Metabolomics Approach in Differentiating RAS Responses in ARDS and SAR-CoV-2

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes host angiotensin converting enzyme 2 (ACE2) for viral entry. This interaction can lead to viral-induced dysfunction of renin angiotensin system (RAS) that has been ascribed to SARS-CoV-2 mediate morbidity and mortality. This chapter highlights the role of how bioactive RAS metabolites and their alteration in SARS-CoV-2 and sepsis correlates with disease pathogenesis. Similarly, alteration of RAS metabolite levels has been associated with poorer clinical outcomes, and thus may be a good biomarker to measure disease. LCMS based metabolomics approach is specific, highly sensitive, and precise in quantifying RAS metabolites. This approach can provide a systemic and comprehensive evaluation of the RAS metabolome which may explain specific defects. Additionally, this type of approach can also identify therapeutic targets for the development of effective therapeutic intervention. Accordingly, we discuss the use of LCMS-based RAS metabolomic to study SARS-CoV-2, sepsis, and acute respiratory distress syndrome (ARDS). The overarching purpose of this chapter is to explicate the role of RAS and its bioactive metabolites in viral infections and related immune response. The ability to determine the overall changes and compensatory mechanism may provide insights as to disease severity and highlight potential therapeutic targets within the RAS pathway for the amelioration of lung fibrosis associated with SARS-CoV-2 infection.