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The Joint Research Centre (JRC) is the European Commission's science and knowledge service which employs scientists to carry out research in order to provide independent scientific advice and support to EU policy.
The risk factors for contracting symptomatic COVID-19 are not yet fully understood, age and certain underlying health conditions are considered to be detrimental in this respect. Case studies revealed an astonishingly low number of current smokers among patients suffering from symptomatic COVID-19 compared to the general population, leading to the conclusion that smoking/nicotine uptake might have a preventive effect. This is difficult to understand seeing that studies found an increased expression of the angiotensin-converting enzyme (ACE-2) in smokers, the entrance gate of the coronavirus into human cells. Consequently, the use of the proportion of smokers in the general population as a reference for deriving prevalence ratios to study the association of smoking with COVID-19 disease outcomes may be inappropriate. Prevalence data for smoking and comorbidities (hypertension, diabetes mellitus, and chronic obstructive pulmonary disease) reported in 25 studies, which partially identified a potentially beneficial effect of smoking/nicotine intake, were re-analysed to investigate the relationship between COVID-19 mortality and national smoking prevalence taking account of known risk factors associated with mortality. The limited agreement of the prevalence of those risk factors in the general population with the cohort data demonstrates indirectly that these patients most likely do not reflect the health status of the general population. In the absence of specifically designed studies, any hypothesis on the effect of nicotine on symptomatic COVID-19 remains speculative. The number of potentially confounding variables would require a multivariate statistical approach and large cohort sizes for providing clarity on the significance of potential effects. However, the structure of the published aggregated data permits only univariate approaches. As such, the hypothesis of a potentially protective effect of nicotine on symptomatic COVID-19 cannot be verified.