NAAC Monthly International Research Update 

November 2021

De Bellis A, Bellastella G, Pernice V, Cirillo P, Longo M, Maio A, Scappaticcio L, Maiorino MI, Bellastella A, Esposito K, Montoya JG. Hypothalamic-Pituitary Autoimmunity and Related Impairment of Hormone Secretions in Chronic Fatigue Syndrome. J Clin Endocrinol Metab. 2021 Nov 19;106(12):e5147-e5155. doi: 10.1210/clinem/dgab429.

De Bellis investigated the potential presence of antipituitary (APA) and antihypothalamic (AHA) antibodies and the role of hypothalamic/ pituitary dysfunctions in ME/CFS patients. There was an association with high titres of APA and AHA and hypothalamic/ pituitary dysfunctions.

Du Preez S, Eaton-Fitch N, Cabanas H, Staines D, Marshall-Gradisnik S. Characterization of IL-2 Stimulation and TRPM7 Pharmacomodulation in NK Cell Cytotoxicity and Channel Co-Localization with PIP2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Int J Environ Res Public Health. 2021 Nov 12;18(22):11879. doi: 10.3390/ijerph182211879.

This study investigated the potential role of Transient Receptor Potential Melastatin Ion Channel 7 (TRPM7) in the mechanism of PIP2-mediated calcium-dependent NK cell cytotoxicity in ME/CFS patients compared to healthy controls. There is evidence of cross-talk between IL-2 and TRPM7.

Fowler-Davis S, Platts K, Thelwell M, Woodward A, Harrop D. A mixed-methods systematic review of post-viral fatigue interventions: Are there lessons for long Covid? PLoS One. 2021 Nov 9;16(11):e0259533. doi: 10.1371/journal.pone.0259533.

This systematic review found that there are limited interventions available for post-viral fatigue syndrome. Current interventions are focused on self-management including cognitive behavioural therapy.

Mathur R, Carnes MU, Harding A, Moore A, Thomas I, Giarrocco A, Long M, Underwood M, Townsend C, Ruiz-Esparza R, Barnette Q, Brown LM, Schu M. mapMECFS: a portal to enhance data discovery across biological disciplines and collaborative sites. J Transl Med. 2021 Nov 8;19(1):461. doi: 10.1186/s12967-021-03127-3.

Mathur et al developed a mapMECFS database that compiles datasets from various labs, peer-reviewed articles and ME/CFS research networks.

Raijmakers R, Roerink M, Keijmel S, Joosten L, Netea M, van der Meer J, Knoop H, Klein H, Bleeker-Rovers C, Doorduin J. No Signs of Neuroinflammation in Women With Chronic Fatigue Syndrome or Q Fever Fatigue Syndrome Using the TSPO Ligand [11C]-PK11195. Neurol Neuroimmunol Neuroinflamm. 2021 Nov 23;9(1):e1113. doi: 10.1212/NXI.0000000000001113

This study investigated signs of neuroinflammation in women with ME/CFS using TSPO Ligand [11C]-PK11195. There were no significant signs of neuroinflammation in women with ME/CFS.

Raanes EFW, Stiles TC. Associations Between Psychological and Immunological Variables in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Systematic Review. Front Psychiatry. 2021 Nov 23;12:716320. doi: 10.3389/fpsyt.2021.716320

This study investigated the associations between psychological and immunological variables in ME/CFS patients. Poorer emotion regulation, interpersonal function, and sleep were associated with higher cytokine levels.

Ruiz-Pablos M, Paiva B, Montero-Mateo R, Garcia N, Zabaleta A. Epstein-Barr Virus and the Origin of Myalgic Encephalomyelitis or Chronic Fatigue Syndrome. Front Immunol. 2021 Nov 15;12:656797. doi: 10.3389/fimmu.2021.656797

This review highlights possible predispositions leading to Epstein- Barr Virus infection in certain ME/CFS patients.

Similä WA, Nøst TH, Helland IB, Rø TB. Factors related to educational adaptations and social life at school experienced by young people with CFS/ME: a qualitative study. BMJ Open. 2021 Nov 18;11(11):e051094. doi: 10.1136/bmjopen-2021-051094

Similä et al interviewed various members of educational institution: teachers, counsellors and school nurses on methods that may improve adaption to school environment to account for loss and absence. Interdisciplinary collaboration, maintained teacher- student relationship and option of digital learning were suggested.

Sukocheva OA, Maksoud R, Beeraka N, Madhunapantula S, Sinelnikov M, Nikolenko VN, Neganova ME, Klochkov SG, Kamal MA, Staines DR, Gradisnik SM. Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome. J. Adv. Res. 2021 Nov. doi: 10.1016/j.jare.2021.11.013

This review assesses overlap in pathomechanism between post COVID-19 condition (long COVID) and ME/CFS. 

October 2021

Balinas C, Eaton-Fitch N, Maksoud R, Staines D, Marshall-Gradisnik S. Impact of Life Stressors on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Symptoms: An Australian Longitudinal Study. Int J Environ Res Public Health. 2021 Oct 11;18(20):10614. doi: 10.3390/ijerph182010614

This study investigated the impact of life stressors such as changes in work or income on ME/CFS symptom severity. Change in sustainability of income correlates with higher symptom severity.

Barhorst EE, Boruch AE, Cook DB, Lindheimer JB. Pain-related post-exertional malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia: A systematic review and three-level meta-analysis. Pain Med. 2021 Oct 20:pnab308. doi: 10.1093/pm/pnab308

This systematic review investigated the pain-related post-exertional malaise in ME/CFS patients. Pain severity in ME/CFS has small-to-moderate increases following exercise.

Clery P, Starbuck J, Laffan A, Parslow RM, Linney C, Leveret J, Crawley E. Qualitative study of the acceptability and feasibility of acceptance and commitment therapy for adolescents with chronic fatigue syndrome. BMJ Paediatr Open. 2021 Oct 1;5(1):e001139. doi: 10.1136/bmjpo-2021-001139

Clery investigated the impact of acceptance and commitment therapy (ACT) in adolescents with ME/CFS. Although the use of ACT by adolescent ME/CFS patients, their parents, and health- care practitioners were acceptable investigations in larger scale randomized control trials is necessary.

Deumer US, Varesi A, Floris V, Savioli G, Mantovani E, López-Carrasco P, Rosati GM, Prasad S, Ricevuti G. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): An Overview. J Clin Med. 2021 Oct 19;10(20):4786. doi: 10.3390/jcm10204786

This review summarises the infectious, genetic and hormonal components of ME/CFS.

Du Preez S, Cabanas H, Staines D, Marshall-Gradisnik S. Potential Implications of Mammalian Transient Receptor Potential Melastatin 7 in the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review. Int J Environ Res Public Health. 2021 Oct 12;18(20):10708. doi: 10.3390/ijerph182010708

This review investigates the potential role Transient Receptor Potential Melastatin 7 has in the pathophysiology of ME/CFS.

Kujawski S, Słomko J, Newton JL, Eaton-Fitch N, Staines DR, Marshall-Gradisnik S, Zalewski P. Network Analysis of Symptoms Co-Occurrence in Chronic Fatigue Syndrome. Int J Environ Res Public Health. 2021 Oct 13;18(20):10736. doi: 10.3390/ijerph182010736

Kujawski conducted a network analysis of symptoms that co-occur in ME/CFS. The most densely related nodes were total number of symptoms, sore throat, and post-exertional malaise (PEM). PEM was most closely positively related to impairment in memory or concentration.

Varesi A, Deumer US, Ananth S, Ricevuti G. The Emerging Role of Gut Microbiota in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Current Evidence and Potential Therapeutic Applications. J Clin Med. 2021 Oct 29;10(21):5077. doi: 10.3390/jcm10215077

This review investigated the role of gut microbiome changes in ME/CFS and potential therapeutic avenues of treating the gut to alleviate symptoms. 

