Smoking Increases COVID-19 Risk… Right?

The FDA and WHO have both made statements that smoking may increase both the risk of COVID-19 as well as severity. This assertion of risk, however, is rooted in expectation rather than data. Meanwhile, the available studies show an unanticipated protective effect on COVID-19 incidence in smokers and a less clear association with disease severity.
Of course, the expectation is not unfounded. Smoking is associated with increased risk of virtually every other respiratory infectious disease. It destroys important defenses such as airway cilia that help to physically move particulate up and out of the airway. Excess and thicker mucus prevents the expectoration of debris, bacteria, and viruses. Over time, it breaks down the vital lung tissue needed for life. Additionally, many have suspected a particularly strong correlation between smoking and COVID-19 second to smoking’s effect on increasing ACE-2 receptors in the lungs. ACE-2 receptors are the entry point for the SARS-CoV-2 virus, and theoretically, an increase in receptor density gives the virus more points of entry to infect and replicate.

Furthermore, a meta-analysis out of China that pooled five studies evaluating the relationship between smoking and severity of illness concluded that smoking “is most likely associated with the negative progression and adverse outcomes of COVID-19.” But even this article lacked confidence in its own conclusions, noting that the data were “limited” and did not adjust for other factors that could have skewed the results. For instance, smokers are more likely to have hypertension, heart disease, and diabetes. Given that these comorbidities are the top three risk factors for COVID-19 mortality, not adjusting for these variables is of considerable significance and limits the ability to draw conclusions. The primary limitation of this paper, however, is that it did not evaluate the effect on disease incidence.
Subsequent research paints a different picture. A short paper by Hua Cai of UCLA attempted to explain the increase in mortality among men infected by COVID-19 by the increased incidence of smoking in the male population; however, Cai’s eventual conclusion was that “the current literature does not support smoking as a predisposing factor in men or any subgroup for infection with SARS-CoV-2.” Furthermore, the paper notes that only 1.4% to 12.6% of men with COVID-19 were smokers, while 50.5% of men in China smoke.

A recently published study from France showed similar figures. Daily smokers accounted for 4.4% to 5.3% of all COVID-19 infections, which compares to 25.4% of the overall French population who smoke. That study also noted an increase in the proportion of smokers with severe illness. These authors did not mince words in their conclusion which “strongly suggests that daily smokers have a very much lower probability of developing symptomatic or severe SARS-CoV-2 infection as compared to the general population.”
Having a better understanding of the mechanism explaining this paradox of reduced disease incidence with potentially increased disease severity will more than likely be instructive in guiding treatment. One possible explanation is that smoking results in increased production of nitric oxide within the nasal passages, which have the important role of cleaning and filtering the air prior to it being pulled down to the lungs. This first pass exposure to nitric oxide in the nose may be key to preventing infection. This gas has been shown to block the ability of SARS-CoV-2 from entering cells as well as impair the ability of the virus to replicate once inside the cell. On the other hand, if the infection ensues, the systemic effect of smoking breaks down the body’s ability to defend itself. The same inflammation that potentially protects against initial infection suddenly becomes the body’s Achilles heel.

It is only natural that we jumped to what looks like the premature conclusion that smoking would result in increased COVID-19 incidence. The premise makes perfect sense, but we cannot ignore the data and continue to report this as an unfounded risk factor rooted in bias. The counter-intuitive relationship will likely be instructive regarding or understanding of the disease and guiding development of therapeutics.
Jason Kidde, MS, MPAS, is a physician assistant at University of Utah Health in Salt Lake City.
https://www.medpagetoday.com/infectiousdisease/covid19/86144