ABSTRACT The heterogeneity in severity and outcome of COVID-19 cases points out the urgent need for early molecular characterization of patients followed by risk-stratified care. The main objective of this study was to evaluate the fluctuations of serum metabolomic profiles of COVID-19 patients with severe illness during the different disease stages in a longitudinal manner. We demonstrate a distinct metabolomic signature in serum samples of 32 hospitalized patients at the acute phase compared to the recovery period, suggesting the tryptophan (tryptophan, kynurenine, and 3-hydroxy-DL-kynurenine) and arginine (citrulline and ornithine) metabolism as contributing pathways in the immune response to SARS-CoV-2 with a potential link to the clinical severity of the disease. In addition, we suggest that glutamine deprivation may further result in inhibited M2 macrophage polarization as a complementary process, and highlight the contribution of phenylalanine and tyrosine in the molecular mechanisms underlying the severe course of the infection. In conclusion, our results provide several functional metabolic markers for disease progression and severe outcome with potential clinical application. IMPORTANCE Although the host defense mechanisms against SARS-CoV-2 infection are still poorly described, they are of central importance in shaping the course of the disease and the possible outcome. Metabolomic profiling may complement the lacking knowledge of the molecular mechanisms underlying clinical manifestations and pathogenesis of COVID-19. Moreover, early identification of metabolomics-based biomarker signatures is proved to serve as an effective approach for the prediction of disease outcome. Here we provide the list of metabolites describing the severe, acute phase of the infection and bring the evidence of crucial metabolic pathways linked to aggressive immune responses. Finally, we suggest metabolomic phenotyping as a promising method for developing personalized care strategies in COVID-19 patients.
【저자키워드】 COVID-19, SARS-CoV-2, metabolomics, longitudinal study, Virus-host interactions, 【초록키워드】 Macrophage, metabolomics, immune response, Pathogenesis, arginine, knowledge, SARS-COV-2 infection, severity, Infection, complement, outcome, molecular mechanism, heterogeneity, metabolism, clinical manifestations, Disease progression, serum, immune responses, Patient, pathway, Tryptophan, Kynurenine, metabolites, molecular, disease, metabolomic profiling, Care, mechanism, metabolite, Glutamine, COVID-19 patients, marker, Phenylalanine, Clinical severity, Evidence, host defense, Pathways, metabolic pathways, COVID-19 cases, Deprivation, COVID-19 patient, complementary, defense mechanisms, evidence of, followed by, tyrosine, clinical manifestation, citrulline, metabolic pathway, serum samples, profile, acute phase, COVID-19 case, disease stage, molecular mechanisms, pathogenesis of COVID-19, ornithine, list, fluctuations, Defense, serum sample, M2 macrophage polarization, Host, biomarker signature, approach, metabolomic, effective, fluctuation, highlight, Course, described, evaluate, addition, the disease, inhibited, functional, hospitalized patient, metabolomic signature, 【제목키워드】 longitudinal, finding, acid, time, Altered,