Tragus Nerve Stimulation Attenuates Postural Orthostatic Tachycardia Syndrome in Post COVID-19 Infection, 2025, Zhuo Wang et al

[Mij]

ABSTRACT
Background
Postural orthostatic tachycardia syndrome (POTS) is characterized by symptoms of orthostatic intolerance and is frequently observed in post-COVID conditions.

Objectives
We conducted controlled, prospective, and randomized clinical trials to explore the potential therapeutic benefits of low-level tragus stimulation (LL-TS) in patients with POTS following COVID-19 infection.

Methods
This study enrolled 57 participants with confirmed post-acute COVID-19 who had been diagnosed with POTS. The ear clip was attached to the right tragus of the patients for stimulation (20 Hz with a 1-ms duration) or sham stimulation. They were divided into two groups: the sham LL-TS group (sham stimulation, n = 26) and the LL-TS group (stimulation for 1 month, n = 31). LL-TS was performed 1 h twice daily for 1 month. Postural tachycardia was evaluated at baseline, 1-month visit, and 1-year visit. Heart rate variability (HRV) and plasma neuropeptide Y (NPY) were evaluated at respective time points.

Results
The mean age of participants was 31.9 ± 7.2 years (61.4% female). LL-TS significantly attenuated the increase in heart rate from supine to a 10-min stand, as well as the average and maximum heart rates after 1 month of treatment. LL-TS also significantly reduced NPY levels. In addition, LL-TS significantly increased the high frequency (HF), but decreased the low frequency (LF) and LF/HF ratio during the postural test (all p < 0.01). These effects persisted during the 1-year follow-up.

Conclusion
LL-TS may be a promising therapeutic approach for attenuating autonomic imbalance in patients with POTS following COVID-19 infection.
LINK

 

[Utsikt]

Grey = treatment group

 

[Utsikt]

They did not measure symptoms related to POT, which is a shame.

It’s surprising that the changes lasted for so long.

 

[Hutan]

A study from Wuhan, China.

Low-level tragus stimulation (LL-TS) is an innovative strategy for selectively activating afferent branches of the vagus nerve through electrical stimulation of specific areas of the external ear [8]. LL-TS has emerged as a novel nonpharmacological approach for treating neuropsychiatric and cardiovascular disorders [9, 10].

LL-TS targets the afferent branches of the vagus nerve to enhance parasympathetic activity while simultaneously reducing sympathetic overactivity.

Neuropeptide Y (NPY), being co-released with norepinephrine from sympathetic nerve fibers, can indirectly reflect changes in sympathetic activity.

Last time we looked, studies of tragus stimulation were flawed and unreliable. The tragus is just the pointy bit of cartilage in front of the ear canal - so, up from the ear lobe, but on the face side of the ear, rather than on the side of the ear that flaps around in the wind. Last time we looked, it was not at all clear that a clip on the tragus would do anything to the vagus nerve. Also, last time we looked, the devices providing stimulation were expensive and being aggressively marketed.

All patients provided informed consent before enrollment in the study. The study complies with the Declaration of Helsinki, and the institutional Ethics Committee of Xiangyang Central Hospital reviewed and approved the study, waiving the requirement for patient consent (approval number: 2023-018).

That's a bit weird. It's not clear what the patients actually consented to.

Selection criteria:

Patients eligible for enrollment in the study met the criteria for POTS after acute COVID-19 infection, which was defined as an increase in HR of > 30 bpm within 10 min of standing from the supine position, without orthostatic hypotension (defined as a drop in blood pressure > 20/10 mmHg), exhibiting chronic symptoms lasting > 3 months and in the absence of any acute cause of orthostatic tachycardia [3, 4, 11].

So, 57 patients, all with POTS. Two groups, one given real tragus stimulation and the other given sham tragus stimulation.
Outcomes are the neuropeptide Y, heart rate variability and heart rate (at baseline after 25 minutes supine , and after 10 minutes standing). It is a shame that there is no global measure of quality of life. I'm surprised there were not more things measured in the blood sample, perhaps they were, but only the NPY is reported?

Measurements at baseline, the end of 1 month of treatment and at 1 year followup.

 

[Hutan]

2.4 The Effects of LL-TS on HR Changes During the 24 h-Holter

There was no significant difference in minimum HR during the 24-h Holter monitoring between the LL-TS group and the sham LL-TS group at baseline. The minimum and maximum HR were significantly decreased at 1 month and 1 year in the LL-TS group compared with the sham LL-TS group (all p < 0.05), as shown in Figure 4. In the LL-TS group, the minimum and maximum HR at 1 month were significantly reduced compared with that at the baseline (p < 0.05). In addition, the minimum and maximum HR at 1 year were significantly reduced compared with that at 1 month in the LL-TS group (p < 0.05).

