Effects of Non-invasive Vagus Nerve Stimulation on Inflammatory Markers in COVID-19 Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

The international healthcare community has encountered several difficulties because of the COVID-19 pandemic brought on by SARS-CoV-2. COVID-19 can lead to an abnormal immune response that features excessive inflammation, so targeting the vagus nerve through non-invasive vagus nerve stimulation (nVNS) may hold promise as an intervention. This meta-analysis aimed to examine the outcomes of using nVNS on different inflammatory biomarkers in COVID-19 patients. Up until May 2023, we performed a review of online databases. We included randomized controlled trials (RCTs) that discussed how nVNS affected patients with COVID-19's clinical outcomes. Using the Revman 5.4 software (Cochrane, London, United Kingdom), a meta-analysis was carried out to find the pooled mean difference (MD), with 95% confidence intervals (CIs), of nVNS effects on different inflammatory biomarkers, including interleukin-10 (IL-10), C-reactive protein (CRP), IL-6, and cortisol levels. The review included four RCTs involving 180 COVID-19 patients. Following nVNS treatment, there was a significant increase in IL-10 levels (MD = 1.53, 95% CI: 0.77, 2.29; p < 0.001). CRP levels (MD = -2.24, 95% CI: -4.52, 0.05; p = 0.06), IL-6 levels (MD = 4.07, 95% CI: -3.16, 11.32; p = 0.27), cortisol levels (MD = 1.45, 95% CI: -11.67, 14.57; p = 0.83), and D-dimer levels (MD = -0.47, 95% CI: -1.31, 0.38; p = 0.28) did not differ significantly. These findings suggest that nVNS may positively impact certain inflammatory markers in COVID-19 patients, suggesting that nVNS could be a beneficial adjunctive treatment.