Tag: treatment

The Effect on Quality of Life of Therapeutic Plasmapheresis and Intravenous Immunoglobulins on a Population of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with Elevated β-Adrenergic and M3-Muscarinic Receptor Antibodies—A Pilot Study

Abstract:

Background/Objectives: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition with not fully understood causes, though evidence points to immune system involvement and possible autoimmunity. ME/CFS could be triggered by various infectious pathogens, like SARS-CoV-2; furthermore, a subset of the post-COVID-19 condition (PCC) patients fulfill the diagnostic criteria of ME/CFS. According to the Canadian Consensus Criteria (CCC), the presence of specific symptoms such as fatigue, post-exertional malaise, sleep dysfunction, pain, neurological/cognitive manifestations, and symptoms from at least two of the following categories lead to the diagnosis of ME/CFS: autonomic, neuroendocrine, and immune manifestation. In this study, the patient selection was based on the identification of ME/CFS patients with elevated autoantibodies, regardless of the triggering factor of their condition.
Methods: The aim of this study was to identify ME/CFS patients among long COVID patients with elevated autoantibodies. In seven cases, plasmapheresis (PE) and intravenous immunoglobulins (IVIGs) with repetitive autoantibody measurements were applied: four PE sessions on days 1, 5, 30, and 60, and a low-dose IVIG therapy after each treatment. Antibodies were measured before the first PE and two weeks after the last PE session. To monitor clinical outcomes, the following somatic and psychometric follow-up assessments were conducted before the first PE, 2 weeks after the second, and 2 weeks after the last PE: the Schellong test, ISI (insomnia), FSS (fatigue), HADS (depression and anxiety), and EQ-5D-5L (quality of life) questionnaires.
Results: There was a negative association between both the β2-adrenergic and M3-muscarinic receptor autoantibody concentration and the quality of life measurements assessed with the EQ-5D-5L questionnaire. Per 1 U/mL increase in the concentration levels of β2-adrenergic receptor antibodies or M3-muscarinic acetylcholine receptor antibodies, the EQ-5D-5L index score [−0.59 to 1] decreased by 0.01 (0.63%) or 0.02 (1.26%), respectively. There were no significant associations between the ISI, HADS, and FSS questionnaires and the β1-adrenergic and M4-muscarinic receptor antibodies titers.
Conclusions: After a thorough selection of patients with present autoantibodies, this pilot study found negative associations concerning autoantibody concentration and somatic, as well as psychological wellbeing. To validate these promising feasibility study results—indicating the potential therapeutic potential of antibody-lowering methods—further investigation with larger sample sizes is needed.
Source: Oesch-Régeni B, Germann N, Hafer G, Schmid D, Arn N. The Effect on Quality of Life of Therapeutic Plasmapheresis and Intravenous Immunoglobulins on a Population of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients with Elevated β-Adrenergic and M3-Muscarinic Receptor Antibodies—A Pilot Study. Journal of Clinical Medicine. 2025; 14(11):3802. https://doi.org/10.3390/jcm14113802 https://www.mdpi.com/2077-0383/14/11/3802 (Full text)

HERV Dysregulation in a Case of Myalgic Encephalomyelitis and Multiple Sclerosis Responsive to Rituximab

Abstract:

This article summarizes the case of 30-year-old male diagnosed with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and its longitudinal follow-up, which provided a secondary diagnosis of Multiple Sclerosis (MS) eight years later. The most impactful result was his response to rituximab treatment after the systematic failure of prior treatments.

Although the expression of endogenous retroviral proteins has been associated with autoimmunity, the patient did not show increased expression of the toxic protein HERV (human endogenous retrovirus)-W ENV, a target of the ongoing clinical trials with temelimab in MS and long COVID-19 cases. However, genome-wide HERV transcriptome analysis by high density microarrays clearly revealed a distinct profile in the patient’s blood supportive of an altered immune system.

Limitations of the study include sub-optimal frequency of magnetic resonance imaging to monitor lesion progression, and similarly for reassessment of HERV profiles after rituximab. Overall, the coincidence of HERV alterations and the impactful response to rituximab presents the possibility of additional, more specific, therapeutic targets encoded by other HERV elements yet to be discovered.

