Muscle sodium content in patients with ME/CFS
Patient selection – CCC “All patients were recruited between August 2020 and November 2020 at the Institute of Medical Immunology at Charité where they were previously diagnosed with ME/CFS based on Canadian Consensus Criteria”
Petter, Scheibenbogen, Linz, Stehning, Wirth, Kuehne and Kelm (Germany) – 09 December 2022 – “Muscle sodium content before and after exercise was higher in ME/CFS than in healthy controls. Furthermore, our findings indicate an inverse correlation between muscle sodium content and handgrip strength. These findings provide evidence that sodium overload may play a role in the pathophysiology of ME/CFS and may allow for potential therapeutic targeting.”

Saliva antibody-fingerprint of reactivated latent viruses after mild/asymptomatic COVID-19 is unique in patients with myalgic-encephalomyelitis/chronic fatigue syndrome
Patient selection – CCC “Patients with ME/CFS included in this study were diagnosed according to the 2003 Canadian Consensus Criteria”
Apostolou, Rizwan, Moustardas, Sjorgen, Bertilson, Bragee, Polo and Rosen (Sweden) – 20 October 2022 – “Reactivation of human herpesviruses 1-6 (HSV1, HSV2, VZV, EBV, CMV, HHV6), and human endogenous retrovirus K (HERV-K) was detected by anti-viral antibody fingerprints in saliva…  Our results denote an altered and chronically aroused anti-viral profile against latent viruses in ME/CFS. … This has not been shown before because the antibody elevation is not detected systemically in the circulation/plasma.”

A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity
Patient selection – CCC
Kedor, Freitag, Meyer-Arndt … Bellmann-Strobl & Scheibenbogen (Germany) – 30 August 2022 – “19 post-COVID-19 syndrome patients [out of 42] fulfill the 2003 Canadian Consensus Criteria for ME/CFS. Disease severity and symptom burden is similar in post-COVID-19 syndrome-ME/CFS and non-COVID-19- ME/CFS patients.”
“Hand grip strength is diminished in most patients compared to normal values in healthy. Association of hand grip strength with hemoglobin, interleukin 8 and C-reactive protein in post-COVID-19 syndrome/non-myalgic encephalomyelitis/chronic fatigue syndrome and with hemoglobin, N-terminal prohormone of brain natriuretic peptide, bilirubin, and ferritin in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome may indicate low level inflammation and hypoperfusion as potential pathomechanisms.”

Metabolic Evidence for Peroxisomal Dysfunction in ME/CFS
Patient selection – Fukuda & CCC
Che, Brydges, Yu, Price, Joshi, Roy, Lee, Barupal, Cheng, Palmer, Levine, Peterson, Vernon, Bateman, Hornig, Montoya, Komaroff, Fiehn & Lipkin (USA) – 18 July 2022 – “Our findings indicate a series of interconnected metabolic alterations in people with ME/CFS that may contribute to the pathogenesis of ME/CFS: (i) reduced levels of plasmalogens, unsaturated phospholipid ethers, and carnitines suggest peroxisomal dysfunction; (ii) reductions in levels of PCs indicate dysregulation of CDP-choline pathway, and (iii) elevations in the levels of dicarboxylic acids, particularly the TCA cycle intermediates alpha-ketoglutarate and succinate, consistent with an impairment in the TCA cycle that may contribute to physical and cognitive fatigue.”

Revisiting IgG Reactivity to Epstein-Barr Virus in ME/CFS and Its Potential Application to Disease Diagnosis
Patient selection – CCC
Sepulveda, Malato, Sotzny, Grabowska, Fonseca, Cordeiro, Graca, Biecek, Behrends, Mautner, Westermeier, Lacerda & Scheibenbogen (Poland, Portugal, Germany, Austria, Chile, UK) – 24 June 2022 – “Thus, given the heterogeneous nature of ME/CFS, it is pivotal to stratify patients adequately, based on age, gender, and disease trigger for biomarker discovery…. An implication of having a different antibody profiling between men and women is that analysis of each gender should be performed separately. … In conclusion, this study identified two candidate antigens whose antibodies could be used to identify ME/CFS patients with an infectious trigger. To strengthen our findings, two other cohorts of patients are currently studied, including the well-characterized ME/CFS patients with different disease triggers and healthy controls from the United Kingdom ME/CFS biobank.”

