Muscle fatigue in patients with severe long COVID: A 2-year follow-up study.

Abstract

Fatigue is recognized as one of the most persistent and debilitating symptoms of long COVID, affecting both functionality and quality of life. However, its long-term effects, especially beyond the first year after infection, remain poorly understood. To investigate self-reported fatigue and muscle fatigability in individuals with severe long COVID compared to matched healthy controls at 18 and 24 months post infection. Longitudinal observational study. The study was conducted at the Laboratory of Muscle and Tendon Plasticity at the University of Brasília. Twenty survivors of severe-COVID and 20 age- and gender-matched controls underwent repeat assessments at 18 and 24 months following hospital discharge. Not applicable. Perceived fatigue was measured using the Fatigue Severity Scale, functionality with the 30-second sit-to-stand test, muscular dimensions and quality assessment were evaluated through ultrasound-derived thickness and echogenicity, and muscle fatigability was assessed using torque, torque-time integral, and rate of force development. The generalized estimating equations method was used with "group" and "assessments" as factors, with the least significant difference test identifying specific differences. Chi-square test compared categorical variables. The severe-COVID group showed consistently poorer functional performance (mean difference: 2.65 [0.45-4.85], p = .018), higher perceived fatigue (2.25 [1.54-2.95], p < .001) and lower rate of force development (-103.68 [-177.22 to -30.13], p = .006) compared to controls. No significant differences were observed in muscle thickness or echogenicity between groups. Long COVID is associated with sustained fatigue, impaired neuromuscular function, and reduced physical performance up to 2 years after infection. These findings underscore the need for long-term, mechanism-based rehabilitation strategies targeting central fatigue and neuromuscular function. NCT04961255.