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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 5  |  Issue : 2  |  Page : 70-75

Role of tobacco in SARS-CoV-2 infection and COVID-19: A scoping review


1 Professor, Department of Community Medicine, Maulana Azad Medical College, New Delhi, India
2 Consultant, Community Processes/Comprehensive Primary Health Care Division, National health Systems Resource Centre, New Delhi, India

Date of Submission15-May-2020
Date of Decision04-Jun-2020
Date of Acceptance10-Jun-2020
Date of Web Publication29-Jun-2020

Correspondence Address:
Dr. Rupsa Banerjee
Consultant, Community Processes/Comprehensive Primary Health Care Division, National Health Systems Resource Centre, New Delhi - 110 067
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jncd.jncd_19_20

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  Abstract 


The role of tobacco smoking in COVID-19 has been studied by several researchers, but conclusive evidence has not yet been established. This calls for assimilation of the findings reported in available published studies. The present review attempts to understand the observation and opinion of various researchers on this aspect. A scoping review was conducted to study the role of tobacco smoking in the occurrence of SARS-CoV-2 infection and severity of COVID-19. The review included 14 studies, of which 7 studies discussed the pathophysiological effects of nicotine in detail, while seven other studies analyzed the risk of tobacco use or otherwise, on occurrence and severity of COVID-19. Based on the existing evidence, it may be concluded that tobacco smoking evokes adverse pathophysiological changes in smokers and is associated with worse progression of COVID-19 to its severe form, with the patients requiring admission in the intensive care unit and placed on ventilator support or may even succumb to the disease. Although one researcher, through several studies, has reported a beneficial effect of nicotine, there is not enough evidence to support this claim. Research is probably in the pipeline to test medicinal nicotine to prevent and treat COVID-19 in providers and patients with moderate and severe illness. Until the results of the proposed research or further longitudinal analytical studies proving beneficial association are published, it will be in the best interest to advise patients and the entire population to refrain from smoking tobacco to prevent an impending upsurge of noncommunicable diseases that might otherwise happen in the near future.

Keywords: Coronavirus, COVID-19, nicotine, severe acute respiratory syndrome coronavirus 2, tobacco


How to cite this article:
Banerjee B, Banerjee R. Role of tobacco in SARS-CoV-2 infection and COVID-19: A scoping review. Int J Non-Commun Dis 2020;5:70-5

How to cite this URL:
Banerjee B, Banerjee R. Role of tobacco in SARS-CoV-2 infection and COVID-19: A scoping review. Int J Non-Commun Dis [serial online] 2020 [cited 2020 Nov 30];5:70-5. Available from: https://www.ijncd.org/text.asp?2020/5/2/70/288246




  Introduction Top


The world is experiencing a severe pandemic of COVID-19, with currently more than 200 countries/territories affected by the disease.[1] The first case was reported from China on December 31, 2019, and a novel coronavirus was identified as the cause.[2] The virus was subsequently named as severe acute respiratory syndrome coronavirus-2 or SARS-CoV-2 and the disease named as coronavirus disease of 2019, in short COVID-19.[3] As on May 14, 2020, 10.00 CEST, total 4,248,389 cases and 294,046 deaths have been reported globally.[1]

COVID-19 has been observed to be more severe and fatal in elderly individuals with preexisting comorbidities, commonly diabetes, and hypertension.[4] Tobacco is a known risk factor for noncommunicable diseases (NCD), including diseases of the lung and is the leading cause for illness and death due to NCDs.[5],[6] Tobacco smoking has also been reported by many authors to have a significant effect on angiotensin-converting enzyme (ACE) 2 pulmonary expression and immune function, which suggests an increased risk for viral binding and entry of SARS-CoV and SARS-CoV-2 in the lungs of smokers.[7],[8],[9],[10],[11],[12] Although one author has suggested that nicotine can even be beneficial in preventing cytokine storm,[13] with much reported negative associations, there is a possibility that tobacco acts as a determinant for the severity of COVID-19 in the presence of NCDs.

