Table 1.
Summary of nVNS Trials Relevant to COVID-19.
| Study | Design | N | Findings relevant to COVID-19 |
|---|---|---|---|
| Respiratory clinical trials | |||
| nVNS for the treatment of acute asthma exacerbations (18) | Prospective, multicenter, open-label study | 4 | Ninety minutes after acute nVNS treatment, FEV1 improved from baseline by a mean of 73%, and mean VAS dyspnea score decreased from 8 (at baseline) to 1 |
| nVNS for the relief of acute bronchoconstriction due to asthma (25,34) | Prospective, multicenter, open-label study | 30 | Ninety minutes after acute nVNS treatment, 93% of patients reported improvement in VAS dyspnea score, and 86% had improvements in FEV1 |
| nVNS for the prophylactic treatment of COPD (19) | Prospective, single-center, randomized, controlled trial | 54 | After 8 weeks of daily treatment, the nVNS group had a significant increase from baseline in distance walked (9.9-m greater improvement than the sham group) on the 6MWT |
| Inflammatory clinical and mechanistic trials | |||
| nVNS decreases whole blood culture–derived cytokines and chemokines (20) | Randomized, blinded, pilot trial in healthy controls | 20 | Twenty-four hours after treatment, the nVNS group had a greater (vs the sham group) percentage decrease in levels of IL-1β, TNF, IL-6, IL-8, MIP-1α, and MCP-1 |
| Effects of nVNS on fatigue and immune responses in patients with primary Sjögren’s syndrome (21) | Prospective, single-center, open-label study | 15 | Ninety minutes after nVNS, levels of MIP-1α, IL-1β, TNF-α, IL-6, and IP-10 were significantly reduced on days 0, 7, and 28 of the study Twelve participants had an improvement in their fatigue scores, seven of whom had a ≥30% reduction in fatigue within 28 days |
6MWT, 6-minute walk test; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; FEV1, forced expiratory volume in one second; IL, interleukin; IP, interferon γ-induced protein; MCP, monocyte chemoattractant protein; MIP, macrophage inflammatory protein; nVNS, non-invasive vagus nerve stimulation; TNF, tumor necrosis factor; VAS, visual analog scale.