Περίληψη: | COVID-19 is a disease caused by a novel coronavirus, SARS-CoV-2. On March 23 we presented evidence of a low prevalence of smoking among hospitalized patients with COVID-19 in China, and we were the first to establish the hypothesis that nicotine may be beneficial for COVID-19 and should be evaluated in clinical trials due to its anti-inflammatory properties. While in many cases the disease is mild, severe COVID-19 is characterized by a hyper-inflammatory response, commonly called cytokine storm, and is characterized by the release of pro-inflammatory cytokines that may lead to Acute Respiratory Distress Syndrome and death. The cholinergic anti-inflammatory pathway is an important immune-regulating system mediated by nAChRs that can control inflammation and function as an immunomodulator through a bi-directional communication between the immune and nervous systems. The clinical manifestations of cytokine storm observed in COVID-19 could be linked to a dysfunction of the cholinergic anti-inflammatory pathway. At the same time, several patients experience neurological symptoms that could be explained by the invasion of the virus to the terminal area of afferent vagus fibers or the origin of the efferent vagus fibers, further dysregulation the inflammatory response. Anosmia has been experienced by several patients, a phenomenon that has been observed in patients with Parkinson’s disease and is caused by impaired cholinergic transmission. Thromboembolic complications, activation of platelets and endothelial damage with increased vascular permeability indicate ineffective control by the nicotinic cholinergic system. Considering that most of the manifestations of COVID-19 are linked to impairment of the nAChRs, we make the hypothesis that COVID-19 may be a disease of the nicotinic cholinergic system. We present regions with four or five amino acids homology between the SARS-CoV-2 and several neurotoxin molecules which act as competitive inhibitors in nAChRs. We propose that nicotine could be used therapeutically and should be urgently evaluated in clinical trials.
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