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Metabolites
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Advances in Understanding Altered Metabolism in SARS-CoV-2 Infection
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Advances in Understanding Altered Metabolism in SARS-CoV-2 Infection

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Integrative Metabolomics".

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 14860

Special Issue Editors

Dr. Ruey Leng Loo

E-Mail Website
Guest Editor
Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University, Perth, WA 6150, Australia
Interests: metabolomics/metabonomics/metabolic phenotyping; molecular nutrition; diet; blood pressure; cardiovascular disease
Dr. Samantha Lodge

E-Mail Website
Guest Editor
Australian National Phenome Centre and Computational and Systems Medicine, Health Futures Institute, Murdoch University, Perth, WA 6150, Australia
Interests: metabonomics in human health and disease

Special Issue Information

Dear Colleagues,

The SARS-CoV-2 pandemic has affected over 760 million people across the world, resulting in nearly 7 million recorded deaths, as well as a series of health-related issues, ranging from serious events, such as multi-organ damage and respiratory failure, to relatively mild but debilitating symptoms, such as fatigue. Concerted efforts have been made to better understand the impact of COVID-19 infection on human health. Omics technologies, such as metabolomics and lipidomics, have been increasingly applied to explore host–virus interactions, understand disease severity and its long-term effects, and investigate the potential for new therapeutic and diagnostic tools.

This Special Issue of Metabolites aims to highlight omics-related approaches that contribute to a better understanding of all aspects of COVID-19 infections, including but not limited to the immune response, disease severity, and related complications. Reviews and original articles involving human or animal models, vaccination programs, as well as the application of new methods or data analysis strategies to interrogate COVID-19 cohorts, will also be considered.

Dr. Ruey Leng Loo
Dr. Samantha Lodge
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metabonomics/metabolomics/metabolic phenotyping
  • SARS-CoV-2
  • SARS-CoV-2 vaccination
  • biomarkers
  • disease biomarkers

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Published Papers (5 papers)

