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 are commendable. It is clear now that the virus can cause far more damage in patients with comorbid conditions—particularly in those with respiratory, cardiovascular, or immune-compromised system—than in patients without such comorbidities. 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, and purported interference with SARS-CoV-2 entry and/or replication.