In response to intriguing data from French scientists showing that smokers are strongly underrepresented among patients with COVID-19 symptoms, French citizens have started to apply nicotine patches to their upper arms. The practice has become so widespread that it created a run on supplies, prompting the government to limit people to one month’s supply of patches and require that they be purchased at pharmacies rather than online.
Last March, Konstantinos Farsalinos, a physician-researcher at the University of West Attica, was one of the first to observe that smokers were under-represented in Chinese patients with COVID. Farsalinos’ team examined 13 Chinese studies that comprised 5,960 patients hospitalized with COVID-19 and found that the prevalence of current smoking among them was “unexpectedly low” at an average of 6.5 percent, or one-quarter the population smoking prevalence of 26.6 percent.
Data from France are similar. Within a sample of 343 COVID-19 patients in a Parisian hospital, 5.3 percent were daily smokers, far below the nation’s 25.4 percent smoking rate. At a high school in Northern France researchers tested 661 staff and students for presence of SARS-CoV-2 antibodies, an indication of prior exposure to the virus. Among those found positive, 7.2 percent were smokers, over 70 percent below the rate of non-smokers in the sample who tested positive, which was 28.0 percent.
The pattern is similar in the United States. Data from the Centers for Disease Control show that, out of 7,162 COVID cases reported to the agency, 1.3 percent were smokers, far below the 13.8 percent smoking rate in the general population. A New York City hospital study of 4,103 COVID cases found that current “tobacco users” represented about 5.2 percent of cases needing hospitalization while 13 percent of New Yorkers smoke. Once hospitalized, tobacco users were no more likely than non-users to deteriorate to the point of needing critical care. In another U.S. study of 585 veterans who tested positive for coronavirus, current smokers were under-represented relative to non-smokers by 55 percent. These results suggest a protective effect against the disease itself, not just an amelioration of symptoms following infection.
Bear in mind that only the Farsalinos’ team review of 13 Chinese studies has been peer-reviewed.
This inverse relationship between smoking and COVID is striking and unexpected—a potential bombshell if proven and if shown to be a robust effect. Right now, available data suggest, but by no means prove, that smokers are protected from becoming infected by the coronavirus or that, once infected, they are less apt to develop the symptoms of COVID-19, or both.
Researchers still need to determine, however, whether actual smokers were undercounted among COVID patients. Were patients feeling too sick to smoke when presenting for care or did they chose not to disclose smoking when coming to a clinic or hospital with a serious respiratory illness? It would also be valuable to verify nicotine use by testing patients for biomarkers of tobacco use, such as metabolites of nicotine in urine, saliva, or blood. Along these lines, a detailed review of 28 studies (including some of those mentioned above) found “substantial uncertainty” regarding a smoking effect due to missing data such as the degree of exposure (e.g. pack-years of smoking) in current or former smokers, the time since quitting for former smokers, and the type of tobacco products used.
If smoking provides a defense, nicotine is presumed to be the agent within the smoke that exerts a protective or therapeutic effect. Either the molecule impedes viral entry into the lung tissue or it interacts with the immune system. One important theory involves the interaction of nicotine and the receptors used for access to the lungs and other organs by the coronavirus. A related line of thought that is well supported by immunological data suggests that the nicotine molecule might suppress the raging inflammatory response triggered by the virus. Although It is too early to accept such theories, they should not be ignored.
Indeed, the popular press has reported that French researchers are now preparing a clinical trial of nicotine patches versus placebo patches for frontline health workers, hospital patients with the COVID-19, and those in intensive care. The trial will test nicotine’s potential to prevent infection and to alter the progress of the disease among those already infected. Important questions will also need to be considered. Would nebulized nicotine taken directly into the lungs be superior to a skin patch? What would be the optimal nicotine dose and timing of exposure?
The implications at this point are that, first, nobody should take up smoking. Any potential beneficial effect of nicotine would be blunted by the adverse effects of smoking on the cardiovascular system and lungs. (Indeed, smokers are over-represented among those patients with the most severe illness.) Second, physicians should not encourage vapers and other non-combustible nicotine users to quit if doing so means a return to smoking. Third, keep perspective: nicotine itself is an extremely low risk intervention, so waiting for perfect data to confirm correlation between smoking and COVID-19 should not pose barriers to clinical trials.
At this time, it is not yet clear whether the apparent under-representation of smokers among hospitalized patients is real or an illusion generated by messy data. The evidence, as my colleague Clive Bates puts it, are “suggestive but not conclusive and the puzzle needs to be pieced together like detective work in which all the pieces, each inadequate on its own, are brought together to develop an overall picture.”
The French are out in front, with a clinical trial of nicotine and public use of a very low-risk DIY (presumptive) preventive. The “nicotine-COVID” hypothesis is fascinating and promising. Scientists should be able to judge its validity over the next few months.
Sally Satel MD is a resident scholar at the American Enterprise Institute and a visiting professor of psychiatry at the Columbia University Irving Medical Center.
Photograph by Kai Schwoerer/Getty Images.
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