The role of tobacco smoking in COVID-19 has been studied by several researchers, but conclusive evidence has not yet been established. Two systematic reviews analyzing five and eleven studies, respectively, conducted in China on patients of COVID-19, concluded that smoking is probably associated with negative progression and adverse outcomes of the disease.[14],[15] On the other hand, another author in two systematic reviews on five and thirteen research work studying prevalence of smoking status on hospitalized patients of COVID-19 in China reported an unexpectedly low prevalence of current smoking among patients with COVID-19 compared to the overall Chinese population.[16],[17] In this background, there is an urgent need to synthesize the findings of available literature and derive a conclusion.


  Methodology Top


A scoping review was conducted to study the role of tobacco smoking in the occurrence of SARS-CoV-2 infection and severity of COVID-19. As there are limited studies on vaping, this was not considered in the present review. For inclusion of publications in this review, the following points were taken into consideration:

  • Research on tobacco use involves ethical implications, and hence, only observational studies are feasible
  • Due to comparatively recent onset of the disease, long-term longitudinal analytical studies have not been conducted, or results are not available
  • For the same reason, ample literature is not yet available on this area
  • Systematic quantitative reviews have already been conducted on the few currently available trials which were usually of very small sample size and without conclusive evidence.


Keeping the above points in view, the present review aimed to focus on the qualitative aspect as opined by various authors while synthesizing findings from available research. Hence, various types of publications were included in this review, namely editorial, letter to the editor, commentary, and viewpoint published from all over the world over the past 6 months before initiation of the present review.

Handsearching was not conducted considering the restricted condition of mobility in the prevailing situation of lockdown in the country. Translation of articles published in other languages was also not attempted for the same reason.

Inclusion criteria

  1. Publications studying the relationship between tobacco and COVID-19
  2. Research published in the English language, available on the Internet.


Exclusion criteria

The use of tobacco in any form other than smoking was the exclusion criteria.

Search strategy

Electronic databases such as PubMed, PubMed Central, BioMed Central, and PLOS were searched. Search terms used in various combinations included “tobacco” OR “tobacco products” OR “nicotine” AND “COVID-19” OR “severe acute respiratory syndrome coronavirus 2” OR “2019-nCoV” OR” “SARS-CoV-2” OR “coronavirus.” Cross-references quoted in articles identified for review were also considered. Data were extracted using a common format.

Findings were presented regarding observation and opinion of the authors of studies reviewed, in the context of risk or otherwise of tobacco, based on pathophysiological effect and disease status and outcome.


  Results Top


A total of 267 studies were identified, of which titles of 29 were relevant to the topic of the present review being on tobacco and COVID-19. The abstracts of these studies were read and 16 studies were found to have discussed area of our proposed research, of which two studies were on vaping and hence excluded. Full papers of these studies were retrieved. Of these studies, seven discussed the pathophysiological effects of nicotine in detail,[7],[8],[9],[10],[11],[12],[13] while seven studies analyzed the risk of tobacco use or otherwise on the occurrence and severity of COVID-19[14],[15],[16],[17],[18],[19],[20] [Figure 1].
Figure 1: Selection of studies for review

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[Table 1] depicts the pathophysiological changes with nicotine use, in relation to SARS-CoV-2 and COVID-19. Although most authors have touched upon this aspect, in seven studies, this was discussed in detail. Most of these seven authors have reported upregulation of ACE2 gene expression in the pulmonary airway and also impaired immune function and thus concluded that smoking poses a risk of uptake of SARS-CoV-2.[7],[8],[9],[10],[11],[12] Only one author has concluded that nicotine can prevent clinical manifestations of cytokine storm in COVID-19 patients and is hence beneficial. The author has also stated that in vivo animal models found nicotine to be protective against acute respiratory distress syndrome.[13]
Table 1: Effect of tobacco on SARS-CoV-2 and COVID-19 based on pathophysiological changes

