Tag: disease stages

Comparing DNA Methylation Landscapes in Peripheral Blood from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Patients

Abstract:

Post-viral conditions, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC), share > 95% of their symptoms, but the connection between disturbances in their underlying molecular biology is unclear. This study investigates DNA methylation patterns in peripheral blood mononuclear cells (PBMC) from patients with ME/CFS, LC, and healthy controls (HC).

Reduced Representation Bisulphite Sequencing (RRBS) was applied to the DNA of age- and sex-matched cohorts: ME/CFS (n = 5), LC (n = 5), and HC (n = 5). The global DNA methylomes of the three cohorts were similar and spread equally across all chromosomes, except the sex chromosomes, but there were distinct minor changes in the exons of the disease cohorts towards more hypermethylation.

A principal component analysis (PCA) analysing significant methylation changes (p < 0.05) separated the ME/CFS, LC, and HC cohorts into three distinct clusters. Analysis with a limit of >10% methylation difference and at p < 0.05 identified 214 Differentially Methylated Fragments (DMF) in ME/CFS, and 429 in LC compared to HC. Of these, 118 DMFs were common to both cohorts. Those in promoters and exons were mainly hypermethylated, with a minority hypomethylated. There were rarer examples with either no change in methylation in ME/CFS but a change in LC, or a methylation change in ME/CFS but in the opposite direction in LC. The differential methylation in a number of fragments was significantly greater in the LC cohort than in the ME/CFS cohort.

Our data reveal a generally shared epigenetic makeup between ME/CFS and LC but with specific, distinct changes. Differences between the two cohorts likely reflect the stage of the disease from onset (LC 1 year vs. ME/CFS 12 years), but specific changes imposed by the SARS-CoV-2 virus in the case of the LC patients cannot be discounted. These findings provide a foundation for further studies with larger cohorts at the same disease stage and for functional analyses to establish clinical relevance.

Source: Peppercorn K, Sharma S, Edgar CD, Stockwell PA, Rodger EJ, Chatterjee A, Tate WP. Comparing DNA Methylation Landscapes in Peripheral Blood from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Patients. Int J Mol Sci. 2025 Jul 10;26(14):6631. doi: 10.3390/ijms26146631. PMID: 40724879. https://www.mdpi.com/1422-0067/26/14/6631 (Full text)

A Natural History of Disease Framework for Improving the Prevention, Management, and Research on Post-viral Fatigue Syndrome and Other Forms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

We propose a framework for the treatment, rehabilitation, and research into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) using a natural history of disease approach to outline the distinct disease stages, with an emphasis on cases following infection to provide insights into prevention.

Moving away from the method of subtyping patients based on the various phenotypic presentations and instead reframing along the lines of disease progression could help with defining the distinct stages of disease, each of which would benefit from large prospective cohort studies to accurately describe the pathological mechanisms taking place therein. With a better understanding of these mechanisms, management and research can be tailored specifically for each disease stage.

Pre-disease and early disease stages call for management strategies that may decrease the risk of long-term morbidity, by focusing on avoidance of further insults, adequate rest to enable recovery, and pacing of activities.

Later disease stages require a more holistic and tailored management approach, with treatment—as this becomes available—targeting the alleviation of symptoms and multi-systemic dysfunction.

More stringent and standardised use of case definitions in research is critical to improve generalisability of results and to create the strong evidence-based policies for management that are currently lacking in ME/CFS.

Source: O’Boyle S, Nacul L, Nacul FE, Mudie K, Kingdon CC, Cliff JM, Clark TG, Dockrell HM and Lacerda EM. A Natural History of Disease Framework for Improving the Prevention, Management, and Research on Post-viral Fatigue Syndrome and Other Forms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front. Med. 8:688159. https://www.frontiersin.org/articles/10.3389/fmed.2021.688159/full (Full text)