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Microbes & Immunity Benefit of noninvasive VNS in vaccine optimization

modalities of noninvasive stimulation are possible, in infants <2 months of age has been associated with
including transcutaneous (noninvasive) stimulation of the profound central autonomic dysfunction with alteration of
cervical or the auricular vagus nerve, surgical implantation, the entire frequency spectrum of HRV concomitant with
and natural methods such as Safe and Sound Protocol apparent life-threatening events and/or prolonged apnea.
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(SSP). Interestingly, transcutaneous noninvasive vagus Moreover, preterm birth by itself confers an even lower
4,5
nerve stimulation (VNS) is well tolerated in infants and vagal tone, possibly contributing to vulnerability in this
has been assessed successfully in different indications, at-risk population. SARS-CoV-2 has also been shown to
24
6
including neonatal opioid withdrawal syndrome and cause bronchiolitis requiring hospitalization. 25
neurorehabilitation. Introducing noninvasive VNS in Exposure to multiple viruses, such as SARS-CoV-2
7,8
infants and young children as an innovative prophylaxis and RSV, would worsen inflammation, lower HRV, and
against both SARS-CoV-2 and respiratory syncytial virus may result in increased morbidity and mortality. Severe
(RSV) responsible for recurrent outbreaks, as well as to
inhibit hyperinflammatory reactions that can occur during COVID-19 illness among children with comorbidities is
vaccinations, could potentially mitigate disease severity noted in roughly 30% of cases with underlying conditions
and inflammatory reactions in this vulnerable population. such as type 1 diabetes, obesity, cardiac or circulatory
congenital abnormalities, and prematurity (for children
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2. Heart rate variability (HRV) for predicting aged <2 years). All these risk factors are also correlated
survival and identifying vulnerable with a lower vagal tone and HRV. 27-34 It has been
pediatric populations hypothesized that the increased morbidity observed in
these at-risk populations results from a disruption of the
HRV, an index of vagus nerve activity, reflects autonomic cholinergic anti-inflammatory pathway by SARS-CoV-2,
nervous system (ANS) dynamics. Low HRV is related to leading to cytokine storm. 2,35-37
9
enhanced sympathetic and/or attenuated parasympathetic
cardiac modulation, notably during stress. Thus, low 3. A putative “all-in-one” solution against
HRV has been correlated to inflammation (resulting, SARS-CoV-2 recurrent infections and/or
among others, from the host immune response). A robust co-infections
inverse relation between the high-frequency power of the
HRV (HF-HRV), interleukin-6, C-reactive protein, and Unlike the RNA vaccines, noninvasive VNS does not
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fibrinogen, with or without covariate adjustment, was target the virus but the host’s defense systems, offering
10
confirmed in a large study involving 836 adults. Low a broad protection against reactions to several pathogens.
HRV is used to prognosticate disease severity, and an early Noninvasive VNS appears particularly relevant not only
39
marker of disease in many populations, including neonates for virulent new variants, but also in response to waning
or COVID-19 patients. 11,12 viral immunity to several common viruses like RSV
caused by the lack of exposure due to isolation during the
Moreover, a direct correlation between HF-HRV and COVID-19 pandemic. Consequently, preventive vagal
40
vagus neuronal electrical activity has been established tone optimization through noninvasive VNS is likely to
in anesthetized rats experiencing an acute baroreflex improve the viral infection outcome in children under
response. Thus, VNS could potentially modulate HRV. As 2 years of age.
13
expected, noninvasive VNS proved to be fully able to increase
HRV in healthy volunteers 14-16 as well as in patients. 17-19 Interestingly, conventional physical therapy and
Since vagal activity upregulates type I interferon response nasotracheal suction, currently used in acute bronchiolitis
41
genes concurrently with downregulation of inflammation for airway clearance, do improve HRV. Thus, it is likely
in human immune cells, by increasing HRV, noninvasive that noninvasive VNS will have a positive preventive effect
20
VNS likely protects against viral infections. Infants and against severe RSV infection.
young children under 2 years old are vulnerable against Moreover, noninvasive VNS has already been
several recurrent pathogens, like the “old” RSV or the more introduced in several clinical trials as an adjunctive therapy
recent SARS-CoV-2 variants. to prevent respiratory failure or cytokine storm during the

Indeed, RSV is a major cause of bronchiolitis-linked COVID-19 pandemic. 2,42-46 Of note, the results released by
morbidity. Risk factors for RSV encompass younger age, the prestigious Harvard Medical School Neuromodulation
21
prematurity, co-infection, and comorbidity. Without Center hold significant promise, lending support to
47
48
considering premature infants, RSV is annually responsible incorporating noninvasive VNS for pediatric use. Indeed,
for the hospitalization of one in every 56 healthy term- a functional interaction between α7nAChR and a region
born infants in high-income settings. RSV infection of the SARS-CoV-2 spike protein (S) (using whole-cell
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Volume 1 Issue 1 (2024) 52 doi: 10.36922/mi.2598