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Disclosures: The authors report no relevant financial disclosures.
March 05, 2021
2 min read

Impact of smoking on development of COVID-19 ‘challenging to address with clinical studies’

Disclosures: The authors report no relevant financial disclosures.
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The use of tobacco products is a potential risk factor for worse COVID-19 outcomes, and a new paper in the Annals of the American Thoracic Society highlights types of research to better understand this relationship.

“The relationship between smoking and COVID-19 is complex, and much of the research to date has been inconclusive or contradictory,” Enid Neptune, MD, professor of medicine in the division of pulmonary and critical care medicine at Johns Hopkins University, said in a related press release. “To resolve this issue, rigorous study design is needed. This research should accurately confirm smoking exposure, with readouts that distinguish infection from sickness and provide an objective assessment of confounding factors.”

Smoking e-cigarette
Source: Adobe Stock.

Currently, evidence has shown an association between tobacco use and higher incidence of worse COVID-19 clinical outcomes and mortality, with current smokers at increased risk for in-hospital death compared with nonsmokers. In the OPENsafely study, smokers and former smokers in the U.K. had increased risk for (25% and 80%, respectively) compared with nonsmokers. In addition, emerging data suggest that e-cigarette use may be linked to a fivefold increased likelihood for a positive COVID-19 diagnosis.

Neptune and Michelle N. Eakin, PhD, associate professor of medicine in the division of pulmonary and critical care medicine at Johns Hopkins University, highlighted several topics to be addressed in future research on the relationship between smoking and COVID-19, including airway/airspace injury, inflammation profiles supporting viral pathogenesis, disturbances in renin angiotensin signaling and nicotine signaling, and its relationship with SARS-CoV-2 infection and illness.

It is important to describe the effects of tobacco smoke on nasal tissue due to SARS-CoV-2 entering through nasal airways, according to Neptune and Eakin. Currently, little research has been conducted regarding the effect of smoking on this specific airway. Research has shown that smoking affects the ability for someone to respond to a respiratory virus, but it is important to also research whether smoking contributes to this inability or compromises an individual’s inflammatory response to viruses like SARS-CoV-2, according to the authors.

Because renin angiotensin proteins control intracellular pathways that affect lung health, some evidence suggests the disruption of these proteins protects against lung injury from cigarette smoking in individuals with COPD. However, it is not yet known if this is true for individuals with COVID-19 infection.

Finally, the authors discussed findings that suggest nicotine exposure and signaling may reduce SARS-CoV-2 infection and illness. Therefore, the effects of nicotine and smoking should be studied because nicotine-delivering e-cigarettes are more widely used, according to Neptune and Eakin.

Other research has focused on whether smoking affects lung angiotensin-converting enzyme 2, but further research on how and if tobacco smoke and nicotine affect SARS-CoV-2 infectivity or viral load is required to provide context to this research, according to the authors.

To understand the relationship between smoking and COVID-19 pathogenesis, Neptune and Eakin developed three objectives for future research:

  • expansive epidemiological population health data including clear metrics for smoking status assessment;
  • preclinical research modeling of relevant aspects of cigarette smoke exposure and SARS-CoV-2 infection to understand mechanisms contributing to disease development and morbidity; and
  • mechanistic parsing of lung nicotine delivery to define important paracrine and autocrine interactions between nicotine signaling and virus engagement and processing.

In addition, the inclusion of smoking and vaping status in COVID-19 vaccine trials may benefit data on infection rates by tobacco product exposure, Neptune noted.

“Our paper shows that the impact of tobacco exposure on the development of COVID-19 is challenging to address with clinical studies and needs rigorous validation with cell and animal studies,” Neptune said. “Taken together, the multiple published studies on smoking and COVID have not yet resolved the issue. Our intention in publishing this paper is to identify the interpretive challenges of the overall data set and recommend ways forward.”

Press Release.