Page 165 - GHES-2-3

Global Health Economics and
Sustainability
Vagal tone restoration for LC

et al., 2020), neurological dysfunction in the brainstem References
and vagus nerve (Lladós et al., 2023), blood–brain Al-Aly, Z., & Topol, E. (2024). Solving the puzzle of Long Covid.
barrier disruption (Yang et al., 2018), and mitochondrial Science, 383(6685):830-832.
dysfunction (Kim et al., 2022).
https://doi.org/10.1126/science.adl0867
Finally, the nVNS approach has the potential to
address healthcare needs in both developing and Bohlson, S.S., O’Conner, S.D., Hulsebus, H.J., Ho, M.M., &
developed countries. Whether through transcutaneous Fraser, D.A. (2014). Complement, C1q, and C1q-related
or percutaneous methods, electrical or mechanical molecules regulate macrophage polarization. Frontiers in
Immunology, 5:402.
stimulation of the auricular or cervical branch of the
vagus nerve offers safe, patient-centered solutions that are https://doi.org/10.3389/fimmu.2014.00402
simple to implement, portable, and affordable (Rangon Cervia-Hasler, C., Brüningk, S.C., Hoch, T., Fan, B., Muzio, G.,
et al., 2021). Given that vaccines do not uniformly prevent Thompson, R.C., et al. (2024). Persistent complement
COVID-19, harnessing nVNS could prove beneficial and dysregulation with signs of thromboinflammation in active
equitable in managing both the acute and chronic phases Long Covid. Science, 383(6680):eadg7942.
of SARS-CoV-2 infection (Rangon & Staats, 2024). Heart https://doi.org/10.1126/science.adg7942
rate variability, an easy-to-monitor index of vagal tone
(notably with smartphones), meets all criteria to become Jakob, M.O., Murugan, S., & Klose, C.S.N. (2020). Neuro-
immune circuits regulate immune responses in tissues and
the eagerly awaited comprehensive marker of LC (Al-Aly organ homeostasis. Frontiers in Immunology, 11:308.
& Topol, 2024). Indeed, heart rate variability assessment
could help to distinguish between different LC subtypes https://doi.org/10.3389/fimmu.2020.00308
besides the prediction of prognosis (Rangon & Staats, Jin, H., Li, M., Jeong, E., Castro-Martinez, F., & Zuker, C.S. (2024).
2024), even in countries where resources for research and A body-brain circuit that regulates body inflammatory
clinical care might be scarce. responses. Nature, 630(8017):695-703.
To date, only nine clinical trials have been launched https://doi.org/10.1038/s41586-024-07469-y
worldwide, including one at the prestigious Mayo Kim, S., Park, I., Lee, J.H., Kim, S., Jang, D.H., & Jo, Y.H.
Clinic (NCT05445427) and notably, two in Turkey (2022). Vagus nerve stimulation improves mitochondrial
(NCT05679505, NCT05764070). These studies are dysfunction in post-cardiac arrest syndrome in the asphyxial
relatively heterogeneous and have enrolled a limited cardiac arrest model in rats. Frontiers in Neuroscience,
number of patients, likely due to the constrained funding 16:762007.
available for clinical trials assessing non-pharmacological https://doi.org/10.3389/fnins.2022.762007
interventions in LC. Nevertheless, one of these pilot trials
has recently been published (Zheng et al., 2024), revealing Kumaria, A., & Ashkan, K. (2023). Neuromodulation as an
significant improvements in various cognitive functions, anticancer strategy. Cancer Medicine, 12(21):20521-20522.
anxiety, depression, and sleep, with benefits persisting or https://doi.org/10.1002/cam4.6624
even progressing at a 1-month follow-up. Lladós, G., Massanella, M., Coll-Fernández, R., Rodríguez, R.,
Given these promising results, research on nVNS Hernández, E., Lucente, G., et al. (2023). Vagus nerve
in LC definitely deserves stronger financial support dysfunction in the post-COVID-19 condition : A pilot
from international stakeholders, notably to promote cross-sectional study. Clinical Microbiology and Infection,
30(4):515-521.
decentralized clinical trials, which allow research to be
conducted outside academic centers, anywhere in the https://doi.org/10.1016/j.cmi.2023.11.007
world. Funding these trials could be a profitable investment, Nakamura, Y., Matsumoto, H., Wu, C.H., Fukaya, D., Uni, R.,
potentially leading to more advanced treatments for Hirakawa, Y., et al. (2023). Alpha 7 nicotinic acetylcholine
chronic diseases, including neurodegenerative disorders receptors signaling boosts cell-cell interactions in
(Rangon et al., 2020) and cancers (Kumaria & Ashkan, macrophages effecting anti-inflammatory and organ
2023). protection. Communications Biology, 6(1):666.
https://doi.org/10.1038/s42003-023-05051-2
Conflict of interest
Papadopoulou, M., Bakola, E., Papapostolou, A., Stefanou, M.I.,
Peter Staats owns patents on VNS for viral infections Andreadou, E., Zouvelou, V., et al. (2023). Autonomic
such as COVID-19 and is the founder of the company dysfunction entwined with post-COVID but absent in
electroCore. Meanwhile, Claire-Marie Rangon declares no non-post-COVID patients: A neurophysiological and
competing of interests. neurosonology study. Therapeutic Advances in Neurological

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