Tag: long covid vs ME/CFS

A Single-Center Pilot Study of Therapeutic Apheresis in Patients with Severe Post-COVID Syndrome

Abstract:

After the COVID-19 pandemic, many patients have reported chronic fatigue and severe post-exertional malaise, with symptoms similar to those of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The accumulation of agonistic receptor autoantibodies targeting beta-adrenergic (β1 and β2) and muscarinic (M3 and M4) neurotransmitter receptors may play a crucial role in the pathomechanism of both ME/CFS and post-COVID conditions.

Therapeutic apheresis has been suggested as an effective treatment option for alleviating and mitigating symptoms in this desperate group of patients. In this single-center pilot study, we analyzed autoantibodies in a cohort of 20 post-COVID patients before and after therapeutic apheresis. Apheresis resulted in a decline of β1 or β2 adrenergic receptor antibodies in all patients. Additionally, the majority of patients experienced a concurrent reduction in symptoms such as fatigue, physical activity restrictions, myalgia, post-exertional malaise, and concentration disorders.

This study clearly demonstrates an association between autoantibodies and the clinical improvement of post-COVID patients. Even if future sham-controlled trials do not show a positive outcome, extracorporeal apheresis may still be valuable for this patient group by temporarily improving microperfusion and symptoms. Success in restoring patients to work and normal life, as observed in many individuals after therapeutic apheresis, should be recognized. Therefore, we believe that extracorporeal therapeutic apheresis, as part of a multimodal treatment, should be considered an early intervention for postinfectious syndromes in selected patients.

Source: Korth J, Steenblock C, Walther R, Barbir M, Husung M, Velthof A. A Single-Center Pilot Study of Therapeutic Apheresis in Patients with Severe Post-COVID Syndrome. Horm Metab Res. 2024 Dec;56(12):869-874. doi: 10.1055/a-2445-8593. Epub 2024 Dec 9. PMID: 39653042. https://pubmed.ncbi.nlm.nih.gov/39653042/

Phase-dependent trends in the prevalence of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) related to long COVID: A criteria-based retrospective study in Japan

Abstract:

Background: The characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) related to COVID-19 have remained uncertain. To elucidate the clinical trend of ME/CFS induced by long COVID, we examined data for patients who visited our outpatient clinic established in a university hospital during the period from Feb 2021 to July 2023.

Methods: Long COVID patients were classified into two groups, an ME/CFS group and a non-ME/CFS group, based on three diagnostic criteria.

Results: The prevalence of ME/CFS in the long COVID patients was 8.4% (62 of 739 cases; female: 51.6%) and factors related to ME/CFS were severe illness, smoking and alcohol drinking habits, and fewer vaccinations. The frequency of ME/CFS decreased from 23.9% in the Preceding period to 13.7% in the Delta-dominant period and to 3.3% in the Omicron-dominant period. Fatigue and headache were commonly frequent complaints in the ME/CFS group, and the frequency of poor concentration in the ME/CFS group was higher in the Omicron period. Serum ferritin levels were significantly higher in female patients in the ME/CFS group infected in the Preceding period. In the ME/CFS group, the proportion of patients complaining of brain fog significantly increased from 22.2% in the Preceding period to 47.9% in the Delta period and to 81.3% in the Omicron period. The percentage of patients who had received vaccination was lower in the ME/CFS group than the non-ME/CFS group over the study period, whereas there were no differences in the vaccination rate between the groups in each period.

Conclusion: The proportion of long COVID patients who developed ME/CFS strictly diagnosed by three criteria was lower among patients infected in the Omicron phase than among patients infected in the other phases, while the proportion of patients with brain fog inversely increased. Attention should be paid to the variant-dependent trends of ME/CFS triggered by long COVID (300 words).

