Association Between Smoking and SARS-CoV-2 Infection: Cross-sectional Study of the EPICOVID19 Internet-Based Survey

Abstract

Background: Several studies have reported a low prevalence of current smoking among hospitalized COVID-19 cases; however, no definitive conclusions can be drawn.

Objective: We investigated the association of tobacco smoke exposure with nasopharyngeal swab (NPS) test results for SARS-CoV-2 infection and disease severity accounting for possible confounders.

Methods: The nationwide, self-administered, cross-sectional web-based Italian National Epidemiological Survey on COVID-19 (EPICOVID19) was administered to an Italian population of 198,822 adult volunteers who filled in an online questionnaire between April 13 and June 2, 2020. For this study, we analyzed 6857 individuals with known NPS test results. The associations of smoking status and the dose-response relationship with a positive NPS test result and infection severity were calculated as odds ratios (ORs) with 95% CIs by means of logistic and multinomial regression models adjusting for sociodemographic, clinical, and behavioral characteristics.

Results: Out of the 6857 individuals (mean age 47.9 years, SD 14.1; 4516/6857, 65.9% female), 63.2% (4334/6857) had never smoked, 21.3% (1463/6857) were former smokers, and 15.5% (1060/6857) were current smokers. Compared to nonsmokers, current smokers were younger, were more educated, were less affected by chronic diseases, reported COVID-19-like symptoms less frequently, were less frequently hospitalized, and less frequently tested positive for COVID-19. In multivariate analysis, current smokers had almost half the odds of a positive NPS test result (OR 0.54, 95% CI 0.45-0.65) compared to nonsmokers. We also found a dose-dependent relationship with tobacco smoke: mild smokers (adjusted OR [aOR] 0.76, 95% CI 0.55-1.05), moderate smokers (aOR 0.56, 95% CI 0.42-0.73), and heavy smokers (aOR 0.38, 95% CI 0.27-0.53). This inverse association also persisted when considering the severity of the infection. Current smokers had a statistically significantly lower probability of having asymptomatic (aOR 0.50, 95% CI 0.27-0.92), mild (aOR 0.65, 95% CI 0.53-0.81), and severe infections (aOR 0.27, 95% CI 0.17-0.42) compared to those who never smoked.

Conclusions: Current smoking was negatively associated with SARS-CoV-2 infection with a dose-dependent relationship. Ad hoc experimental studies are needed to elucidate the mechanisms underlying this association.

Trial registration: ClinicalTrials.gov NCT04471701; https://clinicaltrials.gov/ct2/show/NCT04471701.

Keywords: COVID-19; SARS-CoV-2; cross-sectional design; dose-response relationship; infection severity; nasopharyngeal swab testing; self-reported; smoking habit; web-based survey.

Figure 1

Flowchart of participant recruitment and eligibility for the EPICOVID19 (Italian National Epidemiological Survey on COVID-19) study. NPS: nasopharyngeal swab.

Figure 2

Adjusted odds ratios and relative 95% CIs for smoking status, intensity, and duration (N=6857). Odds ratios were adjusted for age, sex, education, occupation, area of residence, heart diseases, lung diseases, hypertension, metabolic and oncological diseases, contact with confirmed or suspected COVID-19 cases, living area, crowding index, and living with at-risk cohabitants. Dots and vertical lines indicate adjusted odds ratios and 95% CIs, respectively. Mild smokers: ≤10 cigarettes/day for <15 years; moderate smokers: ≤10 cigarettes/day for ≥15 years or >10 cigarettes/day for <15 years; heavy smokers: >10 cigarettes/day for ≥15 years. cig: cigarettes.

Figure 3

Adjusted odds ratios for positive SARS-CoV-2 tests by smoke-related variables: intensity, duration, and pack-years of smoking (N=6857). Odds ratios were adjusted for age, sex, education, occupation, area of residence, heart diseases, lung diseases, hypertension, metabolic and oncological diseases, contact with COVID-19 cases, living area, crowding index, and living with at-risk cohabitants. Dots and vertical lines indicate adjusted odds ratios and 95% CIs, respectively. cig: cigarettes.