Metabolic profiling of COVID-19 severity and mortality: A targeted metabolomics approach

Abstract

Abstract The analysis of metabolites in response to SARS-CoV-2 infection provides a snapshot of the endogenous host metabolism and its role in shaping the interaction with SARS-CoV-2. In this study, using a targeted metabolomics approach, the metabolic signatures of severity and mortality were studied in COVID-19 patients. Our analysis revealed survival and severity-associated shifts in the metabolome of COVID-19 patients, where amino acids, particularly tryptophan and arginine, and fatty acid metabolism were altered in severe patients as compared to mild and asymptomatic cases. Herein, we also report alterations in the sums and ratios of several essential amino acids as well as kynurenine to tryptophan ratio, which is an indicator of indoleamine-2,3-dioxygenase (IDO) activity. Our findings suggest that metabolites of creatine including symmetric dimethylarginine, asymmetric dimethylarginine, and 1-methylhistidine can be used as biomarkers to identify patients at risk of poor outcomes in COVID-19, and that lower levels of these metabolites are associated with higher survival probabilities. Additionally, elevated levels of short chain acylcarnitines and carnitine palmitoyltransferase 1 and 2 enzymes indicators have been observed in critically ill COVID-19 patients, indicating their potential usefulness as predictors of hospital mortality and poor survival outcome, likely due to increased demand for energy, inflammation, and mitochondrial dysfunction. The metabolome analysis of COVID-19 patients can improve our understanding of disease severity by providing insight into the relationship between metabolites and disease progression, which can lead to the development of potential therapeutics and clinical risk models. This work was supported by Emergency Response Grant ID: 252