scholarly journals Metabolomic/lipidomic profiling of COVID-19 and individual response to tocilizumab

Author(s):  
Gaia Meoni ◽  
Veronica Ghini ◽  
Laura Maggi ◽  
Alessia Vignoli ◽  
Alessio Mazzoni ◽  
...  

AbstractThe current pandemic emergence of novel coronavirus disease (COVID-19) poses a relevant threat to global health. SARS-CoV-2 infection is characterized by a wide range of clinical manifestations, ranging from absence of symptoms to severe forms that need intensive care treatment. Here, plasma-EDTA samples of 30 patients compared with age- and sex-matched controls were analyzed via untargeted nuclear magnetic resonance (NMR)-based metabolomics and lipidomics. With the same approach, the effect of tocilizumab administration was evaluated in a subset of patients. Despite the heterogeneity of the clinical symptoms, COVID-19 patients are characterized by common plasma metabolomic and lipidomic signatures (91.7% and 87.5% accuracy, respectively, when compared to controls). Tocilizumab treatment resulted in at least partial reversion of the metabolic alterations due to SARS-CoV-2 infection. In conclusion, NMR-based metabolomic and lipidomic profiling provides novel insights into the pathophysiological mechanism of human response to SARS-CoV-2 infection and to monitor treatment outcomes.Author summaryThe current COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is markedly affecting the world population. Here we report about the small-molecule profile of patients hospitalized during the first wave of the COVID-19 pandemic. Using magnetic resonance spectroscopy, we showed that the infection induces profound changes in the metabolome. The analysis of the specific metabolite changes and correlations with clinical data enabled the identification of potential biochemical determinants of the disease fingerprint. We also followed how metabolic alterations revert towards those of the control group upon treatment with tocilizumab, a recombinant humanised monoclonal antibody against the interleukin-6 receptor. These results open up possibilities for the monitoring of novel patients and their individual response to treatment.

2021 ◽  
Vol 17 (2) ◽  
pp. e1009243
Author(s):  
Gaia Meoni ◽  
Veronica Ghini ◽  
Laura Maggi ◽  
Alessia Vignoli ◽  
Alessio Mazzoni ◽  
...  

The current pandemic emergence of novel coronavirus disease (COVID-19) poses a relevant threat to global health. SARS-CoV-2 infection is characterized by a wide range of clinical manifestations, ranging from absence of symptoms to severe forms that need intensive care treatment. Here, plasma-EDTA samples of 30 patients compared with age- and sex-matched controls were analyzed via untargeted nuclear magnetic resonance (NMR)-based metabolomics and lipidomics. With the same approach, the effect of tocilizumab administration was evaluated in a subset of patients. Despite the heterogeneity of the clinical symptoms, COVID-19 patients are characterized by common plasma metabolomic and lipidomic signatures (91.7% and 87.5% accuracy, respectively, when compared to controls). Tocilizumab treatment resulted in at least partial reversion of the metabolic alterations due to SARS-CoV-2 infection. In conclusion, NMR-based metabolomic and lipidomic profiling provides novel insights into the pathophysiological mechanism of human response to SARS-CoV-2 infection and to monitor treatment outcomes.


2018 ◽  
Vol 24 (22) ◽  
pp. 2515-2523 ◽  
Author(s):  
Tianbin Song ◽  
Xiaowei Han ◽  
Lei Du ◽  
Jing Che ◽  
Jing Liu ◽  
...  

Depression is a mental disorder with serious negative health outcomes. Its main clinical manifestations are depressed mood, slow thinking, loss of interest, and lack of energy. The rising incidence of depression has a major impact on patients and their families and imposes a substantial burden on society. With the rapid development of imaging technology in recent years, researchers have studied depression from different perspectives, including molecular, functional, and structural imaging. Many studies have revealed changes in structure, function, and metabolism in various brain regions in patients with depressive disorder. In this review, we summarize relevant studies of depression, including investigations using structural magnetic resonance imaging (MRI), functional MRI (task-state fMRI and resting-state fMRI), diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), brain network and molecular imaging (positron emission tomography [PET] and single photon emission computed tomography [SPECT]), which have contributed to our understanding of the etiology, neuropathology, and pathogenesis of depressive disorder.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Martin Gajdošík ◽  
Karl Landheer ◽  
Kelley M. Swanberg ◽  
Christoph Juchem

AbstractIn vivo magnetic resonance spectroscopy (MRS) is a powerful tool for biomedical research and clinical diagnostics, allowing for non-invasive measurement and analysis of small molecules from living tissues. However, currently available MRS processing and analytical software tools are limited in their potential for in-depth quality management, access to details of the processing stream, and user friendliness. Moreover, available MRS software focuses on selected aspects of MRS such as simulation, signal processing or analysis, necessitating the use of multiple packages and interfacing among them for biomedical applications. The freeware INSPECTOR comprises enhanced MRS data processing, simulation and analytical capabilities in a one-stop-shop solution for a wide range of biomedical research and diagnostic applications. Extensive data handling, quality management and visualization options are built in, enabling the assessment of every step of the processing chain with maximum transparency. The parameters of the processing can be flexibly chosen and tailored for the specific research problem, and extended confidence information is provided with the analysis. The INSPECTOR software stands out in its user-friendly workflow and potential for automation. In addition to convenience, the functionalities of INSPECTOR ensure rigorous and consistent data processing throughout multi-experiment and multi-center studies.