Source: Martín-Martínez E, Gil-Perotin S, Giménez-Orenga K, Barea-Moya L, Oltra E. HERV Dysregulation in a Case of Myalgic Encephalomyelitis and Multiple Sclerosis Responsive to Rituximab. Int J Mol Sci. 2025 May 20;26(10):4885. doi: 10.3390/ijms26104885. PMID: 40430026; PMCID: PMC12111851. https://pmc.ncbi.nlm.nih.gov/articles/PMC12111851/ (Full text)

The potential therapeutic approaches targeting gut health in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a narrative review

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disorder characterized by persistent fatigue and cognitive impairments, with emerging evidence highlighting the role of gut health in its pathophysiology. The main objective of this review was to synthesize qualitative and quantitative data from research examining the gut microbiota composition, inflammatory markers, and therapeutic outcomes of interventions targeting the microbiome in the context of ME/CFS.

Methods: The data collection involved a detailed search of peer-reviewed English literature from January 1995 to January 2025, focusing on studies related to the microbiome and ME/CFS. This comprehensive search utilized databases such as PubMed, Scopus, and Web of Science, with keywords including “ME/CFS,” “Gut-Brain Axis,” “Gut Health,” “Intestinal Dysbiosis,” “Microbiome Dysbiosis,” “Pathophysiology,” and “Therapeutic Approaches.” Where possible, insights from clinical trials and observational studies were included to enrich the findings. A narrative synthesis method was also employed to effectively organize and present these findings.

Results: The study found notable changes in the gut microbiota diversity and composition in ME/CFS patients, contributing to systemic inflammation and worsening cognitive and physical impairments. As a result, various microbiome interventions like probiotics, prebiotics, specific diets, supplements, fecal microbiota transplantation, pharmacological interventions, improved sleep, and moderate exercise training are potential therapeutic strategies that merit further exploration.

Conclusions: Interventions focusing on the gut-brain axis may help reduce neuropsychiatric symptoms in ME/CFS by utilizing the benefits of the microbiome. Therefore, identifying beneficial microbiome elements and incorporating their assessments into clinical practice can enhance patient care through personalized treatments. Due to the complexity of ME/CFS, which involves genetic, environmental, and microbial factors, a multidisciplinary approach is also necessary. Since current research lacks comprehensive insights into how gut health might aid ME/CFS treatment, standardized diagnostics and longitudinal studies could foster innovative therapies, potentially improving quality of life and symptom management for those affected.

Source: Hsu CY, Ahmad I, Maya RW, Abass MA, Gupta J, Singh A, Joshi KK, Premkumar J, Sahoo S, Khosravi M. The potential therapeutic approaches targeting gut health in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a narrative review. J Transl Med. 2025 May 11;23(1):530. doi: 10.1186/s12967-025-06527-x. PMID: 40350437. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06527-x (Full text)

Autoantibody targeting therapies in post COVID syndrome and myalgic encephalomyelitis/chronic fatigue syndrome

Introduction:

Following the shift of SARS-CoV-2 from pandemic to endemic, post COVID syndrome (PCS) joins the list of already known post-acute infection syndromes (PAIS) and its most severe manifestation, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The exact pathomechanism of PCS has not yet been fully understood. Immune dysregulation with persistent inflammation, microvascular injury with endothelial dysfunction, autonomic nervous system dysfunction, mitochondrial dysfunction, gut microbiome dysbiosis and persistence of SARS-CoV-2 virus or SARS-CoV-2 viral particles have been proposed [1].

Autoimmunity could be a linking element across various mechanisms and there is indeed mounting evidence that autoantibodies (AAbs) in particular play a role in a subset of PCS and ME/CFS. In ME/CFS there are now numerous studies showing elevated levels and altered functions of G-protein coupled receptor autoantibodies (GPCR AAbs) and their correlation with severity of key symptoms [2]. First trials with AAb-targeting therapies show promising though mixed results. These include studies directly targeting AAbs by removal with immunoadsorption or their enhanced degradation with efgartigimod or neutralization with BC007 (rovunaptabin). Further B cell depletion with rituximab or plasma cell depletion with daratumumab has yielded some positive but inconsistent results.