Click here to view


[Table 2] shows conclusions derived in seven publications from various studies that included case series report, systematic review, and meta-analysis. In four of these studies, the authors observed that the disease outcome was worse in smokers, with smokers having significantly higher risk of having a severe form of the disease, be admitted to the intensive care unit, requiring ventilator support, or even succumb to the disease.[14],[15],[18],[19] One meta-analysis found no significant association between active smoking and severity of COVID-19.[20] Only one author in two separate studies reported unusually low prevalence of smoking among patients hospitalized with COVID-19, in comparison to the population prevalence of China. In both the studies, the author concluded that there is no risk and suggested that smoking may, in fact, have a protective effect.[16],[17]
Table 2: Effect of tobacco on SARS-CoV-2 and COVID-19 based on disease status and outcome

Click here to view



  Discussion Top


Tobacco has been reported to kill up to half of its users, killing more than 8 million people each year. More than 7 million of these deaths are the result of direct tobacco use, including smoking and use of smokeless tobacco. Tobacco use is currently one of the leading global risk factors for illness and death from major NCDs. Smokers are also susceptible to various infective and chronic respiratory conditions, including cancer.[5],[6] SARS-CoV-2 infection and COVID-19 is now being added to this list.

Smoking acts as an important causative agent of cardiovascular and pulmonary diseases through its direct actions on various types of nicotinic receptors expressed in the cardiac tissue, lungs, and blood vessels. Smoking is also significantly associated with high mortality rates in respiratory viral infections including seasonal influenza.[11]

The role of tobacco smoking in COVID-19 has been studied by several researchers, and most have reported that smokers have adverse pathophysiological changes [7],[8],[9],[10],[11],[12] and significant risk of developing severe forms of COVID-19 with worse progression and outcome.[14],[15],[18],[19] While two systematic review and meta-analysis reported a significant association between smoking and severity of COVID-19,[14],[15] two other systematic reviews studying the prevalence of smoking status on hospitalized patients of COVID-19 in China reported an unexpectedly low prevalence of current smoking among patients with COVID-19 compared to the overall Chinese population. On the basis of this finding, the reviewers suggested that pharmaceutical nicotine should be considered as a potential treatment option in COVID-19.[16],[17] This ambiguity calls for assimilation of the findings reported in available published studies on this aspect. The present review attempts to understand the observation and opinion of various researchers on this aspect.

ACE2 is a component of the renin–angiotensin system (RAS), whose expression dominates on lung alveolar epithelial cells. In addition, ACE2 plays a key role in systemic blood pressure homeostasis by counterbalancing the deleterious effects of angiotensin II on cardiovascular structure and function. ACE2 is also the only experimentally confirmed human cell receptor of SARS-CoV-2 which has ACE2 receptor-binding capacity. Infection with SARS-CoV-2 therefore results in the loss of function of ACE2, thus compromising normal functioning of the respiratory and cardiovascular systems.[7],[8],[10],[11],[12] The interplay between SARS-CoV-2 and ACE2 is complex and still not clear.

It has been suggested that nicotine upregulates ACE2 on the airway epithelium due to which smokers may be more susceptible to SARS-CoV-2 infection. Patients suffering from chronic obstructive pulmonary disease have significantly higher ACE2 levels and hence more susceptible to infection due to the presence of more potential binding sites. Animal studies, on the other hand, suggested that SARS-CoV-2 adhesion on ACE2 could also downmodulate this enzyme, which, in turn, increases the production of other related ACEs and angiotensin II that are detrimental to the body and cause organ damage. Nicotine is known to influence the homeostasis of the RAS, contributing in turn to the development of cardiovascular and pulmonary diseases.[7],[8],[10],[11],[12],[21]

Cytokine release syndrome or cytokine storm, commonly occurring in severe cases of COVID-19, is a phenomenon characterized by an increased release of pro-inflammatory cytokines that may occur in response to infections and can progress to acute respiratory distress syndrome. Nicotine has been reported to prevent acute lung injury in animal study and to exhibit anti-inflammatory properties in vivo in humans exposed to endotoxins. This has been found to protect against cytokine-mediated conditions that lead to organ damage and death. On the basis of this, Farsalinos et al. have hypothesized that nicotine by its effects on the immune system can be beneficial in reducing this cytokine storm.[13]

