Analysis of Potential Subgroups in Vaes ME/CFS Patient Clusters

Background: Vaes et al. (2023)[@vaes2023] identified 13 symptom clusters in a large cohort of ME/CFS patients. Symptom intensity is broadly correlated with post-exertional malaise (PEM) severity, with variation across clusters that seems disorganized. Despite this research, no broadly accepted organizing principle has emerged from this paper or other attempts at phenotyping ME/CFS. Objective: To identify and characterize potential subgroups defined by symptom domain severity relative to PEM within the original Vaes symptom clusters. Our analysis identified two groups of patient clusters with distinct symptom-domain profiles. Anchoring symptom domains to PEM collapses the 13 Vaes clusters into two reproducible families: one characterized by parallel offsets (autonomic, neuroendocrine, other) and one by amplified slopes (pain, neurocognitive), with high-end convergence after accounting for a single influential cluster. This subgroup's symptom trends could align with those of fibromyalgia. Further exploration with individual patient data is needed to validate these findings.