BackgroundIn December 2022, there was a large Omicron epidemic in Hangzhou, China. Many people were diagnosed with Omicron pneumonia with variable symptom severity and outcome. Computed tomography (CT) imaging has been proven to be an important tool for COVID-19 pneumonia screening and quantification. We hypothesized that CT-based machine learning algorithms can predict disease severity and outcome in Omicron pneumonia, and we compared its performance with the pneumonia severity index (PSI)-related clinical and biological features.MethodsOur study included 238 patients with the Omicron variant who have been admitted to our hospital in China from 15 December 2022 to 16 January 2023 (the first wave after the dynamic zero-COVID strategy stopped). All patients had a positive real-time polymerase chain reaction (PCR) or lateral flow antigen test for SARS-CoV-2 after vaccination and no previous SARS-CoV-2 infections. We recorded patient baseline information pertaining to demographics, comorbid conditions, vital signs, and available laboratory data. All CT images were processed with a commercial artificial intelligence (AI) algorithm to obtain the volume and percentage of consolidation and infiltration related to Omicron pneumonia. The support vector machine (SVM) model was used to predict the disease severity and outcome.ResultsThe receiver operating characteristic (ROC) area under the curve (AUC) of the machine learning classifier using PSI-related features was 0.85 (accuracy = 87.40%,p< 0.001) for predicting severity while that using CT-based features was only 0.70 (accuracy = 76.47%,p= 0.014). If combined, the AUC was not increased, showing 0.84 (accuracy = 84.03%,p< 0.001). Trained on outcome prediction, the classifier reached the AUC of 0.85 using PSI-related features (accuracy = 85.29%,p< 0.001), which was higher than using CT-based features (AUC = 0.67, accuracy = 75.21%,p< 0.001). If combined, the integrated model showed a slightly higher AUC of 0.86 (accuracy = 86.13%,p< 0.001). Oxygen saturation, IL-6, and CT infiltration showed great importance in both predicting severity and outcome.ConclusionOur study provided a comprehensive analysis and comparison between baseline chest CT and clinical assessment in disease severity and outcome prediction in Omicron pneumonia. The predictive model accurately predicts the severity and outcome of Omicron infection. Oxygen saturation, IL-6, and infiltration in chest CT were found to be important biomarkers. This approach has the potential to provide frontline physicians with an objective tool to manage Omicron patients more effectively in time-sensitive, stressful, and potentially resource-constrained environments.