Vagal nerve stimulation for the management of long COVID symptoms
Malik Waleed Zeb Khan, Muhammad Ahmad, Salma Qudrat, Fatma Afridi, Najia Ali Khan, Zain Afridi, Fahad, Touba Azeem, Jibran Ikram
Abstract
• Vagal nerve stimulation (VNS) has the potential to alleviate persistent long COVID symptoms. • The sensory receptors on the vagus nerve can be activated by the cytokine storm associated with COVID-19, contributing to the “involuntary sickness response” that leads to chronic symptoms in long COVID. • Non-invasive VNS techniques (nVNS) provide safe options for managing persistent COVID-19 symptoms with minimal side effects. • The current evidence for VNS as a potential treatment for long COVID is limited and largely based on small pilot studies, underscoring the need for future research to evaluate its effectiveness. This review investigates the therapeutic potential of vagal nerve stimulation (VNS) in managing long COVID, a condition marked by persistent symptoms following acute SARS-CoV-2 infection. Long COVID manifests as ongoing fatigue, cognitive impairment, and autonomic dysfunction, hypothesized to arise from sustained inflammatory and neurological dysregulation. The vagus nerve, central to modulating systemic inflammation and autonomic homeostasis, represents a promising therapeutic target for symptom alleviation through VNS. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science to identify studies evaluating VNS in the context of long COVID. Preliminary evidence from small-scale pilot studies suggests VNS may attenuate systemic inflammation through activation of the cholinergic anti-inflammatory pathway (CAP), thus restoring autonomic balance and ameliorating symptoms such as fatigue, cognitive dysfunction, and anxiety. In targeting the inflammatory cascade that underlies both acute COVID-19 pathophysiology and its prolonged sequelae, VNS holds potential as an innovative intervention for persistent post-viral symptoms. While these initial findings indicate promise, current data remain limited in scope and robustness, underscoring the need for larger, controlled trials to validate the efficacy and mechanisms of VNS in long COVID management. Establishing a clearer understanding of VNS's impact on inflammation and autonomic regulation in this context is crucial to inform clinical guidelines and therapeutic strategies for long COVID, potentially offering a targeted approach for mitigating this disabling condition.