From Stigma to Enigma: The Therapeutic Potential of Nicotine Against COVID-19
Since the beginning of the pandemic, scientists worldwide have embarked on an urgent quest to understand COVID-19. Among the most surprising discoveries is the potential protective role of nicotine, a substance long criticized for its harmful health effects, now emerging as a potential strategy against persistent post-COVID syndrome. From the unexpected smoker’s paradox to the promising therapeutic potential of nicotine, this article explores the challenges, findings, and hopes that position nicotine as a potential ally in the battle against long-term COVID-19.
Since the beginning of the health crisis caused by the pandemic of the novel coronavirus (SARS-CoV-2), we have disseminated a series of articles in The Vaping Today exploring the evidence about the therapeutic potential of nicotine, which has been under scrutiny for its possible role in the prevention and treatment of COVID-19.
In 2021, a study conducted in Lyon, France, observed a higher proportion of COVID-19 patients who were smokers among those treated on an outpatient basis compared to non-smoking patients requiring hospitalization.
The study, led by Mitra Saadatian-Elahi and titled “Smoking and COVID-19 severity: Experience from a prospective hospital cohort study in Lyon, France,” focused on assessing how tobacco consumption affected the severity of COVID-19 disease, differentiating between current smokers, former smokers, and those who had never smoked, with the latter serving as the control group.
The findings of the team of epidemiologists revealed that individuals who had quit smoking faced an elevated risk of requiring intensive care or dying compared to active smokers. That is, surprisingly, those who continued smoking seemed to have a lower risk of facing severe outcomes. However, other risk factors such as advanced age and cardiovascular and renal conditions were identified, which could explain the worse outcomes observed in older ex-smokers and those over 65 years old.
The Complex Protective Hypothesis
The hypothesis proposed by Mitra and her team suggested a potential protective effect of nicotine by interfering with the angiotensin-converting enzyme II. The enzyme (ACE2), the main receptor for SARS-CoV-2 in the human body (the SARS-CoV-2 virus enters lung cells by coupling to ACE2), is an important protein in our body that helps regulate blood pressure. ACE2 adjusts this flow: it can cause arteries to narrow, increasing pressure. This enzyme plays a key role in a larger system that balances blood pressure and ensures all organs receive the oxygen and nutrients needed to function properly.
Ceasing tobacco use, and thereby reducing exposure to nicotine, would leave more ACE2 receptors available for the virus, which could explain the greater severity and higher rates of mortality and admission to intensive care observed in the study.
“This analysis suggests a complex relationship between smoking and the severity of COVID-19 in hospitalized patients. Having been a smoker was associated with an increase in the risk of developing a severe form of COVID-19. At the same time, current smoking showed a trend, although not significant, towards exerting a protective effect against severe disease,” the study’s authors explained. “Information on the timing of tobacco cessation was only available for some participants. It is important to recognize that many individuals quit smoking upon diagnosis of pre-existing conditions, which often coincides with aging.”
The researchers proceeded with caution when considering their findings, admitting that it was unlikely that inhaling cigarette smoke offered real protection. However, the intriguing possibility emerged that by isolating and removing nicotine from cigarette smoke, a more credible protective effect might be discovered.
These initial studies showed that there were fewer smokers among those who contracted and needed hospitalization for COVID-19, sparking discussions on how smoking could influence the ease of contracting the disease and its severity. However, this initial observation faced contradictions with other international studies, which highlighted an increase in the amount of the ACE2 receptor, essential for the virus to enter cells, in smokers and people with chronic obstructive pulmonary disease (COPD).
The Duality of Nicotine: Between Inflammation and Immunological Protection
A group of scientists from the Department of Immunology at the School of Medicine of the University of Tehran, after a detailed analysis of 109 studies, concluded that smoking increases the severity of COVID-19. Moreover, they discovered that nicotine presents a duality in its impact on the immune system, acting as an inflammatory and anti-inflammatory element.
The findings of this team were published in June 2023 in the journal “Asthma, Allergy, and Clinical Immunology,” under the title “The Contradictory Effect of Tobacco and Nicotine on SARS-CoV-2 Infection.” In this work, Mostafa Ghanei and his team detail how the SARS-CoV-2 virus, responsible for COVID-19, affects multiple systems of the organism, including the respiratory, digestive, nervous, cardiovascular, and urogenital systems.
But the good news is that, according to these researchers, the ambivalence in the effects of nicotine suggests the potential for new therapeutic strategies. The influence of nicotine on the body can vary significantly depending on its dosage and mode of consumption. Although it can be harmful to conditions like diabetes, its utility can also be proposed in the management of other diseases, such as multiple sclerosis.