September 2021

Aly MAEG, Saber HG. Long COVID and chronic fatigue syndrome: A survey of elderly female survivors in Egypt. Int J Clin Pract. 2021 Sep 19:e14886. Doi: 10.1111/ijcp.14886. Epub ahead of print.

This study investigated the prevalence of ME/CFS-like symptoms in COVID-19 survivors. From the 89 patients included in this study, 60 were possible and only one was likely to show ME/CFS symptoms.

Bourke JH, Wodehouse T, Clark LV, Constantinou E, Kidd BL, Langford R, Mehta V, White PD. Central sensitisation in chronic fatigue syndrome and fibromyalgia; a case control study. J Psychosom Res. 2021 Sep 21;150:110624. doi: 10.1016/j.jpsychores.2021.110624. Epub ahead of print.

This study investigates the role central sensitization (CS) plays in ME/CFS and fibromyalgia this was assessed using sensory tests including measures of temporal summation and conditioned pain modulation. CS was present in 84% of ME/CFS cases. Pressure pain thresholds were also lower in ME/CFS patients.

Castro-Marrero J, Zacares M, Almenar-Pérez E, Alegre-Martín J, Oltra E. Complement Component C1q as a Potential Diagnostic Tool for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Subtyping. J Clin Med. 2021 Sep 15;10(18):4171. doi: 10.3390/jcm10184171.

This study assessed the potential of complement Component C1q to categorize ME/CFS patients. N 43% of patients there was high levels of circulating complement factor C1q detected.

Jason LA, Yoo S, Bhatia S. Patient perceptions of infectious illnesses preceding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Chronic Illn. 2021 Sep 20:17423953211043106. doi: 10.1177/17423953211043106.

In 1773 patients with ME/CFS, 60.3% of patients reported an infectious trigger prior to onset of ME/CFS.

Gandasegui IM, Laka LA, Gargiulo PÁ, Gómez-Esteban JC, Sánchez JL. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Neurological Entity? Medicina (Kaunas). 2021 Sep 27;57(10):1030. doi: 10.3390/medicina57101030

This study investigated evidence of neurological involvement in ME/CFS, in particular dysautonomia studies.

Komaroff AL, Lipkin WI. Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome. Trends Mol Med. 2021 Sep;27(9):895-906. doi: 10.1016/j.molmed.2021.06.002. Epub 2021 Jun 7.

This review describes potential overlap in molecular mechanisms in ME/CFS and long COVID.

Krumina A, Vecvagare K, Svirskis S, Gravelsina S, Nora-Krukle Z, Gintere S, Murovska M. Clinical Profile and Aspects of Differential Diagnosis in Patients with ME/CFS from Latvia. Medicina (Kaunas). 2021 Sep 11;57(9):958. doi: 10.3390/medicina57090958.

This study found that ME/CFS with comorbidities is associated with greater severity of disease.

Lutz L, Rohrhofer J, Zehetmayer S, Stingl M, Untersmayr E. Evaluation of Immune Dysregulation in an Austrian Patient Cohort Suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Biomolecules. 2021 Sep 14;11(9):1359. doi: 10.3390/biom11091359.

This study investigates immune dysregulation in an Austrian ME/CFS cohort. Various immune changes were detected including immune activation, inflammation, and antibody deficiency.

Montoya JG, Dowell TG, Mooney AE, Dimmock ME, Chu L. Caring for the Patient with Severe or Very Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Healthcare (Basel). 2021 Oct 6;9(10):1331. doi: 10.3390/healthcare9101331

This paper provides information on clinical presentation of severe and very severe ME/CFS and appropriate directions for diagnosis, treatment and management.

Natelson BH, Brunjes DL, Mancini D. Chronic Fatigue Syndrome and Cardiovascular Disease: JACC State-of-the-Art Review. J Am Coll Cardiol. 2021 Sep 7;78(10):1056-1067. doi: 10.1016/j.jacc.2021.06.045

A review of available evidence of cardiovascular changes in ME/CFS patients.

Pereira G, Gillies H, Chanda S, Corbett M, Vernon SD, Milani T, Bateman L. Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Syst Neurosci. 2021 Sep 1;15:698240. doi: 10.3389/fnsys.2021.698240

This study found that ME/CFS patients were more sensitive to the hemodynamic effect of corticotropin-releasing factor receptor type 2 (CRFR2) suggesting upregulation.

Pheby DFH, Friedman KJ, Murovska M, Zalewski P. Turning a Corner in ME/CFS Research. Medicina (Kaunas). 2021 Sep 25;57(10):1012. doi: 10.3390/medicina57101012.

An update on research in ME/CFS including quality of life studies, National Institute of Health and Care Excellence (NICE) guidelines and interventions for ME/CFS.

van Campen CLMC, Rowe PC, Visser FC. Cerebral blood flow remains reduced after tilt testing in myalgic encephalomyelitis/chronic fatigue syndrome patients. Clin Neurophysiol Pract. 2021 Sep 23;6:245-255. doi: 10.1016/j.cnp.2021.09.001

Van Campen investigated cerebral flood flow following tilt-testing in ME/CFS patients. Cerebral blood flow remains reduced in ME/CFS patients following tilt-testing. In more severe patients, recovery of cerebral blood flow takes significantly longer.

Van Oosterwijck J, Marusic U, De Wandele I, Meeus M, Paul L, Lambrecht L, Moorkens G, Danneels L, Nijs J. Reduced Parasympathetic Reactivation during Recovery from Exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. J Clin Med. 2021 Sep 30;10(19):4527. doi: 10.3390/jcm10194527.

This study investigated health parameters including cardiac, respiratory, and electrodermal responses at rest and following exercise in ME/CFS patients. There was reduced parasympathetic reactivation during recovery following exercise in ME/CFS patients. 

August 2021

Freitag H, Szklarski M, Lorenz S, Sotzny F, Bauer S, Philippe A, Kedor C, Grabowski P, Lange T, Riemekasten G, Heidecke H, Scheibenbogen C. Autoantibodies to Vasoregulative G-Protein-Coupled Receptors Correlate with Symptom Severity, Autonomic Dysfunction and Disability in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. J Clin Med. 2021 Aug 19;10(16):3675. doi:  10.3390/jcm10163675.

Freitag et al investigates the association of symptom severity with levels of autoantibodies (AAB) to vasoregulative beta-adrenergic  (AdR), muscarinic acetylcholine receptors (AChR) and Endothelin-1 type A and B (ETA/B) and Angiotensin II type 1 (AT1) in ME/CFS patients. AAB levels in most cases correlated with symptom scores of fatigue and muscle pain in patients with infectious onset. Cognitive impairment severity correlated with AT1-R and ETA-R-AAB and gastrointestinal symptom seveity correlated with alpha1/2-AdR-AAB. Patients with non-infectious onset displayed less symptom correlations.

 Gravelsina S, Nora-Krukle Z, Vilmane A, Svirskis S, Vecvagare K, Krumina A, Murovska M. Potential of Activin B as a Clinical Biomarker in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Biomolecules. 2021 Aug 11;11(8):1189. doi:  10.3390/biom11081189.

This study investigated levels of activin B levels in plasma belonging to ME/CFS patients compared to healthy controls. Activin B levels did not significantly differ between both groups.

 Hajdarevic R, Lande A, Rekeland I, Rydland A, Strand EB, Sosa DD, Creary LE, Mella O, Egeland T, Saugstad OD, Fluge Ø, Lie BA, Viken MK. Fine mapping of the major histocompatibility complex (MHC) in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggests involvement of both HLA class I and class II loci. Brain Behav Immun. 2021 Nov;98:101-109. doi:  10.1016/j.bbi.2021.08.219. Epub 2021 Aug 14.

