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| REVIEW ARTICLE |
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| Year : 2020 | Volume
: 8
| Issue : 2 | Page : 9-12 |
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Tobacco consumption as a risk factor for coronavirus disease 2019?
Snehal Yerne
Department of Pharmacology and Toxicology, Swargiya Dadasaheb Kalmegh Smruti Dental College and Hospital, Nagpur, Maharashtra, India
| Date of Submission | 03-May-2020 |
| Date of Acceptance | 11-Jul-2020 |
| Date of Web Publication | 12-Jul-2021 |
Correspondence Address:
Dr. Snehal Yerne
Swargiya Dadasaheb Kalmegh Smruti Dental College and Hospital, Ameya Apartment, Gopal Nagar, Nagpur . 440 022, Maharashtra
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijcd.ijcd_4_20
In December 2019, a novel coronavirus, now named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused a series of acute atypical respiratory diseases in Wuhan, Hubei Province, China. After virus identification and isolation, the pathogen for this pneumonia was originally called 2019 novel CoV-2, but has subsequently been officially named SARS-CoV-2 by the WHO. On January 30, 2020, the WHO declared the outbreak of SARS-CoV-2 a Public Health Emergency of International Concern. Compared with the SARS-CoV that caused an outbreak of SARS in 2003, SARS-CoV-2 has a stronger transmission capacity. The rapid increase in confirmed cases makes the prevention and control of coronavirus disease 2019 (COVID-19) extremely serious. The virus is transmittable between humans and has caused pandemic worldwide. The number of death tolls continues to rise, and a large number of countries have been forced to do social distancing and lockdown. Lack of targeted therapy continues to be a problem. Studies have shown that SARS-CoV-2 infects host cells through angiotensin-converting enzyme 2 receptors, leading to COVID-19-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system. The gastrointestinal symptoms include abdominal pain, diarrhea, appetite loss, nausea, and vomiting, and neurologic symptoms include cerebrovascular strokes and encephalitis.
Keywords: Angiotensin-converting enzyme 2, coronavirus disease 2019, Guillain–Barre syndrome, severe acute respiratory syndrome coronavirus 2
How to cite this article:
Yerne S. Tobacco consumption as a risk factor for coronavirus disease 2019?. Int J Community Dent 2020;8:9-12 |
| Introduction | |  |
Coronavirus is a zoonotic virus which has crossed species to infect the human populations. Globally it has created a havoc and millions have summed to death. Unlike its other two counterparts namely the severe acute respiratory syndrome corona virus (SARS- CoV ) and the Middle East Respiratory Syndrome coronavirus (MERS-CoV) the SARS-CoV causes disease which leads to severe respiratory distress and has more virulence potential additionally its rate of spread is approximately ten times faster as compared with its other two counterparts due to its ability to preferentially attack the Angiotensin-converting enzyme 2 receptors. Currently no vaccine is available and the patients are essentially been treated with anti-viral drugs whereas plasma therapy is reserved for severe cases. In such a global emergency it is essential to identify the high risk population in order to decrease the health burden. This article suggests that tobacco consumption in smokeless as well as smoked form may act as a risk factor for the novel coronavirus disease due to the common pathway of action which involves ACE2 receptors.
