ME/CFS Research Published 6 – 12 February 2024

The weekly research round-up includes all recent publications about ME/CFS and Long Covid, which includes the key terms: Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, ME/CFS, Long Covid and Post Covid syndrome.

The list is inclusive of all research published to keep our community informed, however, this does not necessarily mean we endorse the studies. We briefly highlight and analyse particularly studies which have caught our attention.

RESEARCH INDEX

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

VIEW THE ME/CFS AND LONG COVID RESEARCH INDEX

Audio Commentary by Dr Katrina Pears

There have been six new ME/CFS studies and forty-one new Long Covid studies.

We have highlighted one of the ME/CFS studies in more detail below:

Paper four (4) is on assessing post-exertional malaise (PEM) which is a hallmark symptom of ME/CFS. This study aimed at increasing our understanding of PEM and the best way to measure it through semi structured qualitative interviews (QIs) alongside visual analogue scale (VAS) measures after a cardiopulmonary exercise test (CPET).

• The Visual Analog Scale (VAS) is frequently used to assess PEM. This scale is designed to rate a person’s intensity to certain sensations and feelings and is typically used as a pain rating scale. More information about this scale can be found here.
• Qualitative interviews (QI) can also be used to capture the onset, changes in PEM severity, trajectory and symptoms overtime (including the most bothersome), although data collected through this is hard to quantify. QIs are very useful to compliment the use of VAS and capture information correctly.

Prior to this study, there has been very little validation of the use of VAS and QIs to assess PEM following CPET.

In this study ten ME/CFS participants and nine healthy controls participated in CPET. For each participant, PEM symptom VAS (12 symptoms) and semi structured QIs were administered at six timepoints over 72 hours before and after a single CPET. The data was used to plot the severity of PEM at each time point and identify the self-described most bothersome symptom for participant.

Capturing PEM is known to be difficult, and this study sought to address the problems in measuring PEM. They found that a quantitative–qualitative mixed model approach is needed, as QIs were able to capture changes in PEM severity and symptom over time, even when VAS scales failed to do so. Other findings included:

• Each ME/CFS participant had a unique PEM experience, with differences noted in the onset, severity, trajectory over time and most bothersome symptom.
• Only one ME/CFS participant returned to their pre-CPET levels within the 72-hour timepoint.
• A large variation was seen in the peak timing of PEM, with several of the participants reporting more than one peak in PEM (which was unable to be captured using VAS alone).
• Most bothersome symptoms were captured through QIs- physical fatigue (40%), mental fatigue (20%), headache (30%) and muscle ache (10%).
• No healthy volunteers experienced PEM.
• QI and VAS captured information differently about the course of PEM, with QIs having a more measurement of granularity and face validity.
• QI and VAS fatigue data corresponded well an hour prior to exercise but poorly at peak PEM and with the change from pre-CPET to peak.
• When the most bothersome symptom identified from QIs was used, these correlations improved and reduced the observed VAS scale ceiling effects.

A few things to note about this study:

• This research is part of a larger NIH study looking into phenotyping of ME/CFS and healthy controls through a CPET intervention designed to induce PEM with serial follow- up performed over 72 hours.
• All ME/CFS participants met the IOM 2015 ME/CFS diagnosis criteria.
• Where possible healthy controls meant the same demographic characteristics of the ME/CFS participants (age, sex etc). Although there is not information of whether the controls were sedentary.
• QIs were conducted before VAS, so its not know how this would have affected the results if done in the reverse.
• It would also have been useful in this study to combine the DePaul Post-Exertional Malaise Questionnaire (DSQ) which is another common tool to assess PEM.
• It is a shame no biomedical samples were taken to further support the results, for example measuring lactate levels, with more elevated levels been previously found in more severe PEM.

This was a very small exploratory study showing that QIs are more sensitive to PEM than VAS, although it questions how feasible this would be to conduct on a larger scale (interviews are time heavy for both researchers and participants). Furthermore, I do not feel this study tells us anything new about the PEM experience of people with ME/CFS.

You may also be interested in reading our previous review on the evidence for post-exertional malaise (PEM) in ME/CFS and Long Covid, which can be found here.

