Research Roundup

ME/CFS and Long Covid Research: 12 – 18 September 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

It’s been a quieter week for research, probably due to the start of the academic year. There have been four new ME/CFS studies and nineteen new Long Covid studies this week.

There was not much which caught our eyes this week, with several review articles. We have highlighted one of the ME/CFS studies in more detail below:

Paper one (1) reviews the similar conditions of post-treatment Lyme Disease (PTLDS) and ME/CFS. This review looks at 18 studies in which the details of PTLDS are listed, and uses analytical techniques to compare these to ME/CFS.

In brief, Lyme disease is caused by a bacterial infection called Borrelia burgdorferi, which is spread by animal ticks. When not treated in the early stages, this can develop into a chronic and untreatable form of Lyme disease, which can cause joint, heart and neurological complications. Which has many similar symptoms to ME/CFS. Unfortunately, 10 to 20% of people with Lyme disease develop chronic symptoms, known as post-treatment Lyme disease. Furthermore, it is now recognised as a medical condition, there are controversies and uncertainties surrounding the diagnostic tests being used and the methods of treatment in both the NHS and the private medical sector.

The study found:

  • In the majority of the PTLDS studies, at least four of the six major symptoms of ME/CFS were also noted, including substantial impairment in activity level and fatigue for more than 6 months, post-exertional malaise, and unrefreshing sleep.
  • The most common overlapping symptoms were fatigue and brain fog.
  • Of the 29 ME/CFS symptoms which were studied, all but three lymphadenopathy (disease affecting the lymph nodes), susceptibility to viruses, and food sensitivities) were reported in at least one of the 18 PTLDS articles studied.
  • In one of the included PTLDS articles, 26 of the 29 ME/CFS symptoms were noted.
  • Symptoms that appeared to be unique to PTLDS included paresthesia (abnormal sensation such as tingling and prickling), tremor, and stiff neck, with paresthesia being the most common.

This review is concise but adds to the expanding literature on the post-active phase of infection syndromes, it suggests that chronic illnesses such as PTLDS and ME/CFS have similar pathogenesis despite different infectious origins. The review is limited by the small-scale studies which have previously been conducted. It is a shame that the authors focused on symptoms present and did not review biomarkers in the blood for a more thorough comparison.

The MEA have more information available on Lyme disease on their website, in a leaflet and in the medical matters section.

This week you may also be interested in reading Paper two (2) which reviews Epstein-Barr virus (EBV) and immunodeficiency in ME/CFS and Long Covid. This is an extremely lengthy complex review (30 pages!) with several different sections, such as: sex differences, microclots, development of autoimmune diseases and treatment. We have previously written a research summary on the reactivation of human herpesviruses which can be found here.

ME/CFS Research References (5 – 11 September 2023)

1. Post treatment Lyme disease syndrome and myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review and comparison of pathogenesis

Bai NA, Richardson CS.

Chronic Dis Transl Med. 2023 Jun 11;9(3):183-190. 


Lyme disease is the most common vector-borne illness in the United States and has been causing significant morbidity since its discovery in 1977. It is well-documented that about 10% of patients properly treated with antibiotics never fully recover, but instead go on to develop a chronic illness dubbed, posttreatment Lyme disease syndrome (PTLDS) characterized by severe fatigue, cognitive slowing, chronic pain, and sleep difficulties.

This review includes 18 studies that detail the symptoms of patients with PTLDS and uses qualitative analysis to compare them to myalgic encephalitis/chronic fatigue syndrome (ME/CFS), a strikingly similar syndrome.

In the majority of the PTLDS studies, at least four of the six major symptoms of ME/CFS were also noted, including substantial impairment in activity level and fatigue for more than 6 months, post-exertional malaise, and unrefreshing sleep.

In one of the included PTLDS articles, 26 of the 29 ME/CFS symptoms were noted. This study adds to the expanding literature on the post-active phase of infection syndromes, which suggests that chronic illnesses such as PTLDS and ME/CFS have similar pathogenesis despite different infectious origins.

2. Epstein-Barr virus-acquired immunodeficiency in myalgic encephalomyelitis-Is it present in long COVID?

Ruiz-Pablos M, Paiva B, Zabaleta A.

J Transl Med. 2023 Sep 17;21(1):633.


Both myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) and long COVID (LC) are characterized by similar immunological alterations, persistence of chronic viral infection, autoimmunity, chronic inflammatory state, viral reactivation, hypocortisolism, and microclot formation. They also present with similar symptoms such as asthenia, exercise intolerance, sleep disorders, cognitive dysfunction, and neurological and gastrointestinal complaints.

In addition, both pathologies present Epstein-Barr virus (EBV) reactivation, indicating the possibility of this virus being the link between both pathologies. Therefore, we propose that latency and recurrent EBV reactivation could generate an acquired immunodeficiency syndrome in three steps: first, an acquired EBV immunodeficiency develops in individuals with “weak” EBV HLA-II haplotypes, which prevents the control of latency I cells.

Second, ectopic lymphoid structures with EBV latency form in different tissues (including the CNS), promoting inflammatory responses and further impairment of cell-mediated immunity.

