CSI Update 2
First Vaping, Then Smoking Subject of Media Coverage of COVID-19
Last week, after The Food and Drug Administration, allowed a spokesperson to claim that e-cigarette use increased the risk of COVID-19, the agency revised its advice two weeks ago to acknowledge that the relationship is currently unknown. As Bloomberg News reported, an advisory from the American Cancer Society notes that there “is currently no evidence supporting a direct connection between e-cigarette use and getting COVID-19” and there is “very little direct evidence that e-cigarette use affects COVID-19 outcomes.”
While the “vaping increases COVID-19” meme has died down somewhat, it has been replaced by the “smoking might treat COVID-19” angle.
The rationale behind this effort is explained in one of the thousands of pre-publication articles being published on COVID-19. The paper: " A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications" collected data “from 480 patients tested positive for COVID-19. Out of that 350 patients were hospitalized and only 4.4 percent were regular smokers with an average age of 65. Out of people who did not hospitalize 5.3 percent were smokers with an average age of 44. They
The authors surmise that nicotine competes with the virus for the ACE2 receptor on cells: “The epidemiological/clinical evidence and the in-silico findings may suggest that Covid-19 infection is a nAChR disease that could be prevented and may be controlled by nicotine. Nicotine would then sterically or allosterically compete with the SARS-CoV-2 binding to the nAChR. This legitimates the use of nicotine as a protective agent against SARS-CoV-2 infection and the subsequent deficits it causes in the CNS. Thus, in order to prevent the infection and the retro-propagation of the virus through the CNS, we plan a therapeutic assay against Covid-19 with nicotine (and other nicotinic agents) patches or other delivery methods (like sniffing/chewing) in hospitalized patients and in the general population.”
Other small retrospective studies show that COVID-19 rates are lower in smokers than non-smokers. It could very well be that other factors – including genetic – that explain the difference. And we will need much large data sets to establish a cause and effect or statistically reliable association.
One reason that the “smoking might treat COVID-19” has gotten traction is that the evidence for claiming “Smoking increases COVID-19 risk” is pretty thin as well. The most interesting stab at identifying a possible relationship is presented in an article entitled:
ACE-2 Expression in the Small Airway Epithelia of Smokers and COPD Patients: Implications for COVID-19
The author looked at the lung tissue of people with COPD and compared cells from those smoked and those that didn’t. The researchers concluded: “active cigarette smoking and COPD up-regulate ACE-2 expression in lower airways, which in part may explain the increased risk of severe COVID-19 in these populations. These findings highlight the importance of smoking cessation for these individuals and increased surveillance of these risk subgroups for prevention and rapid diagnosis of this potentially deadly disease.”
As we have noted, there are many good reasons not take up smoking or use e-cigarettes and for quitting both. The contribution of smoking to COVID-19 is not one of them. The evidence of the possible impact of smoking on COVID-19 risk or transmission consists finding ACE2 gene and protein expression increases in the airway epithelium obtained from cytologic brushings of sixth to eighth generation airways in individuals with and without COPD. As the authors noted: the study had several limits:
“First, the study was cross-sectional and as such, we could not determine whether interventions such as inhaled corticosteroids or bronchodilators (for those with COPD) could modulate ACE-2 gene expression in the airways. Second, the precise attributable risk (for coronavirus infections) imposed by cigarette smoking and COPD is uncertain. Third, although the airway epithelia is the major source of entry for COVID-19, the virus can gain host entry through other ports including gastrointestinal mucosa, which was not evaluated in this study. Fourth, we did not have access to upper airway tissues, which may also become infected with SARS-CoV-2.
To which we add a fifth: COPD is a result of long-term lung damage and itself may be a risk factor independent of ACE-2 gene expression. Using that data to implicate e-cigarettes is a stretch.
What Do We Know and What Don’t We Know?
1. We know that smoking is harmful to health and a leading cause of death.
2. We don’t know if either smoking itself or the diseases that it causes can be shown to cause an increased risk of COVID-19 or increased severity of COVID-19. All we have now are studies of lung tissue from patients with COPD.
3. We don’t know if nicotine has a protective effect and if so, in what patients. All we have is a plausible mechanism derived from retrospective observational case reports that are now being tested in vivo or invitro.
The Commonsense Perspective
A plausible hypothesis is based on data the suggests a causal relationship between the use of a product and specific biological changes. More important, that hypothesis should be testable. To our mind, the nicotine-COVID-19 connection should be regarded as more substantial – because of the data already generated in humans -- than a conjecture about what happens to humans-based studies of cell cultures. We hope media coverage of research on nicotine, tobacco, e-cigarettes and COVID-19 is less sensational and more informational.
As CMPI President Peter Pitts recently told the media: “Smoking is the world's #1 preventable health crisis. While anecdotal evidence does show that a small cohort of cigarette smokers and e-cigarette vapers have had better responses to COVID-19, the plural of anecdote is not data. However, it does point to yet reason why e-cigarettes are a far safer alternative to combustible smoking.”
About the Commonsense Science Institute (CSI)
CSI is a clearinghouse for expert commentary and research evaluating the net public health benefit of alternatives to smoking. You can follow CSI commentary on the drugwonks.com blog.
About the Center for Medicine in the Public Interest (CMPI)
The Center for Medicine in the Public Interest is a nonprofit, nonpartisan research and educational organization that seeks to advance the discussion and development of patient-centered health care.You can obtain more information about CSI and CMPI by contacting:
Dr. Robert Goldberg: rgoldberg@cmpi.org 862-216-5731 @drbobgoldberg
