Thursday, 12 August 2021

Smoking and COVID-19: a new evidence update

Updated 5 January 2022

Studies which find smokers to be significantly less likely to get COVID-19 continue to be published, even if they are ignored by the media. There are so many of them that it's difficult to keep up. 

The indefatigable Phil has found over 4,000 studies in which smoking status is recorded (see this heroic thread), although the vast majority do not look at smoking specifically as a risk factor, so we can only compare smoking rates among Covid patients/cases with the smoking rate of the general population. Most of them seem to show smokers significantly under-represented among Covid patients/cases, but it is a crude method and is not considered conclusive (interestingly, however, the over-representation of fat people in Covid wards is considered sufficient evidence to mark obesity as a risk factor).

It is better to focus on studies which use epidemiological methods and adjust for other factors. There are quite a few of them now, including a growing number looking at antibodies in unvaccinated populations to see who has had Covid. These studies help address sampling bias because whole populations are tested; it does not rely on people's willingness to come forward or on their ability to identify their symptoms. 

There is an ongoing meta-analysis, but it hasn't been updated since March (UPDATE: the seventh and final version has been published in Addiction). The main conclusion is that smokers are less likely to be infected and ex-smokers are more likely to be hospitalised if they catch the virus. The early finding that smokers are less likely to be hospitalised with Covid seems to be explained by them being less likely to be infected in the first place.

What follows is not a comprehensive list. These are just the studies that have crossed my radar. Please let me know about other evidence in the comments, including any studies that contradict the general conclusion that smokers are less likely to be infected with the virus. Most of these studies have been published and peer-reviewed, but a few are pre-prints.

1. This British study published in the Lancet found that 'active smoking was linked with decreased odds of a positive test result' with an odds ratio of 0.49 (0.34–0.71). 

2. This British study found that smokers were 27% less likely to test positive for COVID-19 although you have to look carefully to find the evidence because the lead author is the chairman on Action on Smoking and Health and he buries it as much as he can. The odds ratio is 0.73 (0.65-0.81). 

3. This large study from Germany - currently still in pre-print - which found, based on a seroprevalence survey, that regular smokers are 52% less likely to have had COVID-19 (0.48 (0.31-0.72)).

4. Meanwhile this British study published in Nature looked at the likelihood of dying from COVID-19 and found that smokers were slightly more at risk, or slightly less at risk, or neither, depending on how the figures were adjusted.

5. Then there is this study from the USA which looked at 3,789 US military veterans aged between 54 and 75 who were tested for COVID-19, of whom 585 tested positive. Smokers were 55% less likely to test positive, with an odds ratio of 0.45 (0.35-0.57). 

6. This study (a pre-print) from a badly hit area of France where 661 people were tested for COVID-19 and smokers were 67% less likely to test positive. Odds ratio after adjusting for age: 0.23 (0.09 –0.59). 

7. Study from the USA finds smokers 90% less likely to test positive. Odds ratio: 0.1 (0.01-0.8). 

8. This study - another one from Britain, this time using the Biobank data, but still in pre-print - claims in the abstract that smokers were "slightly more likely" to test positive. In fact, the results section show that there was no statistically significant difference.

9. By contrast, this study using Biobank data and also in pre-print shows smokers under-represented (with an implied odds ratio of 0.73 (0.6-09). 

10. French study (pre-print) finds that daily smokers are 76% less likely to be infected with COVID-19 (after adjusting for age and sex). Odds ratio for inpatients: 0.24 (0.14-0.40). For outpatients: 0.24 (0.12-0.48). 

11. This study from Italy found that "current smokers were significantly less likely to be hospitalized for COVID-19 compared with non-smokers (Odds ratio 0.23; 95% CI, 0.11-0.48 after adjusting for age and gender). 

12. Interesting study of a Covid outbreak on a French Navy aircraft carrier. 76% of the crew members got the disease but smokers were 36% less likely to get it. There was also a "trend towards a lower risk among e-cigarettes users". 

13. Web-based study from Italy finds smokers were half as likely to get COVID-19 than nonsmokers. There was a dose-response relationship, with heavy smokers 62% less likely. 

14. Study of 4,137 Covid patients in South Korea finds smokers 67% less likely to be infected (0.33, CI = 0.28–0.38). 

15. Study of Covid hospital patients in Turkey finds no difference in disease severity between smokers and nonsmokers, but finds that the "mortality rate was significantly increased in ex-smokers (p= 0.037) and non-smokers (p= 0.001) in comparison to active smokers (p= 0.123)". 

16. This study (pre-print), involved testing 114,545 people for the virus. The smoking rate was 9.8% among those who tested positive (the national rate is 19%). After adjustments, the authors found that smokers were half as likely to test positive, with an odds ratio of 0.46 (0.41-0.51). This is, as the authors conclude, an 'intriguing finding' which 'may reveal unique infection mechanisms present for COVID-19 which may be targeted to combat the disease and reduce its infection rate.' 

17. Study of 10,614 nurses in Madrid finds smokers 77% less likely to have had COVID-19 (0.23 (0.20-0.27)). The finding is not mentioned in the abstract.