The effects of LL-TS on HR during the 24 h-holter. (A) LL-TS had no effects on minimum HR during the 24 h-holter. (B) LL-TS significantly decreased the average HR during the 24 h-holter. (C) LL-TS significantly decreased the maximum HR during the 24 h-holter. HR, heart rate; △HR, HR at 10-min standing – HR at resting; LL-TS indicates low-level tragus stimulation; Max, maximum; Min, minimum. n = 26 in the sham LL-TS group, n = 31 in the LL-TS group.

There's an error in the text - there were no differences in the minimum heart rate recorded in the 24-hour holter measurements, neither at different measurement times or between groups. The bolded 'minimum's should be 'average'.

 

[Hutan]

Clinically, while POTS presents with orthostatic tachycardia as a hallmark feature, it also encompasses a broader range of symptoms associated with autonomic dysregulation, including headache, cognitive impairment, nausea, and gastrointestinal dysmotility. The potential mechanisms are likely related to an imbalance between sympathetic and parasympathetic activity, as well as hemodynamic abnormalities such as reduced systemic venous return, augmented splanchnic and extremity pooling, decreased cardiac output, and decreased cerebral perfusion. This dysregulation manifests as a decrease in parasympathetic tone and an increase in sympathetic activity, particularly during postural changes from supine to upright positions.

The differences look robust, the study seems to be mostly ok, apart from the glitch in wording I noted above. I didn't see any information about dropouts though, which may perhaps be driving the changes. The figure captions suggests that there were no dropouts, which would be very unusual. Also, it doesn't look as if the assessors were blinded.

There are no reported conflicts of interest. If one month use of the tragus stimulator permanently improved the POTS symptoms and that improvement continued for the next year until participants had almost normal responses to standing, it really would be a remarkable finding. I remain rather skeptical though.

 

[Hutan]

Here's our vagal nerve stimulation discussion thread, which includes a fair bit on tragus clips.

Vagus Nerve Stimulation

I haven't read over the thread in detail lately, but my impression is that members have mostly not reported it being the miracle cure that this study suggests it is. When they have reported initial improvements, it does not appear that the improvements have been sustained.

 

[Utsikt]

Here's our vagal nerve stimulation discussion thread, which includes a fair bit on tragus clips.

Vagus Nerve Stimulation

I haven't read over the thread in detail lately, but my impression is that members have mostly not reported it being the miracle cure that this study suggests it is. When they have reported initial improvements, it does not appear that the improvements have been sustained.

It might be that this study stumbled upon a sweet spot of 20 Hz with a 1-ms duration? I have not read the VNS thread yet.

 

[Hutan]

Does it make sense that the frequency that works (assuming it works, which I think is rather unlikely) would be exactly the same for everyone, regardless of their size, and other things?

 

[Utsikt]

Does it make sense that the frequency that works (if it works) would be exactly the same for everyone, regardless of their size, and other things?

I can only speculate, but I can imagine that the right frequency could be tied to the physical properties of the nervous system? I’m not sure if those are different in different people.

 

[rapidboson]

Looks like this study has also showed similar results:

Edit: posted elsewhere

https://www.sciencedirect.com/science/article/pii/S2405500X2300806X

 

[Utsikt]

Looks like this study has also showed similar results:

https://www.sciencedirect.com/science/article/pii/S2405500X2300806X

Discussed here:
https://www.s4me.info/threads/nonin...hycardia-syndrome-2023-stavrakis-et-al.36968/

 

[Yann04]

I’m not sure if the blinding was necessarily well done.

Because when my VNS is on I can feel a slight electrical tingling on my ear. I’m willing to bet since the “sham” was sending no current the controls didn’t feel that.

I really feel like they should be comparing frequencies instead of doing an impossible blinding.

 

[Utsikt]

Because when my VNS is on I can feel a slight electrical tingling on my ear. I’m willing to bet since the “sham” was sending no current the controls didn’t feel that.

According to other patients, the feeling depends on the Amp - you don’t feel it if it’s low enough. I can’t find the Amp figures in this study, though.

 

[Yann04]

According to other patients, the feeling depends on the Amp - you don’t feel it if it’s low enough. I can’t find the Amp figures in this study, though.

I honestly know nothing about electronics so Amp Frequency Volt make no sense to me.

I was sick with my COVID infection that eventually got me here when we were covering that in school haha. (So I’ll trust your judgement).

 

[Utsikt]

@Yann04 Here’s a brief summary in case anyone are interested.

Amp and Volt are two different measures of how much electricity that’s flowing through the cable. If you multiply them with eachother, you get Watts.

Higher Amp is like a wider water pipe, but the same water pressure. Higher Volt is like more water pressure, but the same size pipe. Higher Watts just means more water through the pipe in total, irrespective of how it was achieved.

Ohm is resistance, i.e. how ‘easy’ or ‘hard’ it is for the electricity to flow through the cable.

Hz (frequency) says how often the current switches from positive to negative. 60 hz = 60 switches in one second. This is only relevant for AC (alternate current). DC (direct current) doesn’t switch.