Source: Morita S, Tokumasu K, Otsuka Y, Honda H, Nakano Y, Sunada N, Sakurada Y, Matsuda Y, Soejima Y, Ueda K, Otsuka F. Phase-dependent trends in the prevalence of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) related to long COVID: A criteria-based retrospective study in Japan. PLoS One. 2024 Dec 9;19(12):e0315385. doi: 10.1371/journal.pone.0315385. PMID: 39652555; PMCID: PMC11627433. https://pmc.ncbi.nlm.nih.gov/articles/PMC11627433/ (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)

Upregulation of olfactory receptors and neuronal-associated genes highlights complex immune and neuronal dysregulation in Long COVID patients

Abstract:

A substantial portion of patients infected with SARS-CoV-2 experience prolonged complications, known as Long COVID (LC). A subset of these patients exhibits the most debilitating symptoms, similar to those defined in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We performed bulk RNA sequencing (RNAseq) on the whole blood of LC with ME/CFS, at least 12 months post-onset of the acute disease, and compared them with controls.

We found that LC patients had a distinct transcriptional profile compared to controls. Key findings include the upregulation of genes involved in immune dysregulation and neuronal development, such as Fezf2, BRINP2, HOXC12, MEIS2, ZFHX3, and RELN. These genes are linked to neuroinflammatory responses, cognitive impairments, and hematopoietic disturbances, suggesting ongoing neurological and immune disturbances in LC patients. RELN, encoding the Reelin protein, was notably elevated in LC patients, potentially serving as a biomarker for LC pathogenesis due to its role in inflammation and neuronal function.

Immune cell analysis showed altered profiles in LC patients, with increased activated memory CD4 + T cells and neutrophils, and decreased regulatory T cells and NK cells, reflecting immune dysregulation. Changes in cytokine and chemokine expression further underscore the chronic inflammatory state in LC patients. Notably, a unique upregulation of olfactory receptors (ORs) suggest alternative roles for ORs in non-olfactory tissues. Pathway analysis revealed upregulation in ribosomal RNA processing, amino acid metabolism, protein synthesis, cell proliferation, DNA repair, and mitochondrial pathways, indicating heightened metabolic and immune demands. Conversely, downregulated pathways, such as VEGF signaling and TP53 activity, point to impaired tissue repair and cellular stress responses.

Overall, our study underscores the complex interplay between immune and neuronal dysfunction in LC patients, providing insights into potential diagnostic biomarkers and therapeutic targets. Future research is needed to fully understand the roles and interactions of these genes in LC pathophysiology.

Source: Shahbaz S, Rezaeifar M, Syed H, Redmond D, Terveart JWC, Osman M, Elahi S. Upregulation of olfactory receptors and neuronal-associated genes highlights complex immune and neuronal dysregulation in Long COVID patients. Brain Behav Immun. 2024 Nov 28:S0889-1591(24)00721-9. doi: 10.1016/j.bbi.2024.11.032. Epub ahead of print. PMID: 39615603. https://www.sciencedirect.com/science/article/pii/S0889159124007219 (Full text)

The effects of 3-month supplementation with synbiotic on patient-reported outcomes, exercise tolerance, and brain and muscle metabolism in adult patients with post-COVID-19 chronic fatigue syndrome (STOP-FATIGUE): a randomized Placebo-controlled clinical trial

Abstract:

Purpose: Considering the observed gastrointestinal issues linked to post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), beneficially modulating the gut microbiota could offer a safe, cost-effective nutritional strategy. This trial aimed to evaluate the effects of medium-term synbiotic supplementation on patient-reported outcomes, exercise tolerance, and tissue metabolism in patients with post-COVID-19 ME/CFS.

Methods: Between September 2022 and December 2023, we investigated the impact of 3-month supplementation with a synbiotic mixture including L. rhamnosus DSM 32550, Humiome® L. plantarum DSM 34532, B. lactis DSM 32269, B. longum DSM 32946, fructooligosaccharides and zinc, on predetermined primary and secondary outcome measures in twenty six post-COVID-19 ME/CFS patients utilizing a parallel-group, randomized, placebo-controlled, double-blind design.

Results: Both the synbiotic and placebo intake resulted in a significant reduction in general fatigue after 3 months compared to the baseline values (P ≤ 0.05). This was accompanied by a significant interaction effect (time vs. treatment) for post-exercise malaise (P = 0.02), with synbiotic superior to placebo to attenuate post-exercise malaise. The synbiotic also demonstrated a significant advantage over placebo in increasing choline levels at the thalamus (P = 0.02), and creatine levels at left frontal white matter (P = 0.05) and left frontal grey matter (P = 0.04).

