Page 164 - GHES-2-3

Global Health Economics and
Sustainability

LETTER TO EDITOR
Global solutions for long COVID: The necessity of

sustainable vagal tone restoration

Claire-Marie Rangon * and Peter Staats 2
1
1 One Clinic, Child Neurology, Montmorency, France
2 Office of the Chief Medical Officer, National Spine and Pain Centers, Atlantic Beach, Florida, United
States of America

Long COVID (LC) is a major global health challenge, threatening not only the quality
of life but also the ability to work for a growing number of individuals who are still
awaiting effective therapeutic solutions. Interestingly, the repurposing of non-invasive
vagus nerve stimulation (nVNS) offers a sustainable paradigm to alleviate the economic
burden of LC. This is particularly relevant given that two recent studies, published in
Science (Al-Aly & Topol, 2024; Cervia-Hasler et al., 2024), have highlighted the potential
of addressing microbiome dysbiosis and complement dysfunction – two domains where
nVNS has shown efficacy – as crucial strategies for solving LC. Nevertheless, despite
these compelling insights, there has yet to be a renewed impetus for clinical trials
investigating nVNS in the context of LC, even though nVNS is a validated, ready-to-use,
safe, and affordable therapeutic tool. This letter aims to emphasize the scientific rationale
for accelerating research on the use of nVNS in LC, on a global scale.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has
Academic editor: been shown to induce long-lasting disruptions in the gut microbiota, specifically in
Mihajlo Jakovljevic M.D. Ph.D. MAE COVID-19-recovered patients who subsequently develop LC (Zhang et al., 2023).
*Corresponding author: Nevertheless, vagotomy experiments have convincingly demonstrated that the integrity
Claire-Marie Rangon of the vagus nerve is necessary for mediating the effects of gut microbiota changes on
(dr.clairemarierangon@one.fr)
brain functions, thereby maintaining homeostasis (Siopi et al., 2023). Moreover, recent
Citation: Rangon, C., & Staats, P. research published in Nature acknowledges the vagus nerve as a pivotal component of
(2024). Global solutions for
long COVID: The necessity of the body–brain circuit that regulates the immune response (Jin et al., 2024). Consistent
sustainable vagal tone restoration. with this, selective atrophy of the vagus nerve has been observed in patients with LC
Global Health Econ Sustain, (Papadopoulou et al., 2023), alongside the activation of complement pathways and
2(3):3556.
https://doi.org/10.36922/ghes.3556 platelets (Cervia-Hasler et al., 2024). The complement system plays a critical role in
both gut microbiota composition (Petrisko et al., 2023) and macrophage polarization
Received: May 1, 2024
(Bohlson et al., 2014). Interestingly, macrophages that produce complement proteins
Published Online: September 9, (Pendse et al., 2023) and contribute to inflammation can also express the α7-nicotinic
2024 acetylcholine receptor (α7nAChR), a key protein in the cholinergic anti-inflammatory
Copyright: © 2024 Author(s). pathway that links the nervous and immune systems, thereby providing organ protection
This is an Open-Access article (Nakamura et al., 2023).
distributed under the terms of the
Creative Commons Attribution Vagus nerve stimulation (VNS) can efficiently activate the α7nAChR on complement-
License, permitting distribution,
and reproduction in any medium, producing macrophages (Sévoz‐Couche et al., 2024), which, in turn, inhibits the
provided the original work is production of proinflammatory cytokines (Pendse et al., 2023), while leaving anti-
properly cited. inflammatory cytokines unaffected. Besides, α7nAChR is expressed by platelets
Publisher’s Note: AccScience (Schedel et al., 2011) and several other cell types, supporting VNS-mediated mitigation
Publishing remains neutral with of the multiple etiologies underpinning LC pathogenesis (Rangon, 2024), including
regard to jurisdictional claims in
published maps and institutional coagulation disorders (Van Westerloo et al., 2006), microbiota dysbiosis (Zhou et al.,
affiliations. 2013), autoimmune conditions, immune dysregulation fostering viral reservoirs (Jakob

Volume 2 Issue 3 (2024) 1 https://doi.org/10.36922/ghes.3556