| Biology of Coronavirus Disease 2019 | | |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-sense single-stranded RNA virus with a single linear RNA segment.[1] It belongs to the family Coronaviridae, genus Betacoronavirus. Its RNA sequence is approximately 30,000 bases in length. SARS-CoV-2 is unique among known Betacoronaviruses in its incorporation of a polybasic cleavage site, a characteristic known to increase pathogenicity and transmissibility in other viruses.[2] Each SARS-CoV-2 virion is approximately 50200 nm in diameter.[3] Like other coronaviruses, SARS-CoV-2 has four structural proteins, known as the S (spike), E (envelope), M (membrane), and N (nucleocapsid) proteins; the N protein holds the RNA genome, and the S, E, and M proteins together create the viral envelope.[4] The spike protein, which has been imaged at the atomic level using cryogenic electron microscopy,[5],[6] is the protein responsible for allowing the virus to attach to and fuse with the membrane of a host cell.[7]
Protein modeling experiments on the spike protein of the virus soon suggested that SARS-CoV-2 has sufficient affinity to the receptor angiotensin-converting enzyme 2 (ACE2) on human cells to use them as a mechanism of cell entry.[8] By January 22, 2020, a group in China working with the full virus genome and a group in the United States using reverse genetic methods independently and experimentally demonstrated that ACE2 could act as the receptor for SARS-CoV-2.[9],[10] Studies have shown that SARS-CoV-2 has a higher affinity to human ACE2 than the original SARS virus strain.[11],[12] SARS-CoV-2 may also use basigin to assist in cell entry.[13]
Initial spike protein priming by transmembrane protease, serine 2 (TMPRSS2) is essential for entry of SARS-CoV-2.[14] After a SARS-CoV-2 virion attaches to a target cell, the cell's protease TMPRSS2 cuts open the spike protein of the virus, exposing a fusion peptide. The virion then releases RNA into the cell and forces the cell to produce and disseminate copies of the virus, which infects more cells.[15]
SARS-CoV-2 produces at least three virulence factors that promote shedding of new virions from host cells and inhibit immune response.[16]
| Location of Angiotensin-Converting Enzyme 2 Receptors in the Body | | |
This virus enters the human body through ACE2 receptors, which are attached to the cell membrane of mainly lung Type II alveolar cells. Apart from the lungs, expression of the ACE2 receptor is also found in many extrapulmonary tissues including heart, kidney, endothelium, and intestine.[17],[18] Importantly, ACE2 is highly expressed on the luminal surface of intestinal epithelial cells, functioning as a coreceptor for nutrient uptake, in particular for amino acid resorption from food,[19] also involved in amino acid transportation. We, therefore, predict that the intestine might also be a major entry site for SARS-CoV-2 and that the infection might have been initiated by eating food from the Wuhan market, the putative site of the outbreak. As the source of outbreak is a market place therefore a strong possibility of coronavirus infecting the gut epithelium exists. A study showed that the ACE2 protein is abundantly expressed in the glandular cells of gastric, duodenal, and rectal epithelia, supporting the entry of SARS-CoV-2 into the host cell and therefore has important implications for fecal–oral transmission and containment of viral spread. The key findings of the study published online in gastroenterology suggest that:
- A significant portion of coronavirus patients experience diarrhea, nausea, vomiting, and/or abdominal discomfort before the onset of respiratory symptoms
- Viral RNA is detectable in fecal samples from suspected cases, indicating that the virus sheds into the stool
- Viral gastrointestinal infection and potential fecal–oral transmission can last even after viral clearance from the respiratory tract.[20]
Here, we consider the ability of SARS-CoV2 to enter and infect the human gastrointestinal tract (GIT) and nervous system based on the strong expression of the ACE2 target throughout the GIT and brain. Moreover, we predict that nicotine exposure through various kinds of tobacco consumption (smokeless form and smoked form) can increase the risk for coronavirus disease 2019 (COVID-19). The gastrointestinal system,brain,respiratory system can also get affected by COVID-19 due to the presence of ACE2 receptors within them. The coronavirus can damage the innate and adaptive immune arms. Cigarette smoke is shown to augment the production of numerous proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor which are also involved in hyperinflammatory syndrome which leads fulminant and fatal hypercytokinemia with multiorgan failure in COVID-19 patients. Hence, smoked forms of tobacco not only affect the binding of the virus to the receptor but also may contribute to increased mortality associated with hyperinflammatory syndrome.
