Targeting the cholinergic anti-inflammatory pathway with vagus nerve stimulation in patients with Covid-19?

Bruno Bonaz,Sonia Pellissier,Valérie Sinniger

doi:10.1186/s42234-020-00051-7

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), at the origin of the worldwide COVID-19 pandemic, is characterized by a dramatic cytokine storm in some critical patients with COVID-19. This storm is due to the release of high levels of pro-inflammatory cytokines such as interleukin (IL)-1 β, IL-6, tumor necrosis factor (TNF), and chemokines by respiratory epithelial and dendritic cells, and macrophages. We hypothesize that this cytokine storm and the worsening of patients’ health status can be dampened or even prevented by specifically targeting the vagal-driven cholinergic anti-inflammatory pathway (CAP). The CAP is a concept that involves an anti-inflammatory effect of vagal efferents by the release of acetylcholine (ACh). Nicotinic acetylcholine receptor alpha7 subunit (α7nAChRs) is required for ACh inhibition of macrophage-TNF release and cytokine modulation. Hence, targeting the α7nAChRs through vagus nerve stimulation (VNS) could be of interest in the management of patients with SARS-CoV-2 infection. Indeed, through the wide innervation of the organism by the vagus nerve, especially the lungs and gastrointestinal tract, VNS appears as a serious candidate for a few side effect treatment that could dampen or prevent the cytokine storm observed in COVID-19 patients with severe symptoms. Finally, a continuous vagal tone monitoring in patients with COVID-19 could be used as a predictive marker of COVID-19 illness course but also as a predictive marker of response to COVID-19 treatment such as VNS or others.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) first appeared in December 2019, in Wuhan, Hubei Province of China, and rapidly spread in a worldwide pandemic
SARS-CoV-2 ranges from asymptomatic disease to mild symptoms such as fever, sore throat, cough, loss of smell and taste, myalgia, headache, fatigue, to severe pneumonia with respiratory failure, acute
Proinflammatory responses play a role in the pathogenesis of human coronavirus

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) first appeared in December 2019, in Wuhan, Hubei Province of China, and rapidly spread in a worldwide pandemic. It can be a predictive marker of response to COVID treatment such as VNS It could be used as a predictive marker of COVID illness course with the idea that people with very low vagal tone at the onset of the symptoms may be at high risk to develop a dysregulated overstimulated pro-inflammatory response during the infection leading to sudden death or intensive care unit transfer. VNS could accelerate the post-COVID recovery and further VNS could reduce the posttraumatic stress syndrome classically described in such patients (Xiao et al 2020)

Conclusion

Findings

Availability of data and materials NA