Survey of Anti-Pathogen Antibody Levels in ME/CFS
Patient selection – CCC
O’Neal, Glass, Emig, Vitug, Henry, Shungu, Mao, Levine & Hanson (USA) – 10 June 2022 – “While most of the differences were not significant, the opposite trends between male and female antibody levels indicate it is inappropriate to combine data from the two sexes. … Age-based cohort stratification provides additional insight into humoral immune biology, with a large number of antigens identified with significantly different antibody levels between subjects under 50 and those over 50. … The subtle serological alterations between healthy controls and ME/CFS subjects found here should be interpreted cautiously, but these findings do contribute to the growing body of evidence that the immune system of ME/CFS patients is dysregulated.”

The Pathobiology of ME/CFS: The Case for Neuroglial Failure
Patient selection – CCC
Renz-Polster, Tremblay, Bienzle & Fischer (Germany & Canada) – 09 May 2022 – “From this review we conclude that the multifaceted pathobiology of ME/CFS may be attributable in a unifying manner to neuroglial dysfunction. Because the two key features – post exertional malaise and decreased cerebral blood flow – are also recognized in a subset of patients with post-acute sequelae COVID, we suggest that our findings may also be pertinent to this entity.”

Diagnosis of ME/CFS Syndrome With Partial Least Squares Discriminant Analysis: Relevance of Blood Extracellular Vesicles
Patient selection – CCC & Fukuda
Gonzalez-Cebrian, Almenar-Perez, Xu, Y, Huang, Gimenez-Orenga, Hutchinson, Lodge, Nathanson, Morten, Ferrer & Oltra (Spain, U.K. & U.S.) – 01 April 2022 – Possible biomarker using extracellular vesicles (EV) – “Strikingly, EV physical features, including EV size and z-potential measures were detected by this model as relevant features for the effective diagnosis of patients indicating a potential important role of EVs in ME/CFS.”

Decreased NO production in endothelial cells exposed to plasma from ME/CFS patients
Patient selection – CCC & Fukuda
Rayhan and Baraniuk (Chile, Canada, Austria & Poland) – April 2022 – “In conclusion, this study in vitro shows a decreased NO production in HUVECs exposed to plasma from ME/CFS patients, suggesting an unreported role of eNOS in the pathophysiology of this disease. … Study references indicates the following patient selection: “Patients with ME/CFS were diagnosed by a clinician according to the Canadian Consensus and/or CDC-1994 (“Fukuda”) criteria, as determined by the responses on the Symptoms Assessment form to confirm case definition compliance and study eligibility.”

Plasma metabolomics reveals disrupted response and recovery following maximal exercise in ME/CFS
Patient selection – CCC
Germain, Giloteaux, Moore, Levine, Chia, Keller, Stevens, Franconi, Mao, Shungu, Grimson and Hanson (U.S.) – 31 March 2022 – “The effects of exertion in the ME/CFS cohort predominantly highlighted lipid-related as well as energy-related pathways and chemical structure clusters, which were disparately affected by the first and second exercise sessions. The 24-hour recovery period was distinct in the ME/CFS cohort, with over a quarter of the identified pathways statistically different from the controls. The pathways that are uniquely different 24 hours after an exercise challenge provide clues to metabolic disruptions that lead to PEM. Numerous altered pathways were observed to depend on glutamate metabolism, a crucial component of the homeostasis of many organs in the body, including the brain.”

IgG stimulated β2 adrenergic receptor activation is attenuated in patients with ME/CFS
Patient selection – CCC
Hartwig, Sotzny, Bauer, Heidecke, Riemekasten, Dragun, Meisel, Dames, Grabowski and Scheibenbogen (Germany) – 05 February 2022 – “There is emerging evidence of a network of natural autoantibodies against GPCR [G-protein coupled receptors] which is dysregulated in various diseases. β2 adrenergic and M3 and M4 cholinergic receptor (β2 AdR and M3/4 mAChR) antibodies were found to be elevated in a subset of ME/CFS patients. … We provide evidence that IgG can activate β2 AdR. The β2 AdR activation by IgG is attenuated in ME/CFS patients. A dysregulation of β2 AdR function could explain many symptoms of ME/CFS.”