Thursday, 3 June 2021

A lazy hit job from the BMJ

The BMJ put up a story today claiming that studies showing smokers at less risk of infection from SARS-CoV-2 have been "roundly disproved" and predictably implying that the whole thing is a tobacco industry ruse. You can read it here and see my "Rapid Response" here or below.

Dear Editor,

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. [1]) suggests that smoking is a risk factor for Covid-19 - and that was based on an online survey.
Of the others, Hopkinson et al. [2] 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 [3]) found no statistically significant association with smoking. Horel and Keyzer assert that Williamson et al. [4] "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. [5] 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)) [6]. 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) [7]. 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)) [8]. A study from Iran found that: "Patients with positive history of smoking were less likely to die of COVID-19 than their counterparts." [9]

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) [10] and the study from Spain which reported a similar finding (OR 0.57 (95% CI: 0.42-0.79)) [11].

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.


[1] 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.

[2] 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.

[3] 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.

[4] 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

[5] 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]

[6] Holuka, et al. Adverse Life Trajectories Are a Risk Factor for SARS-CoV-2IgA Seropositivity. Journal of Clinical Medicine 2021

[7] 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.

[8] 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

[9] 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.

[10] Harries, M. et al. SARS-CoV-2 seroprevalence in Germany - a population based sequential study in five regions 2021 [preprint]

[11] Belen, VS. Seroprevalence of SARS-CoV-2 Antibodies and Factors Associated with Seropositivity at the University of Salamanca: The DIANCUSAL Study 2021 [preprint]

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