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Research

18 pages, 2784 KiB  
Article
Searching for New Biomarkers to Assess COVID-19 Patients: A Pilot Study
by Nikolay V. Goncharov, Piotr P. Avdonin, Natalia G. Voitenko, Polina A. Voronina, Polina I. Popova, Artemy V. Novozhilov, Maria S. Blinova, Victoria S. Popkova, Daria A. Belinskaia and Pavel V. Avdonin
Metabolites 2023, 13(12), 1194; https://doi.org/10.3390/metabo13121194 - 10 Dec 2023
Viewed by 1637
Abstract
During the initial diagnosis of urgent medical conditions, which include acute infectious diseases, it is important to assess the severity of the patient’s clinical state as quickly as possible. Unlike individual biochemical or physiological indicators, derived indices make it possible to better characterize [...] Read more.
During the initial diagnosis of urgent medical conditions, which include acute infectious diseases, it is important to assess the severity of the patient’s clinical state as quickly as possible. Unlike individual biochemical or physiological indicators, derived indices make it possible to better characterize a complex syndrome as a set of symptoms, and therefore quickly take a set of adequate measures. Recently, we reported on novel diagnostic indices containing butyrylcholinesterase (BChE) activity, which is decreased in COVID-19 patients. Also, in these patients, the secretion of von Willebrand factor (vWF) increases, which leads to thrombosis in the microvascular bed. The objective of this study was the determination of the concentration and activity of vWF in patients with COVID-19, and the search for new diagnostic indices. One of the main objectives was to compare the prognostic values of some individual and newly derived indices. Patients with COVID-19 were retrospectively divided into two groups: survivors (n = 77) and deceased (n = 24). According to clinical symptoms and computed tomography (CT) results, the course of disease was predominantly moderate in severity. The first blood sample (first point) was taken upon admission to the hospital, the second sample (second point)—within 4–6 days after admission. Along with the standard spectrum of biochemical indicators, BChE activity (BChEa or BChEb for acetylthiocholin or butyrylthiocholin, respectively), malondialdehyde (MDA), and vWF analysis (its antigen level, AGFW, and its activity, ActWF) were determined and new diagnostic indices were derived. The pooled sensitivity, specificity, and area under the receiver operating curve (AUC), as well as Likelihood ratio (LR) and Odds ratio (OR) were calculated. The level of vWF antigen in the deceased group was 1.5-fold higher than the level in the group of survivors. Indices that include vWF antigen levels are superior to indices using vWF activity. It was found that the index [Urea] × [AGWF] × 1000/(BChEb × [ALB]) had the best discriminatory power to predict COVID-19 mortality (AUC = 0.91 [0.83, 1.00], p < 0.0001; OR = 72.0 [7.5, 689], p = 0.0002). In addition, [Urea] × 1000/(BChEb × [ALB]) was a good predictor of mortality (AUC = 0.95 [0.89, 1.00], p < 0.0001; OR = 31.5 [3.4, 293], p = 0.0024). The index [Urea] × [AGWF] × 1000/(BChEb × [ALB]) was the best predictor of mortality associated with COVID-19 infection, followed by [Urea] × 1000/(BChEb × [ALB]). After validation in a subsequent cohort, these two indices could be recommended for diagnostic laboratories. Full article
(This article belongs to the Special Issue Advances in Understanding Altered Metabolism in SARS-CoV-2 Infection)
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29 pages, 38102 KiB  
Article
Quantitative Serum NMR Spectroscopy Stratifies COVID-19 Patients and Sheds Light on Interfaces of Host Metabolism and the Immune Response with Cytokines and Clinical Parameters
by Titus Rössler, Georgy Berezhnoy, Yogesh Singh, Claire Cannet, Tony Reinsperger, Hartmut Schäfer, Manfred Spraul, Manfred Kneilling, Uta Merle and Christoph Trautwein
Metabolites 2022, 12(12), 1277; https://doi.org/10.3390/metabo12121277 - 16 Dec 2022
Cited by 12 | Viewed by 3053
Abstract
The complex manifestations of COVID-19 are still not fully decoded on the molecular level. We combined quantitative the nuclear magnetic resonance (NMR) spectroscopy serum analysis of metabolites, lipoproteins and inflammation markers with clinical parameters and a targeted cytokine panel to characterize COVID-19 in [...] Read more.
The complex manifestations of COVID-19 are still not fully decoded on the molecular level. We combined quantitative the nuclear magnetic resonance (NMR) spectroscopy serum analysis of metabolites, lipoproteins and inflammation markers with clinical parameters and a targeted cytokine panel to characterize COVID-19 in a large (534 patient samples, 305 controls) outpatient cohort of recently tested PCR-positive patients. The COVID-19 cohort consisted of patients who were predominantly in the initial phase of the disease and mostly exhibited a milder disease course. Concerning the metabolic profiles of SARS-CoV-2-infected patients, we identified markers of oxidative stress and a severe dysregulation of energy metabolism. NMR markers, such as phenylalanine, inflammatory glycoproteins (Glyc) and their ratio with the previously reported supramolecular phospholipid composite (Glyc/SPC), showed a predictive power comparable to laboratory parameters such as C-reactive protein (CRP) or ferritin. We demonstrated interfaces between the metabolism and the immune system, e.g., we could trace an interleukin (IL-6)-induced transformation of a high-density lipoprotein (HDL) to a pro-inflammatory actor. Finally, we showed that metadata such as age, sex and constitution (e.g., body mass index, BMI) need to be considered when exploring new biomarkers and that adding NMR parameters to existing diagnoses expands the diagnostic toolbox for patient stratification and personalized medicine. Full article
(This article belongs to the Special Issue Advances in Understanding Altered Metabolism in SARS-CoV-2 Infection)
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18 pages, 2191 KiB  
Article
Urine Metabolites Enable Fast Detection of COVID-19 Using Mass Spectrometry
by Alexandre Varao Moura, Danilo Cardoso de Oliveira, Alex Ap. R. Silva, Jonas Ribeiro da Rosa, Pedro Henrique Dias Garcia, Pedro Henrique Godoy Sanches, Kyana Y. Garza, Flavio Marcio Macedo Mendes, Mayara Lambert, Junier Marrero Gutierrez, Nicole Marino Granado, Alicia Camacho dos Santos, Iasmim Lopes de Lima, Lisamara Dias de Oliveira Negrini, Marcia Aparecida Antonio, Marcos N. Eberlin, Livia S. Eberlin and Andreia M. Porcari
Metabolites 2022, 12(11), 1056; https://doi.org/10.3390/metabo12111056 - 2 Nov 2022
Cited by 5 | Viewed by 2660
Abstract
The COVID-19 pandemic boosted the development of diagnostic tests to meet patient needs and provide accurate, sensitive, and fast disease detection. Despite rapid advancements, limitations related to turnaround time, varying performance metrics due to different sampling sites, illness duration, co-infections, and the need [...] Read more.
