A pilot randomized controlled trial of supervised, at-home, self-administered transcutaneous auricular vagus nerve stimulation (taVNS) to manage long COVID symptoms

Abstract

Background Although the coronavirus disease 19 (COVID-19) pandemic has now impacted the world for over two years, the persistent secondary neuropsychiatric effects are still not fully understood. These “long COVID” symptoms, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), can persist for months after infection without any effective treatments. Long COVID involves a complex heterogenous symptomology and can lead to disability and limit work. Long COVID symptoms may be due to sustained inflammatory responses and prolonged immune response after infection. Interestingly, vagus nerve stimulation (VNS) may have anti-inflammatory effects, however, until recently, VNS could not be self-administered, at-home, noninvasively. Methods We created a double-blind, noninvasive transcutaneous auricular VNS (taVNS) system that can be self-administered at home with simultaneous remote monitoring of physiological biomarkers and video supervision by study staff. Subsequently, we carried out a pilot (n = 13) randomized, sham-controlled, trial with this system for four weeks to treat nine predefined long covid symptoms (anxiety, depression, vertigo, anosmia, ageusia, headaches, fatigue, irritability, brain fog). No in-person patient contact was needed, with informed consent, trainings, ratings, and all procedures being conducted remotely during the pandemic (2020–2021) and equipment being shipped to individuals’ homes. This trial was registered onClinicalTrials.gov under the identifier: NCT04638673. Results Four-weeks of at-home self-administered taVNS (two, one-hour sessions daily, delivered at suprathreshold intensities) was feasible and safe. Although our trial was not powered to determine efficacy as an intervention in a heterogenous population, the trends in the data suggest taVNS may have a mild to moderate effect in reducing mental fatigue symptoms in a subset of individuals. This innovative study demonstrates the safety and feasibility of supervised self-administered taVNS under a fully contactless protocol and suggests that future studies can safely investigate this novel form of brain stimulation at-home for a variety of neuropsychiatric and motor recovery applications.

Understanding the Pivotal Role of the Vagus Nerve in Health from Pandemics

“…A recent double-blind, sham-controlled pilot study assessed the impact of a four-week at-home treatment with self-administered electrical transcutaneous auricular vagus nerve stimulation (Soterix Medical, Inc. (Woodbridge, New Jersey, United States); 25 Hz, 500 μs pulse width, tonically on for 1 h, twice daily, 6 days per week, twice individual perceptual threshold intensity) to manage long-COVID symptoms. This VNS treatment was not only safe and highly compliance-rated, but also revealed interesting trends in reducing mental fatigue scores [ 115 ]. Therefore, transcutaneous auricular VNS appears to be a promising therapeutic option to manage chronic fatigue syndrome.…”

Vagus Nerve Stimulation for the Treatment of Post–COVID-19 Condition

“…1 Early evidence from similar devices suggests that noninvasive neurostimulation could help alleviate some symptoms related to the long-term effects of COVID-19. 13,14 Who Might Benefit?…”

“…A preprint paper from the US reported results from a study where people with at least 1 symptom associated with post-COVID-19 condition self-administered noninvasive vagus nerve stimulation (using a device similar to the Dolphin Neurostim) at home. 13 In total, 24 people were assigned to either a sham or active treatment group for a 4-week study period, with each group having 12 participants. The study reported that the participants confidently administered the therapy without assistance after 3 days of guided virtual sessions.…”

“…The results suggested that after 4 weeks, people in the active treatment group may have experienced greater symptoms reduction than those in the sham group; however, the study was not powered to compare results between the study groups. 13 A pilot study in France used semipermanent needles to the ear to administer vagus nerve stimulation or a sham treatment to patients admitted into hospital with severe cases of acute infection of No differences in clinical outcomes were observed between the 2 groups over a 14-day study period. However, the study was not powered to detect clinically meaningful differences.…”

Association of Heart Rate Variability with Pulmonary Function Impairment and Symptomatology Post-COVID-19 Hospitalization

“…A few studies with a small sample sizes have shown that patients suffering from PCC had a range of functional and/or structural alterations in the vagus nerve, supporting the existence of a correlation between PCC and autonomic imbalance in which vagal nerve activity is decreased [20,21]. The activity of the vagus nerve can be indexed by the measurement of heart-rate-variability (HRV).…”