18. UK study finds smokers are 27% less likely to be hospitalised with COVID-19. The authors do not mention this finding in the text (0.63 (0.44-0.88)). 

19. Study of German health workers finds smokers are around half as likely to have antibodies for SARS-CoV-2.

20. Study from Mexico finds smokers are 22% less likely to get Covid and 18% less likely to die from it.

21. Study from Russia finds smokers are 54% less likely to have had Covid (as measured by antibody tests).

22. American study finds smokers are 57% less likely to be diagnosed with Covid. Vapers were no more and no less likely to get the virus than nonsmokers.

23. Study from Luxembourg finds smokers are 50% less likely to have had Covid.

24. Study of healthcare workers in Chile finds smokers are 62% less likely to have had Covid. 

25. Study in the Journal of the American Medical Association finds smokers to be 40% less likely to have had Covid.

26. Study from Spain finds smokers are 43% less likely to have had Covid.

27. Study from the UK finds no inverse relationship between smoking and Covid. Naturally, this one got plenty of media attention. I wrote about it here.

28. Study from Palestine finds that smokers are half as likely to have been infected with SARS-CoV-2 (0·47: 0·31–0·72).

29. Study of 8,124 people in Indiana, USA, finds that smokers - but not vapers - are half as likely to get COVID-19 (0.49: 0.32-0.74).  

30. Italian study finds that smokers are 58% less likely to get SARS-CoV-2 (OR 0.42: 0.29–0.60). Unusually, it also finds that former smokers are at reduced risk (OR 0.49: 0.33–0.75).

31. Study from South Africa finds that daily smokers are half as likely to be infected with SARS-CoV-2 as non-smokers (0.50: 0.38-0.67).

32. Mendelian Randomisation study finds that smoking is not associated with lower risk of infection. Although the study is titled 'Smoking is significantly associated with increased risk of COVID-19 and other respiratory infections', the text makes it clear that the association is only with people with a 'genetic liability for smoking'. Strangely, it is only MR studies that find such an association with 'smoking' (see 27 above).

33. Study of 31,549 people tested in Wisconsin, USA last year finds smokers 66% less likely to have COVID-19 (0.34; significant at p < 0.001). Former smokers were 21% less likely. Those who did were more likely to be hospitalised. Smokers with Covid were no more likely to die of it than nonsmokers, but former smokers were.

34. Study of nearly half a million dialysis patients in the USA finds that tobacco use is associated with a 16% reduction in risk of COVID-19 diagnosis (OR 0.84: 0.81-0.87).

35. Study from Switzerland finds smokers are 56% less likely to be infected with SARS-CoV-2 after adjusting for potentially important confounders (OR 0.44 (0.35-0.77).

36. Study from Italy finds smokers 30% less likely to be diagnosed with SARS-CoV-2 (0.70 (0.54–0.91)).

37. Study of Behçet's syndrome patients finds smokers are 34% less likely to be diagnosed with SARS-CoV-2 (0.66 (0.47-0.93)).

38. Study of municipal workers in Kosovo finds smokers are half as likely to have had SARS-CoV-2 (0.52, 0.28-0.97). 

39. Study from Austria (currently in pre-print) finds that smokers are around half as likely to have had SARS-CoV-2 than nonsmokers.

40. Study (pre-print) from Gauteng, South Africa finds that daily smoking is associated with a 31% reduction in infection risk (0.69 (0.59-0.80)). Note that this is the first study of this kind involving Omicron. 

41. Study from the Netherlands finds that smoking is associated with a 58% reduction in infection risk (0.42 (0.18-0.99).

42. We found one! Study of healthcare workers in Italy finds that smokers are more likely to get SARS-CoV-2 than nonsmokers (1.6 (1.1–2.4).

43. Study from Chile find that tobacco consumption is associated with lower risk of SARS-CoV-2 infection, with effects ranging from 0.62 to 0.85. 

44. Web-based study from the Netherlands finds smokers are 36% less likely to get SARS-CoV-2 (0.64 (0.46 to 0.91)).

45. Study from Serbia finds that smokers are 71% less likely to have COVID-19 (0.29 (0.15–0.55)).

There is also an ecological study that compared smoking rates and COVID-19 mortality rates in 38 European countries and found an inverse relationship. 

The UK's weekly ONS infection survey consistently shows that smokers about half as likely to catch the virus as nonsmokers. This is almost never remarked upon.

As for why this finding keeps emerging, opinions differ. One suggestion is that smokers spend more time outside, but this sounds rather like a cope given the size of the effect. Smokers do not spend all that much more time outside and it seems unlikely that this would give frontline healthcare workers, for example, significantly more protection.

It may be due to the nicotine, although it is notable that study 23 and study 29 did not find any benefits from vaping. 

Various biological mechanisms have been proposed which are beyond my level of scientific understanding. In any case, the consistency of these findings is very interesting and the lack of interest shown towards them by the public health establishment is revealing.

Meanwhile, the legacy 'public health' research community is annoyed that people are freely sharing such information on Twitter

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