Hajdarevic et al found that there is an involvement of major histocompatibility complex (MHC) in particular the HLA-DQB1 gene in ME/CFS.

 Hng KN, Geraghty K, Pheby DFH. An Audit of UK Hospital Doctors’ Knowledge and Experience of Myalgic Encephalomyelitis. Medicina (Kaunas). 2021 Aug 27;57(9):885. doi:  10.3390/medicina57090885.

This study investigated UK doctors attitudes and understanding towards ME/CFS. Very few doctors received formal training on ME/CFS, however had some experience of it. Some doctors lacked confidence in managing patients with ME/CFS and there was little knowledge on definitions of ME/CFS, diagnosis and clinical presentation.

Hoel F, Hoel A, Pettersen IK, Rekeland IG, Risa K, Alme K, Sørland K, Fosså A, Lien K, Herder I, Thürmer HL, Gotaas ME, Schäfer C, Berge RK, Sommerfelt K, Marti HP, Dahl O, Mella O, Fluge Ø, Tronstad KJ. A map of metabolic phenotypes in patients with myalgic encephalomyelitis/chronic fatigue syndrome. JCI Insight. 2021 Aug 23;6(16):149217. doi:  10.1172/jci.insight.149217.

This study describes metabolic phenotypes in ME/CFS and potential associations with clinical patient profiles.

 Josev EK, Cole RC, Scheinberg A, Rowe K, Lubitz L, Knight SJ. Health, Wellbeing, and Prognosis of Australian Adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Case-Controlled Follow-Up Study. J Clin Med. 2021 Aug 16;10(16):3603. doi:  10.3390/jcm10163603.

ME/CFS patients had significantly poorer fatigue, pain and health-related quality of life compared to healthy controls. ME/CFS patients showed improvement in most health and psychological wellbeing domains over time.

Lee JS, Lacerda EM, Nacul L, Kingdon CC, Norris J, O’Boyle S, Roberts CH, Palla L, Riley EM, Cliff JM. Salivary DNA Loads for Human Herpesviruses 6 and 7 Are Correlated With Disease Phenotype in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Med (Lausanne). 2021 Aug 6;8:656692. doi:  10.3389/fmed.2021.656692.

Lee et al investigated salivary DNA loads for human herpesviruses 6 and 7 and the association with disease phenotypes in ME/CFS patients. Higher HHV-6B and HHV-7 viral loads were detected in people with ME/CFS compared with healthy controls. One group of ME/CFS patients showed fluctuating patterns of herpesviruses over time these positively correlated with symptom scores.

 Mantovani E, Mariotto S, Gabbiani D, et al. Chronic fatigue syndrome: an emerging sequela in COVID-19 survivors?. J Neurovirol. 2021;27(4):631-637. doi: 10.1007/s13365-021-01002-x

This study assessed the incidence of ME/CFS-like symptoms (based on the CCC criteria) in a cohort of long-COVID patients. In their sample, 27% of patients exhibited ME/CFS-like symptoms.

 Nkiliza A, Parks M, Cseresznye A, Oberlin S, Evans JE, Darcey T, Aenlle K, Niedospial D, Mullan M, Crawford F, Klimas N, Abdullah L. Sex-specific plasma lipid profiles of ME/CFS patients and their association with pain, fatigue, and cognitive symptoms. J Transl Med. 2021 Aug 28;19(1):370. doi:  10.1186/s12967-021-03035-6.

This study assessed the role of sex-specific lipid metabolism in ME/CFS pathology. phosphatidylethanolamine (PE), omega-6 arachidonic acid-containing PE, and total hexosylceramides (HexCer) were significantly decreased in female ME/CFS patients and levels of total HexCer, monounsaturated PE, phosphatidylinositol (PI), and saturated triglycerides (TG) were increased in male ME/CFS patients compared to controls. These lipids may have a role in immune dysfunction and inflammation.

 Thapaliya K, Marshall-Gradisnik S, Staines D, Barnden L. Diffusion tensor imaging reveals neuronal microstructural changes in myalgic encephalomyelitis/chronic fatigue syndrome. Eur J Neurosci. 2021 Aug 6. doi:  10.1111/ejn.15413.

This study used diffusion tensor imaging (DTI) to assess microstructural changes in ME/CFS patients. DTI was sensitive to microstructural changes in patients diagnosed using the International Consensus Criteria (ICC).

 Weir W, Speight N. ME/CFS: Past, Present and Future. Healthcare (Basel). 2021 Aug 3;9(8):984. doi:  10.3390/healthcare9080984.

This review looks into historical and current approaches to ME/CFS. 

July 2021

Cabanas H, Muraki K, Eaton-Fitch N, Staines DR, Marshall-Gradisnik S. Potential Therapeutic Benefit of Low Dose Naltrexone in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Role of Transient Receptor Potential Melastatin 3 Ion Channels in Pathophysiology and Treatment. Front Immunol. 2021 Jul 13;12:687806. doi:  10.3389/fimmu.2021.687806 

This study investigates the effects of the opioid antagonist, low dose naltrexone (LDN, 3.0- 5.0 mg/ day) on ME/CFS patients TRPM3 ionic currents. ME/CFS patients that take LDN have restored TRPM3-like ionic currents. 

Cheshire A, Ridge D, Clark LV, White PD. Sick of the Sick Role: Narratives of What “Recovery” Means to People With CFS/ME. Qual Health Res. 2021 Jan;31(2):298-308. doi:  10.1177/1049732320969395 

This study investigates what the term “recovery” means for people with ME/CFS.  

De Bellis A, Bellastella G, Pernice V, Cirillo P, Longo M, Maio A, Scappaticcio L, Maiorino MI, Bellastella A, Esposito K, Montoya JG. Hypothalamic-Pituitary autoimmunity and related impairment of hormone secretions in chronic fatigue syndrome. J Clin Endocrinol Metab. 2021 Jul 13:dgab429. doi:  10.1210/clinem/dgab429 

Anti-pituitary (APA) and anti-hypothalamic (AHA) antibodies were found and this correlated with hypothalamic/ pituitary dysfunction.   

Eaton-Fitch N, Cabanas H, du Preez S, Staines D, Marshall-Gradisnik S. The effect of IL-2 stimulation and treatment of TRPM3 on channel co-localisation with PIP2 and NK cell function in myalgic encephalomyelitis/chronic fatigue syndrome patients. J Transl Med. 2021 Jul 15;19(1):306. doi:  10.1186/s12967-021-02974-4 

This study investigated the localisation of Transient Receptor Potential Melastatin 3 (TRPM3) on the NK cell plasma membrane and co-localisation with phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid component of the plasma membrane. This study also looked at the effect of IL-2 priming and treatment using pregnenolone sulfate (PregS) and ononetin on TRPM3 compared to healthy controls (HC). There were significant changes in plasma membrane co-localisation therefore this may be due to PIP2- dependent TRPM3 function. IL-2 stimulation improved cytotoxic function in ME/CFS patients.  

Lim EJ, Son CG. Prevalence of Chronic Fatigue Syndrome (CFS) in Korea and Japan: A Meta-Analysis. J Clin Med. 2021 Jul 21;10(15):3204. doi:  10.3390/jcm10153204 

This meta-analysis aims to estimate and compare the prevalence of ME/CFS in Korea and Japan. There were a total of eight studies five based in Korea and three based in Japan. The prevalence of ME/CFS in Korea was 0.77% and 0.76% in Japan. There was a two-fold higher difference in prevalence of ME/CFS in females than males in Korea but this difference was less prominent in Japan (0.76% female and 0.65% male).  

