Smoking and COVID-19 - the evidence gets stronger

I've found it impossible to keep up with all the research on smoking and COVID-19 recently. The tireless @phil_w888 has now catalogued over 700 studies of COVID-19 patients that have data on smoking prevalence. 

In the last week, the largest observational study yet conducted found that smokers (in Mexico) were 23 per cent less likely to test positive for COVID-19. This is in line with the results of an ongoing meta-analysis by some researchers who would clearly prefer the hypothesis to be disproved but who nevertheless have found a 26 per cent reduction in infection risk for current smokers. 

A study published in the Lancet a couple of weeks ago looked at the factors associated with COVID-19 caseloads at the national level. It found that countries with higher rates of smoking tended to have lower rates of Covid infection.

And a newly published prospective study of nearly 20,000 Covid cases tells a familiar story. Your chances of ending up in intensive care with the virus are increased if you are male, non-white, from a low income area, obese ... or a nonsmoker. 

Note the telltale dose-response relationship. The heaviest smokers are an incredible 88 per cent less likely to end up in ICU with COVID-19.

The same rules apply to your chances of testing positive for COVID-19. Indeed, it seems increasingly clear that smokers are less likely to end up in intensive care with COVID-19 because they are less likely to catch it in the first place.

Factors such as obesity, deprivation and being BAME are now universally acknowledged as risks for COVID-19. The UK government, in particular, has gone to town on the obesity finding. 

The smoking finding, by contrast, continues to be ignored, although the evidence for a protective effect is about as a strong as the evidence for obesity being a risk factor. 

And yet the association with smoking is not even mentioned in the abstract of the latest study (above), nor is it mentioned in the abstract of the Lancet study. The authors of the latter describe it as an 'unexpected finding' which 'requires further investigation'. The authors of the other study describe it as a 'counterintuitive finding' , although they do acknowledge that it is 'consistent with very low rates of smoking seen in patients presenting with COVID-19 in Wuhan and similar data from the USA and with the findings of a more limited analysis of patients with COVID-19 in France.

They also propose several possible causal mechanisms: 

This may reflect a general immunomodulatory effect, a mechanism that is thought to explain the lower incidence of sarcoidosis, extrinsic allergic alveolitis and ulcerative colitis in current smokers. Alternatively, smoking may cause increased ACE2 mRNA expression in human lung much as ACE inhibitors or ARBs are believed to, suggesting a possible common protective mechanism for severe COVID-19 disease. Additional possible mechanisms include a direct protective effect of nicotinic receptor stimulation or an association of smoking with another protective factor. This finding arose when including smoking status as a confounder and should be interpreted cautiously. Further studies are required to verify the apparent protective association, determine whether it is independent of other risk factors, and investigate potential mechanisms. 

The 'public health' lobby has done a good job of ignoring these findings so far, but how long can it continue? With the world economy crippled by lockdowns and social distancing - not to mention the human cost of the virus - is it ethical for them to overlook a possible solution? That solution may not involve smoking per se. It is likely to merely involve harmless nicotine. 

These findings get stronger by the day and are extremely interesting, and yet I do not see much interest in them from the people who are supposed to be protecting our health. It could be a fatal oversight.

 

UPDATE

Imperial College's antibody testing study arrived at a familiar finding:

Those who were overweight or obese had higher prevalence than those with normal weight, and current smokers had a lower prevalence than non-smokers (3.2% vs. 5.2%(OR 0.64 [0.58,0.71])

That's a 36% lower risk.