Conclusion: Taking the synbiotic mixture for three months improves tissue metabolism and mitigates clinical features of post-COVID-19 fatigue syndrome. The presented data show promise in addressing the widespread issue of ME/CFS following the COVID-19 pandemic; however, further validation is needed before endorsing the synbiotics within this clinical context. The study is registered at ClinicalTrials.gov (NCT06013072).

Source: Ranisavljev M, Stajer V, Todorovic N, Ostojic J, Cvejic JH, Steinert RE, Ostojic SM. The effects of 3-month supplementation with synbiotic on patient-reported outcomes, exercise tolerance, and brain and muscle metabolism in adult patients with post-COVID-19 chronic fatigue syndrome (STOP-FATIGUE): a randomized Placebo-controlled clinical trial. Eur J Nutr. 2024 Nov 26;64(1):28. doi: 10.1007/s00394-024-03546-0. PMID: 39592468. https://pubmed.ncbi.nlm.nih.gov/39592468/

On the Prevalence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome after a SARS-CoV-2 infection

Introduction:

There is an increasing body of evidence connecting the post-acute SARS-CoV-2 condition (PASC, commonly known as long COVID) to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a debilitating disease of unknown cause characterized by persistent and unexplained fatigue, post-exertional malaise (PEM), among other symptoms. This connection implies that, in the clinic, some PASC cases comply with the official case definitions of ME/CFS. As such, there is a necessity to quantify the burden of ME/CFS among the PASC population in order to delineate effective healthcare interventions for the benefit of these patients who are often neglected or, in some extreme cases, stigmatized by medical staff and society.
To answer this urgent research question, Dehlia and Guthridge performed a systematic review and meta-analysis of recent data on PASC adults and reported an ME/CFS prevalence estimate of 51% (95% CI, 42%-60%); this systematic review and meta-analysis will be referred to as PASC-ME/CFS study. In the present Letter to Editor, we aimed to discuss the reliability of this estimate using the research protocol from the European Network on ME/CFS (EUROMENE) for systematic reviews and meta-analysis on the epidemiology burden of ME/CFS in Europe.

Source: Sepúlveda N, Westermeier F. On the Prevalence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome after a SARS-CoV-2 infection. J Infect. 2024 Nov 16:106353. doi: 10.1016/j.jinf.2024.106353. Epub ahead of print. PMID: 39557089. Sepúlveda N, Westermeier F. On the Prevalence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome after a SARS-CoV-2 infection. J Infect. 2024 Nov 16:106353. doi: 10.1016/j.jinf.2024.106353. Epub ahead of print. PMID: 39557089. https://www.journalofinfection.com/article/S0163-4453(24)00288-3/fulltext (Full text)

Blood virome research in myalgic encephalomyelitis/chronic fatigue syndrome: challenges and opportunities

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with a complex clinical presentation and an unknown etiology. Various viral infections have been proposed as potential triggers of ME/CFS onset, but no specific pathogen has been identified in all cases of postinfectious ME/CFS.

The symptomatology of the postacute sequelae of SARS-CoV-2, or long COVID, mirrors that of ME/CFS, with nearly half of long COVID patients meeting ME/CFS diagnostic criteria. The influx of newly diagnosed patients has reinvigorated interest in ME/CFS pathogenesis research, with an emphasis on viral triggers.

This review summarizes the current understanding of ME/CFS research on viral triggers, including blood virome screening studies. To further elucidate the molecular basis of ME/CFS, there is a need to develop innovative bioinformatics tools capable of analyzing complex virome data and integrating multiomics information.

Source: Obraitis D, Li D. Blood virome research in myalgic encephalomyelitis/chronic fatigue syndrome: challenges and opportunities. Curr Opin Virol. 2024 Nov 12:101437. doi: 10.1016/j.coviro.2024.101437. Epub ahead of print. PMID: 39537445. https://www.sciencedirect.com/science/article/pii/S1879625724000518 (Full text)

Overlapping conditions in Long COVID at a multisite academic center

Abstract:

Background: Many patients experience persistent symptoms after COVID-19, a syndrome referred to as Long COVID (LC). The goal of this study was to identify novel new or worsening comorbidities self-reported in patients with LC.

