Smoking, Comorbidities, and Severity of Disease in Hospitalized COVID-19 Patients in Japan

Background: The aim of this study was to identify associations between smoking status and the severity of COVID-19 using a large-scale data registry of hospitalized COVID-19 patients in Japan (COVIREGI-JP) and to explore the reasons for the inconsistent results previously reported on this subject. Methods: The analysis included 17,702 COVID-19 inpatients aged 20-89 years (10,279 men and 7,423 women). We graded the severity of COVID-19 (grade 0 to 5) according to the most intensive treatment required during hospitalization. Associations of smoking status with severe grade 3/4/5 (invasive mechanical ventilation/extracorporeal membrane oxygenation/death) and separately with grade 5 (death) were analyzed using multiple logistic regression with grade 0 (no oxygen) as the control group. Results were expressed as odds ratios (OR) and 95% confidence intervals (CI) adjusted for age and other factors considering the potential intermediate effects of comorbidities. Findings: Among men, former smoking significantly increased the risk of grade 3/4/5 and grade 5, with age-adjusted ORs (95% CI) of 1·50 (1·18-1·90) and 1·65 (1·23-2·21), respectively. An additional adjustment for comorbidities weakened these ORs to 1·29 (1·00-1·66) and 1.41 (1·01-1·95), respectively. Similar results were seen for women. Current smoking did not significantly increase the risk of grade 3/4/5 and grade 5 in either sex. Interpretation: Smoking cessation should be recommended even if the observed relationship between current smoking and the severity of COVID-19 is null because current smoking increases the risks of future comorbidities due to different diseases that increase the risk of severe COVID-19. Funding Information: This research was funded by the Health and Labour Sciences Research grant (19HA1003, 20CA2031) and the National Center for Global Health and Medicine (20A-3002). Declaration of Interests: All authors report no conflict of interest. Ethics Approval Statement: This study was approved by the National Center for Global Health and Medicine (NCGM) ethics review (NCGM-G-003494-0).