Is smoking protective against COVID-19?

Current data from the Office of National Statistics (ONS) from 2018 suggests that around 7.2 million adults smoke cigarettes which is a 5% decrease since 2011.1

While there are several health benefits that accrue from smoking cessation, recent press reports seem to suggest that smokers are somehow protected from COVID-19. Indeed, early reports from China on the clinical characteristics of patients admitted to hospital with COVID-19 found that the proportion of smokers was less than expected based on the estimated prevalence of smoking in the country which is 27.7%.2

For instance, in one study, the proportion of smokers was found to be considerably less than the average at 1.4%3 and while higher at 7% in another study,4 this was still lower than the average. Since these early reports, several other studies from different countries have also demonstrated that a lower than expected number of smokers have been hospitalised with COVID-19. In a study of those hospitalised with COVID-19 in New York, the prevalence of smokers was 5.1%5 which is less than half of the most recent estimate of the overall US smoking prevalence of 13.7%.6 Similarly, a retrospective analysis of 441 patients admitted to a hospital in northern Italy, found that less than 5% of patients were smokers, compared to an estimated age-adjusted prevalence of 14.9%.7 In a study of 340 patients in a French university hospital, it was found that 6.1% of patients were smokers compared to a population rate of 25.4%.8 Finally, in a yet to be peer-reviewed meta-analysis of available studies, Spanish researchers calculated that smokers were statistically less likely (odds ratio = 0.18, 95% CI 0.14 – 0.23) to be hospitalised for COVID-19.9

But are these observations simply a fluke or is there a plausible explanation that could account for the reduced incidence of COVID-19 among smokers? One hypothesis proposes that it is nicotine which provides a degree of protection against the virus. This is based on an observation in 1990, that acute nicotine inhalation can increase both systolic and diastolic blood pressure and that this effect is mediated via an increase in angiotensin converting enzyme activity.10 In addition, other work has shown how the nicotine-induced rise in the level of ACE is also associated with a downregulation of the level of ACE-2,11 which is now considered to be a functional receptor for COVID-19 entry into cells.12 Other work has shown that nicotine is able to activate nicotinic acetylcholine receptors on immune cells and that this effect leads to an inhibition of the release of pro-inflammatory cytokines and protects against acute inflammation in lung tissue.13

While this appears to represent a rationale for how nicotine may be protective against COVID-19, other and more recent work published as a research letter to the European Respiratory Journal,14 found that in both smokers and those with COPD, there was an increased airway expression of ACE-2. The authors concluded that this offered a possible explanation as to why those with COPD are at an increased risk of infection but the data effectively countered the potentially protective role of nicotine. In an effort to untangle the association between smoking and COVID-19, an as yet non-peer reviewed analysis of 67 observational studies conducted in several different studies concluded that there is substantial uncertainty about the associations between smoking and COVID-19 outcomes.15 Moreover, an evidence review by Healthcare improvement Scotland, also concluded that there is no significant association between smoking and severe disease.16 In contrast, the most recent meta-analysis of 19 peer-reviewed papers that included 11,590 patients concluded that smoking is a risk factor for the progression of COVID-19, with smokers having a higher odds of COVID-19 progression.17

In summary and based on the available evidence, it seems unlikely that smoking offers some degree of protection from the effects of COVID-19. The ONS report1 shows that smoking rates are the lowest at 7.9% in those 65 years and over and it is possible that the lower incidence of infection among smokers, simply reflects the fact that fewer older people smoke rather than an intrinsic and protective effect among smokers. Until more definitive evidence emerges, it would seem prudent that current healthcare advice to stop smoking is continued rather than patients relying on a potentially spurious belief that somehow smoking will prevent them from becoming infected with COVID-19.

References

1. Office for National Statistics. Adult smoking habits in the UK: 2018.
   www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/healthandlifeexpectancies/bulletins/adultsmokinghabitsingreatbritain/2018 (accessed May 2020).
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3. Zhang JJ et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy 2020; Feb 19.
4. Huang C et al. Clinical features of patients infected with novel 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.
5. Goyal P et al. Clinical characteristics of Covid-19 in New York City. N Engl J Med 2020; Apr 17.
6. Centers for Disease Control and Prevention. Smoking & Tobacco Use.
   www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/index.htm (accessed May 2020).
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   https://www.qeios.com/read/WPP19W.4
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14. Leung JM et al. ACE-2 expression in the small airway epithelia of smokers and COPD patients: implications for COVID-19. Eur Respir J 2020;55:20000688.
15. Simons D et al. The association of smoking status with SARS-CoV-2 infections, hospitalisation and mortality from COVID-19: a living rapid evidence review. Qeiosi. www.qeios.com/read/UJR2AW.4.
16. Healthcare improvement Scotland. Assessment of COVID-19 in primary care. https://eprints.gla.ac.uk/215857/1/215857.pdf (accessed May 2020).
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