of motor-evoked potential [MEP-A] and latency of motor-evoked potential [MEP-L]) was detected in the two groups. 

Results: After treatment, the physical fatigue score, mental fatigue score and total score of FS-14, as well as RMT of motor cortex in the EA group were decreased compared with those before treatment (P<0.01), the physical fatigue score and total score of FS-14 in the sham EA group were decreased compared with those before treatment (P<0.05); each item score and total score of FS-14 and RMT of motor cortex in the EA group were lower than those in the sham EA group (P<0.01, P<0.05).  

After treatment, each item score and total score of SF-36 and MEP-A of motor cortex in the EA group were increased compared with those before treatment (P<0.01), which were higher than those in the sham EA group (P<0.01, P<0.05). 

Conclusion: EA at back-shu points of five zang can effectively improve the fatigue status and quality of life in patients with CFS, its mechanism may be related to the up-regulating excitability of cerebral motor cortex. 

Long-COVID Research References  

  1. Long COVID: Rapid Evidence Review 
  1. Long COVID: mechanisms, risk factors and recovery 
  1. HEART rate variability biofeedback for long COVID symptoms (HEARTLOC): protocol for a feasibility study 
  1. Post COVID-19 syndrome with impairment of flow-mediated epicardial vasodilation and flow reserve 
  1. Cardiac function in relation to functional status and fatigue in patients with post-COVID syndrome 
  1. Life stressors significantly impact long-term outcomes and post-acute symptoms 12-months after COVID-19 hospitalization 
  1. Clinical assessment of endothelial function in convalescent COVID-19 patients: a meta-analysis with meta-regressions 
  1. Mindfulness Meditation Interventions for Long COVID: Biobehavioral Gene Expression and Neuroimmune Functioning 
  1. HERV-W ENV antigenemia and correlation of increased anti-SARS-CoV-2 immunoglobulin levels with post-COVID-19 symptoms 
  1. Vital Measurements of Hospitalized COVID-19 Patients as a Predictor of Long COVID: An EHR-based Cohort Study from the RECOVER Program in N3C 
  1. Neuropsychiatric Aspects of Long COVID: A Comprehensive Review 
  1. The role of sleep and dreams in long-COVID 
  1. Impact of SARS-CoV-2 RNAemia and other risk factors on long-COVID: A prospective observational multicentre cohort study 
  1. Association between long COVID symptoms and employment status 
  1. Post-COVID-19 Menstrual Symptom Disorders Relating to Anxiety and Long COVID-19 Symptoms 
  1. Acute and longterm psychiatric symptoms associated with COVID19 (Review) 
  1. What is the quality of life in patients with long COVID compared to a healthy control group? 
  1. Resilience resources and coping strategies of COVID-19 female long haulers: A qualitative study 
  1. Is Long COVID Syndrome a Transient Mitochondriopathy Newly Discovered: Implications of CPET 

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent
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