Transcutaneous vagus nerve stimulation improves Long COVID symptoms in a female cohort: a pilot study

Abstract

Background: Long COVID, also known as Post-COVID-19 syndrome, is characterized by multisystemic symptoms that persists for weeks to years beyond acute infection. It disproportionately affects women and those with pre-existing anxiety/depression, conditions more prevalent in females. The vagus nerve, with its extensive innervation and regulation of critical bodily functions, has become a focal point for therapeutic interventions. Transcutaneous vagus nerve stimulation (t-VNS) has emerged as a promising non-invasive treatment for COVID-19 conditions.

Methods: This pilot study assessed the efficacy of t-VNS in 24 female Long COVID patients (45.8 ± 11.7 years old; 20.2 ± 7.1 months since infection), who underwent a 10-day t-VNS intervention at home (30 min/session, twice a day). Cognition was considered the primary outcome, with anxiety, depression, sleep, fatigue, and smell as secondary outcomes. Outcomes were measured at baseline, post-intervention, and 1-month follow-up.

Results: Significant improvements were observed in various cognitive functions, anxiety, depression, and sleep at post-intervention, with benefits remaining or progressing at 1-month follow-up. Improvements in fatigue were delayed, reaching statistical significance at 1-month follow-up compared to baseline. No significant changes were noted in olfactory performance.

Conclusion: This pilot study provides preliminary evidence supporting the potential of t-VNS as a therapeutic intervention for female Long COVID patients. The encouraging results justify further rigorous investigation through larger, randomized controlled trials to confirm the efficacy of t-VNS, assess its generalizability to male cohorts, and explore biological markers to inform personalized treatment approaches. Our findings support the allocation of resources to conduct such trials and advance the understanding of t-VNS as a potential treatment for Long COVID.

Keywords: Long COVID; fatigue; female health; mood and cognition; neuromodulation; sleep; transcutaneous vagus nerve stimulation (t-VNS).

Figure 1

CONSORT flow diagram for a single-group pilot study.

Figure 2

Prevalence of Long COVID symptoms at baseline. Brain fog (cognitive impairment) was an inclusion criterion; thus it is reported in all participants.

Figure 3

T-VNS intervention outcomes. This figure illustrates changes in cognition, anxiety, depression, fatigue, and sleep across three timepoints: pre-intervention, post-intervention, and 1-month follow-up. Boxplots are used for primarily nonparametric data, whereas column graphs depict parametric data. Error bars reflect standard error. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001.