Various authors have summed up findings of the available research work. However, it is interesting to note that a few common studies featured in all the systematic reviews and meta-analysis yet interpreted differently by different authors. While Vardavas and Nikitaraconcluded after a systematic review of five studies that smokers were 1.4 times more likely to have a severe form of COVID-19 and 2.4 times more likely to be admitted in the intensive care unit,[14] another report by Farsalinos et al. from the same five studies observed that the prevalence of current smoking among hospitalized patients was 10.2% which was significantly lower than the population prevalence of 31.3% in China, and on this basis, they suggested that smoking may even have a protective effect for COVID-19.[16]

Another ambiguity was pointed out by Guo [19] regarding a meta-analysis of five studies by Lippi and Henry.[20] Lippi and Henry had reported that out of the five studies included in meta-analysis, in only one study active smoking was found to be a significant predictor of COVID-19 severity, whilst in the other four studies the association was not statistically significant.[20] Guo pointed out errors in calculation on performing meta-analysis again on corrected data and he reported pooled OR of 2.20, indicating active smoking to be significantly associated with the risk of developing severe COVID-19.[19]


  Conclusion Top


Based on the existing evidence, it may be concluded that tobacco smoking evokes adverse pathophysiological changes in the smokers [7],[8],[9],[10],[11],[12] and is associated with worse progression of COVID-19 to its severe form, with the patients requiring admission in intensive care unit and placed on ventilator support or may even succumb to the disease.[14],[15],[18],[19] Although one researcher, through several studies, has reported a beneficial effect of nicotine,[13],[16],[17] there is not enough evidence to support this claim. This might, in fact, be alarming by promoting tobacco use in a population with the not-yet-proven belief of nicotine's preventive effect on SARS-CoV-2 and COVID-19, the fear of which is currently lurking in everyone's mind.

Research is probably in the pipeline to test medicinal nicotine to prevent and treat COVID-19 in providers and patients with moderate and severe illness.[22] Until the results of the proposed research or further longitudinal analytical studies proving beneficial association are published, it will be in the best interest to advise patients and the entire population to refrain from smoking tobacco to prevent an impending upsurge of NCDs in the near future.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
World Health Organization. Coronavirus Disease (COVID-2019) Situation Report – 115. Geneva: World Health Organization; 2020. Available from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200514-covid-19-sitrep-115.pdf? sfvrsn=3fce8d3c_. [Last accessed on 2020 May 15].  Back to cited text no. 1
    
2.
WHO Timeline – COVID-19. Geneva: World Health Organization; 2020. Available from: https://www.who.int/news-room/detail/08-04-2020-who-timeline---covid-19. [Last accessed on 2020 May 03].  Back to cited text no. 2
    
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World Health Organization. Naming the Coronavirus Disease (COVID-19) and the Virus That Causes it. Geneva: World Health Organization. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus- that-causes-it. [Last accessed on 2020 May 03].  Back to cited text no. 3
    
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World Health Organization. Clinical Management of Severe Acute Respiratory Infection (SARI) When COVID-19 Disease is Suspected Interim Guidance. Geneva: World Health Organization; 2020. Available from: https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when- novel-coronavirus-(ncov)-infection-is- suspected. [Last accessed on 2020 May 03].  Back to cited text no. 4
    
5.
World Health Organization. Factsheet on Tobacco. Geneva: World Health Organization; 2019. Available from: https://www.who.int/news-room/fact-sheets/detail/tobacco. [Last accessed on 2020 May 14].  Back to cited text no. 5
    
6.
WHO Highlights Huge Scale of Tobacco-Related Lung Disease Deaths. Geneva: World Health Organization; 2019. Available from: https://www.who.int/news-room/detail/29-05-2019-who-highlights-huge-scale-of- tobacco-related-lung-disease-deaths. [Last accessed on 2020 May 14].  Back to cited text no. 6
    
7.
Brake SJ, Barnsley K, Lu W, McAlinden KD, Eapen MS, Sohal SS. Editorial: Smoking upregulates angiotensin-converting enzyme-2 receptor: A potential adhesion site for novel coronavirus SARS-CoV-2 (Covid-19). J Clin Med 2020;9:841.  Back to cited text no. 7
    