2021 ◽  
Author(s):  
Xiaohan Yuan ◽  
Xiaomei Zhu ◽  
Yang Chen ◽  
Wangyan Liu ◽  
Wen Qian ◽  
...  

Abstract Background: Energetics alteration plays a key role in the process of myocardial injury in chronic hypoxic diseases (CHD). 31P magnetic resonance spectroscopy (MRS) can investigate alterations in cardiac energetics in vivo. This study was aimed to characterize the potential value of 31P MRS in evaluating cardiac energetics alteration of chronic hypoxia rats (CHR).Methods: Twenty-four CHRs were induced by SU5416 combined with hypoxia, and six rats were raised as control group. 31P MRS was performed weekly and the ratio of concentrations of phosphocreatine (PCr) to adenosine triphosphate (ATP) (PCr/ATP) was obtained. The index of cardiac structure and systolic function parameters, including the right ventricular function (RVEF), right ventricular end-diastolic volume index (RVEDVi), right ventricular end-systolic volume index (RVESVi), the left ventricular function parameters were also measured.Results: The declension of resting cardiac PCr/ATP ratio in CHR was observed at the 1st week, compared to control group (2.90±0.35 vs. 3.31±0.45, p =0.045), while the RVEF,RVEDVi and RVESVi decreased at the 2nd week (p<0.05). The PCr/ATP ratio displayed a significant correlation with RVEF(r = 0.605, p = 0.001),RVEDVi and RVESVi (r = -0.661, r = -0.703; p<0.001).Conclusions: 31P MRS can early detect the cardiac energetics alteration in CHR model before the onset of ventricular dysfunction. The decrease of PCr/ATP ratio likely revealed myocardial injury and cardiac dysfunction.


Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 537 ◽  
Author(s):  
Renuka Sriram ◽  
Mark Van Criekinge ◽  
Justin DeLos Santos ◽  
Fayyaz Ahamed ◽  
Hecong Qin ◽  
...  

Non-invasive assessment of the biological aggressiveness of prostate cancer (PCa) is needed for men with localized disease. Hyperpolarized (HP) 13C magnetic resonance (MR) spectroscopy is a powerful approach to image metabolism, specifically the conversion of HP [1-13C]pyruvate to [1-13C]lactate, catalyzed by lactate dehydrogenase (LDH). Significant increase in tumor lactate was measured in high-grade PCa relative to benign and low-grade cancer, suggesting that HP 13C MR could distinguish low-risk (Gleason score ≤3 + 4) from high-risk (Gleason score ≥4 + 3) PCa. To test this and the ability of HP 13C MR to detect these metabolic changes, we cultured prostate tissues in an MR-compatible bioreactor under continuous perfusion. 31P spectra demonstrated good viability and dynamic HP 13C-pyruvate MR demonstrated that high-grade PCa had significantly increased lactate efflux compared to low-grade PCa and benign prostate tissue. These metabolic differences are attributed to significantly increased LDHA expression and LDH activity, as well as significantly increased monocarboxylate transporter 4 (MCT4) expression in high- versus low- grade PCa. Moreover, lactate efflux, LDH activity, and MCT4 expression were not different between low-grade PCa and benign prostate tissues, indicating that these metabolic alterations are specific for high-grade disease. These distinctive metabolic alterations can be used to differentiate high-grade PCa from low-grade PCa and benign prostate tissues using clinically translatable HP [1-13C]pyruvate MR.


2018 ◽  
Vol 6 (12) ◽  
pp. 2348-2353
Author(s):  
Seyyed Arash Mahdawy ◽  
Babak Shekarchi ◽  
Mahshid Zaman

BACKGROUND:  During the eight years of the imposed war, Iraq used various chemical agents such as sulfur mustard and nerve agents (mainly tabun and sometimes soman) on Iran's soldiers. Using information obtained from specialist sequences and analysing information obtained from magnetic resonance imaging (MRI) in a susceptibility weighted imaging (SWI) sequence and magnetic resonance spectroscopy (MRS) provides valuable information on continuation of treatment and identifying functional disorders. AIM: The objective of this research was to evaluate the rate of metabolic variations in chemically injured veterans based on chemical neuromarkers using the chemical sequence MRS, which would help patients and physicians in terms of time, economics, and selection of appropriate therapeutic methods, so if the can physician can get complete information about the metabolic properties of the brain through paraclinical (especially MRI) tools before treatment, he might change his treatment program to reduce the complications caused by it. METHODOLOGY: In this research, 40 chemically injured veterans with brain dysfunction admitted to the screening centre for MRI with specialized MRS sequence participated. Accordingly, we examined the rate of brain metabolic variations about the level of neuromarkers and evaluated the relationship between the level of neuromarkers and brain damages. RESULTS: The results of this research revealed that while the demographic characteristics such as age of the two groups of chemically injured veterans and control was similar, only the median of the NAA/Cr (N-acetylaspartate to creatine ratio) ratio in PONS of chemically injured patients was significantly lower than that of the control group, and this ratio was similar in other parts of the brain in two groups. The results also showed that the ratio of NAA to total choline and Cr was similar in all parts of the brain in two groups. CONCLUSION: Based on the research results, using the MR (Magnetic Resonance) spectroscopy device and determination of the value and ratio of markers such as creatinine and N-acetylaspartate and choline, the brain injuries of chemically injured veterans can be examined. By conducting further studies and larger sample size, the brain damages in veterans can be diagnosed early, which would be a great contribution in their treatment.


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