Covid 19: How harm reduction advocates and the tobacco industry capitalised on the pandemic to promote nicotineBMJ 2021; 373 doi: https://doi.org/10.1136/bmj.n1303 (Published 02 June 2021) Cite this as: BMJ 2021;373:n1303
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Re: Covid 19: How harm reduction advocates and the tobacco industry capitalised on the pandemic to promote nicotine
In their recent article in the BMJ “Covid 19: How harm reduction advocates and the tobacco industry capitalised on the pandemic to promote nicotine Horel and Keyzer totally confuse the issue regarding smoking and COVID-19 by failing to distinguish two separate main questions. “Does smoking affect the probability of being infected?” and “Among those who get infected does smoking affect the probability of death?” Thus they present evidence from the Open Safely dataset and other studies on increased mortality in smokers as an attempt to “roundly disprove” a hypothesis “that smoking protects against COVID-19”, when that evidence does not actually address that hypothesis.
As regards the first question, Farsalinos, as pointed out in the article, observed that the prevalence of smoking among patients hospitalized with COVID-19 was substantially lower than that expected from national statistics. While this could well be due partly to the incompleteness of smoking data in hospital records in a number of the studies, better and quite clear evidence supporting a reduced risk of COVID-19 positivity in current smokers comes from studies of those tested for COVID-19 (e.g. [2-6]). Although the overall evidence relating to positivity is perhaps less clear from studies of other populations or using other designs, there is little or no suggestion in the epidemiological evidence that I have studied that smokers are more likely to get the virus.
In relation to the second question, the evidence on mortality among patients with COVID-19 does indeed suggest that smoking is associated with a clearly increased risk of death in unadjusted analyses. However, this increase seems to disappear when adjustment is made for comorbidities (e.g. [4-7]). In other words a smoker and a non-smoker with equivalent medical history pre-pandemic seem to have a very similar risk of mortality if they get COVID-19.
Horel and Keyzer also strongly imply that tobacco industry consultants only work so as to promote a view of the evidence that is favourable to the industry. As a consultant to the tobacco industry for over 30 years that is not at all my experience. When I started work as a consultant to one of the major tobacco companies I was told that they wanted my unbiased assessment of what the evidence showed. As a past national champion at both chess and bridge whose main interest in life is in accurate problem solving, I have always attempted to give the true picture and have published widely in the literature, including major reviews underlining the extremely strong relationship between smoking and major diseases (e.g. [8 9]).
Horel and Keyzer seem far too concerned with undisclosed financial links to the industry, and in implying that any results emanating from the industry are not to be trusted. They should spend more time actually looking at the evidence on smoking and COVID-19, which they misleadingly present.
Please note that this response was not financially supported by the tobacco industry.
Peter N. Lee
P.N. Lee Statistics and Computing Ltd.
17 Cedar Road
Sutton, Surrey, SM2 5DA
1. Horel S, Keyzer T. Covid 19: How harm reduction advocates and the tobacco industry capitalised on the pandemic to promote nicotine. BMJ 2021;373:n1303.
2. Adorni F, Prinelli F, Bianchi F, Giacomelli A, Pagani G, Bernacchia D, et al. Self-reported symptoms of SARS-CoV-2 infection in a nonhospitalized population in Italy: Cross-sectional study of the EPICOVID19 web-based survey. JMIR Public Health Surveill 2020;6(3):e21866.
3. Chadeau-Hyam M, Bodinier B, Elliott J, Whitaker MD, Tzoulaki I, Vermeulen R, et al. Risk factors for positive and negative COVID-19 tests: a cautious and in-depth analysis of UK Biobank data. Int J Epidemiol 2020;49(5):1454-67.
4. Ioannou GN, Locke E, Green P, Berry K, O'Hare AM, Shah JA, et al. Risk factors for hospitalization, mechanical ventilation, or death among 10 131 US veterans with SARS-CoV-2 infection. JAMA Netw Open 2020;3(9):e2022310.
5. Israelsen SB, Kristiansen KT, Hindsberger B, Ulrik CS, Andersen O, Jensen M, et al. Characteristics of patients with COVID-19 pneumonia at Hvidovre Hospital, March-April 2020. Dan Med J 2020;67(6).
6. Petrilli CM, Jones SA, Yang J, Rajagopalan H, O'Donnell L, Chernyak Y, et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. BMJ 2020;369:m1966.
7. Jackson BR, Gold JAW, Natarajan P, Rossow J, Neblett Fanfair R, da Silva J, et al. Predictors at admission of mechanical ventilation and death in an observational cohort of adults hospitalized with COVID-19. Clin Infect Dis 2020;Published online ahead of print Sep 24, 2020 (doi: 10.1093/cid/ciaa1459).
8. Lee PN, Forey BA, Coombs KJ. Systematic review with meta-analysis of the epidemiological evidence in the 1900s relating smoking to lung cancer. BMC Cancer 2012;12:385.