Maes M, Kubera M, Stoyanova K, Leunis JC. The reification of the clinical diagnosis of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) as an immune and oxidative stress disorder: construction of a data-driven nomothethic network and exposure of ME/CFS subgroups. Curr Top Med Chem. 2021 Jul 27. doi:  10.2174/1568026621666210727170147 

This study used a data-driven nomothethic network to validate the role of bacterial translocation and immune pathways in ME/CFS. Variation of symptoms could be explained by cell-mediated immune activation CD38+ activation IgM OSENO, IgA LPS, lysozyme (all positive) and coenzyme Q10.   

Malato J, Sotzny F, Bauer S, Freitag H, Fonseca A, Grabowska AD, Graça L, Cordeiro C, Nacul L, Lacerda EM, Castro-Marrero J, Scheibenbogen C, Westermeier F, Sepúlveda N. The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in myalgic encephalomyelitis/chronic fatigue syndrome: A meta-analysis of public DNA methylation and gene expression data. Heliyon. 2021 Aug;7(8):e07665. doi:  10.1016/j.heliyon.2021.e07665 

This study analyses public DNA methylation and gene expression data on human angiotensin-converting enzyme 2 (ACE2), a major cell entry receptor for SARS-CoV-2. ME/CFS patients had decreased methylation levels on four CPG probes in the ACE locus, particularly  ACE2.  

Mantovani E, Mariotto S, Gabbiani D, Dorelli G, Bozzetti S, Federico A, Zanzoni S, Girelli D, Crisafulli E, Ferrari S, Tamburin S. Chronic fatigue syndrome: an emerging sequela in COVID-19 survivors? J Neurovirol. 2021 Aug 2:1–7. doi:  10.1007/s13365-021-01002-x 

This study investigated ME/CFS symptom prevalence among SARS-CoV survivors and whether axonal, inflammatory and/ or lung changes may contribute to ME/CFS-like symptoms.  

Morizot R, de Korwin JD, Feugier P, Broséus J, Troussard X, Lesesve JF. Patients with Persistent Polyclonal B-Cell Lymphocytosis Share the Symptomatic Criteria of Systemic Exertion Intolerance Disease. J Clin Med. 2021 Jul 29;10(15):3374. doi:  10.3390/jcm10153374 

Persistent Polyclonal B-Cell Lymphocytosis (PPBL) shares similar symptomatic criteria as ME/CFS (Institute of Medicine 2015 criteria). 72% of PPBL patients met criteria for ME/CFS.  

Mozhgani SH, Rajabi F, Qurbani M, Erfani Y, Yaslianifard S, Moosavi A, Pourrostami K, Baradaran Bagheri A, Soleimani A, Behzadian F, Safavi M, Rezaei F. Human Herpesvirus 6 Infection and Risk of Chronic Fatigue Syndrome: A Systematic Review and Meta-Analysis. Intervirology. 2021 Jun 23. doi:  10.1159/000517930 

This meta-analysis investigates the development of ME/CFS following human herpesvirus 6 infection. Although there is substantial evidence showing this association further evidence is required.  

June 2021

 Addiego FM, Zajur K, Knack S, Jamieson J, Rayhan RU, Baraniuk JN. Subcortical brain segment volumes in Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Life Sci. 2021 Jun 29:119749. doi:  10.1016/j.lfs.2021.119749. Epub ahead of print.

Addiego et al assessed subcortical brain segment volumes in ME/CFS patients, Gulf War Illness (GWI) and Healthy controls (HC). Women with ME/CFS had smaller left putamen, right caudate and left cerebellum white matter than HC. ME/CFS had larger left hippocampus than GWI.

Bornstein SR, Voit-Bak K, Donate T, Rodionov RN, Gainetdinov RR, Tselmin S, Kanczkowski W, Müller GM, Achleitner M, Wang J, Licinio J, Bauer M, Young AH, Thuret S, Bechmann N, Straube R. Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis? Mol Psychiatry. 2021 Jun 17:1–4. doi:  10.1038/s41380-021-01148-4. Epub ahead of print.

This review investigates the therapeutic potential of extracorporeal apheresis in chronic post-COVID-19 syndrome and ME/CFS.

Castro-Marrero J, Zaragozá MC, López-Vílchez I, Galmés JL, Cordobilla B, Maurel S, Domingo JC, Alegre-Martín J. Effect of Melatonin Plus Zinc Supplementation on Fatigue Perception in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Antioxidants (Basel). 2021 Jun 23;10(7):1010. doi:  10.3390/antiox10071010.

This is a proof- of – concept study where patients have received oral melatonin (1mg) in combination with zinc (10mg) or a placebo daily for 16-weeks. There was a significant reduction of perception of physical fatigue in the melatonin/ zinc group compared to placebo at follow- up (p < 0.05). Urinary 6-sulfatoxymelatonin levels were significantly elevated during thee study in the ME/CFS group, however zinc concentration remained the same.

Ekberg KM, Torres C, Jason LA. Parent-child discrepancies in health-related quality of life of children and adolescents with myalgic encephalomyelitis/chronic fatigue syndrome. Qual Life Res. 2021 Jun 30. doi:  10.1007/s11136-021-02919-w. Epub ahead of print.

This study compared symptomology and health- related quality of life reporting by parents with children and adolescents. Based on calculated intra-class correlation coefficient scores it was suggested that there was discrepancies between each parent-child pair. 

Fernandez-Guerra P, Gonzalez-Ebsen AC, Boonen SE, Courraud J, Gregersen N, Mehlsen J, Palmfeldt J, Olsen RKJ, Brinth LS. Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study. Biomolecules. 2021 Jun 29;11(7):961. doi:  10.3390/biom11070961.

This study investigated mitochondrial metabolic parameters based on bioenergetics and protein profiles. ME/CFS patients’ PBMCs had significantly lower coupling efficiency, had proteome alterations such as altered mitochondrial metabolism and a decreased ability to provide adequate intracellular ATP levels.

Froehlich L, Hattesohl DBR, Jason LA, Scheibenbogen C, Behrends U, Thoma M. Medical Care Situation of People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Germany. Medicina (Kaunas). 2021 Jun 23;57(7):646. doi:  10.3390/medicina57070646.

This study investigated medical care of ME/CFS patients in Germany. Patients reported low satisfaction when receiving medical care from their physician. The study also assessed the use of a German translation of DePaul Symptom Questionnaire Short Form (DSQ-SF) for ME/CFS diagnostics. DSQ-SF showed good reliability and correlated with the SF-36.

Gimeno Torrent X. The circuit of symbolic violence in chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) (I): A preliminary study. Health Care Women Int. 2021 Jun 14:1-36. doi:  10.1080/07399332.2021.1925900. Epub ahead of print.

Gimeno explored features of symbolic violence in ME/CFS patients based on “letters to the editor” to Spanish Newspapers.

Ghali A, Lacout C, Ghali M, Gury A, Delattre E, Lavigne C, Urbanski G. Warning Signals of Post-Exertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Retrospective Analysis of 197 Patients. J Clin Med. 2021 Jun 7;10(11):2517. doi:  10.3390/jcm10112517.

Ghali et al investigated post-exertional malaise (PEM) onset and potential warning signals. It was suggested that new or non-typical symptoms prior onset of baseline symptom exacerbation in ME/CFS could suggest onset of PEM. The most frequently associated symptom was mood disorders.

González-Hermosillo JA, Martínez-López JP, Carrillo-Lampón SA, Ruiz-Ojeda D, Herrera-Ramírez S, Amezcua-Guerra LM, Martínez-Alvarado MDR. Post-Acute COVID-19 Symptoms, a Potential Link with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A 6-Month Survey in a Mexican Cohort. Brain Sci. 2021 Jun 8;11(6):760. doi:  10.3390/brainsci11060760.

González-Hermosillo et al assesses the clinical evolution of post-acute COVID-19 symptoms over six months. Fatigue was the most reported symptom. Following multivariate adjustment, patients with fatigue were statistically more likely to be aged between 40-50 years old. Seventeen patients met the Institute of Medicine’s criteria for “systemic exertion intolerance disease”.