The COVID-19 pandemic boosted the development of diagnostic tests to meet patient needs and provide accurate, sensitive, and fast disease detection. Despite rapid advancements, limitations related to turnaround time, varying performance metrics due to different sampling sites, illness duration, co-infections, and the need for particular reagents still exist. As an alternative diagnostic test, we present urine analysis through flow-injection–tandem mass spectrometry (FIA-MS/MS) as a powerful approach for COVID-19 diagnosis, targeting the detection of amino acids and acylcarnitines. We adapted a method that is widely used for newborn screening tests on dried blood for urine samples in order to detect metabolites related to COVID-19 infection. We analyzed samples from 246 volunteers with diagnostic confirmation via PCR. Urine samples were self-collected, diluted, and analyzed with a run time of 4 min. A Lasso statistical classifier was built using 75/25% data for training/validation sets and achieved high diagnostic performances: 97/90% sensitivity, 95/100% specificity, and 95/97.2% accuracy. Additionally, we predicted on two withheld sets composed of suspected hospitalized/symptomatic COVID-19-PCR negative patients and patients out of the optimal time-frame collection for PCR diagnosis, with promising results. Altogether, we show that the benchmarked FIA-MS/MS method is promising for COVID-19 screening and diagnosis, and is also potentially useful after the peak viral load has passed. Full article
(This article belongs to the Special Issue Advances in Understanding Altered Metabolism in SARS-CoV-2 Infection)
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14 pages, 2355 KiB  
Article
Metabolomics Markers of COVID-19 Are Dependent on Collection Wave
by Holly-May Lewis, Yufan Liu, Cecile F. Frampas, Katie Longman, Matt Spick, Alexander Stewart, Emma Sinclair, Nora Kasar, Danni Greener, Anthony D. Whetton, Perdita E. Barran, Tao Chen, Deborah Dunn-Walters, Debra J. Skene and Melanie J. Bailey
Metabolites 2022, 12(8), 713; https://doi.org/10.3390/metabo12080713 - 30 Jul 2022
Cited by 16 | Viewed by 4336
Abstract
The effect of COVID-19 infection on the human metabolome has been widely reported, but to date all such studies have focused on a single wave of infection. COVID-19 has generated numerous waves of disease with different clinical presentations, and therefore it is pertinent [...] Read more.
The effect of COVID-19 infection on the human metabolome has been widely reported, but to date all such studies have focused on a single wave of infection. COVID-19 has generated numerous waves of disease with different clinical presentations, and therefore it is pertinent to explore whether metabolic disturbance changes accordingly, to gain a better understanding of its impact on host metabolism and enable better treatments. This work used a targeted metabolomics platform (Biocrates Life Sciences) to analyze the serum of 164 hospitalized patients, 123 with confirmed positive COVID-19 RT-PCR tests and 41 providing negative tests, across two waves of infection. Seven COVID-19-positive patients also provided longitudinal samples 2–7 months after infection. Changes to metabolites and lipids between positive and negative patients were found to be dependent on collection wave. A machine learning model identified six metabolites that were robust in diagnosing positive patients across both waves of infection: TG (22:1_32:5), TG (18:0_36:3), glutamic acid (Glu), glycolithocholic acid (GLCA), aspartic acid (Asp) and methionine sulfoxide (Met-SO), with an accuracy of 91%. Although some metabolites (TG (18:0_36:3) and Asp) returned to normal after infection, glutamic acid was still dysregulated in the longitudinal samples. This work demonstrates, for the first time, that metabolic dysregulation has partially changed over the course of the pandemic, reflecting changes in variants, clinical presentation and treatment regimes. It also shows that some metabolic changes are robust across waves, and these can differentiate COVID-19-positive individuals from controls in a hospital setting. This research also supports the hypothesis that some metabolic pathways are disrupted several months after COVID-19 infection. Full article
(This article belongs to the Special Issue Advances in Understanding Altered Metabolism in SARS-CoV-2 Infection)
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8 pages, 714 KiB  
Article
Biomarkers of Endothelial Damage in Distinct Phases of Multisystem Inflammatory Syndrome in Children
by Monica Gelzo, Antonietta Giannattasio, Marco Maglione, Stefania Muzzica, Carolina D’Anna, Filippo Scialò, Thaililja Gagliardo, Michela Grieco, Vincenzo Tipo and Giuseppe Castaldo
Metabolites 2022, 12(8), 680; https://doi.org/10.3390/metabo12080680 - 24 Jul 2022
Cited by 8 | Viewed by 1977
Abstract
Endothelial hyperinflammation and vasculitis are known hallmarks of acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C). They are due to the direct effect of the virus on endothelial cells enhanced by pro-inflammatory modulators and may cause venous/arterial thrombosis. Therefore, it is essential [...] Read more.
Endothelial hyperinflammation and vasculitis are known hallmarks of acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C). They are due to the direct effect of the virus on endothelial cells enhanced by pro-inflammatory modulators and may cause venous/arterial thrombosis. Therefore, it is essential to identify patients with endothelial damage early in order to establish specific therapies. We studied the monocyte chemoattractant protein 1 (MCP-1), the perinuclear anti-neutrophil cytoplasmic antibodies (pANCA), and the vascular endothelial growth factor A (VEGF-A) in serum from 45 MIS-C patients at hospital admission and 24 healthy controls (HC). For 13/45 MIS-C patients, we measured the three serum biomarkers also after one week from hospitalization. At admission, MIS-C patients had significantly higher levels of MCP-1 and VEGF-A than the HC, but no significant differences were observed for pANCA. While after one week, MCP-1 was significantly lower, pANCA was higher and VEGF-A levels were not significantly different from the admission values. These findings suggest an involvement of epithelium in MIS-C with an acute phase, showing high MCP-1 and VEGF-A, followed by an increase in pANCA that suggests a vasculitis development. The serum biomarker levels may help to drive personalized therapies in these phases with anticoagulant prophylaxis, immunomodulators, and/or anti-angiogenic drugs. Full article
(This article belongs to the Special Issue Advances in Understanding Altered Metabolism in SARS-CoV-2 Infection)
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