Covid-19: the new and paradoxical virtues of nicotine

At the start of the Covid-19 epidemic, it was a simple statistical curiosity. We imagine that people who smoke tobacco are more at risk than the average to be reached, but they seem less exposed vis-à-vis the infection by SARS-CoV-2. Four months later, it’s a new therapeutic path which opens, a hypothesis that the French health authorities take very seriously and which will soon lead to the launch of the first original clinical trials based on nicotine.

The first detailed observation of this paradoxical phenomenon is described by a Chinese research team and published in late February in The New England Journal of Medicine. Scientists then observed, on a group of a thousand patients, a proportion of individuals who smoke lower than that of the Chinese population as a whole (12.6% against 28%). Other similar observations follow. In France, the first data from the Assistance Publique-Hôpitaux de Paris (AP-HP) confirm, out of nearly 11,000 patients with Covid-19, the rate of people who use tobacco is 8.5% – while it is 25% in the general population.

A finding based on solid studies

Why? Are these figures reliable? Dr. Makoto Miyara and Professor Zahir Amoura, two internal medicine specialists from La Pitié-Salpêtrière (AP-HP), wanted to understand. They confirm this paradoxical observation by eliminating statistical biases (such as age and gender) are often confounding factors in this type of observational study. Out of a group of 343 hospitalized patients, only 4.4% smoke tobacco daily. And among the 139 patients followed on an outpatient basis, the proportion is 5.3%.

This study provides a solid basis for asserting that people with a heavy addiction to tobacco use have a much lower probability of developing SARS-CoV-2 infection (of moderate or severe intensity) than the rest of the general population – a risk divided by a factor of five. In other words, we then have statistical evidence confirming that smoking protects against infection by the virus. However, the mystery remains: why?

If the true causes of this protection are not established, it quickly became apparent that the first candidate capable of explaining this phenomenon was the nicotine. We have known for a long time that this toxic substance is naturally present in tobacco leaves, that it acts on the central nervous system and that it is responsible for massive addiction phenomena. A larger group of French researchers was then formed to extend the first observations and conclusions. This group brings together, in addition to members of the AP-HP, others belonging to the CNRS, Inserm, the University of the Sorbonne, the Collège de France and the Institut Pasteur.

The nicotinic receptor, the key to success

Their hypothesis is that infection with SARS-CoV-2 involves a specific molecular structure (a nicotinic receptor), a “key” that facilitates the entry of the virus into cells – a key that would be less functional in people who use tobacco who have become addicted to nicotine. This would explain in particular the frequency observed of certain neuropsychiatric manifestations during Covid-19 – such as the loss of the sense of olfaction and, in certain patients, various neurological disorders which can eventually lead to sudden respiratory arrest. . “SARS-CoV-2 could thus spread from the olfactory mucosa, then from neurons in the brainstem, in some cases going to the respiratory centers”, estimates the research team.

This same hypothesis would still explain some of the spectacular inflammatory or immune manifestations observed in certain patients. Finally, it would help to understand why obesity and diabetes seem to be risk factors and are frequently found in severe cases of Covid-19.

One could imagine that nicotine could be administered via the practice of vaping.

It is this innovative hypothesis which is now developed in biology reviews from the American Academy of Sciences by a small group led by the French neurobiologist Jean-Pierre Changeux, known for his innovative work on this nicotinic receptor.

This theoretical work is already experiencing new extensions: in view of the pandemic health emergency, the people behind this work consider it necessary to rapidly assess the therapeutic impact of their observations and their hypothesis. Of clinical studies should be quickly implemented. Nicotine patches, of the type used to obtain cessation of tobacco addiction, will be applied to different categories of people: caregivers (for preventive purposes), hospitalized patients and others in intensive care. An original enterprise led with the support of Olivier Véran, Minister of Solidarity and Health. One could also imagine that potentially protective nicotine could be administered via the practice of vaping.

A substance that kills

Demonstrate that nicotine protects against Covid-19? The case may be less simple than one might imagine since people who do not smoke can not tolerate (without being victims of headache or vomiting) that very small doses of nicotine which a priori would complicate its use for preventive or curative purposes. Would these low doses be enough to block enough receptors and oppose the viral infection?

As of now, a question of public health is openly posed: how can we ensure that the media coverage of this work, this hypothesis and these perspectives does not have negative consequences? How, by popularizing this scientific approach, not encourage the continuation (or resumption) of daily tobacco consumption? Consumption which would now be perceived as prevention of infection even though its major toxicity has been amply demonstrated (more than 75,000 premature deaths every year in France). How can we explain, at the same time, that people who smoke are less exposed to the risk of Covid-19 without pushing for tobacco consumption? How to promote this experiment without permanently ruining all the efforts of the fight against smoking?

For the time being, the scientists behind this work are trying to warn by explaining that cigarette smoke and the countless toxic substances it contains have no protective effect. The health authorities are doing the same. Professor Jérôme Salomon, Director General of Health, explains that people who do not smoke must in no way resort, on their own initiative, to nicotine substitutes (reimbursed by social security) in the hope of protecting themselves against infection with SARS-CoV-2.

Some fear the effects of media promotion of nicotine substitutes which, if it took place before rigorous testing is conducted, would quickly lead to a situation equivalent to that resulting from the promotion of hydroxychloroquine against the Covid-19.

“You have to be very careful in these observational studies, the smoking rate varies a lot according to sex, country and age, explained Professor Salomon. All this deserves total confirmation. We must not forget the harmful effects of nicotine. Research must be encouraged, but I invite the French not to confuse lines of research with established facts. ”

This is not the least paradox of this approach than hearing today the Director General of Health have to declare: “We strongly advise people not to resume smoking.”

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