Effect of Percutaneous Auricular Nerve Stimulation on Fatigue in Adults with Post-COVID Fatigue (PAuSing-pCF): Results of a Randomised, Sham-Controlled Trial
Background
Post-COVID fatigue (pCF) affects 2.3% of the UK population and causes physical and mental fatigue, impacting daily life. Management is largely adapted from chronic fatigue syndrome, with limited evidence in post-COVID populations. Fatigue in pCF is linked to dysfunction in central, peripheral, and autonomic nervous systems, suggesting a role for vagus nerve dysfunction. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive, home-based intervention, but its effectiveness in pCF remains unclear.
Methods
PAuSing-pCF was a single-site, single-blind, randomised, sham-controlled trial in adults with pCF. Participants were assigned to active non-invasive vagus nerve stimulation (taVNS), sham tragus, or active pinna stimulation for 8 weeks, then all crossed over to taVNS for another 8 weeks. The primary outcome was change in Fatigue Visual Analogue Scale (F-VAS) at 8 weeks. Analyses used an intention-to-treat basis, applying regression and mixed-effects models, with additional complier average causal effect (CACE) analyses. Secondary outcomes included patient-reported questionnaires and neurophysiological measures from wearable devices.
Results
Of 114 participants (taVNS n = 39; sham n = 36; placebo n = 39), 90 completed the trial. Fatigue decreased over time across all groups.
At 8 weeks, F-VAS change did not differ between taVNS and controls (sham vs taVNS: 2.76, 95% CI −5 to 11, p = 0.50; placebo vs taVNS: 2.05, 95% CI −6 to 10, p = 0.62), with similar results in CACE analyses.
In the taVNS group, regression analyses showed associations between fatigue and baseline neurophysiological measures at 16 weeks, but not 8 weeks. Extending taVNS to 16 weeks yielded no further improvement.
Among secondary outcomes, only the fatigue impact scale score showed a significant effect at 8 weeks, with higher fatigue in placebo than taVNS.
Conclusions
Non-invasive vagus nerve stimulation did not significantly improve fatigue at 8 weeks compared to sham or placebo. Further research is needed to clarify mechanisms and identify subgroups who may benefit from neuromodulation in pCF.
Web | DOI | PDF | NIHR Open Research | Preprint
Shahmandi, Marzieh; Cherlin, Svetlana; Germann, Maria; Maffitt, Natalie J.; Burton, Olivia A.; Ashhad, Amn; Baker, Anne M. E.; Charlton, Norman; Baker, Aidan S.; Zaaimi, Boubker; Ng, Wan-Fai; Soteropoulos, Demetris S.; Baker, Stuart N.; Wason, James M.S.; Baker, Mark R.
Background
Post-COVID fatigue (pCF) affects 2.3% of the UK population and causes physical and mental fatigue, impacting daily life. Management is largely adapted from chronic fatigue syndrome, with limited evidence in post-COVID populations. Fatigue in pCF is linked to dysfunction in central, peripheral, and autonomic nervous systems, suggesting a role for vagus nerve dysfunction. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive, home-based intervention, but its effectiveness in pCF remains unclear.
Methods
PAuSing-pCF was a single-site, single-blind, randomised, sham-controlled trial in adults with pCF. Participants were assigned to active non-invasive vagus nerve stimulation (taVNS), sham tragus, or active pinna stimulation for 8 weeks, then all crossed over to taVNS for another 8 weeks. The primary outcome was change in Fatigue Visual Analogue Scale (F-VAS) at 8 weeks. Analyses used an intention-to-treat basis, applying regression and mixed-effects models, with additional complier average causal effect (CACE) analyses. Secondary outcomes included patient-reported questionnaires and neurophysiological measures from wearable devices.
Results
Of 114 participants (taVNS n = 39; sham n = 36; placebo n = 39), 90 completed the trial. Fatigue decreased over time across all groups.
At 8 weeks, F-VAS change did not differ between taVNS and controls (sham vs taVNS: 2.76, 95% CI −5 to 11, p = 0.50; placebo vs taVNS: 2.05, 95% CI −6 to 10, p = 0.62), with similar results in CACE analyses.
In the taVNS group, regression analyses showed associations between fatigue and baseline neurophysiological measures at 16 weeks, but not 8 weeks. Extending taVNS to 16 weeks yielded no further improvement.
Among secondary outcomes, only the fatigue impact scale score showed a significant effect at 8 weeks, with higher fatigue in placebo than taVNS.
Conclusions
Non-invasive vagus nerve stimulation did not significantly improve fatigue at 8 weeks compared to sham or placebo. Further research is needed to clarify mechanisms and identify subgroups who may benefit from neuromodulation in pCF.
Web | DOI | PDF | NIHR Open Research | Preprint
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