Transcutaneous Auricular Vagal Nerve Stimulation Against Fatigue Syndrome in Patients with Long COVID…, 2026, Gierthmuehlen+

[SNT Gatchaman]

Transcutaneous Auricular Vagal Nerve Stimulation Against Fatigue Syndrome in Patients with Long COVID: Results of the Randomized, Placebo-Controlled Clinical Pilot Trial COVIVA

Spoiler: Authors

Gierthmuehlen, Mortimer; Schmieder, Kirsten; Thon, Niklas; Gierthmuehlen, Petra Christine

INTRODUCTION
Fatigue is the most prevalent symptom in “long COVID”, affecting 6–7% of patients after COVID-19 infection. Its pathophysiology remains unclear, with viral persistence, immune dysregulation, and mitochondrial dysfunction among proposed mechanisms. Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive neuromodulatory approach, has been suggested as a potential treatment.

METHODS
We conducted a randomized, sham-controlled, single-blinded pilot study to evaluate adherence and clinical effects of taVNS in long COVID-related fatigue. Forty-five patients were randomized 1:1:1 to sham stimulation, sub-threshold taVNS, or above-threshold taVNS for 4 weeks using the Conformite Europeenne (CE)-certified tVNS-L device (25 Hz, 250 µs, 4 h/day). The primary co-endpoints were fatigue severity (MFI-20) and adherence, defined as mean daily stimulation duration. Secondary endpoints included depressive symptoms (BDI-II), health-related quality of life (SF-36), and post-COVID symptom burden (PCS).

RESULTS
Of 45 enrolled patients (mean age 42.4 years; 73% female), 4 (8.9%) dropped out early. Mean stimulation time was 236 min/day, fulfilling the adherence criterion in > 80% of participants. Adverse events were mild, including skin irritation (6.7%) and vertigo (6.7%). Across all groups, questionnaire scores improved over time; however, no statistically significant differences were observed between the sham and active stimulation groups. Baseline fatigue and quality-of-life scores were markedly impaired compared with normative data.

CONCLUSION
taVNS was safe, feasible, and associated with high adherence in long COVID-related fatigue, but showed no superiority over sham stimulation. Larger multicenter trials with more homogeneous populations and objective biomarkers are required to determine whether taVNS confers therapeutic benefit in this condition.

TRIAL REGISTRATION
The trial was approved by the ethics committee (23/7798) and registered at the German Clinical Trials Register, identifier DRKS00031974.

Web | DOI | PDF | Neurology and Therapy | Open Access

 

[SNT Gatchaman]

Participants in this group received sham stimulation. During the initial instruction session, patients were familiarized with the sensation of active stimulation in the left ear. Subsequently, the intensity was reduced until no tingling is perceived. In contrast to Verum1, participants were instructed to maintain this setting. Without their awareness, they were then provided with a non-functional placebo electrode for home use. Stimulation was prescribed for 4 h per day, with sessions lasting at least 1 h each, in the left ear.

During the blinding process, patients were subsequently informed more explicitly that allocation to one of three possible groups was determined by a randomization procedure. It was clearly explained that participants would not perceive stimulation in two of the groups, whereas stimulation would be noticeable in one group; however, this perception would not allow reliable conclusions as to whether they were assigned to the active or a control condition.

By assuring participants that, in the event of allocation to a control group, they would subsequently receive a guaranteed 4-week period of active stimulation, participant compliance increased substantially. Following this adjustment, no further critical concerns were raised by participants.

Across the study population, we observed improvements in nearly all domains of the fatigue, quality-of-life, and depression questionnaires. Nevertheless, no differences were detected between the intervention and control groups. It therefore remains uncertain whether the purely clinical diagnosis of “fatigue” in long COVID reflects the same underlying pathophysiological mechanisms as fatigue observed in autoimmune conditions.

 

[ChronicallyOverIt]

4 hours a day?? Back in my snake oil days I did this, at most 20min a day. It’s even recommended by many ME/CFS patients to go super super slow working up a few min at a time. I did a longer session once cause I read a POTS paper where they did a hour, and it irritated my ear nerve so bad. My ear was buzzing pain on and off lightly for 2 weeks. I stopped after that.

 

[Felis Catus]

4 hours a day?? Back in my snake oil days I did this, at most 20min a day. It’s even recommended by many ME/CFS patients to go super super slow working up a few min at a time. I did a longer session once cause I read a POTS paper where they did a hour, and it irritated my ear nerve so bad. My ear was buzzing pain on and off lightly for 2 weeks. I stopped after that.

Yes, that's a common advice in patient groups.

A couple of years ago, a doctor told me if I was to use it, I should be using it at least 4h a day. So I'm curious where that comes from.

I briefly opened the paper and didn't see a reference next to 4h in Methods and search on my phone missed all occurrences of "4h" and "4h/day". It's too inconvenient for me to go through the references on my phone but I might do it if I remember when I'm able to use the laptop again :/

 

[Trish]

I thought one of the main aims of pilot studies was to see whether there was any sign of efficacy to inform decisions about future studies. It's clear from this pilot that there's no efficacy, so why suggest a larger trial. Surely that would just be a waste of money and everyone's efforts.

 

[Felis Catus]

Note the authors are based in Germany - another candidate for funding from the National Decade Against Post-Infectious Diseases.

 

[Utsikt]

Blue = sham, Red = verum1, Yellow = verum2

There is nothing here to indicate that the intervention has any effect.

The authors also appear to have some hostility towards the patients:

The discontinuation rate was higher than in other studies [23], which may be attributable to the more demanding and heterogeneous patient population.

By assuring participants that, in the event of allocation to a control group, they would subsequently receive a guaranteed 4-week period of active stimulation, participant compliance increased substantially. Following this adjustment, no further critical concerns were raised by participants.

Those pesky, critical and demanding patients..

Seems like they had some issues with the ethics committee as well:

This trial received ethical approval from the Ethics Commission Bochum (Reference number: 23/7798) on 12/05/2023. The approved version of the study protocol is version 5.

 

[rvallee]

Across the study population, we observed improvements in nearly all domains of the fatigue, quality-of-life, and depression questionnaires. Nevertheless, no differences were detected between the intervention and control groups.

taVNS ... showed no superiority over sham stimulation

no statistically significant differences were observed between the sham and active stimulation groups. Baseline fatigue and quality-of-life scores were markedly impaired compared with normative data.

Larger multicenter trials with more homogeneous populations and objective biomarkers are required to determine whether taVNS confers therapeutic benefit in this condition.

This industry is a sham. What the hell are they even doing? How is no one involved able to see how this is completely broken? Who is this even for??! And as usual for something that isn't even plausible, that did not even warrant a pilot trial.