Khanpour Ardestani S, Karkhaneh M, Stein E, Punja S, Junqueira DR, Kuzmyn T, Pearson M, Smith L, Olson K, Vohra S. Systematic Review of Mind-Body Interventions to Treat Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Medicina (Kaunas). 2021 Jun 24;57(7):652. doi:  10.3390/medicina57070652.

This systematic review assesses mind-body interventions (MBIs) for the treatment of ME/CFS symptoms. Twelve studies were included in this review. Topics researched include mindfulness- based cognitive therapy, mindfulness-based stress reduction, acceptance and commitment therapy and isometric yoga. Primary outcomes measured include: fatigue severity, anxiety/ depression and quality of life. MBIs are suggestive to improve these outcomes. These results are limited based on sample sizes, non-heterogenous diagnostic criteria and bias and further research is required.

Komaroff AL, Lipkin WI. Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome. Trends Mol Med. 2021 Jun 7:S1471-4914(21)00134-9. doi:  10.1016/j.molmed.2021.06.002.

This review describes pathological features of ME/CFS and potential overlap with post-acute COVID-19 syndrome.

Kujawski S, Bach AM, Słomko J, Pheby DFH, Murovska M, Newton JL, Zalewski P. Changes in the Allostatic Response to Whole-Body Cryotherapy and Static-Stretching Exercises in Chronic Fatigue Syndrome Patients vs. Healthy Individuals. J Clin Med. 2021 Jun 25;10(13):2795. doi:  10.3390/jcm10132795.

Kujawski et al investigated the role of whole-body cryotherapy (WBC) in combination with static-stretching (SS). Primary outcomes measured include fatigue, cognitive, cardiovascular, and autonomic function as well as arterial stiffness. Parameters were measured before and after 10 sessions of WBC and SS. There was significantly higher stress and eccentricity in the ME/CFS group compared to healthy controls. These differences in fatigue was related to baroreceptor function and aortic stiffness.

O’Neal AJ, Hanson MR. The Enterovirus Theory of Disease Etiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Critical Review. Front Med (Lausanne). 2021 Jun 18;8:688486. doi:  10.3389/fmed.2021.688486.

This review discusses the enterovirus theory and its contribution to disease etiology. 

May 2021

Blauensteiner J, Bertinat R, León LE, Riederer M, Sepúlveda N, Westermeier F. Altered endothelial dysfunction-related miRs in plasma from ME/CFS patients. Sci Rep. 2021 May 19;11(1):10604. doi:  10.1038/s41598-021-89834-9

Blauensteiner et al analyses circulating microRNAs (miRs) in ME/CFS patients compared to healthy controls. They identified five significant miRs that through bioinformatic analysis had roles in endothelial function- related signaling pathways.

Brigden A, Shaw A, Crawley E. “it’s a medical condition … you need to support as much as possible”: a qualitative analysis of teachers’ experiences of chronic fatigue syndrome / myalgic encephalomyelitis (CFS/ME). BMC Pediatr. 2021 Jan 4;21(1):6. doi:  10.1186/s12887-020-02461-7

This qualitative study investigates teacher’s perspectives and experiences with having a primary school student with ME/CFS. Teachers’ were able to provide descriptions of symptoms experienced by their student with great detail. They reported that they were able to understand student needs and accommodate through facilitation of rest breaks, limitation of strenuous activities, ongoing communication with child during absence and offering support to the child. Outcomes from this study signified the importance of collaboration with clinical services to better equip educators with tools to best support their student.

Capdevila L, Castro-Marrero J, Alegre J, Ramos-Castro J, Escorihuela RM. Analysis of Gender Differences in HRV of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Mobile-Health Technology. Sensors (Basel). 2021 May 28;21(11):3746. doi:  10.3390/s21113746

This study explores the suitability of heart rate variability (HRV) as a non-invasive, objective marker for ME/CFS and whether there are any differences between male and female patients. There was a significant correlation between fatigue symptomatology and HRV parameters in ME/CFS patients compared to healthy men. Significant gender differences in autonomic dysfunction symptoms and HF and HFnu HRV parameters.

Catchpole S, Garip G. Acceptance and identity change: An interpretative phenomenological analysis of carers’ experiences in myalgic encephalopathy/chronic fatigue syndrome. J Health Psychol. 2021;26(5):672-687. doi: 10.1177/1359105319834678

Catchpole and Garip interviewed seven family carers of ME/CFS patients on their experience with various elements of ME/CFS. It was observed that carers experience identity change and that acceptance assisted with coping. 

Chu, L., Elliott, M., Stein, E., & Jason, L. A. (2021). Identifying and Managing Suicidality in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Healthcare. 2021 May 7. 9(6), 629.  h10.3390/healthcare9060629

This is a review on identification and management of suicidality in ME/CFS patient in an outpatient medical setting. Multiple factors were identified as contributing factors to suicidality in this patient group including severe functional limitations and the absence of targeted treatment. Barriers of adequate care may be attributed to undereducated healthcare professionals, public stigma, and limited support. Application of evidence-based medicine by outpatient medical professionals may mitigate suicidality in ME/CFS patients.

Fennell PA, Dorr N, George SS. Elements of Suffering in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Experience of Loss, Grief, Stigma, and Trauma in the Severely and Very Severely Affected. Healthcare (Basel). 2021 May 9;9(5):553. doi:  10.3390/healthcare9050553

This review explores elements of suffering in severe and very severe ME/CFS patients through the lens of the Fennell Four-Phase model of chronic illness.

Groven N, Reitan SK, Fors EA, Guzey IC. Kynurenine metabolites and ratios differ between Chronic Fatigue Syndrome, Fibromyalgia, and healthy controls. Psychoneuroendocrinology. 2021 May 27;131:105287. doi: 10.1016/j.psyneuen.2021.105287.

This study investigates kynurenine pathway metabolite status in ME/CFS patients, fibromyalgia, and healthy controls (HC). These metabolites include: Tryptophan, kynurenine, kynurenic acid (KA), 3-hydroxykykynurenine (HK), anthranilic acid, xanthurenic acid (XA), 3-hydroxyanthranilic acid, quinolinic acid (QA) and picolinic acid. The neuroprotective ratio given by KA/QA was lower for ME/CFS patients compared to HC.

Kujawski S, Słomko J, Hodges L, Pheby DFH, Murovska M, Newton JL, Zalewski P. Post-Exertional Malaise May Be Related to Central Blood Pressure, Sympathetic Activity and Mental Fatigue in Chronic Fatigue Syndrome Patients. J Clin Med. 2021 May 26;10(11):2327. doi:  10.3390/jcm10112327

This study aims to investigate aortic stiffness, autonomic nervous system function and severity of fatigue as predictors of post-exertional malaise (PEM) in ME/CFS. Higher mental fatigue and sympathetic activity was related to an increased risk of PEM. Higher central systolic blood pressure correlated with lower levels of PEM. Following, correction with false discovery rate (FDR), however, no between group differences were found.

Matsui T, Hara K, Iwata M, Hojo S, Shitara N, Endo Y, Fukuoka H, Matsui M, Kawaguchi H. Possible involvement of the autonomic nervous system in cervical muscles of patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). BMC Musculoskelet Disord. 2021 May 5;22(1):419. doi:  10.1186/s12891-021-04293-7

This study investigates the effect of cervical muscle physical therapy during hospitalisation in ME/CFS patients. The recovery rate following therapy was 55.5%.

Maksoud R, Eaton-Fitch N, Matula M, Cabanas H, Staines D, Marshall-Gradisnik S. Systematic Review of Sleep Characteristics in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Healthcare. 2021; 9(5):568.  10.3390/healthcare9050568

This systematic review investigated sleep characteristics measured using polysomnography and multiple sleep latency testing in ME/CFS patients compared to healthy controls. Many of the parameters measured were inconsistent across the studies. Future well-designed studies are required to understand sleep quality in ME/CFS patients.