8.
Cai G, Bossé Y, Xiao F, Kheradmand F, Amos CI. Tobacco smoking increases the lung gene expression of ACE2, the receptor of SARS-CoV-2. Am J Respir Crit Care Med 2020;201:1557-9. [doi: 10.1164/rccm. 202003-0693LE].  Back to cited text no. 8
    
9.
Komiyama M, Hasegawa K. Smoking cessation as a public health measure to limit the coronavirus disease 2019 pandemic. Eur Cardiol 2020;15:e16.  Back to cited text no. 9
    
10.
Leung JM, Yang CX, Tam A, Shaipanich T, Hackett TL, Singhera GK, et al. ACE-2 expression in the small airway epithelia of smokers and COPD patients: Implications for COVID-19. Eur Respir J 2020;55:2000688. [doi: 10.1183/13993003.00688-2020].  Back to cited text no. 10
    
11.
Olds JL, Kabbani N. Is nicotine exposure linked to cardiopulmonary vulnerability to COVID-19 in the general population? FEBS J 2020: p.1-5. [doi: 10.1111/febs.15303].  Back to cited text no. 11
    
12.
Russo P, Bonassi S, Giacconi R, Malavolta M, Tomino C, Maggi F. COVID-19 and smoking. Is nicotine the hidden link? Eur Respir J 2020;55:2001116. [doi: 10.1183/13993003.01116-2020].  Back to cited text no. 12
    
13.
Farsalinos K, Niaura R, Houezec JL, Barbouni A, Tsatsakis A, Kouretas D, et al. Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system. Toxicol Rep 2020;7:658-63.  Back to cited text no. 13
    
14.
Vardavas CI, Nikitara K. COVID-19 and smoking: A systematic review of the evidence. Tob Induc Dis 2020;18:20.  Back to cited text no. 14
    
15.
Zhao Q, Meng M, Kumar R, Wu Y, Huang J, Lian N, et al. The impact of COPD and smoking history on the severity of Covid-19: A systemic review and meta-analysis. J Med Virol 2020: p. 1-7. [doi: 10.1002/jmv. 25889].  Back to cited text no. 15
    
16.
Farsalinos K, Barbouni A, Niaura R. Smoking, vaping, and hospitalization for COVID-19. Qeios 2020; Preprintv13. [doi: 10.32388/Z69O8A.2].  Back to cited text no. 16
    
17.
Farsalinos K, Barbouni A, Niaura R. Systematic review of the prevalence of current smoking among hospitalized COVID19 patients in China: Could nicotine be a therapeutic option? [Epub ahead of print]. Intern Emerg Med 2020; p. 1-8. [doi: 10.1007/s11739-020-02355-7].  Back to cited text no. 17
    
18.
Berlin I, Thomas D, Faou AL, Cornuz J. Commentary COVID-19 and Smoking. Nicotine Tob Res 2020; p. 1-3. [doi: 10.1093/ntr/ntaa059].  Back to cited text no. 18
    
19.
Guo FR. Active smoking is associated with severity of coronavirus disease 2019 (COVID-19): An update of a meta-analysis. Tob Induc Dis 2020;18:37.  Back to cited text no. 19
    
20.
Lippi G, Henry BM. Active smoking is not associated with severity of coronavirus disease 2019 (COVID-19). Eur J Intern Med 2020;75:107-8.  Back to cited text no. 20
    
21.
Alifano M, Alifano P, Forgez P, Iannelli A. Renin-angiotensin system at the heart of COVID-19 pandemic. Biochimie 2020;174:30-3.  Back to cited text no. 21
    
22.
Tindle HA, Newhouse PA, Freiberg MS. Beyond smoking cessation: Investigating medicinal nicotine to prevent and treat COVID-19. Nicotine Tob Res 2020. pii: ntaa077.  Back to cited text no. 22
    


    Figures

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    Tables

  [Table 1], [Table 2]



 

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