ME/CFS Research References

1. Improving Quality of Life in Chronic Fatigue Syndrome using Antioxidant Complex Twendee M®
2. Is reduced heart rate variability associated with functional somatic disorders? A cross-sectional population-based study; DanFunD
3. Integrated Causal Inference Modeling Uncovers Novel Causal Factors and Potential Therapeutic Targets of Qingjin Yiqi Granules for Chronic Fatigue Syndrome
4. Mixed methods system for the assessment of post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: an exploratory study
5. From Viral Infection to Autoimmune Reaction: Exploring the Link between Human Herpesvirus 6 and Autoimmune Diseases
6. How does post COVID differ from other post-viral conditions in childhood and adolescence (0-20 years old)? A systematic review

Long-COVID Research References

1. Postacute Sequelae of SARS-CoV-2 in Children
2. High Prevalence of Long COVID in Common Variable Immunodeficiency: An Italian Multicentric Study
3. Long COVID is associated with severe cognitive slowing: a multicentre cross-sectional study
4. The global prevalence of depression, anxiety, and sleep disorder among patients coping with Post COVID-19 syndrome (long COVID): a systematic review and meta-analysis
5. Analysis and clinical determinants of post-COVID-19 syndrome in the Lombardy region: evidence from a longitudinal cohort study
6. The Persistence of SARS-CoV-2 and Its Role in Long Covid
7. Potential Beneficial Effects of Naringin and Naringenin on Long COVID—A Review of the Literature
8. People with a connective tissue disorder may be especially vulnerable to the endothelial damage that characterizes long COVID due to the fragility of their vasculature and slow wound healing
9. Association of psychiatric disorders with clinical diagnosis of long COVID in US veterans
10. Unraveling Links between Chronic Inflammation and Long COVID: Workshop Report 
11. Cognitive and Mental Health Trajectories of COVID-19: Role of Hospitalisation and Long-COVID Symptoms
12. Comparing surveyed adults with long COVID and those with just a positive test helps put COVID into perspective
13. Reaching out to Patients with Long COVID to Better Understand Their Life Experiences and How to Support Their Recovery: A Patient-Oriented Knowledge Sharing Session
14. Prevalence of depression, stress and suicide tendency among individuals with long COVID and determinants: a protocol of a systematic review and meta-analysis
15. The Long-COVID Syndrome—how to assess in real-time an individuals well-being—the COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm)
16. Dysregulated platelet function in patients with postacute sequelae of COVID-19
17. Clinical and Laboratory Characteristics of Fatigue-dominant Long-COVID subjects: A Cross-Sectional Study
18. Predictors of non-recovery from fatigue and cognitive deficits after COVID-19: a prospective, longitudinal, population-based study
19. Cluster Analysis to Identify Long COVID Phenotypes Using 129Xe Magnetic Resonance Imaging: A Multi-centre Evaluation
20. Clinical effectiveness of an online supervised group physical and mental health rehabilitation programme for adults with post-covid-19 condition (REGAIN study): multicentre randomised controlled trial
21. Factors associated with cognitive impairment in patients with persisting sequelae of Covid-19
22. Post-COVID in women after SARS-CoV-2 infection during pregnancy – a pilot study with follow-up data from the COVID-19-related Obstetric and Neonatal Outcome Study (CRONOS)
23. Development of post-acute sequelae of SARS-CoV-2 (PASC) after infection in pregnancy: NIH RECOVER-Pregnancy Cohort
24. Burnout, Compassion Fatigue and the Long Haul of Caring for Long COVID
25. How does COVID-19 vaccination affect long-COVID symptoms?
26. SSRI Use During Acute COVID-19 Infection Associated with Lower Risk of Long COVID Among Patients with Depression
27. The Long-COVID Syndrome—how to assess in real-time an individuals well-being—the COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) 
28. Headache or Disturbed Smell and Taste During Acute COVID-19 as Predictors of Long COVID at One Year
29. The impact of “long COVID” on menstruation in Chinese female college students and the intervention of acupuncture
30. Cardiorespiratory abnormalities in ICU survivors of COVID-19 with Post-acute Sequelae of SARS-CoV-2 infection are unrelated to invasive mechanical ventilation
31. A Prospective Multicenter Longitudinal Analysis of Suicidal Ideation among Long-COVID-19 Patients
32. Post-COVID-19 patients suffer from chemosensory, trigeminal, and salivary dysfunctions
33. Altered mitochondrial respiration in peripheral blood mononuclear cells of post-acute sequelae of SARS-CoV-2 infection
34. Exploring the Use of Mobile Health for the Rehabilitation of Long COVID Patients: A Scoping Review
35. Bidirectional relationship between sleep problems and long COVID: a longitudinal analysis of data from the COVIDENCE UK study
36. Can longitudinal electronic health record data identify patients at higher risk of developing long COVID?
37. Improved Functioning and Activity According to the International Classification of Functioning and Disability after Multidisciplinary Telerehabilitation for Post-COVID-19 Condition—A Randomized Control Study
38. Potential Predictors of Long COVID in Italian Children: A Cross-Sectional Survey
39. Cytokines (IL1β, IL6, TNFα) and serum cortisol levels may not constitute reliable biomarkers to identify individuals with post-acute sequelae of COVID-19
40. Autonomic dysfunction and exercise intolerance in post-COVID-19 – An as yet underestimated organ system?
41. Mechanisms underlying exercise intolerance in long COVID: An accumulation of multisystem dysfunction

Dr Katrina Pears,
Research Correspondent.
The ME Association.