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World J Crit Care Med. Jul 9, 2022; 11(4): 228-235
Published online Jul 9, 2022. doi: 10.5492/wjccm.v11.i4.228
Medicinal nicotine in COVID-19 acute respiratory distress syndrome, the new corticosteroid
Farrukh Ahmad
Farrukh Ahmad, Department of Internal Medicine, Saint Vincent Hospital, Worcester, MA 01608, United States
Author contributions: Ahmad F contributed hypothesis generation, evidence gathering, drafting and editing of manuscript.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Farrukh Ahmad, MD, Staff Physician, Department of Internal Medicine, Saint Vincent Hospital, 123, Summer Street, Worcester, MA 01608, United States. farrukh2.ahmad@stvincenthospital.com
Received: November 14, 2021
Peer-review started: November 14, 2021
First decision: April 7, 2022
Revised: April 23, 2022
Accepted: June 18, 2022
Article in press: June 18, 2022
Published online: July 9, 2022
Abstract

The cholinergic anti-inflammatory pathway (CAP) refers to the anti-inflammatory effects mediated by the parasympathetic nervous system. Existence of this pathway was first demonstrated when acetylcholinesterase inhibitors showed benefits in animal models of sepsis. CAP functions via the vagus nerve. The systemic anti-inflammatory effects of CAP converges on the α7 nicotinic acetylcholine receptor on splenic macrophages, leading to suppression of pro-inflammatory cytokines and simultaneous stimulation of anti-inflammatory cytokines, including interleukin 10. CAP offers a novel mechanism to mitigate inflammation. Electrical vagal nerve stimulation has shown benefits in patients suffering from rheumatoid arthritis. Direct agonists like nicotine and GTS-1 have also demonstrated anti-inflammatory properties in models of sepsis and acute respiratory distress syndrome, as have acetylcholinesterase inhibitors like Galantamine and Physostigmine. Experience with coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome indicates that immunomodulators have a protective role in patient outcomes. Dexamethasone is the only medication currently in use that has shown to improve clinical outcomes. This is likely due to the suppression of what is referred to as a cytokine storm, which is implicated in the lethality of viral pneumonia. Nicotine transdermal patch activates CAP and harvests its anti-inflammatory potential by means of an easily administered depot delivery mechanism. It could prove to be a promising, safe and inexpensive additional tool in the currently limited armamentarium at our disposal for management of COVID-19 induced acute hypoxic respiratory failure.

Keywords: COVID-19, Acute respiratory distress syndrome, Medicinal nicotine, Cholinergic anti-inflammatory pathway, Corticosteroid

Core Tip: Cholinergic anti-inflammatory pathway is novel pathway of the inflammatory reflex. Activation of this pathway can suppress maladaptive inflammatory response seen in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). Nicotine is a potent activator of this pathway and may offer benefits in the management of COVID-19 ARDS, via immune suppressive effects similar to dexamethasone.