Exploring metabolic anomalies in COVID-19 and post-COVID-19: a machine learning approach with explainable artificial intelligence

The COVID-19 pandemic, caused by SARS-CoV-2, has led to significant challenges worldwide, including diverse clinical outcomes and prolonged post-recovery symptoms known as Long COVID or Post-COVID-19 syndrome. Emerging evidence suggests a crucial role of metabolic reprogramming in the infection's long-term consequences. This study employs a novel approach utilizing machine learning (ML) and explainable artificial intelligence (XAI) to analyze metabolic alterations in COVID-19 and Post-COVID-19 patients. Samples were taken from a cohort of 142 COVID-19, 48 Post-COVID-19, and 38 control patients, comprising 111 identified metabolites. Traditional analysis methods, like PCA and PLS-DA, were compared with ML techniques, particularly eXtreme Gradient Boosting (XGBoost) enhanced by SHAP (SHapley Additive exPlanations) values for explainability. XGBoost, combined with SHAP, outperformed traditional methods, demonstrating superior predictive performance and providing new insights into the metabolic basis of the disease's progression and aftermath. The analysis revealed metabolomic subgroups within the COVID-19 and Post-COVID-19 conditions, suggesting heterogeneous metabolic responses to the infection and its long-term impacts. Key metabolic signatures in Post-COVID-19 include taurine, glutamine, alpha-Ketoglutaric acid, and LysoPC a C16:0. This study highlights the potential of integrating ML and XAI for a fine-grained description in metabolomics research, offering a more detailed understanding of metabolic anomalies in COVID-19 and Post-COVID-19 conditions.