Fig. 1
From: Autonomic balance determines the severity of COVID-19 courses
The cholinergic anti-inflammatory pathway (CAP) and its impairment in the case of SARS-2-CoV infection. Cellular virus invasion leads despite local liberation of pro-inflammatory cytokines (i.e. IL 1β, IL 6, IL 8, TNF α) to afferent vagal signaling. In central vagal structures (solitary nucleus (NTS), dorsal motor nucleus of the vagus (DMV)) this signal is after receiving (NTS) and interactional communication to different central instances via a M1 agonist responsive cholinergic brain network transformed into an appropriate efferent vagal impulse (DMV), which is liberating acetylcholine (ACh) at the spot of injury. Thus, cytokine distribution is controlled by somatotopically vagal secreted acetylcholine (ACh) coupling to α7-nicotinergic-acetylcholine receptors (α7AChR´s), this way blocking the cytokine transcriptional factor nuclear factor kappa B (nf-κB). This mechanism is dependent on appropriate parasympathetic (vagal) representation within the autonomic nervous system (ANS). Depressed vagal tone leads to functional impairment of CAP with subsequent excessive cytokine distribution (cytokine storm) followed by tissue injury, pulmonal dysfunction, ARDS and immune paralysis, whereas in the case of ANS balance, controlled cytokine distribution is generating tissue repair and virus elimination