9. Forey BA, Thornton AJ, Lee PN. Systematic review with meta-analysis of the epidemiological evidence relating smoking to COPD, chronic bronchitis and emphysema. BMC Pulm Med 2011;11:36.
Competing interests: I am a long term consultant to the tobacco industry
Re: Covid 19: How harm reduction advocates and the tobacco industry capitalised on the pandemic to promote nicotine
In the current times with unnumerable scientific papers being written and being published, the scientific method can easily be hijacked by individuals or institutions with other interests than improving lives with science. Nevertheless for the adepts it is not very hard to pinpoint the shortcomings of such flawed research. Most hypotheses are false and when the a priori chance of the hypothesis being correct is very low (smoking is healthy) the probablity of type 1 error is disproportionatelly high (null hypothesis being: smoking is not healthy). One tends to find false positives. False conclusions are being drawn from flawed data but are presented in a familiar scientific way.
These false conclusions result in worst case in the spread of dangerous misinformation and in best case in the diversion of scientific and educational efforts towards exposing of the falsities instead of the consolidation of knowledge. Rapid dissemination of non-peer reviewed preprints through social media contributes highly to the expansion of this problem. There has never been this much misinfornation around and debunkers have never worked as hard. The scientific method however is robust in the long term so that correct information will prevail eventually. Unfortunately debunking and disproving does take effort and time in which damage can be done to policies and individuals' health. This is especially true in the case of smoking as it is a widespread habit. There are two ways of dealing with scientific misinformation i.e. with biased, low value studies with conflicted interests:
1. Systematic analysis of the evidence presented in these studies.
2. Maintaining a high index of suspicion of bias.
Number 1 means assessing the merits of the evidence. This can be easily done following structured checklists such as for CONSORT, STROBE and PRISMA. In addition we should ask: What does this study demonstrate? A correlation or causation? What is the level of evidence? Was the study a RCT, a prosepective cohort, case-control or cross-sectional analysis? Each type of study will be accompanied by specific flaws and biasses. The most important and the broadest of them being selection bias. Its effects are most exaggerated in cross sectional studies, the commonest type of study which has shown beneficial effects of tobacco on covid. More concrete, we should ask: how were the patients selected in this study? Who have been left out? How valid was the definition of smoking? For which variables were the analyses adjusted? What was the control group? Etc.
Number 2 means that each time an improbable hypothesis is confirmed in a paper (the null hypothesis being rejected, i.e. false positive) the data should be looked at with increased suspicion. The current state of evidence is such that a beneficial effect of smoking on health, especially concerning the respiratory system is highly improbable. What's more, after all the crushing evidence for the detrimental effects of smoking on all organ systems no endeavour into finding a positive health effect of smoking should be undertaken. The scientific position on smoking is clear! No further research is necessary. We now need to implement the knowledge. Harm reduction is just another diversion from acting to this knowledge. Now, when one comes across a study with an improbable hypothesis suggesting a benefit from smoking (e.g. protection against covid) written by an author paid by the tobacco industry, one should be very suspicious indeed. Even a perfectly performed study will suffer from sponsorship because of the publication bias as we only get to see the positive ones.
Although this two-stepped aproach works well for the members of the scientific community, figuring out the flaws of bad research by the general public depends more on exposure to the voices of good scientist. This is why we need to continually provide the public with facts and correct interpretation of them.
Competing interests: No competing interests
I didn't encourage anyone to 'Smoke fags, save lives'. That was the provocative headline put on an article I wrote last April. I don't write the headlines, but looking back at the article I notice that it gives a more accurate overview of the topic than Horel and Keyzer manage here.
The work of Professor Jean-Pierre Changeux cannot be dismissed on the basis of past funding from a "tobacco industry front group" although the fact that this funding took place a quarter of a century ago shows that there is no statute of limitations for ad hominem arguments. If I were to stoop to playing the man rather than the ball, I would note that The Investigative Desk receives funding from Bath University whose Tobacco Control Research Group has received $20 million from Bloomberg Philanthropies. Bloomberg Philanthropies was founded and is funded by Michael Bloomberg, a billionaire who uses his vast wealth to campaign against e-cigarettes. Why isn't this listed as a competing interest?
On the more substantive issue, the authors assert that it has been "roundly disproved that smoking protects against covid-19". This is simply untrue. Of the four studies they cite as evidence, only one (Jackson et al. ) suggests that smoking is a risk factor for Covid-19 - and that was based on an online survey.
Of the others, Hopkinson et al.  found that smokers were more likely to report a 'classic symptom' of Covid-19, which is perhaps unsurprising since one of the main symptoms is coughing, but it also found that "smoking was negatively associated with the risk of having a positive PCR for SARS-CoV-2 infection (OR (95% CI) 0.73 (0.65 to 0.81)".