Muirhead N, Muirhead J, Lavery G, Marsh B. Medical School Education on Myalgic Encephalomyelitis. Medicina. 2021; 57(6):542. doi:  10.3390/medicina57060542

Muirhead et al investigated United Kingdom (UK) medical school education on ME/CFS during 2018-2019. A total of 22 out of 34 UK medical schools provided responses to the survey (65%). From the 22 medical schools, 59% taught ME/CFS this was delivered through lectures, discussion, case studies and E-learning by lecturers from ten specialities. The need to update medical school syllabus to include more up-to-date information on ME/CFS has been acknowledged by 64% of the medical schools.

Scheibenbogen C, Sotzny F, Hartwig J, Bauer S, Freitag H, Wittke K, Doehner W, Scherbakov N, Loebel M, Grabowski P. Tolerability and Efficacy of s.c. IgG Self-Treatment in ME/CFS Patients with IgG/IgG Subclass Deficiency: A Proof-of-Concept Study. J Clin Med. 2021 May 29;10(11):2420. doi:  10.3390/jcm10112420.

This proof-of-concept study investigates the therapeutic potential of IgG substitution in ME/CFS patients experiencing recurrent infections and mild IgG or IgG subclass deficiency. Seventeen patients were included in this study. Clinical improvement in measured primary outcomes including fatigue assessed by Chalder Fatigue Scale (CFQ) and physical functioning assessed by SF-36 was found. Five patients ceased treatment due to adverse effects.

Stanculescu D, Larsson L, Bergquist J. Theory: Treatments for Prolonged ICU Patients May Provide New Therapeutic Avenues for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Med (Lausanne). 2021 May 7;8:672370. doi:  10.3389/fmed.2021.672370

This hypothesis article discusses the potential applications treatment trials for prolonged intensive care unit (ICU) patients may have on developing therapeutic avenues for ME/CFS patients.

van Campen CLMC, Rowe PC, Visser FC. Deconditioning does not explain orthostatic intolerance in ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome). J Transl Med. 2021 May 4;19(1):193. doi:  10.1186/s12967-021-02819-0

Van Campen et al investigated the impact deconditioning has on orthostatic intolerance experienced by ME/CFS patients. Deconditioning is represented by the following CPET response: %peak VO2 ≥ 85% = no deconditioning, %peak VO2 65-85% = mild deconditioning, and %peak VO2 < 65% = severe deconditioning. There were no differences in CBF reduction among ME/CFS patients with no, mild or severe deconditioning. 

April 2021 

Baxter H, Speight N, Weir W. Life-Threatening Malnutrition in Very Severe ME/CFS. Healthcare (Basel). 2021 Apr 14;9(4):459. doi:  10.3390/healthcare9040459

Baxter et al provides five cases of life-threatening malnutrition in very severe ME/CFS as well as important discussion points for addressing this in clinical practice.

Jäkel B, Kedor C, Grabowski P, Wittke K, Thiel S, Scherbakov N, Doehner W, Scheibenbogen C, Freitag H. Hand grip strength and fatigability: correlation with clinical parameters and diagnostic suitability in ME/CFS. J Transl Med. 2021 Apr 19;19(1):159. doi:  10.1186/s12967-021-02774-w

This study attempted to evaluate maximum hand grip strength and muscle fatigability and its correlation with clinical parameters such as in ME/CFS patients. ME/CFS patients had significantly lower Fmax and Fmean hand grip strength. The fatigue ratio which measures decline in strength during hand grip strength was higher in ME/CFS patients and recovery was lower. Lower hand grip strength correlated with disease severity, post- exertional malaise, and muscle pain. Clinical parameters creatinine kinase and lactate dehydrogenase were higher in ME/CFS patients following exertion.

Kujawski S, Cossington J, Słomko J, Zawadka-Kunikowska M, Tafil-Klawe M, Klawe JJ, Buszko K, Jakovljevic DG, Kozakiewicz M, Morten KJ, Dawes H, Strong JWL, Murovska M, Van Oosterwijck J, Estevez-Lopez F, Newton JL, Hodges L, Zalewski P, On Behalf Of The European Network On Me/Cfs Euromene. Relationship between Cardiopulmonary, Mitochondrial and Autonomic Nervous System Function Improvement after an Individualised Activity Programme upon Chronic Fatigue Syndrome Patients. J Clin Med. 2021 Apr 6;10(7):1542. doi:  10.3390/jcm10071542

This study evaluates the effect of Individualized Activity Program (IAP) on cardiovascular, mitochondrial and fatigue parameters in ME/CFS  patients. The parameters include Chalder Fatigue Questionnaire (CFQ), Fatigue Severity Score (FSS) and the Fatigue Impact Scale (FIS). VO2peak, VO2submax and heart rate (HR). Autonomic function was assessed using the Head-Up Tilt Test (HUTT). Mfn1 and Mfn2, a mitochondria marker that may be able to explain exercise tolerance was also measured in plasma. There was a significant decrease in CFQ, FSS, and FIS parameters. Mfn1 and Mfn2 significantly increased in response to this program. Caution over implementing this program is required as the exercise involved was not well tolerated in 51% of patients.

Kuo CF, Shi L, Lin CL, Yao WC, Chen HT, Lio CF, Wang YT, Su CH, Hsu NW, Tsai SY. How peptic ulcer disease could potentially lead to the lifelong, debilitating effects of chronic fatigue syndrome: an insight. Sci Rep. 2021 Apr 6;11(1):7520. doi:  10.1038/s41598-021-87018-z

This study investigated the risk factors associated with developing ME/CFS in people with or without peptic ulcer disease (PUD). It was suggested that there was an increased risk of developing ME/CFS following PUD this association was higher in females and the aging population.

Miwa K. Oral Minocycline Therapy Improves Symptoms of Myalgic Encephalomyelitis, Especially in the Initial Disease Stage. Intern Med. 2021 Apr 26. doi:  10.2169/internalmedicine.6082-20

This study investigated Minocycline Therapy in 100 patients with ME/CFS. Symptom parameters were measured using performance status score (0-9), orthostatic intolerance (OI) during the 10-min standing test, neurologic disequilibrium, and neuropathic pain. A total of 38 patients withdrew from the study. Those who did participate and reported OI (n=6) showed either improvement (n=2) or complete resolution of this issue (n=4). Postural Orthostatic Tachycardia and disequilibrium was improved in five out of eight patients and fibromyalgia or neuropathic pain was controlled in four of five patients. These improvements were greater in those who were in earlier stages of ME/CFS.

Moncorps F, Jouet E, Bayen S, Fornasieri I, Renet S, Las-Vergnas O, Messaadi N. Specifics of chronic fatigue syndrome coping strategies identified in a French flash survey during the COVID-19 containment. Health Soc Care Community. 2021 Apr 6. doi:  10.1111/hsc.13376

A French flash survey was used to assess coping strategies in ME/CFS patients compared to other chronic diseases. Coping strategies include more emphasis on emotion focused coping but there is less seek social support and problem- focused copings.

Pheby DFH, Araja D, Berkis U, Brenna E, Cullinan J, de Korwin JD, Gitto L, Hughes DA, Hunter RM, Trepel D, Wang-Steverding X. The Role of Prevention in Reducing the Economic Impact of ME/CFS in Europe: A Report from the Socioeconomics Working Group of the European Network on ME/CFS (EUROMENE). Medicina (Kaunas). 2021 Apr 16;57(4):388. doi:  10.3390/medicina57040388

This report investigates the impact prevention measures may have on the socioeconomic outcomes for ME/CFS patients. It stated that there is limited ability to implicate primary prevention programs due to the multidisciplinary onset patterns and contributing factors of ME/CFS. Suggestions, however, include early diagnosis and mitigation of environmental risk factors such as organophosphates.

