Current smoking, former smoking, and adverse outcome among hospitalized COVID-19 patients: a systematic review and meta-analysis

Background: The purpose of this study was to examine the prevalence and effects of current smoking on adverse outcomes among hospitalized COVID-19 patients. Methods: A systematic review of the literature (PubMed) identified 18 (from a total of 1398) relevant studies. Pooled current smoking prevalence was compared with the gender-adjusted and gender and age-adjusted, population-based expected prevalence by calculating prevalence odds ratio (POR). The association between current, compared with non-current and former, smoking and adverse outcome was examined. A secondary analysis was performed by including 12 pre-publications (30 studies in total). All analyses were performed using random-effects meta-analysis. Results: Among 6515 patients, the pooled prevalence of current smoking was 6.8% [95% confidence interval (CI): 4.8-9.1%]. The gender-adjusted POR was 0.20 (95% CI: 0.16-0.25,p < 0.001), and the gender and age-adjusted POR was 0.24 (95% CI: 0.19-0.30,p < 0.001). Current smokers were more likely to have an adverse outcome compared with non-current smokers [odds ratio (OR): 1.53, 95%CI: 1.06-2.20,p = 0.022] but less likely compared with former smokers (OR: 0.42, 95% CI: 0.27-0.74,p = 0.003). When pre-publications were added (n = 10,631), the gender-adjusted POR was 0.27 (95% CI: 0.19-0.38,p < 0.001) and the gender and age-adjusted POR was 0.34 (95% CI: 0.24-0.48,p < 0.001). Conclusion: This meta-analysis of retrospective observational case series found an unexpectedly low prevalence of current smoking among hospitalized patients with COVID-19. Hospitalized current smokers had higher odds compared with non-current smokers but lower odds compared with former smokers for an adverse outcome. Smoking cannot be considered a protective measure for COVID-19. However, the hypothesis that nicotine may have a protective effect in COVID-19 that is partially masked by smoking-related toxicity and by the abrupt cessation of nicotine intake when smokers are hospitalized should be explored in laboratory studies and clinical trials using pharmaceutical nicotine products.