Holt et al. (a preprint ) found no statistically significant association with smoking. Horel and Keyzer assert that Williamson et al.  "found that smoking, when adjusted for age and sex, was associated with a 14% increased chance of covid-19 related death". In fact, it found a statistically significant reduction in risk for smokers in the fully adjusted model (HR 0.89 (0.82–0.97)) and no statistically significant association in either direction after further adjustments were made (HR 0.98 (0.90–1.06)).
Horel and Keyzer do not mention the thorough ongoing meta-analysis by Simons et al.  which reports that: "Current compared with never smokers were at reduced risk of SARS-CoV-2 infection (RR = 0.71, 95% Credible Interval (CrI) = 0.61-0.82, τ = 0.34)."
The Simons et al. meta-analysis was last updated in early May. A number of peer-reviewed studies have since been published supporting the 'nicotine hypothesis'. For example, a study from Luxembourg found smokers to be half as likely to have been infected with SARS-CoV-2 (RR 0.50 (0.30–0.83; 0.004)) . A study of healthcare workers in Chile found smokers to be 62 per cent less likely to have had COVID-19 (HR 0.38, 95% CI 0.16–0.93; p = 0.03) . A study from Spain found smokers to be 77 per cent less likely to have had COVID-19 (OR 0.23 (0.20-0.27)) . A study from Iran found that: "Patients with positive history of smoking were less likely to die of COVID-19 than their counterparts." 
These are some of the studies that have been published in the last month alone, in addition to preprints such as the large study from Germany which found that regular smokers were half as likely to have had COVID-19 (aOR 0.5, 95%CI 0.3-0.7)  and the study from Spain which reported a similar finding (OR 0.57 (95% CI: 0.42-0.79)) .
Far from being "roundly disproved", the evidence that smokers are at reduced risk of SARS-CoV-2 infection is much stronger today than it was when the hypothesis first emerged last March. This evidence cannot be dismissed on the basis of tenuous financial links of a handful of researchers to the tobacco and vaping industries. Why do we keep seeing this strong inverse association between smoking and SARS-CoV-2 infection? Is it the nicotine? Is it the smoke? Is it something else? We do not know and we are not going to find out by burying our heads in the sand.
 Jackson SE, Brown J, Shahab L, et al. Covid-19, smoking and inequalities: a study of 53 002 adults in the UK. Tob Control 2020 (published online 21 Aug). doi:10.1136/tobaccocontrol-2020-055933.
 Hopkinson NS, Rossi N, El-Sayed Moustafa J, et al. Current smoking and COVID-19 risk: results from a population symptom app in over 2.4 million people. Thorax 2021 (published online 5 Jan). doi:10.1136/thoraxjnl-2020-216422.
 Holt H, Talaei M, Greenig M, et al. Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK). medRxiv 2021 [preprint]. doi:10.1101/2021.03.27.21254452.
 Williamson EJ, Walker AJ, Bhaskaran K, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature2020;584:430-6. doi:10.1038/s41586-020-2521-4. pmid:32640463
 Simons, D., Shahab, L., Brown, J and Perski, O. The association of smoking status with SARS-CoV-2 infection, hospitalisation and mortality from COVID-19: A living rapid evidence review with Bayesian meta-analyses (version 11) [preprint] https://www.qeios.com/read/UJR2AW.13
 Holuka, et al. Adverse Life Trajectories Are a Risk Factor for SARS-CoV-2IgA Seropositivity. Journal of Clinical Medicine 2021 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157140/pdf/jcm-10-02159.pdf
 Iruretagoyena, M. et al. Longitudinal assessment of SARS-CoV-2 IgG seroconversionamong front-line healthcare workers during the first wave of the Covid-19 pandemic at a tertiary-care hospital in Chile. BMC Infectious Diseases 2021; 21: 478. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149923/
 Candel, FJ. et al. The Demography and Characteristic of SARS-CoV-2 Sero-positive Residents and Staff of Nursing Homes for Older Adults in the Community of Madrid: the SeroSOS Study. Age and Ageing, afab096 2021 https://academic.oup.com/ageing/advance-article/doi/10.1093/ageing/afab0...
 Sohrabi, M. Sociodemographic determinants and clinical risk factors associated with COVID-19 severity: a cross-sectional analysis of over 200,000 patients in Tehran, Iran. BMC Infectious Diseases 2021 21: 474.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146170/
 Harries, M. et al. SARS-CoV-2 seroprevalence in Germany - a population based sequential study in five regions 2021 [preprint] https://www.medrxiv.org/content/10.1101/2021.05.04.21256597v1
 Belen, VS. Seroprevalence of SARS-CoV-2 Antibodies and Factors Associated with Seropositivity at the University of Salamanca: The DIANCUSAL Study 2021 [preprint] https://europepmc.org/article/ppr/ppr335544
Competing interests: In the clumsy and tautological words of the authors, the IEA is "an industry sponsored think tank supported by the tobacco industry." The IEA does not do commissioned research and the views of IEA staff do not necessarily reflect the views of its donors. I am a vaper.