Persistent Muscle Dysfunction 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, predictive models of symptom persistence, and matched cohort analyses of serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP).
RESULTS
Compared with 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 capacity (p = 0.04). Lower BL Fmean and higher fatigability predicted greater symptom burden at FU, including fatigue severity and overall PCS severity (standardized β 0.25–0.38; all p < 0.05). NfL and GFAP levels were modestly higher in PCS than in matched recovered controls but showed no association with muscle function.
CONCLUSIONS
Objective muscle dysfunction persists over at least six months in PCS and aligns with patient-reported symptom burden. Multidimensional HGS assessment may provide a practical objective marker of functional impairment and symptom persistence in chronic PCS. Neuroaxonal injury markers were modestly elevated in PCS but appeared unrelated to peripheral muscle dysfunction, suggesting partially distinct underlying mechanisms.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT05635552. Registered 1 December 2022 Retrospectively registered, https://clinicaltrials.gov/study/NCT05635552
Web | DOI | PDF | Preprint: Research Square | Open Access
Michael Wunderle; Andrea Ribeiro; Isabelle Lethen; Christoph Schmaderer; Timon Wallraven
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, predictive models of symptom persistence, and matched cohort analyses of serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP).
RESULTS
Compared with 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 capacity (p = 0.04). Lower BL Fmean and higher fatigability predicted greater symptom burden at FU, including fatigue severity and overall PCS severity (standardized β 0.25–0.38; all p < 0.05). NfL and GFAP levels were modestly higher in PCS than in matched recovered controls but showed no association with muscle function.
CONCLUSIONS
Objective muscle dysfunction persists over at least six months in PCS and aligns with patient-reported symptom burden. Multidimensional HGS assessment may provide a practical objective marker of functional impairment and symptom persistence in chronic PCS. Neuroaxonal injury markers were modestly elevated in PCS but appeared unrelated to peripheral muscle dysfunction, suggesting partially distinct underlying mechanisms.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT05635552. Registered 1 December 2022 Retrospectively registered, https://clinicaltrials.gov/study/NCT05635552
Web | DOI | PDF | Preprint: Research Square | Open Access