COVID-19, propelled by smoking, could destroy entire nations

Airway diseases
Respiratory infections
Public health

Blog Author(s): Kathryn Barnsley [1] and Sukhwinder Singh Sohal [2] / 30 March, 2020

Smoking is a risk factor for many diseases. COVID-19 is in a whole new class of its own (1). Many countries are just starting to come to terms with the fact that smokers are 14 times more likely to die from COVID-19 (2, 3), but few have issued warnings to quit smoking (4) and to our knowledge, no country has ramped up its tobacco control prevention measures. In the face of this pandemic we know of no country that has widely distributed free nicotine replacement therapy or cessation support drugs, yet many countries have implemented “economic support packages”, and less developed nations face the threat of disaster (4, 5).

However, in its seventh update on COVID-19, the European Centre for Disease Prevention and Control (ECDC) recently suggested that possible preventable determinants of severe COVID-19 such as smoking and medications should be identified, as they may contribute to an increase in the number of severe cases and thus impact hospital capacity (6).

It is ironic that the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) Secretariat is part of the same WHO currently leading action on COVID-19, yet we have not yet heard any of the WHO COVID-19 leadership team urge countries to adopt the FCTC to ramp up action on tobacco control and to urge smokers to quit. The WHO coronavirus website mentions smoking, but not as one of the things making it more likely for people to become severely ill (7, 8), yet it refers to pre-existing conditions (9). Two of the countries which failed to ratify the FCTC, the USA and Indonesia, are recording high death rates (10). Furthermore, the FCTC has a strategy for 2020 that has apparently not been mentioned as a priority by the WHO coronavirus leadership team (11).

There is an abundance of evidence regarding the vulnerability of smokers and those with COPD to contract influenza, tuberculosis and other lung conditions (12-16). References in WHO and country COVID-19 literature for members of the public and the media refer elliptically to “pre-existing conditions”, without expanding on this adequately, nor clarifying the causal link to smoking, including cardiovascular disease, cancer, chronic obstructive pulmonary disease (COPD) and diabetes. Hopefully, this will be updated soon.

We found, as some others recently noted, that angiotensin-converting enzyme-2 (ACE2) receptor increases in the lungs of smokers and patients with COPD, a potential therapeutic target for COVID-19 and the importance of smoking cessation. We reported that ACE2 is upregulated in the lungs of smokers and patients with COPD (17). In this early report, we found that ACE2 receptor is upregulated in small airway epithelium including brush borders, type-2 pneumocytes and alveolar macrophages (17). The expression was more in patients with COPD compared to normal lung function smokers, and none or little in never smokers, which shows that smoking upregulates ACE2 expression and having COPD further exaggerates it, hence more susceptibility for COVID-19 in this population.

The histopathology suggested that there are multiple binding sites, and not just the small airway epithelium. This is the first early immunohistochemical evidence of ACE2 receptor in the tissue from smokers and patients with COPD (17). This has been recently confirmed by JM Leung and colleagues in a very elegant study with a larger cohort, reporting ACE2 gene and protein expression increases in the airway epithelium obtained from cytologic brushings of sixth to eighth generation airways in individuals with and without COPD (18). The authors also reported that there was a significant inverse relationship between ACE2 gene expression and FEV1% of predicted, indicating implications for lung function decline in this situation (18).

Guoshuai Cai reported higher ACE2 gene expression in smokers compared to never-smokers (19). Zhao et al. observed that ACE2 is expressed explicitly in type-2 pneumocytes, in which genes regulating viral reproduction and transmission are highly expressed, similar to what we found in the tissue from smokers and patients with COPD (20). Wang et al. also noted an ACE2 connection to smoking and Covid-19 (21). ACE2 expression could also be true for patients with other chronic lung diseases such as idiopathic pulmonary fibrosis (22).

The increases seen in smokers further raises the question of whether this is also true for people engaged in waterpipe smoking and those switching to electronic cigarettes and “heat-not-burn” IQOS devices (17, 23-25). It is essential to recognise that these devices are not “safer”, they are still a tobacco product that produces vapor or smoke and similarly could cause infectious lung damage as we see with traditional cigarettes (26, 27). Use of waterpipes and e-cigarettes are a risk for transmission of COVID-19, as the user exhales vapour droplets, which would carry SARS-Cov-2 (24).

The attachment of the virus to cell surface ACE2 protects them from immune surveillance mechanisms, leaving them tagged to the host for relatively longer periods, thus making them an efficient carrier and vulnerable host for future infections and spread. The eventual engulfment of ACE2 further provides the virus access to the host cells system, thus providing a flourishing environment, not just to sustain and proliferate but also to mutate and modify host evasion mechanisms. Taken together these studies grant preliminary but very importantly suggest that smokers and patients with COPD are at increased risk of serious COVID-19 infection and highlight the importance of smoking cessation in reducing the risk.

COVID-19 is a dress rehearsal for the next pandemic, and the next, and the one after that - the new normal. Wang et al comment on emerging zoonotic viruses (EZV): "Now is not a time for blame. Rather, there are lessons the global health community can and should learn and act on so that we can better respond to the next EZV event, which is almost certain to happen again. These lessons are definitely not unique to China (28)."

Veterinary and other scientific experts are in no doubt that zoonoses will continue to materialise, and dishearteningly, there are few paths to predict when or where (29, 30). However, if countries allocate additional resources to zoonoses pandemic prediction research, and implement recommendations for action, there might be progress (31). The old aphorism, "when you are up to your ears in alligators, remember your first objective was to drain the swamp”, applies here. Smoking is an additional invisible immediate threat, which is a major contributor driving the more severe cases of COVID-19 which in turn will almost certainly bankrupt entire countries, decimate health systems, collapse hospitals, disarticulate social cohesion, undermine political systems and kill thousands – perhaps millions – of citizens.

We strongly recommend that the WHO and countries act to advance their efforts to reduce smoking, vaping and waterpipe use; that they re-examine the provisions of the FCTC; and develop comprehensive strategies to implement all aspects of the FCTC. During a pandemic it is difficult to focus on anything other than the immediate threat. The "primacy of rescue" has overwhelmed preventive action (32, 33). Additional research into the relationship of smoking to infection, transmission and progression of COVID-19 is required. As ACE2 could be a novel adhesion molecule for COVID-19 and potential therapeutic target for prevention of fatal microbial infections it should be fast-tracked and prioritised for further research.

Author affiliations:

[1] School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
[2] Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Tasmania, Australia. Contact: sukhwinder.sohal@utas.edu.au

Acknowledgements: SS Sohal is supported by Clifford Craig Foundation Launceston General Hospital.

References:

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