Trude Schei

For those interested in PEM, see our perspective with lead author @fcowester. link.springer.com/article/10… PEM has traditionally been viewed as symptom exacerbation and/or emergence of new symptoms following exertion. This perspective proposes that PEM may instead reflect disrupted coordination across interconnected physiological systems operating over distinct post-exertional timescales. Key questions •Does PEM reflect disrupted coordination across physiological systems and timescales? •Can distinct post-exertional physiological trajectories define patient subgroups? •Does recurrent post-exertional physiological dysregulation contribute to cumulative cardiometabolic burden? •How do the timing of assessment and disease heterogeneity influence the identification of post-exertional physiological trajectories? •Can longitudinal cardiometabolic profiling identify biomarkers associated with distinct post-exertional trajectories? Together, addressing these questions may help determine whether PEM represents disruption of the coordinated physiological responses that shape post-exertional physiological trajectories, and how these alterations contribute to the multisystem and cardiometabolic manifestations of ME/CFS and Long COVID. Ultimately, advancing our understanding of PEM may require moving beyond symptom characterization toward the longitudinal investigation of post-exertional physiological trajectories across interconnected physiological systems and timescales, while integrating cardiometabolic health as an important source of biological heterogeneity, particularly in individuals with obesity and T2D, in future mechanistic and interventional studies.