Amino Acid Metabolism is Significantly Altered at the Time of Admission in Hospital for Severe COVID-19 Patients: Findings from Longitudinal Targeted Metabolomics Analysis

Ansone, Laura; Brīvība, Monta; Silamiķelis, Ivars; Terentjeva, Anna; Pērkons, Ingus; Birzniece, Līga; Rovīte, Vita; Rozentāle, Baiba; Vīksna, Ludmila; Koļesova, Oksana; Klavins, Kristaps; Kloviņš, Jānis

doi:10.1128/spectrum.00338-21

Cited by 62 publications

(80 citation statements)

References 27 publications

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“…Ansone et al analyzed the serum samples of patients at the acute phase of the disease to track the metabolites that changed during the recovery phase, finding alteration of several metabolites involved in: D-glutamine and D-glutamate metabolism (glutamine, glutamic acid), phenylalanine metabolism, and arginine and proline metabolism especially via the urea cycle (citrulline and ornithine). The decrease in tryptophan and the up-regulation of kynurenine and 3-hydroxy-DL-kynurenine in the acute phase confirm the alteration of the tryptophan/kynurenine pathway [ 65 ]. The dysregulation of glucose and energy metabolism in the COVID-19 disease progression, in particular related to the urea cycle and the tricarboxylic acid (TCA) cycle, was also suggested by Jia [ 66 ].…”

Section: Metabolomics Of Covid-19mentioning

confidence: 99%

COVIDomics: The Proteomic and Metabolomic Signatures of COVID-19

Costanzo

Caterino

Fedele

et al. 2022

IJMS

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Omics-based technologies have been largely adopted during this unprecedented global COVID-19 pandemic, allowing the scientific community to perform research on a large scale to understand the pathobiology of the SARS-CoV-2 infection and its replication into human cells. The application of omics techniques has been addressed to every level of application, from the detection of mutations, methods of diagnosis or monitoring, drug target discovery, and vaccine generation, to the basic definition of the pathophysiological processes and the biochemical mechanisms behind the infection and spread of SARS-CoV-2. Thus, the term COVIDomics wants to include those efforts provided by omics-scale investigations with application to the current COVID-19 research. This review summarizes the diverse pieces of knowledge acquired with the application of COVIDomics techniques, with the main focus on proteomics and metabolomics studies, in order to capture a common signature in terms of proteins, metabolites, and pathways dysregulated in COVID-19 disease. Exploring the multiomics perspective and the concurrent data integration may provide new suitable therapeutic solutions to combat the COVID-19 pandemic.

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Section: Metabolomics Of Covid-19mentioning

confidence: 99%

COVIDomics: The Proteomic and Metabolomic Signatures of COVID-19

Costanzo

Caterino

Fedele

et al. 2022

IJMS

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“…Nineteen full-text papers were eligible for the systematic review after 11 records were removed from the initial number of articles. Finally, the meta-analysis involved 14 articles as 5 papers were excluded for reasons listed in ESF, Table 3 (Blasco, Bessy et al 2020, Fraser, Slessarev et al 2020, Kimhofer, Lodge et al 2020, Robertson, Gostner et al 2020, Thomas, Stefanoni et al 2020, Ansone, Briviba et al 2021, D’Amora, Silva et al 2021, Herrera-Van Oostdam, Castaneda-Delgado et al 2021, Lawler, Gray et al 2021, Lionetto, Ulivieri et al 2021, Mangge, Herrmann et al 2021, Marin-Corral, Rodriguez-Morato et al 2021, Michaelis, Zelzer et al 2021, Xiao, Nie et al 2021).…”

Section: Resultsmentioning

confidence: 99%

“…, Ansone, Briviba et al 2021, D'Amora, Silva et al 2021, Herrera-Van Oostdam, Castaneda- Delgado et al 2021, Lawler, Gray et al 2021, Lionetto, Ulivieri et al 2021, Mangge, Herrmann et al 2021, Marin-Corral, Rodriguez-Morato et al 2021, Michaelis, Zelzer et al 2021, Xiao, Nie et al 2021.In this meta-analysis, we considered case-control and retrospective studies. Thisstudy examined 804 subjects in study cohort 1 (329 COVID-19 patients and 475 non-COVID-19 controls), and 773 individuals in the second cohort (involving 270 severe/critical COVID-19 patients and 503 mild/moderate COVID-19 patients).…”

