Smoking Status and Factors associated with COVID-19 In-Hospital Mortality among US Veterans

INTRODUCTION: The role of smoking in risk of death among patients with COVID-19 remains unclear. We examined the association between in-hospital mortality from COVID-19 and smoking status and other factors in the United States Veterans Health Administration (VHA). METHODS: This is an observational, retrospective cohort study using the VHA COVID-19 shared data resources for February 1 to September 11, 2020. Veterans admitted to the hospital who tested positive for SARS-CoV-2 and hospitalized by VHA were grouped into Never (as reference, NS), Former (FS), and Current smokers (CS). The main outcome was in-hospital mortality. Control factors were the most important variables (among all available) determined through a cascade of machine learning. We reported adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) from logistic regression models, imputing missing smoking status in our primary analysis. RESULTS: Out of 8 667 996 VHA enrollees, 505 143 were tested for SARS-CoV-2 (NS = 191 143; FS = 240 336; CS = 117 706; Unknown = 45 533). The aOR of in-hospital mortality was 1.16 (95%CI 1.01, 1.32) for FS vs. NS and 0.97 (95%CI 0.78, 1.22; p > .05) for CS vs. NS with imputed smoking status. Among other factors, famotidine and nonsteroidal anti-inflammatory drugs (NSAID) use before hospitalization were associated with lower risk while diabetes with complications, kidney disease, obesity, and advanced age were associated with higher risk of in-hospital mortality. CONCLUSIONS: In patients admitted to the hospital with SARS-CoV-2 infection, our data demonstrate that FS are at higher risk of in-hospital mortality than NS. However, this pattern was not seen among CS highlighting the need for more granular analysis with high-quality smoking status data to further clarify our understanding of smoking risk and COVID-19-related mortality. Presence of comorbidities and advanced age were also associated with increased risk of in-hospital mortality. IMPLICATIONS: Veterans who were former smokers were at higher risk of in-hospital mortality compared to never smokers. Current smokers and never smokers were at similar risk of in-hospital mortality. The use of famotidine and nonsteroidal anti-inflammatory drugs (NSAIDs) before hospitalization were associated with lower risk while uncontrolled diabetes mellitus, advanced age, kidney disease, and obesity were associated with higher risk of in-hospital mortality.