Source: Wohlrab F, Eltity M, Ufer F, Paul F, Scheibenbogen C, Bellmann-Strobl J. Autoantibody targeting therapies in post COVID syndrome and myalgic encephalomyelitis/chronic fatigue syndrome. Expert Opin Biol Ther. 2025 Apr 10. doi: 10.1080/14712598.2025.2492774. Epub ahead of print. PMID: 40211686. https://www.tandfonline.com/doi/full/10.1080/14712598.2025.2492774#d1e211 (Full text)

Stellate Ganglion Block reduces symptoms of SARS-CoV-2-induced ME/CFS: A prospective cohort pilot study

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition characterized by fatigue, orthostatic intolerance (OI), post-exertional malaise (PEM) and unrefreshing sleep. Our previous work has shown that modulating the autonomic nervous system can alleviate symptoms of Long COVID, which shares striking similarities with ME/CFS.

Objective: Determine the effect of stellate ganglion block (SGB) on symptoms of ME/CFS.

Methods: Subjects who met the WHO criteria for Long COVID and the Institute of Medicine criteria for ME/CFS were treated with sequential bilateral SGBs separated by 18–24 hours for three consecutive weeks (n = 10). At baseline, and at 2-weeks and 2-months post-treatment, we collected subjective assessments (SF-36 and DSQ2) of symptoms, objective assessments of orthostatic intolerance and cognitive performance, and saliva to measure morning cortisol. During the entire study period, a wearable device collected physiological data several nights a week to measure sleep parameters.

Results: DSQ2 measures of PEM, Unrefreshing Sleep, Cognitive Impairment, and OI improved significantly following treatment. SF-36 measures of Vitality, Physical Function, and Social Function improved significantly following treatment. Objective symptoms of POTS associated with infectious onset resolved following treatment. Objective measures of cognitive impairment were reduced following treatment, most notably in the areas of Immediate and Delayed Recognition. Morning cortisol and measures of sleep architecture did not change significantly following treatment.

Conclusions: Symptoms of ME/CFS were reduced after treatment with SGBs in this small prospective cohort pilot study. Given the lack of FDA-approved treatments for ME/CFS, replication of results in a large clinical trial is warranted.

Source: Duricka, D. L., & Liu, L. D. (2025). Stellate Ganglion Block reduces symptoms of SARS-CoV-2-induced ME/CFS: A prospective cohort pilot study. Fatigue: Biomedicine, Health & Behavior, 13(2), 97–114. https://doi.org/10.1080/21641846.2025.2455876 https://www.tandfonline.com/doi/full/10.1080/21641846.2025.2455876#d1e276 (Full text)

Efficacy Of SARS–CoV-2 Specific Antiviral Therapy for Enteroviral Myalgic Encephalomyelitis/ChronicFatigue Syndrome

Abstract:

Background: Etiology remains elusive for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and no treatment exists. Antivirals had no efficacy in randomized clinical trials (RCT) for Epstein-Barr Virus and HHV-6. Enteroviruses (EV) have been implicated, but no antivirals are available. Many patients who received SARS–CoV-2-specific antiviral drugs for acute Covid-19 (COV19) infection experienced significant improvement of prior ME/CFS symptoms. This study summarizes their responses to antivirals for SARS-Cov-2.
Methods: Neutralizing Antibody (NA) for Coxsackievirus B (CVB)1-6 and Echovirus 6, 7, 9, 11, 30 were done by ARUP lab. Enterovirus Protein (EVP) of Peripheral Blood Leukocytes (PBL) was determined by Western Blot. ME/CFS patients fulfilled Canadian consensus criteria, and had either elevated NA for enteroviruses and/or positive EVP in PBL. ME/CFS patients hospitalized for acute COV19 infection and patients without COV19, were given 5-10 days of IV Remdesivir (Rem) +/- immune modulators. Controls: 20 ME/CFS patients seen concurrently without Remdesivir treatment. Other ME/CFS patients (non-COV19) were given Nirmaltrelvir/Ritonavir (PAX) daily for 10 days +/- one repeat. The energy index (EI) was monitored by the patients before, during and after treatment. Significant improvement was defined as > 30%.
Results: 15/20 (75%) ME/CFS patients – 10/12 hospitalized, 5/8 non-COV19 patients – responded to IV Rem 2-6 weeks after infusions; remission lasted 6-8 weeks to 6-9 months before relapse. Of Controls: 2/20 had mild improvement (< 0.001, X 2 ).

