French scientists suggest nicotinic agonists could treat COVID-19

By Angela Betsaida B. Laguipo, BSNApr 28 2020

Contrary to the warnings issued by health agencies worldwide against cigarette smoking amid the coronavirus disease (COVID-19), a new paper suggests the possibility that nicotine, a component of tobacco, could prevent coronavirus infection.

A previous study by Chinese scientists has shown that smokers contract more severe cases of COVID-19 than nonsmokers. They are also at high risk of severe disease, which can be life-threatening. Now, a team of French scientists from the Institut Pasteur hypothesizes that nicotinic agonists, of which nicotine is one, could help prevent the infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Novel Coronavirus SARS-CoV-2 - Colorized scanning electron micrograph of a cell showing morphological signs of apoptosis, infected with SARS-COV-2 virus particles (orange), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Fewer smokers infected with coronavirus

Published in the science portal Qeios, the study contradicts previous researches and shows that there seems to be only a small number of smokers infected with COVID-19.

The team examined 343 coronavirus patients, along with 139 infected with the coronavirus infection with milder symptoms. The results of the study show that a low number of the patients infected are smoking, compared to the smoking rates of about 35 percent in France’s general population.

In comparison to the number of smokers in the general population, about 40 percent for people from 44 to 53 years old, and 9 to 11 percent for those between 65 and 75 years old, the team discovered that fewer smokers seem to have been infected, or at least experienced severe symptoms.

Among the patients, only 5 percent were smokers, which means that there were approximately 80 percent fewer smokers among the COVID-19 patients that in the general population if the same age and gender cohort.

“Our cross-sectional study strongly suggests that those who smoke every day are much less likely to develop a symptomatic or severe infection with SARS-CoV-2 compared with the general population,” the authors of the study said.

Nicotine as a protective agent

The study findings reveal that current smoking status appears to be a protective factor against SARS-CoV-2 infection. The team suggests that the nicotinic acetylcholine receptor (naChR) plays a pivotal role in the pathophysiology of COVID-19 infection, potentially representing a target for the prevention and control of the viral infection.

As the knowledge about the coronavirus has evolved, scientists have found that the angiotensin-converting enzyme 2 (ACE2) represents the major receptor molecule for SARS-CoV-2. ACE2 is expressed at the transcriptomic level in the lung and other parts of the body.

In the brain, ACE2 is expressed in the brain cells and the glia, particularly in the brain stem and the part of the brain responsible for regulating cardiovascular functions. For years, studies have investigated the link between nicotine and ACE2 in various cardiovascular and respiratory diseases. Nicotine boosts the expression and activity of renin, AT1R, and ACE. On the other hand, nicotine also suppresses the expression and activity of AT2R and ACE2, suggesting the potential contribution of acetylcholine receptors in the regulation of ACE2.

“There is strong evidence for a neurotropic action of SARS-CoV-2 infection. It has been demonstrated that β-coronaviruses to which the SARS- CoV-2 belongs, do not limit their presence to the respiratory tract and have been shown to frequently invade the CNS. This propensity has been convincingly documented for the SARS-CoV-1, MERS-CoV, and the coronavirus responsible for porcine hemagglutinating encephalomyelitis (HEV 67N),” the authors wrote.

Since SARS-CoV-1 and the novel coronavirus are similar, SARS-CoV-2 likely has similar potential. The team suggests that the virus could enter the body through the olfactory system via neurons, and through the lungs, leading to various clinical manifestations and outcomes. The findings are different from the known ACE2 receptor as the main entrance of the novel coronavirus into cells.

This could explain the reason why most patients with COVID-19 has loss of smell or anosmia, alongside the loss of taste. Several studies have also reported that SARS-CoV-2 infection has other manifestations, such as headache and nausea and vomiting. Another study about COVID-19 patients also reported that about 88 percent of the patients who are critically ill had neurologic manifestations, such as impaired consciousness and acute cerebrovascular diseases.

The investigators conclude that naChRs play a vital role in the pathophysiology of COVID-19. They propose that nicotine and nicotinic orthosteric and allosteric agents may show promise as therapies for patients infected with SARS-CoV-2.

They also caution that nicotine is still a drug of abuse, which is responsible for smoking addiction. They note that smoking has many severe effects on the body.

“Yet under controlled settings, Nicotinic agents could provide an efficient treatment for an acute infection such as Covid-19,” the team suggested.

However, other evidence shows that once smokers are diagnosed with the virus, they appear to be more likely to get sick, needing mechanical ventilation.