HMGB1: A Potential Target of Nervus Vagus Stimulation in Pediatric SARS-CoV-2-Induced ALI/ARDS

Abstract

From the start of pandemics, children were described as the ones who were less affected by SARS-Cov-2 or COVID-19, which was mild in most of the cases. However, with the growing vaccination rate of the adult population, children became more exposed to the virus and more cases of severe SARS-CoV-2-induced ARDS are being diagnosed with the disabling consequences or lethal outcomes associated with the cytokine storm. Thus, we do hypothesize that some of the children could benefit from nervus vagus stimulation during COVID-19 ARDS through the inhibition of HMGB1 release and interaction with the receptor, resulting in decreased neutrophil accumulation, oxidative stress, and coagulopathy as well as lung vascular permeability. Moreover, stimulation through alpha-7 nicotinic acetylcholine receptors could boost macrophage phagocytosis and increase the clearance of DAMPs and PAMPs. Further rise of FGF10 could contribute to lung stem cell proliferation and potential regeneration of the injured lung. However, this stimulation should be very specific, timely, and of proper duration, as it could lead to such adverse effects as increased viral spread and systemic infection, especially in small children or infants due to specific pediatric immunity state and anatomical features of the respiratory system.

Keywords: ALI; COVID-19; HMGB1; SARS-CoV-2; pediatric.

Figure 1

Potential anti-inflammatory effect of vagus nerve stimulation. DAMPs, danger associated molecular patterns; PAMPs, pathogen associated molecular patterns; TLR, toll-like receptor; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells; HMGB1, High-mobility group box protein 1; RAGE, receptor for advanced glycation end product; TNFα, tumor necrosis factor alpha; IL, interleukin; α7nAChR, alpha 7 nicotinic acetylcholine receptor.