104/200 (52%) of PAX-treated ME/CFS patients improved, often within 2-3 days; all relapsed within days to weeks after treatment. 66%, 33% and 44% of CVB4+, CVB3+, non-CVB3,4+ patients responded to treatment, respectively. EVP decreased and increased with clinical response and relapse.

Conclusion: Rem and PAX demonstrated clinical efficacy in ME/CFS patients with chronic enterovirus infections. Placebo-controlled RCT will be needed to clarify the role of antivirals in ME/CFS.
Source: John K Chia, David Wang, P-2363. Efficacy Of SARS–CoV-2 Specific Antiviral Therapy for Enteroviral Myalgic Encephalomyelitis/ChronicFatigue Syndrome, Open Forum Infectious Diseases, Volume 12, Issue Supplement_1, February 2025, ofae631.2514, https://doi.org/10.1093/ofid/ofae631.2514 https://academic.oup.com/ofid/article/12/Supplement_1/ofae631.2514/7988721?login=false 

Clinical Remission After Therapeutic Apheresis in a Patient Suffering from Long Term Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Case Report

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating multifactorial illness characterized by profound fatigue persisting for more than six months, post-exertional malaise, cognitive impairments, and a range of systemic symptoms. Until now, no accepted causal treatment regimens have been available; therapeutic options include different approaches, such as alleviation of symptoms and promotion of energy conservation.

In this study, we report the case of a 49-year-old female presented to our center suffering from ME/CFS for more than 15 years, characterised by a strong energy loss and neurological and systemic symptoms; previous therapies remained unsuccessful. Therefore, we decided to perform double-filtration apheresis.

After comprehensive laboratory evaluation, including investigation of persistent viral infections, the patient was treated eight times with double-filtration apheresis within a period of 2 years, which resulted in a remarkable sustained clinical remission and significant improvement in her quality of life. Therefore, we conclude that double-filtration apheresis could be an effective therapeutic tool for the treatment of ME/CFS.

Source: Burgard H. Clinical Remission After Therapeutic Apheresis in a Patient Suffering from Long Term Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Case Report. Int Med Case Rep J. 2024 Dec 6;17:997-1002. doi: 10.2147/IMCRJ.S476044. PMID: 39660109; PMCID: PMC11629661. https://pmc.ncbi.nlm.nih.gov/articles/PMC11629661/ (Full text)

Patient-Reported Treatment Outcomes in ME/CFS and Long COVID

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID are persistent multi-system illnesses affecting many patients. With no known effective FDA-approved treatments for either condition, patient-reported outcomes of treatments are invaluable for guiding management strategies in patient care and generating new avenues for research. Here, we present the results of an ME/CFS and Long COVID treatment survey with responses from 3,925 patients.

We assessed the experiences of these patients with more than 150 treatments, as well as their demographics, symptoms, and comorbidities. Patients with each condition who participated in the study shared similar symptom profiles, including all the core symptoms of ME/CFS, e.g., 89.7% of ME/CFS and 79.4% of Long COVID reported post-exertional malaise (PEM). Treatments with the greatest perceived benefits were identified, which had varied effects on different core symptoms.

In addition, treatment responses were significantly correlated (R² = 0.68) between the two patient groups. Patient subgroups with distinct profiles of symptoms and comorbidities showed varied responses to treatments, e.g., a POTS-dominant cluster benefiting from autonomic modulators and a cognitive-dysfunction cluster from CNS stimulants.

This study underscores the symptomatic and therapeutic similarities between ME/CFS and Long COVID and highlights the commonalities and nuanced complexities of infection-associated chronic diseases and related conditions. Insights from patient-reported experiences, in the absence of approved treatments, provide urgently needed real-world evidence for targeted therapies in patient care and for developing future clinical trials.

