Persistent impairments in muscle function and symptom burden in post-COVID syndrome: a prospective longitudinal study.

BACKGROUND

Post-COVID syndrome (PCS) is characterized by persistent heterogeneous symptoms after SARS-CoV-2 infection, yet objective biomarkers for symptom severity and longitudinal disease trajectories remain limited. We aimed to characterize muscle function over time in PCS and examine its relationship with symptom burden and neuroaxonal injury markers.

METHODS

In this prospective observational study, patients fulfilling WHO criteria for PCS underwent standardized assessments at baseline (BL) and six-month follow-up (FU). Muscle function was assessed using a multidimensional handgrip strength (HGS) protocol capturing mean force (Fmean), fatigability (fatigue ratio), and recovery capacity alongside clinical symptom measures. Analyses included longitudinal assessment within the PCS cohort, comparisons with COVID-19 recovered controls, analysis of symptom persistence, and matched cohort analyses including HGS measures and circulating neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP).

RESULTS

Among 204 participants (102 PCS, 102 recovered controls) PCS patients showed lower Fmean and higher fatigability at BL and FU (both p < 0.01). Muscle function parameters remained largely stable over six months, with only modest improvement in recovery (p = 0.015). HGS parameters correlated with symptom burden (ρ ≈ -0.28 to -0.33), and BL impairments were associated with worse fatigue and depressive symptoms at FU (e.g., Fmean-PHQ-9: β = -0.11, p = 0.022; fatigue ratio-FSS: β = 1.66, p = 0.008). Exploratory analyses suggested slightly higher NfL and GFAP levels in PCS in some models, without consistent associations with muscle function or symptoms.

CONCLUSIONS

HGS is persistently reduced in PCS over at least six months and aligns with symptom burden. Multidimensional HGS assessment may provide a practical objective marker of functional impairment and symptom persistence in PCS. Neuroaxonal injury markers showed modest elevations in PCS in some analyses but appeared unrelated to muscle performance, suggesting partially distinct mechanisms.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT05635552. Registered 1 December 2022 - Retrospectively registered, https://clinicaltrials.gov/study/NCT05635552?term=NCT05635552&rank=1&tab=study.