(1) Background: The new SARS-COV-2 pandemic overwhelmed intensive care units, clinicians, and radiologists, so the development of methods to forecast the diagnosis’ severity became a necessity and a helpful tool. (2) Methods: In this paper, we proposed an artificial intelligence-based multimodal approach to forecast the future diagnosis’ severity of patients with laboratory-confirmed cases of SARS-CoV-2 infection. At hospital admission, we collected 46 clinical and biological variables with chest X-ray scans from 475 COVID-19 positively tested patients. An ensemble of machine learning algorithms (AI-Score) was developed to predict the future severity score as mild, moderate, and severe for COVID-19-infected patients. Additionally, a deep learning module (CXR-Score) was developed to automatically classify the chest X-ray images and integrate them into AI-Score. (3) Results: The AI-Score predicted the COVID-19 diagnosis’ severity on the testing/control dataset (95 patients) with an average accuracy of 98.59%, average specificity of 98.97%, and average sensitivity of 97.93%. The CXR-Score module graded the severity of chest X-ray images with an average accuracy of 99.08% on the testing/control dataset (95 chest X-ray images). (4) Conclusions: Our study demonstrated that the deep learning methods based on the integration of clinical and biological data with chest X-ray images accurately predicted the COVID-19 severity score of positive-tested patients.