Source: Martha Eckey, Peng Li, Braxton Morrison, Ronald W Davis, Wenzhong Xiao. Patient-Reported Treatment Outcomes in ME/CFS and Long COVID. medRxiv 2024.11.27.24317656; doi: https://doi.org/10.1101/2024.11.27.24317656 https://www.medrxiv.org/content/10.1101/2024.11.27.24317656v1.full-text (Full text)

Assessment of the therapeutic potential of salubrinal for ME/CFS and long-COVID

Highlights:

  • Long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are enigmatic diseases sharing many characteristics.
  • The most debilitating aspects of these diseases are cognitive dysfunction, ‘brain fog’, and exercise intolerance, ‘post-exertional malaise’.
  • There is no cure for these diseases; treatment is palliative only.
  • Mitochondrial dysfunction with endoplasmic reticulum (ER) stress occurs in both diseases.
  • Salubrinal inhibits the phosphatase that dephosphorylates phospho-eukaryotic initiation factor-2α (peIF2α), a protective protein for cells undergoing ER stress when phosphorylated.
  • Salubrinal reduces the formation of Wiskott–Aldrich syndrome protein family member 3 (WASF3), a protein that causes mitochondrial dysfunction that is overexpressed in a cohort of ME/CFS patients.
  • Salubrinal reduces WASF3 expression, restoring mitochondrial function in fibroblasts of a patient with ME/CFS.

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating condition with no cure that shares commonality with long-COVID.

This review examines current understanding of long-COVID symptoms, characteristics of the affected population, the connection with ME/CFS, and the potential for salubrinal, an agent known for its influence on cellular stress pathways, to mitigate these disorders.

It also describes the historical development and mechanism of action of salubrinal, to mitigate endoplasmic reticulum (ER)/cellular stress responses, that could potentially contribute to symptom improvement in both ME/CFS and long-COVID patients.

Further research and clinical trials are warranted to advance our understanding of the potential role of salubrinal in improving the quality of life for individuals with long-COVID-related ME/CFS symptoms as well as ME/CFS patients.

Source: Aseel Warrayat, Ayah Ali, Joulin Waked, Darcy Tocci, Robert C. Speth. Assessment of the therapeutic potential of salubrinal for ME/CFS and long-COVID. Trends in Molecular Medicine, 2024. ISSN 1471-4914, https://doi.org/10.1016/j.molmed.2024.10.001. https://www.sciencedirect.com/science/article/abs/pii/S1471491424002685

Six-Week Supplementation with Creatine in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Magnetic Resonance Spectroscopy Feasibility Study at 3 Tesla

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic medical condition with no specific pharmacological treatment. Creatine, a nutrient essential for maintaining energy homeostasis in the cells, is a candidate for interventions in ME/CFS.

Methods: Fourteen participants with ME/CFS received supplementation with 16 g creatine monohydrate for 6 weeks. Before starting creatine and on the last day of treatment, participants underwent brain magnetic resonance spectroscopy (MRS) scanning of the pregenual anterior cingulate cortex (pgACC) and dorsolateral prefrontal cortex (DLPFC), followed by symptom, cognition, and hand-grip strength assessments.

Results: Eleven participants completed the study. Creatine treatment increased creatine concentration in both the pgACC and DLPFC (p = 0.004 and 0.012, respectively), decreased fatigue and reaction time (RT) on congruent and incongruent trials of the Stroop test (p = 0.036 and 0.014, respectively), and increased hand-grip strength (p = 0.0004). There was a positive correlation between increases in pgACC creatine and changes in RT on Stroop congruent and incongruent trials (p = 0.048 and p = 0.022, respectively). Creatine was well tolerated, and none of the participants stopped treatment.

Conclusion: Creatine supplementation over six weeks in ME/CFS patients increased brain creatine and improved fatigue and some aspects of cognition. Despite its methodological limitations, this study encourages placebo-controlled investigations of creatine treatment in ME/CFS.

Source: Godlewska BR, Sylvester AL, Emir UE, Sharpley AL, Clarke WT, Martens MAG, Cowen PJ. Six-Week Supplementation with Creatine in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Magnetic Resonance Spectroscopy Feasibility Study at 3 Tesla. Nutrients. 2024 Sep 30;16(19):3308. doi: 10.3390/nu16193308. PMID: 39408275. https://www.mdpi.com/2072-6643/16/19/3308 (Full text)