Pathophysiological mechanisms of post-exertional malaise: an integrative analysis based on the metabolism-immune-neuro interaction model.
Jin, Hongjiao, An, Yi, Huang, Jingwei et al.·Frontiers in immunology·2026
This systematic review proposes a framework for understanding post-exertional malaise (PEM)—the worsening of symptoms after mild activity—by examining how energy production, immune activation, and brain inflammation may be associated with each other in people with Long COVID and chronic fatigue conditions. The authors suggest that in vulnerable individuals, exercise may trigger an abnormal cascade involving damaged mitochondria (cellular energy factories), inflammatory molecules, and changes in how the brain perceives fatigue and pain. However, this is a theoretical model based on existing literature; individual mechanisms have not been directly tested in a single study.