Finally, immune exhaustion occurs due to chronic exposure to viral antigens, with consolidation of the disease. In the case of LC, prior to the first step, there is the possibility of previous SARS-CoV-2 infection in individuals with “weak” HLA-II haplotypes against this virus and/or EBV.

3. Two-month period of 500 mg lecithin-based delivery form of quercetin daily dietary supplementation counterbalances chronic fatigue symptoms: A double-blind placebo controlled clinical trial

Mariangela Rondanelli, Antonella Riva, Giovanna Petrangolini, Clara Gasparri, Simone Perna.

Biomedicine & Pharmacotherapy, Volume 167, 2023, 115453.


Background: Chronic fatigue (CF) is a complex phenomenon without clear etiology that may require long-term treatment, but to date, no specific therapy has been identified for it. Some botanicals might be helpful in the management of CF. Among these botanicals, quercetin demonstrates its capacity to modulate multiple biological pathways and acknowledged major properties in CF: antioxidant, anti-inflammatory, immunomodulating, improving exercise endurance, enhancing mitochondrial biogenesis, repairing mitochondrial dysfunction.

Purpose: Given this background, the aim of this study was to evaluate if a 2-month period of daily Quercetin Phytosome™ 500 mg supplementation is of benefit for the relief of CF.

Methods: The primary end point has been the evaluation of fatigue, by Fatigue Impact Scale (FIS-40). The secondary end points have been the assessment of sleep, by Pittsburgh Sleep Quality Index (PSQI), evaluation of muscle performance, by short physical performance battery and by wearable armband-shaped sensor in order to evaluate the number of steps, body composition, by DXA and quality of life by Short‐Form 12–Item Health Survey (SF‐12).

Results: Seventy-eight subjects (42 F; 36 M) (mean age 56 ± 9) reporting CF symptoms, completed the study (placebo/supplement 38/40). The FIS-40 mean difference changes between groups (supplement minus placebo) was − 10.583 points (CI95% −11.985; −9.182) (p < 0.001). Also, statistically significant changes between groups have been recorded in Pittsburgh Sleep Quality Index − 2.040 points (CI95%: −2.770; −1.309), p < 0.01), number of steps 1443.152 (CI95%: 1199.556; 1686.749), and SPPB (score) 0.248 (CI95%: 0.105; 0.391) (p < 0.001).

Conclusion: The quercetin supplementation counterbalances CF symptoms.

4. Sleep Disorders and Chronic Pain Syndromes in the Pediatric Population

Ann Oh, Angelina Koehler, Marcy Yonker, Matthew Troester.

Seminars in Pediatric Neurology, 2023, 101085.


Sleep problems are widespread in children and adolescents suffering from chronic pain disorders. Sleep loss intensifies the experience of pain, and is detrimental to the budding self-efficacy of a young individual with limitless horizons.

Addressing sleep disorders may prevent the chronification of pain and prevent adverse health outcomes, such as functional impairment, psychiatric comorbidities and overall poor quality of life. This review will explore the cyclical nature between sleep, pain and mood, as well as the functional impact of this relationship on children and adolescents.

There will be a discussion about sleep assessment and diagnostic testing, followed by a description of sleep disturbances found in specific pain conditions, ranging from headache, musculoskeletal/abdominal pain, to rheumatologic disorders.

Finally, there will be a brief review of pharmacologic and behavioral interventions designed to improve sleep quality, and when possible, to alleviate pain.

Long-COVID Research References (5 – 11 September 2023)

  1. Lactate dehydrogenase contribution to symptom persistence in long COVID: A pooled analysis
  2. Clinical and epidemiological factors causing longer SARS-CoV 2 viral shedding: the results from the CoviCamp cohort
  3. The quality and pattern of rehabilitation interventions prescribed for post-COVID-19 infection patients: A systematic review and meta-analysis
  4. Hypothetical framework for post-COVID 19 condition based on a fibromyalgia pathogenetic model
  5. Stellate Ganglion Block Relieves Long COVID-19 Symptoms in 86% of Patients: A Retrospective Cohort Study
  6. Long-COVID-19 clinical and health outcomes: an umbrella review
  7. Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death
  8. The Effect of Long Covid Syndrome on Physical Activity
  9. Risk of long COVID main symptoms after SARS-CoV-2 infection: a systematic review and meta-analysis
  10. Treatable traits for long COVID
  11. Omega-3 polyunsaturated fatty acids and the psychiatric post-acute sequelae of COVID-19: A one-year retrospective cohort analysis of 33,908 patients
  12. TCM “medicine and food homology” in the management of post-COVID disorders
  13. Cardiovascular autonomic dysfunction in “Long COVID”: pathophysiology, heart rate variability, and inflammatory markers
  14. Alpha-2 macroglobulin activity in SARS-CoV-2 induced infection and in the post-COVID-19 period
  15. Long COVID: what is known and what gaps need to be addressed
  16. Quantifying the adverse effects of long COVID on individuals’ health after infection: A Propensity Score Matching design study
  17. Long-term effects of the COVID-19 pandemic on five mental and psychological disorders: in terms of the number of disease visits, drug consumption, and scale scores
  18. Effect of traditional Chinese exercise on the treatment of “long-COVID” A protocol for systematic review and meta-analysis
  19. Rehabilitation Interventions for Physical Capacity and Quality of Life in Adults With Post–COVID-19 Condition

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent
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