mentioning

confidence: 99%

The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis

Almulla

Supasitthumrong

Tunvirachaisakul

et al. 2022

Preprint

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Coronavirus disease 2019 (COVID-19) is accompanied by activated immune-inflammatory pathways and oxidative stress, which both may induce indoleamine-2,3-dioxygenase (IDO), a key enzyme of the tryptophan (TRP) catabolite (TRYCAT) pathway. The aim of the current study was to systematically review and meta-analyze the TRYCAT pathway status including levels of TRP and kynurenine (KYN) and IDO activity, as assessed using the KYN/TRP ratio. This systematic review was performed in December 2021 and searched data in PubMed, Google Scholar, and Web of sciences. In our meta-analysis we included 14 articles which examine TRP and TRYCATs in COVID-19 patients versus non-COVID-19 controls, and severe/critical versus mild/moderate COVID-19. Overall, the analysis was performed on 1269 individuals, namely 794 COVID-19 patients and 475 controls. The results show a significant (p <0.0001) increase in the KYN/TRP ratio (standardized mean difference, SMD=1.099, 95% confidence interval, CI: 0.714; 1.484) and KYN (SMD= 1.123, 95% CI: 0.730;1.516) and significantly lower TRP ((SMD= -1.002, 95%CI: -1.738; -0.266) in COVID-19 versus controls. The KYN/TRP ratio (SMD= 0.945, 95%CI: 0.629; 1.262) and KYN (SMD= 0.806, 95%CI: 0.462; 1.149) were also significantly (p <0.001) higher and TRP lower (SMD= -0.909, 95% CI: -1.569; -0.249) in severe/critical versus mild/moderate COVID-19. No significant difference was detected in the kynurenic acid (KA)/KYN ratio and KA between COVID-19 patients and controls. Our results indicate increased activity of the IDO enzyme in COVID-19 and in severe/critical patients. The TRYCAT pathway is probably implicated in the pathophysiology and progression of COVID-19 and may signal a worse outcome of the disease.

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“…L-Arginine is an immunomodulatory metabolite that plays a critical role in the pathways involving inflammation, immune regulation, and via its metabolism leading to the generation of nitric oxide (NO), which plays an intrinsic role in Th cell activation and differentiation ( 32 ). Notably, metabolites involved in arginine biosynthesis have been reported to be significantly altered in severe COVID-19 patients ( 26 ). We also found a significant increase in Norvaline during COVID-19 ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Although there are reports that longitudinally studied the patient metabolomic signature (26) and single-cell transcriptomic landscape in COVID-19 patients (35), no study correlated the functional innate and T cell response with the metabolic landscape. Our literature survey did not find any study comparing the T cell immune response in COVID-19 active patients against the spike proteins of ancestral, delta, and omicron variants.…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory innate cytokines and metabolomic signatures shape the T cell response in active COVID-19

Binayke

Zaheer

Dandotiya

et al. 2022

Preprint

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The underlying factors contributing to the evolution of SARS-CoV-2-specific T cell response during COVID-19 infection remain unidentified. To address this, we characterized innate and adaptive immune responses with metabolomic profiling longitudinally at three different time points (0-4, 7-9, and 14-16 days post-COVID-19 positivity) from young mildly symptomatic active COVID-19 patients who got infected with ancestral virus. We observed the induction of anti-RBD and SARS-CoV-2 neutralizing antibodies together with antigen-specific T cell responses as early as 0-4 days post-infection. T cell responses were largely preserved against the delta and omicron variants as compared to the ancestral strain. We determined innate immune responses at an early (days 0-4 post-COVID-19 positivity) time point of active infection in response to TLR 3/7/8 mediated activation. Interestingly, the innate immune response exhibited by the elevated levels of IL-6, IL-1β, and IL-23 correlated with a robust SARS-CoV-2-specific Th1 response at the later time point (14-16 days post covid positivity). To further understand the association of metabolic pathways induced upon active COVID-19 infection with innate and T cell response, metabolomic profiling was performed. As compared to healthy individuals, COVID-19 patients displayed a distinct metabolic signature with an enrichment of pyroglutamate, itaconate, and azelaic acid, which correlated with the SARS-CoV-2-induced innate and T cells response. Our observations reveal mechanisms and potential interventional approaches that may assist in COVID-19 therapeutics and vaccine adjuvant strategies.

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Amino Acid Metabolism is Significantly Altered at the Time of Admission in Hospital for Severe COVID-19 Patients: Findings from Longitudinal Targeted Metabolomics Analysis

Cited by 62 publications

References 27 publications

COVIDomics: The Proteomic and Metabolomic Signatures of COVID-19

COVIDomics: The Proteomic and Metabolomic Signatures of COVID-19

The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis

Proinflammatory innate cytokines and metabolomic signatures shape the T cell response in active COVID-19

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