Vagus nerve stimulation (VNS) has been shown to be a potent modulator of pathologic immune reactions, specifically suppressing inflammatory cytokine levels via activation of the cholinergic anti-inflammatory pathway (CAP).

Viral infections are capable of producing an extreme immune reaction in the host. This inflammatory response is often referred to as a cytokine storm, which results in elevated levels of inflammatory cytokines. For example, interleukin (IL)-6. IL-6, which is produced by activated leukocytes and acts on several cell and tissue types, and is believed to be a key cytokine in COVID-19 severity and progression.

Symptomatic control has been complicated by concerns about inadvertent viral spread associated with the use of nebulizers and steroids. This realization has been suggested as a driving force behind the emergency use of nVNS to allow the patient to reduce and/or discontinue the use of opioid and cough suppressant medications.  

Two mechanisms are proposed for the use of VNS. 

1. The smooth muscles found in the walls of bronchi and bronchioles regulate the flow of air into the lungs. 
   When the inflammatory response is insufficient, bronchoconstriction develops and limits the flow of air to and from the lungs.
   VNS may inhibit  airway constriction via the parasympathetic-sympathetic reflex arc. This stimulates the afferent vagal nerve and results in the release of catecholamines that facilitates smooth muscle relaxation. 
2. The CAP is the inflammatory reflex arm of the vagus nerve. Evidence indicates that CAP stimulation leads to acetylcholine (ACh) binding to a-7-nicotinic ACh receptors (a7nAChRs), and resulting in a reduction in the production of the inflammatory cytokines (tumor necrosis factor-alpha, IL-1ß, and IL-6. 

(Staats et al., 2020)