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Abstract Introduction Identifying clinical factors that increase the risk of mortality in COVID-19 patients is crucial. This enables targeted screening, optimizing treatment, and prevention of severe complications, ultimately reducing death rates. This study aimed to develop prediction models for the death of patients (i.e., survival or death) during the COVID-19 pandemic in Shiraz, exploring the main influencing factors. Method We conducted a retrospective cohort study using hospital-based records of 1030 individuals diagnosed with COVID-19, who were hospitalized for treatment between March 21, 2021, and March 21, 2022, in Shiraz, Iran. Variables related to the final outcome were selected based on criteria and univariate logistic regression. Hierarchical multiple logistic regression and classification and regression tree (CART) models were utilized to explore the relationships between potential influencing factors and the final outcome. Additionally, methods were employed to identify the high-risk population for increased mortality rates during COVID-19. Finally, accuracy was evaluated the performance of the models, with the area under the receiver operator characteristic curve(AUC), sensitivity, and specificity metrics. Results In this study, 558 (54.2%) individuals infected with COVID-19 died. The final model showed that the type of medicine antiviral (OR: 11.10, p = 0.038) than reference (antiviral and corticosteroid), and discharge oxygen saturation(O2) (OR: 1.10, p |