Poenaru S, Abdallah S, Corrales-Medina V, Cowan J. COVID-19 and post-infectious Myalgic encephalomyelitis/chronic fatigue syndrome: a narrative review. TAI. 2021 Apr 20. doi:  10.1177/20499361211009385

This study investigates the pathological overlap between ME/CFS and COVID-19 patients with post-viral symptoms. ME/CFS has been associated with infectious agents such as Epstein–Barr Virus, Q fever, influenza, and other coronaviruses. There are also other clinical similarities, however, there is currently insufficient evidence available to assess whether COVID-19 may lead to ME/CFS.

Sørland K, Sandvik MK, Rekeland IG, Ribu L, Småstuen MC, Mella O, Fluge Ø. Reduced Endothelial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Results From Open-Label Cyclophosphamide Intervention Study. Front Med (Lausanne). 2021 Mar 22;8:642710. doi:  10.3389/fmed.2021.642710

Sørland et al investigates endothelial function in ME/CFS patients. ME/CFS patients had significantly reduced endothelial function.

Szklarski M, Freitag H, Lorenz S, Becker SC, Sotzny F, Bauer S, Hartwig J, Heidecke H, Wittke K, Kedor C, Hanitsch LG, Grabowski P, Sepúlveda N, Scheibenbogen C. Delineating the Association Between Soluble CD26 and Autoantibodies Against G-Protein Coupled Receptors, Immunological and Cardiovascular Parameters Identifies Distinct Patterns in Post-Infectious vs. Non-Infection-Triggered Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Immunol. 2021 Apr 6;12:644548. doi:  10.3389/fimmu.2021.644548

This study investigates Soluble cluster of differentiation 26 (sCD26) correlation with clinical and paraclinical parameters in ME/CFS. The enzymatic marker, sCD26 was lower in ME/CFS patients. There were many patterns found. In infection-triggered ME/CFS patients, sCD26 was associated with activated T cells, liver enzymes, creatin kinase and lactate dehydrogenase as well as inversely related to interleukin-1 beta (IL-1b). Non-infection triggered ME/CFS was associated with higher heart rate after orthostatic challenge and postural orthostatic tachycardia syndrome (POTS).

Wirth KJ, Scheibenbogen C. Pathophysiology of skeletal muscle disturbances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). J Transl Med. 2021 Apr 21;19(1):162. doi:  10.1186/s12967-021-02833-2

Wirth et al investigated bioenergetic disturbance in skeletal muscle in ME/CFS patients in this hypothesis paper. A key idea is that there is impaired transport via the sodium- calcium exchanger (NCX) for calcium transfer. This impaired calcium regulation may affect mitochondria, cytoplasmic metabolism and endothelium leading to symptoms such as post-exertional malaise. Changes in proton concentrations may lead to activation of other channels and disbalance of other ions such as sodium via the sodium-proton-exchanger subtype-1 (NHE1), a key proton pump in skeletal muscle.

Wong TL, Weitzer DJ. Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systemic Review and Comparison of Clinical Presentation and Symptomatology. Medicina (Kaunas). 2021 Apr 26;57(5):418. doi:  10.3390/medicina57050418

This systematic review compares clinical presentation and symptomology between Long COVID and ME/CFS. Twenty-five out of 29 reported ME/CFS symptoms were reported in at least one included Long COVID study. 

March 2021

Cullinan J, Pheby DFH, Araja D, Berkis U, Brenna E, de Korwin JD, et al. Perceptions of European ME/CFS Experts Concerning Knowledge and Understanding of ME/CFS among Primary Care Physicians in Europe: A Report from the European ME/CFS Research Network (EUROMENE). Medicina (Kaunas). 2021;57(3). doi:  10.3390/medicina57030208

This study investigated patient perceptions on general practitioner (GP) management of ME/CFS. Based on survey data, patients showed concern over GPs’ knowledge and understanding of ME/CFS as well as confidence diagnosing the condition. There was also lack of availability of specialists centres which patients could be referred to by their GP. GPs’ disbelief and/or mismanagement was reported among patients. 

Lupo GFD, Rocchetti G, Lucini L, Lorusso L, Manara E, Bertelli M, et al. Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME). Sci Rep. 2021;11(1):7043. doi:  10.1038/s41598-021-86425-6

Lupo et al investigated fecal and oral metabolome in ME/CFS patients compared to healthy controls (HC) using illumina sequencing. There was evidence of changes in microbiome in ME/CFS patients including an increase of oral rothia dentocariosa. ME/CFS microbiome showed composition changes, however, further studies are needed to understand the pathological consequences.

R. Manca, K. Khan, M. Mitolo, et al., Modulatory effects of cognitive exertion on regional functional connectivity of the salience network in women with ME/CFS: A pilot study, Journal of the Neurological Sciences. 2021. doi:  10.1016/j.jns.2021.117326

This study investigates post-exertional malaise in ME/CFS patients and brain changes in functional connectivity (FC) of two networks: the salience network (SN) and the default-mode network (DMN). ME/CFS patients had greater FC of the right insular seed and frontal and subcortical areas, these regions are important for reward processing and cognitive control. There was an association between these regions, cognitive exertion and worsening of ME/CFS symptoms.

Toogood PL, Clauw DJ, Phadke S, Hoffman D. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Where will the drugs come from? Pharmacol Res. 2021;165:105465.  doi:  10.1016/j.phrs.2021.105465

This review summarises available clinical research on effective treatments for ME/CFS as well as outlines promising innovations that may allow development of new medicines. 

Vergauwen K, Huijnen IPJ, Smeets RJEM, Kos D, van Eupen I, Nijs J, et al. An exploratory study of discrepancies between objective and subjective measurement of the physical activity level in female patients with chronic fatigue syndrome. Journal of Psychosomatic Research. 2021;144:110417. doi:  10.1016/j.jpsychores.2021.110417

This study reported that there are discrepancies between objective and subjective measures of physical activity level in female ME/CFS patients. Some of the major conclusions include that sleep diaries are not a suitable replacement for monitoring systems and that illness-related complaints, health-related quality of life or demographic factors do not explain this observed difference. 

February 2021

Ahn SH, Kim JL, Kim JR, Lee SH, Yim HW, Jeong H, Chae JH, Park HY, Lee JJ, Lee H. Association between chronic fatigue syndrome and suicidality among survivors of Middle East respiratory syndrome over a 2-year follow-up period. J Psychiatr Res. 2021 Feb 17;137:1-6. doi:  10.1016/j.jpsychires.2021.02.029

Ahn et al investigated the effects of ME/CFS on suicidality among survivors of Middle East Respiratory Syndrome (MERS) over a two- year period. From the 63 participants, 29 were diagnosed with ME/CFS after 12 months (T1). Suicidality rates were 22.2% at T1, 15.1% at 18 months (T2) and 10% at 24 months (T3). Suicidality was more common among those that were diagnosed with ME/CFS.

Asprusten, T.T., Sletner, L. & Wyller, V.B.B. Are there subgroups of chronic fatigue syndrome? An exploratory cluster analysis of biological markers. J Transl Med 19, 48 (2021). doi:  10.1186/s12967-021-02713-9

This study investigates potential ME/CFS subgrouping based on biological markers using hierarchical cluster analyses within a cohort of adolescent patients. There were six highly overlapping clusters found including: pain tolerant & good cognitions, restored HPA dynamics, orthostatic intolerance, low-grade inflammation, pain intolerant & poor cognitions, and high vagal (parasympathetic) activity but no distinct subgroups could be distinguished. Pain intolerant and poor cognitions-cluster is associated with low functional abilities and quality of life and to the Canadian Consensus Criteria however no other statistically significant associations were found.

