Nicotine and the nicotinic cholinergic system in COVID-19

There is an urgent need to address the devastating pandemic, COVID-19, caused by SARS-CoV-2. The efforts to understand the details of this disease in hope of providing effective treatments is commendable. It is clear now that the virus can cause far more damage in patients with co-morbid conditions - particularly in those with respiratory, cardiovascular or immune-compromised system - than in patients without such co-morbidities. Drug use can further exacerbate the condition. In this regard, the ill effects of smoking are amply documented, and no doubt can be a confounding factor in COVID-19 progression. Although conflicting hypotheses on the potential role of nicotine in COVID-19 pathology have recently been offered, we believe that nicotine itself, through its interaction with the nicotinic cholinergic system, as well as ACE2, may not only be of use in a variety of neuropsychiatric and neurodegenerative diseases, but may also be of potential use in COVID-19. Thus, on one hand, while we strongly support smoking cessation as a means of harm reduction associated with COVID-19, on the other hand, we support a potential therapeutic role for nicotine, nicotinic agonists or positive allosteric modulators of nicotinic cholinergic receptors in COVID-19, owing to their varied effects including mood regulation, anti-inflammatory as well as purported interference with SARS-CoV-2 entry and/or replication.

Keywords: ACE2; Allosteric Modulators; Covid-19; Inflammation; Nicotine; SARS-CoV-2; Smoking; nAChR.