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COVID-19 has re-established the significance of analyzing the organism through a metabolic perspective to uncover the dynamic interconnections within the biological systems. The role of micronutrient status and metabolic health emerge as pivotal in COVID-19 pathogenesis and the immune system's response. Metabolic disruption, proceeding from modifiable factors, has been proposed as a significant risk factor accounting for infection susceptibility, disease severity and risk for post-COVID complications. Metabolomics, the comprehensive study and quantification of intermediates and products of metabolism, is a rapidly evolving field and a novel tool in biomarker discovery. In this article, we propose that leveraging insulin resistance biomarkers along with biomarkers of micronutrient deficiencies, will allow for a diagnostic window and provide functional therapeutic targets. Specifically, metabolomics can be applied as: a. At-home test to assess the risk of infection and propose nutritional support, b. A screening tool for high-risk COVID-19 patients to develop serious illness during hospital admission and prioritize medical support, c(i). A tool to match nutritional support with specific nutrient requirements for mildly ill patients to reduce the risk for hospitalization, and c(ii). for critically ill patients to reduce recovery time and risk of post-COVID complications, d. At-home test to monitor metabolic health and reduce post-COVID symptomatology. Metabolic rewiring offers potential virtues towards disease prevention, dissection of high-risk patients, taking actionable therapeutic measures, as well as shielding against post-COVID syndrome., Graphical abstract Image 1

Metabolites are the downstream product of genome, transcriptome and proteome expression, and their dynamic levels are affected by environmental factors including the microbiome, the diet, underlying disease, and drug intake. Their close relationship with the phenotype has led to the development of diagnostic and therapeutic tools based on the study of metabolites, metabolomics. Current advancements of the clinical application of metabolomics will be discussed in this chapter, focusing on noncommunicable diseases. In addition, metabolomics can be utilized to unmask nutritional imbalances related to noncommunicable diseases and to proceed to their replenishment and maintenance of metabolic homeostasis. Pharmacometabolomics is a potent tool for the selection, monitoring, and optimization of treatment based on the personal metabolic profile. Overall, metabolomics provides an emerging approach for the early diagnosis and prediction of underlying noncommunicable diseases and the proper selection of existing treatment or discovery of novel therapeutic targets.

Metabolomics approaches are categorized into two analytical platforms, untargeted, which offers a comprehensive scanning of the metabolome formulating the hypothesis, while targeted metabolomics explores the generated question toward validation. The identification of the metabolic entities can be intricating, due to the physicochemical diversities of the metabolites, the interlaboratory variations, and the unknown actual metabolic spectrum. Nuclear magnetic resonance and mass spectrometry detectors, coupled with liquid chromatography or gas chromatography, include the state-of-the-art methodologies of the laboratory setting for both targeted and untargeted metabolomics studies. These analytical techniques can provide detailed characterization of hundreds to thousands of metabolites that assist research efforts for metabolomics-based biomarker discovery of clinical relevance enabling the transition to precision medicine strategies. However, the integration of metabolic biomarkers to clinical applications entails challenges in terms of validation, which is discussed hereafter, along with the future perspectives on clinical metabolomics translational potentials.