Interestingly, nicotine could have a dual influence on the progression of COVID-19, mainly because the higher expression of the ACE2 receptor in smokers would facilitate the entry of the virus into the body. However, the presence of the ACE2 receptor itself does not automatically lead to a higher risk of SARS-CoV-2 infection.
The Iranian researchers emphasize the importance of studying the immunological response that viral infection provokes in depth, highlighting the urgency of further research to understand these processes fully.
The scientists stress the need to meticulously investigate how different levels of nicotine can impact individuals affected by COVID-19, considering the immune status of the patients, as well as any other risk or pre-existing condition.
The purpose of these studies is to identify a dose of nicotine that may be beneficial, or at least not harmful, for patients, minimizing significant adverse effects. It is crucial to distinguish between the specific effects of nicotine consumption and those associated with the smoking habit per se to avoid erroneous or confusing conclusions.
The researchers also suggest that the study on nicotine and COVID-19 should examine how it interacts with the renin-angiotensin system, which regulates blood pressure and fluid balance, and with the cholinergic system, related to the transmission of nerve impulses, providing a more complete understanding of how nicotine could influence the evolution and treatment of the disease.
Nicotine: Hope for Patients with Persistent COVID Syndrome
Dr. Marco Leitzke, from the Department of Anesthesiology at Helios Clinics in Leisnig, Germany, has directed his research toward the post-COVID syndrome. Leitzke hypothesizes that nicotine when administered in its pure form and not through tobacco smoke, could prevent COVID-19 from binding to the ACE2 receptor. This action has the potential to alleviate symptoms associated with long COVID, offering a new pathway to treat the persistent complications of the disease.
In his research, Dr. Marco Leitzke investigated the benefits of nicotine patches in patients suffering from persistent symptoms of COVID-19 after their recovery. The participants, all non-smokers, experienced notable improvements in symptoms such as fatigue, breathing difficulties, and loss of taste and smell senses shortly after starting with nicotine. Fatigue, in particular, improved rapidly, usually within six days of applying the patch, while recovery of taste and smell occurred between thirteen and sixteen days.
The study also reported a prompt improvement in the sensation of chest tightness and palpitations, typically the day after starting treatment. However, one case was recorded where chest tightness was completely resolved after twenty-two days. The research underscores the need to tailor the dosage of nicotine and the frequency of its application, taking into account individual differences in the number of acetylcholine receptors that the virus might be affecting in each person.
A particular case highlighted the dangers of an accidental overdose of nicotine, resulting in adverse symptoms such as intense nausea, excessive sweating, and recurrent vomiting. Despite this, both these symptoms and those associated with COVID-19 were mitigated after discontinuing the excessive treatment.
According to Leitzke, the methodology of administering nicotine through the skin, employed in the study, ensures a constant release of nicotine into the bloodstream without causing marked peaks and troughs, which is crucial to prevent dependence on this substance.
The research advances the hypothesis that prolonged COVID could result from an alteration in signal transmission through the cholinergic system, aggravated by the affinity shown by SARS-CoV-2 for acetylcholine receptors (AChR), and suggests that treatment with nicotine could mitigate symptoms by preventing the virus from binding to these receptors, thus offering a new perspective in managing the prolonged effects of COVID-19.
Despite the encouraging results, Dr. Leitzke calls for caution, particularly in those patients suffering from serious cardiovascular or respiratory diseases, emphasizing the need for broader and controlled studies to validate the effectiveness of transcutaneously administered nicotine in the treatment of post-COVID syndrome.
Nicotine patches provided an almost immediate improvement in post-COVID-19 syndrome symptoms
Dr. Leitzke suggests that the post-COVID-19 syndrome, affecting some individuals after recovering from the disease, could be linked to an imbalance in the nervous system related to acetylcholine nicotinic receptors. This is because SARS-CoV-2 could block these receptors, altering the transmission of nerve signals essential for numerous body functions.
In his research, Dr. Leitzke found that the use of transcutaneous nicotine patches provided an almost immediate improvement in post-COVID-19 syndrome symptoms. The rapid and complete recovery reflected the diversity of symptoms associated with the syndrome. This treatment stands out for its simplicity and the ease with which minor side effects can be managed.
Given these promising findings, Dr. Leitzke advocates for more rigorous studies, including randomized and double-blind trials, to explore this therapeutic alternative thoroughly. From his perspective, the treatment with nicotine patches for post-COVID-19 syndrome appears to be significantly more effective and practical than current rehabilitation strategies, which tend to be costly, complicated, and often unsatisfactory or disappointing for patients.
Long COVID and the CC Experiment
According to an estimate