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Background: Covid-19 is an infectious disease caused by an invasion of the alveolar epithelial cells by coronavirus 19. The most severe outcome of the disease is the Acute Respiratory Distress Syndrome (ARDS) combined with hypoxemia and cardiovascular damage. ARDS and co-morbidities are associated with inflammatory cytokine storms, sympathetic hyperactivity, and respiratory dysfunction. Hypothesis: In the present paper, we present and justify a novel potential treatment for Covid19-originated ARDS and associated co-morbidities, based on the non-invasive stimulation of the auricular branch of the vagus nerve. Methods: Auricular vagus nerve stimulation activates the parasympathetic system including anti-inflammatory pathways (the cholinergic anti-inflammatory pathway and the hypothalamic pituitary adrenal axis) while regulating the abnormal sympatho-vagal balance and improving respiratory control. Results: Along the paper (1) we expose the role of the parasympathetic system and the vagus nerve in the control of inflammatory processes (2) we formulate our physiological and methodological hypotheses (3) we provide a large body of clinical and preclinical data that support the favorable effects of auricular vagus nerve stimulation in inflammation, sympatho-vagal balance as well as in respiratory and cardiac ailments, and (4) we list the (few) possible collateral effects of the treatment. Finally, we discuss auricular vagus nerve stimulation protective potential, especially in the elderly and co-morbid population with already reduced parasympathetic response. Conclusions: Auricular vagus nerve stimulation is a safe clinical procedure and it could be either an effective treatment for ARDS originated by Covid-19 and similar viruses or a supplementary treatment to actual ARDS therapeutic approaches.

Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging technology in the field of bioelectronic medicine with applications in therapy. Modulation of the afferent vagus nerve affects a large number of physiological processes and bodily states associated with information transfer between the brain and body. These include disease mitigating effects and sustainable therapeutic applications ranging from chronic pain diseases, neurodegenerative and metabolic ailments to inflammatory and cardiovascular diseases. Given the current evidence from experimental research in animal and clinical studies we discuss basic aVNS mechanisms and their potential clinical effects. Collectively, we provide a focused review on the physiological role of the vagus nerve and formulate a biology-driven rationale for aVNS. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the framework of EU COST Action “European network for innovative uses of EMFs in biomedical applications (BM1309).” Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on physiological aspects – a discussion of engineering aspects is provided by our accompanying article (Kaniusas et al., 2019). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.