Methods: Patients diagnosed with LC (n = 732) at the Mayo Long COVID Care Clinic in Rochester, Minnesota and Jacksonville, Florida were sent questionnaires to assess the development of new or worsening comorbidities following COVID-19 compared to patients with SARS-CoV-2 that did not develop LC (controls). Both groups were also asked questions screening for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), generalized joint hypermobility (GJH) and orthostatic intolerance. 247 people with LC (33.7%) and 40 controls (50%) responded to the surveys.

Results: In this study LC patients averaged 53 years of age and were predominantly White (95%) women (75%). The greatest prevalence of new or worsening comorbidities following SARS-CoV-2 infection in patients with LC vs. controls reported in this study were pain (94.4% vs. 0%, p < 0.001), neurological (92.4% vs. 15.4%, p < 0.001), sleep (82.8% vs. 5.3%, p < 0.001), skin (69.8% vs. 0%, p < 0.001), and genitourinary (60.6% vs. 25.0%, p = 0.029) issues. 58% of LC patients screened positive for ME/CFS vs. 0% of controls (p < 0.001), 27% positive for GJH compared to 10% of controls (p = 0.026), and a positive average score of 4.0 on orthostatic intolerance vs. 0 (p < 0.001). The majority of LC patients with ME/CFS were women (77%).

Conclusion: We found that comorbidities across 12 surveyed categories were increased in patients following SARS-CoV-2 infection. Our data also support the overlap of LC with ME/CFS, GJH, and orthostatic intolerance. We discuss the pathophysiologic, research, and clinical implications of identifying these conditions with LC.

Source: Grach SL, Dudenkov DV, Pollack B, Fairweather D, Aakre CA, Munipalli B, Croghan IT, Mueller MR, Overgaard JD, Bruno KA, Collins NM, Li Z, Hurt RT, Tal MC, Ganesh R, Knight DTR. Overlapping conditions in Long COVID at a multisite academic center. Front Neurol. 2024 Oct 25;15:1482917. doi: 10.3389/fneur.2024.1482917. PMID: 39524912; PMCID: PMC11543549. https://pmc.ncbi.nlm.nih.gov/articles/PMC11543549/ (Full text)

Stroop task and practice effects demonstrate cognitive dysfunction in long COVID and myalgic encephalomyelitis / chronic fatigue syndrome

Abstract:

Background: The Stroop task was used to investigate differences in cognitive function between Long COVID (LC), Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) and healthy control subjects.

Methods: Subjects viewed four color words or neutral (XXXX) stimuli with the same (congruent) or different color ink (incongruent). Cognitive conflict was inferred from response times for pairings of prestimuli and subsequent stimuli. Overall effects were assessed by univariate analysis with time courses determined for binned response times.

Results: LC and ME/CFS had significantly longer response times than controls indicating cognitive dysfunction. Initial response times were ranked LC > ME > HC, and decreased according to power functions. At the end of the task (900s), times were ranked LC = ME > HC. Response times were significantly slower for stimuli following an incongruent prestimulus. Time series for Stroop effect, facilitation, interference, surprise index and practice power law parameters were generally similar in LC, ME/CFS and HC suggesting comparable patterns for recruitment of cognitive resources. The prestimulus data were analyzed and generated positive Stroop and interference effects that were distinct from stimulus effects.

Conclusion: LC and ME/CFS have global slowing of response times that cannot be overcome by practice suggesting impaired communications between network nodes during problem solving. Analysis of matched prestimulus – stimulus effects adds a new dimension for understanding cognitive conflict.

Brief summary: Cognitive dysfunction in Long COVID and ME/CFS was demonstrated using the Stroop task which found global slowing of response times and limitations of practice effects.

Source: Baraniuk JN, Thapaliya K, Inderyas M, Shan ZY, Barnden LR. Stroop task and practice effects demonstrate cognitive dysfunction in long COVID and myalgic encephalomyelitis / chronic fatigue syndrome. Sci Rep. 2024 Nov 5;14(1):26796. doi: 10.1038/s41598-024-75651-3. PMID: 39500939; PMCID: PMC11538523. https://pmc.ncbi.nlm.nih.gov/articles/PMC11538523/ (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