BACKGROUNDPatients with COVID-19 could develop severe disease requiring admission to the Intensive Care Unit (ICU). This manuscript presents a novel method that predicts whether a patient will need admission to the ICU and assess the risk of in-hospital mortality by training a deep learning model that combines a set of clinical variables and features in the Chest-X-Rays.METHODSThis was a prospective diagnostic test study. Patients with confirmed SARS-CoV-2 infection between March 2020 and January 2021 were included. This study was designed to build predictive models obtained by training convolutional neural networks for Chest-X-ray images using an artificial intelligence (AI) tool and a Random Forest analysis to identify critical clinical variables. Then, both architectures were connected and fine-tuned to provide combined models.RESULTSA total of 2552 patients were included in the clinical cohort. The variables independently associated with ICU admission were age, the fraction of inspired oxygen - FiO2 on admission, dyspnoea on admission, and obesity. Moreover, the variables associated with hospital mortality were age, the fraction of inspired oxygen - FiO2 on admission, and dyspnoea. When implementing the AI model to interpret the Chest-X-rays and the clinical variable identified by random forest, we developed a model that accurately predicts ICU admission (AUC:0.92±0.04) and hospital mortality (AUC:0.81±0.06) in patients with confirmed COVID-19.CONCLUSIONSThis automated Chest-X-ray interpretation algorithm, along with clinical variables, is a reliable alternative to identify patients at risk of developing severe COVID-19 that might require admission to the ICU.