COVID-19 and Comorbidities: What Has Been Unveiled by Metabolomics?

The COVID-19 pandemic has brought about diverse impacts on the global population. Individuals with comorbidities were more susceptible to the severe symptoms caused by the virus. Within the crisis scenario, metabolomics represents a potential area of science capable of providing relevant information for understanding the metabolic pathways associated with the intricate interaction between the viral disease and previous comorbidities. This work aims to provide a comprehensive description of the scientific production pertaining to metabolomics within the specific context of COVID-19 and comorbidities, while highlighting promising areas for exploration by those interested in the subject. In this review, we highlighted the studies of metabolomics that indicated a variety of metabolites associated with comorbidities and COVID-19. Furthermore, we observed that the understanding of the metabolic processes involved between comorbidities and COVID-19 is limited due to the urgent need to report disease outcomes in individuals with comorbidities. The overlap of two or more comorbidities associated with the severity of COVID-19 hinders the comprehension of the significance of each condition. Most identified studies are observational, with a restricted number of patients, due to challenges in sample collection amidst the emergent situation.

Comprehending Cardiac Dysfunction by Oxidative Stress: Untargeted Metabolomics of In Vitro Samples.

Cardiovascular diseases (CVDs) are noncommunicable diseases known for their complex etiology and high mortality rate. Oxidative stress (OS), a condition in which the release of free radical exceeds endogenous antioxidant capacity, is pivotal in CVC, such as myocardial infarction, ischemia/reperfusion, and heart failure. Due to the lack of information about the implications of OS on cardiovascular conditions, several methodologies have been applied to investigate the causes and consequences, and to find new ways of diagnosis and treatment as well. In the present study, cardiac dysfunction was evaluated by analyzing cells' alterations with untargeted metabolomics, after simulation of an oxidative stress condition using hydrogen peroxide (H2O2) in H9c2 myocytes. Optimizations of H2O2 concentration, cell exposure, and cell recovery times were performed through MTT assays. Intracellular metabolites were analyzed right after the oxidative stress (oxidative stress group) and after 48 h of cell recovery (recovery group) by ultra-high-performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) in positive and negative ESI ionization mode. Significant alterations were found in pathways such as "alanine, aspartate and glutamate metabolism", "glycolysis", and "glutathione metabolism", mostly with increased metabolites (upregulated). Furthermore, our results indicated that the LC-MS method is effective for studying metabolism in cardiomyocytes and generated excellent fit (R2Y > 0.987) and predictability (Q2 > 0.84) values.

Metabolomics Data Treatment: Basic Directions of the Full Process.

The present chapter describes basic aspects of the main steps for data processing on mass spectrometry-based metabolomics platforms, focusing on the main objectives and important considerations of each step. Initially, an overview of metabolomics and the pivotal techniques applied in the field are presented. Important features of data acquisition and preprocessing such as data compression, noise filtering, and baseline correction are revised focusing on practical aspects. Peak detection, deconvolution, and alignment as well as missing values are also discussed. Special attention is given to chemical and mathematical normalization approaches and the role of the quality control (QC) samples. Methods for uni- and multivariate statistical analysis and data pretreatment that could impact them are reviewed, emphasizing the most widely used multivariate methods, i.e., principal components analysis (PCA), partial least squares-discriminant analysis (PLS-DA), orthogonal partial least square-discriminant analysis (OPLS-DA), and hierarchical cluster analysis (HCA). Criteria for model validation and softwares used in data processing were also approached. The chapter ends with some concerns about the minimal requirements to report metadata in metabolomics.