Urine metabolomics links dysregulation of the tryptophan-kynurenine pathway to inflammation and severity of COVID-19.

SARS-CoV-2 causes major disturbances in serum metabolite levels, associated with severity of the immune response. Despite the numerous advantages of urine for biomarker discovery, the potential association between urine metabolites and disease severity has not been investigated in coronavirus disease 2019 (COVID-19). In a proof-of-concept study, we performed quantitative urine metabolomics in patients hospitalized with COVID-19 and controls using LC-MS/MS. We assessed whether metabolites alterations were associated with COVID-19, disease severity, and inflammation. The study included 56 patients hospitalized with COVID-19 (26 non-critical and 30 critical disease); 16 healthy controls; and 3 controls with proximal tubule dysfunction unrelated to SARS-CoV-2. Metabolomic profiling revealed a major urinary increase of tryptophan metabolites kynurenine (P < 0.001), 3-hydroxykynurenine (P < 0.001) and 3-hydroxyanthranilate (P < 0.001) in SARS-CoV-2 infected patients. Urine levels of kynurenines were associated with disease severity and systemic inflammation (kynurenine, r 0.43, P = 0.001; 3-hydroxykynurenine, r 0.44, P < 0.001). Increased urinary levels of neutral amino acids and imino acid proline were also common in COVID-19, suggesting specific transport defects. Urine metabolomics identified major alterations in the tryptophan-kynurenine pathway, consistent with changes in host metabolism during SARS-CoV-2 infection. The association between increased urinary levels of kynurenines, inflammation and COVID-19 severity supports further evaluation of these easily available biomarkers.

Dewulf JP ，Martin M ，Marie S ，Oguz F ，Belkhir L ，De Greef J ，Yombi JC ，Wittebole X ，Laterre PF ，Jadoul M ，Gatto L ，Bommer GT ，Morelle J ... -  《Scientific Reports》

Saliva metabolomic profile of COVID-19 patients associates with disease severity.

Coronavirus disease 2019 (COVID-19) is strongly linked to dysregulation of various molecular, cellular, and physiological processes that change abundance of different biomolecules including metabolites that may be ultimately used as biomarkers for disease progression and severity. It is important at early stage to readily distinguish those patients that are likely to progress to moderate and severe stages. This study aimed to investigate the utility of saliva and plasma metabolomic profiles as a potential parameter for risk stratifying COVID-19 patients. LC-MS/MS-based untargeted metabolomics were used to profile the changes in saliva and plasma metabolomic profiles of COVID-19 patients with different severities. Saliva and plasma metabolites were screened in 62 COVID-19 patients and 18 non-infected controls. The COVID-19 group included 16 severe, 15 moderate, 16 mild, and 15 asymptomatic cases. Thirty-six differential metabolites were detected in COVID-19 versus control comparisons. SARS-CoV-2 induced metabolic derangement differed with infection severity. The metabolic changes were identified in saliva and plasma, however, saliva showed higher intensity of metabolic changes. Levels of saliva metabolites such as sphingosine and kynurenine were significantly different between COVID-19 infected and non-infected individuals; while linoleic acid and Alpha-ketoisovaleric acid were specifically increased in severe compared to non-severe patients. As expected, the two prognostic biomarkers of C-reactive protein and D-dimer were negatively correlated with sphingosine and 5-Aminolevulinic acid, and positively correlated with L-Tryptophan and L-Kynurenine. Saliva disease-specific and severity-specific metabolite could be employed as potential COVID-19 diagnostic and prognostic biomarkers.

Saheb Sharif-Askari N ，Soares NC ，Mohamed HA ，Saheb Sharif-Askari F ，Alsayed HAH ，Al-Hroub H ，Salameh L ，Osman RS ，Mahboub B ，Hamid Q ，Semreen MH ，Halwani R ... -  《-》

COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status.

Thomas T ，Stefanoni D ，Reisz JA ，Nemkov T ，Bertolone L ，Francis RO ，Hudson KE ，Zimring JC ，Hansen KC ，Hod EA ，Spitalnik SL ，D'Alessandro A ... -  《JCI Insight》

Evaluation of inflammatory biomarkers and vitamins in hospitalized patients with SARS-CoV-2 infection and post-COVID syndrome.

Concentrations of neopterin, kynurenine and kynurenine/tryptophan ratios predict prognosis and the need for oxygen therapy in patients hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aims of the present study were to evaluate the changes of these biomarkers early in the course of infection, the association with the prior coronavirus disease (COVID-19) vaccination and therapeutic administration of Anti-SARS-CoV-2 monoclonal antibodies, investigation of other potential biomarkers including neuropilin, 8-hydroxy-2-deoxyguanosine and 8-hydroxyguanosine in patients hospitalized with SARS-CoV-2 infection and an assessment of these biomarkers and vitamins A, E and D in patients with post-COVID syndrome. Urine and blood samples were obtained on the 1st to the 4th day and 4th to 7th day from 108 patients hospitalized with COVID-19. Chromatography tandem mass spectrometry methods were used to analyse neopterin, kynurenine, tryptophan, liposoluble vitamins, and DNA damage biomarkers. A statistically significant decrease of neopterin, kynurenine and kynurenine/tryptophan ratios was observed on after 4th to 7th day of hospitalization, and concentrations of these biomarkers were increased in patients with poor prognosis and subsequent post-COVID syndrome. The concentrations of remaining biomarker and vitamins were not associated with outcomes, although markedly decreased concentrations of vitamin A, E and D were noted. The concentrations of neopterin, kynurenine and kynurenine/tryptophan ratios decrease during the course of infection SARS-CoV-2 and are associated with the post-COVID syndrome. No other prognostic biomarkers were identified.

Krčmová LK ，Javorská L ，Matoušová K ，Šmahel P ，Skála M ，Kopecký M ，Suwanvecho C ，Přívratská N ，Turoňová D ，Melichar B ... -  《-》

Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation.

Ceballos FC ，Virseda-Berdices A ，Resino S ，Ryan P ，Martínez-González O ，Peréz-García F ，Martin-Vicente M ，Brochado-Kith O ，Blancas R ，Bartolome-Sánchez S ，Vidal-Alcántara EJ ，Albóniga-Díez OE ，Cuadros-González J ，Blanca-López N ，Martínez I ，Martinez-Acitores IR ，Barbas C ，Fernández-Rodríguez A ，Jiménez-Sousa MÁ ... -  《Frontiers in Immunology》