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Current smoking and COVID-19 risk: results from a population symptom app in over 2.4 million people
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  • Published on: 15 June 2021
    Dog bites man - COVID-19 and smoking.
    • Nicholas S Hopkinson, Reader in Respiratory Medicine National Heart and Lung Institute, Imperial College London
    • Other Contributors:
      • Niccolò Rossi, Research Fellow
      • Anthony A Laverty, Lecturer
      • Jennifer K Quint, Professor of Respiratory Epidemiology
      • Claire J Steves, Reader in Aging Research
      • Mario Falchi, Reader in Computational Medicine

    The idea that smoking might have a protective effect against COVID-19 is an intriguing, man bites dog type of story, which gives it a certain attraction. Happily, it appears to be false and the assumption of harm has turned out to be correct[1-5].
    Our data show clearly that in the 2.4 million Zoe COVID Symptom Study App users, people who smoked were at increased risk of symptomatic COVID-19[2] and were at risk of more severe disease, which is consistent with a systematic review of patients hospitalized with COVID-19[4]. Our findings are also consistent with The UCL COVID-19 Social Study3 which found increased risk of test confirmed COVID-19 (OR=2.14 (1.49–3.08)) and with the COVIDENCE study where smokers had an OR of1.42 (0.99-2.05) for test-confirmed COVID-19[1].
    The OpenSafely dataset based on data from the primary care records of 17.3 million adults in the UK found that, adjusted for age and sex, also identifies smoking as a risk factor - current smoking was associated with a hazard ratio for COVID-19-related death of 1.14 (1.05–1.23)5. The apparently protective effect in the “fully adjusted” model is due to over-correction producing collider bias.
    Since any protective effect of smoking in COVID-19 appears to be illusory, pursuing a mechanism for it is unlikely to be productive.

    References
    1 Holt H, Talaei M, Greenig M, et al. Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK). medRxiv 2021:2021.2003...

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    Conflict of Interest:
    None declared.
  • Published on: 15 June 2021
    Current smoking as a risk factor for COVID-19
    • Peter Sasieni, Biostatistician King's College London
    • Other Contributors:
      • Peter Hajek, Clinical psychologist

    There is no question that the harms of smoking hugely outweigh any potential health benefits. Many people, ourselves included, assumed at the beginning of the pandemic that greater susceptibility to COVID-19 would be another harm of tobacco smoking to be added to the long list. Surprisingly, most of the epidemiological data published over the last year do not support this claim. Indeed whereas ex-smokers are consistently found to be at increased risk of both SARS-CoV-2 infection and severe COVID-19, current smokers are consistently at lower risk than ex-smokers and in many studies they appear to be at a lower risk than never smokers. The lower infection rate in smokers compared to non-smokers and ex-smokers has been found across 62 studies (1, 2), including now a full cohort with a dose-response pattern (3).

    The authors’ response does not counter the observation that among nearly 27,000 individuals who had a SARS-CoV-2 test in their study, smoking prevalence was lower in those who tested positive than in those who tested negative.

    In the OpenSAFELY study (4) too, the direction of the association between smoking and death from COVID-19 depends critically on what adjustments are made. The primary analysis appears to be based on a fully adjusted Cox regression model in which the hazard ratio for current smokers relative to never smokers was 0.89 (95% CI 0.82-0.97). The value (1.14; 1.05-1.23) cited by Hopkinson and colleagues is after adjusting for age and sex...

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    Conflict of Interest:
    None declared.
  • Published on: 15 June 2021
    Current smoking as a risk for COVID-19
    • Nicholas S Hopkinson, Reader in Respiratory medicine Imperial College, London
    • Other Contributors:
      • Niccolò Rossi, Research Fellow
      • Anthony Laverty, Lecturer
      • Jennifer K Quint, Professor of Respiratory Epidemiology
      • Claire J Steves, Senior Clinical Lecturer
      • Mario Falchi, Reader in Computational Medicine

    We thank the authors for their letter in response to our paper(1). We disagree however that the data among the tested subgroup are more informative than our other findings. This is because the small subgroup (1.1% of app users - 0.7% negative, 0.3% positive, 0.1% result unknown) who reported that they had undergone testing for COVID-19 at this relatively early stage in the pandemic (the month from 24th March 2020) were heavily selected. Testing policies focused on healthcare workers and others interacting with healthcare - in particular, patients tested who may have been attending healthcare settings for other, non-COVID-19 related, conditions. As numerous health conditions are smoking-related this would tend to increase the exposure of smokers without COVID-19 to testing. For these reasons, as discussed in the paper, the finding that smoking rates were lower in those testing positive is likely to be due to sampling bias. Rather than being “more relevant”, extrapolation from this subgroup to population risk is entirely inappropriate.
    The letter does appear to misunderstand the groups presented – the “standard user” group were not asymptomatic during the study. Rather, as set out in the first paragraph of the results, they were individuals who at the point of registration with the Zoe COVID Symptom Study App did not think that they already had COVID-19. Among this group of “standard users” current smokers were more likely to report the onset of new symptoms suggesting...

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    Conflict of Interest:
    None declared.
  • Published on: 15 June 2021
    Symptom app data are consistent with smokers having increased risk of COVID-19-like symptoms, but a decreased risk of actual SARS-CoV-2 infection
    • Peter D Sasieni, Biostatistician King's College London
    • Other Contributors:
      • Peter Hajek, Clinical psychologist

    The paper by Hopkinson et al (1) provides unique and important data on smoking prevalence and COVID-19 symptoms, but their conclusion does not reflect the data well. The authors conclude “these data are consistent with people who smoke being at an increased risk of developing symptomatic COVID-19”. The study includes over 150,000 people with self-reported COVID-19 symptoms and over two million without such symptoms. It also includes data on over 25,000 people who were tested for SARS-CoV-2 and their test results. Based on our analysis of these more relevant data, we interpret the study differently. Our conclusion would be “these data are consistent with smokers having an increased risk of symptoms such as cough and breathlessness, but a decreased risk of having SARS-CoV-2 infection”.

    The difficulty in interpreting these results is that both symptoms and testing are likely colliders in a causal model of smoking and COVID-19. The data reported on SARS-CoV-2 test results make it possible to compare smoking prevalence by age-group and sex in three groups: those who tested positive for SARS-CoV-2 (n=7,123); those who tested negative (n=16,765); and untested asymptomatic users (n=2,221,088, called “standard users” by the authors). Overall smoking prevalence was less in those tested (8.9%) than in all users of the app (11.0%). This might be thought of as a surprising finding – smoking-related symptoms should lead to testing – but can probably be explained by most asymptom...

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    Conflict of Interest:
    None declared.