Comella PH, Gonzalez-Kozlova E, Kosoy R, Charney AW, Peradejordi IF, Chandrasekar S, Tyler SR, Wang W, Losic B, Zhu J, Hoffman GE, Kim-Schulze S, Qi J, Patel M, Kasarskis A, Suarez-Farinas M, Gümüş ZH, Argmann C, Merad M, Becker C, Beckmann ND, Schadt EE. A Molecular network approach reveals shared cellular and molecular signatures between chronic fatigue syndrome and other fatiguing illnesses. medRxiv [Preprint]. 2021 Feb 2:2021.01.29.21250755. doi:  10.1101/2021.01.29.21250755

This study compares whole blood molecular signatures in ME/CFS patients compared to other illnesses where fatigue is a primary symptom such as long haul COVID-19. Immune cell molecular signatures of ME/CFS patients overlapped with those from other illnesses, this may indicate a common molecular etiology.

Germain A, Levine SM, Hanson MR. In-Depth Analysis of the Plasma Proteome in ME/CFS Exposes Disrupted Ephrin-Eph and Immune System Signaling. Proteomes. 2021;9(1). doi:  10.3390/proteomes9010006

Germain et al identified 19 protein level differences between ME/CFS patients and healthy controls. These proteins are involved in a variety of pathways including extracellular matrix, the immune system and cell-cell communication. Cluster analysis in particular highlight pathways relating to the ephrin pathway that has important roles in cell- cell signalling and other critical cellular processes.

Kedor C, Freitag H, Meyer-Arndt L, Wittke K, Zoller T, Steinbeis F, et al. Chronic COVID-19 Syndrome and Chronic Fatigue Syndrome (ME/CFS) following the first pandemic wave in Germany – a first analysis of a prospective observational study. medRxiv. 2021. doi:   10.1101/2021.02.06.21249256

This prospective observational study evaluated 42 COVID-19 patients that have presented with moderate to severe fatigue six months following infection. An array of symptoms was described including: cognitive symptoms, headache and muscle pain. Post-exertional malaise was the most frequently reported symptom described in 97.6% of the patients. Nineteen of the 42 patients met the Canadian Consensus Criteria of ME/CFS.

Maksoud R, Balinas C, Holden S, Cabanas H, Staines D, Marshall-Gradisnik S. A systematic review of nutraceutical interventions for mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome. J Transl Med. 2021;19(1):81. doi:  10.1186/s12967-021-02742-4

This systematic review included nine intervention studies and assessed the effectiveness of a variety of different mitochondrial -targeting nutraceuticals including nicotinamide adenine dinucleotide hydrogen (NADH), coenzyme Q10 (CoQ10), Ubiquinol-10 and Acetyl L-Carnitine (ALC) on fatigue and mitochondrial function in ME/CFS patients. Improvement in the primary outcome measure fatigue was observed in six of the nine studies. Due to several limitations of these studies such as low availability of studies investigating this topic, lack of consistency of measuring tools for fatigue used, low sample size and short study duration there is still limited support for these interventions for improvements in mitochondrial function and future well-designed studies are required.

Metselaar PI, Mendoza-Maldonado L, Li Yim AYF, Abarkan I, Henneman P, Te Velde AA, Schönhuth A, Bosch JA, Kraneveld AD, Lopez-Rincon A. Recursive ensemble feature selection provides a robust mRNA expression signature for myalgic encephalomyelitis/chronic fatigue syndrome. Sci Rep. 2021 Feb 25;11(1):4541. doi:  10.1038/s41598-021-83660-9

In this study, recursive ensemble feature selection (REFS), a predictive machine- learning based software tool was used on publicly available mRNA expression data in peripheral blood mononuclear cells (PBMCs). Using this program, 23 genes that may be able to distinguish ME/CFS patients with healthy controls (HC) with a high accuracy. Ten of these genes were associated with disrupted immune system. Additionally, 48 gene -associated methylation markers were identified that could assist with distinguishing patients compared to HC with high accuracy.

Strassheim V, Newton JL, Collins T. Experiences of Living with Severe Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. Healthcare (Basel). 2021 Feb 5;9(2):168. doi:  10.3390/healthcare9020168

This is a qualitative study that investigates experiences of five severe ME/CFS patients based on semi-structured interviews. Major themes across the interviews included: lived experience, challenges to daily life and management of the condition.

van Campen C, Rowe PC, Verheugt FWA, Visser FC. Numeric Rating Scales Show Prolonged Post-exertional Symptoms After Orthostatic Testing of Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Med (Lausanne). 2020;7:602894. doi:  10.3389/fmed.2020.602894

Van Campen et al investigated the effect of head-up tilt testing (HUT) that contributes to orthostatic stress on post exertional malaise (PEM) using numeric rating scales (NRS). Pain, fatigue and concentration NRS scores were significantly higher seven days post-HUT compared to pre-HUT in ME/CFS patients with or without fibromyalgia.  

January 2021

Brittain, E.; Muirhead, N.; Finlay, A.Y.; Vyas, J. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Major Impact on Lives of Both Patients and Family Members. Medicina 2021, 57, 43.  10.3390/medicina

This study investigates the impact of ME/CFS on the lives of patients and family members using Abbreviated World Health Organization Quality of Life questionnaire and Family Reported Outcome Measure-16 quality of life assessment. ME/CFS negatively affected both the patient and their family members. Quality of life (QOL) of patients were impacted mostly by physical health while families of those affected were impacted by worry, family activities, frustration, and sadness.  

Conroy K, Bhatia S, Islam M, Jason LA. Homebound versus Bedridden Status among Those with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Healthcare (Basel). 2021;9(2). doi:  10.3390/healthcare9020106

This study investigates the homebound and bedridden status in those with ME/CFS. In an international sample of 2138 participants with ME/CFS, 549 were housebound (severe) and 89 were bedridden (very severe). An association between severity of ME/CFS and post-exertional malaise (PEM) symptom domain was found.

Feder HM, Wormser GP. Studying College Students for the Development of Infectious Mononucleosis and ME/CFS. Clin Infect Dis. 2021. doi:  10.1093/cid/ciab075

In this prospective cohort study, 23% of 238 participants with infectious mononucleosis (IM) met criteria for ME/CFS. The participants with severe ME/CFS were compared to 67 asymptomatic controls. There were no significant differences found between the two groups in stress, coping, anxiety and depression. There were significant differences in behavioural measures and IL-6 and IL-13. At the time of developing IM, both ME/CFS groups had greater autonomic complaints and behavioural symptoms while the severe- ME/CFS group had higher levels of IL-12 and lower levels of IL-13 compared to the asymptomatic group. 

R. Manca, K. Khan, M. Mitolo, et al., Modulatory effects of cognitive exertion on regional functional connectivity of the salience network in women with ME/CFS: A pilot study, Journal of the Neurological Sciences. 2021. doi:  10.1016/j.jns.2021.117326

This study investigates post-exertional malaise in ME/CFS patients and brain changes in functional connectivity (FC) of two networks: the salience network (SN) and the default-mode network (DMN). ME/CFS patients had greater FC of the right insular seed and frontal and subcortical areas, these regions are important for reward processing and cognitive control. There was an association between these regions, cognitive exertion and worsening of ME/CFS symptoms.  

Wormgoor MEA, Rodenburg SC. The evidence base for physiotherapy in myalgic encephalomyelitis/chronic fatigue syndrome when considering post-exertional malaise: a systematic review and narrative synthesis. J Transl Med. 2021;19(1):1. doi:  10.1186/s12967-020-02683-4

Wormgoor et al investigates the effect of physiotherapy on symptoms and functioning with focus on post- exertional malaise (PEM). Due to limited studies being available that require patients to have PEM as a required symptom there is no scientific evidence on effective physiotherapy for ME/CFS patients.