Smoking and COVID-19: The Real Deal

The coronavirus disease (COVID-19) pandemic has had a devastating impact globally with millions of individuals infected and a rising death toll that now surpasses one million (1). It is therefore critical to identify risk factors for worse outcomes related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The use of tobacco products is such a potential risk factor, given its adverse effects on health and the high prevalence of use. Both electronic and combustible tobacco products have been shown to cause damage to the lungs (2, 3) and to alter the immune system response leading to increased susceptibility to most respiratory viruses. Although research is ongoing, there are several proposed mechanisms by which SARS-CoV-2 may increase susceptibility to infection or lead to worse clinical outcomes. Overall, the epidemiological data are mixed on whether tobacco use increases the risk of COVID-19 infection. However, there is clear evidence that tobacco use is associated with worse clinical outcomes, including the risk of mortality, with current smokers having a greater risk of in-hospital death (9.4% compared with 5.6% for nonsmokers) (4–6). The OpenSAFELY study linked electronic health records with in-hospital deaths in the United Kingdom, for approximately 17 million individuals in the United Kingdom. Accounting only for age and sex, smokers and former smokers had a 25% and 80%, respectively, higher risk of mortality compared with nonsmokers (7). With regard to incident infection, metaanalyses have shown that current smokers are at a reduced risk of SARS-CoV-2 infection (8). However, the literature is generally flawed by significant heterogeneity on how smoking status was determined, leading to missing data, inability to separate current, former, and never-smokers, reliance on self-report or electronic medical records, and lack of data on frequency and duration of use of tobacco products. Furthermore, in many of these studies, there is a high representation of healthcare workers who are less likely to smoke than the general population but are at greater risk of exposure to SARS-CoV-2. Conversely, emerging evidence suggests that the use of electronic cigarette products is linked to a fivefold greater likelihood of testing positive for COVID-19 (9). This study, however, relied on an Internet panel and self-report. These data suggest a smoking paradox for COVID19, with current smokers being at a lower risk for infection but at a significantly greater risk for worse outcomes. What are the possible mechanisms by which smoking could affect SARS-CoV-2 infection and the outcome of COVID-19? The smoking-related comorbidities (cardiovascular disease, chronic obstructive pulmonary disease [COPD]) provide the most coherent connection between smoking and COVID-19 severity. However, several disease mechanisms, anchored in smokingassociated lung injury, altered host defenses, and the unique aspects of SARS-CoV-2 infectivity, are also relevant.