| Role of Nicotine | | |
Tobacco contains a number of toxicologically significant chemicals and groups of chemicals, including polycyclic aromatic hydrocarbon (benzopyrene), tobacco-specific nitrosamines (NNK and NNN), aldehydes (acrolein and formaldehyde), carbon monoxide, hydrogen cyanide, nitrogen oxides, benzene, toluene, phenols (phenol and cresol), aromatic amines (nicotine, 4-aminobiphenyl), and harmala alkaloids. Nicotine constitutes approximately 0.6%–3.0% of the dry weight of tobacco, and it acts as a receptor agonist at most nicotinic acetylcholine receptors (nAChRs).[21]
COVID-19 has the ability to bind the ACE2 on epithelial cells as a primary mechanism of entry into the host.[22] Critical cases of COVID-19 infection commonly manifest as cardiopulmonary symptoms and, in severe cases, advance into organ failure and sepsis as a result of a “cytokine storm” over activation of the immune system.[23]
Nicotine, the psychoactive component of tobacco smoke, has profound immunological effects. It is an agonist at nAChRs, which causes it to interfere with immune responses in a receptor-mediated manner.[24]
Nicotine suppresses the migration of leukocytes to the inflammation/infection site; the decreased inflammation correlates with lower chemotaxis/chemokinesis of peripheral blood mononuclear cells (PBMCs) toward formyl-methionyl-leucyl-phenylalanine and monocyte chemoattractant protein-1 without affecting the density of their respective receptors. However, nicotine suppressed the chemokine-induced Ca2 + response in PBMC, indicating impaired chemokine signaling. Thus, because nicotine suppresses leukocyte migration, it might contribute to the increased incidence of respiratory infections among smokers.[25] This proves that, although nicotine may serve as an anti-inflammatory agent, it may, in turn, increase the incidence of COVID-19 infections.
Functional interactions between nicotine exposure and ACE2 expression in the lungs and other organ systems such as heart and kidneys as well as nicotine and other components of the renin–angiotensin system suggest that nicotine can promote COVID-19 cellular entry through nAChR signaling. Notably, nAChRs are known to be on many of the same cells that express ACE2 in the lungs, kidneys, circulation, and brain.[26],[27],[28] Thus, nicotine can impact COVID-19 pathophysiology and clinical outcome in several organ systems.
Differential host factors such as age, health, simultaneous infection, and genetics are known determinants of susceptibility to a viral infection. Smoking tobacco is a strong factor in predicting an individual's likelihood of developing and managing a viral infection and especially a respiratory infection.[25],[29] The mechanism of increased susceptibility to infections in smokers is multifactorial and includes alteration of the structural and immunologic host defenses. Here, we try to establish a link between nicotine-associated comorbidity to COVID-19 in the context of the brain, GIT, and respiratory system based on published evidence that the viral target receptor ACE2 is expressed in the various extrapulmonary sites and functionally interacts with nAChRs.[30],[31] We consider if neural cells, such as epithelial cells, are more vulnerable to infection in smokers as well as people consuming smokeless forms of tobacco because nicotine stimulation of the nAChR can increase ACE2 expression within them.[32] This issue is critical because evidence shows that mRNA from the closely related SARS virus, which also binds ACE2 as a mechanism of cell entry, was detected in brain and cerebrospinal fluid of infected individuals.[33],[34],[35] Moreover, SARS ability to enter neurons is established in experimental systems using recombinant human ACE2 as the point of entry,[36],[37] as SARS-CoV-2 can actively infect and replicate in the GIT. It has important implications for the disease management, transmission, and infection control.
| Conclusion | | |
Therefore, we conclude that, due to this interaction between ACE2 and nAChR, the chances of acquiring COVID-19 infection might be significantly high among people consuming tobacco either in smoked or smokeless form. As nicotine present in the tobacco may enhance the severity of respiratory infection due to its immunomodulatory mechanisms, it might lead to increased chances of acquiring acute respiratory distress syndrome in COVID-19 infections. According to recent studies, Guillain–Barre syndrome can be considered as neurological complications of infection with COVID-19, which indicates that infection with COVID-19 can result in long-term neural damage in both symptomatic and asymptomatic individuals, and if, in such cases, history of chronic nicotine exposure through smoked and smokeless forms of tobacco is present, it increases the risk of developing COVID-19-associated neuropathology through interactions between nAChRs and ACE2 in neurons and glia,[38] contributing to lifelong morbidity.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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