Metabolomics reveals sex-specific metabolic shifts and predicts the duration from positive to negative in non-severe COVID-19 patients during recovery process

Zheng, Hong; Jin, Shengwei; Li, Ting; Ying, Weiyang; Ying, Binyu; Dong, Chen; Ning, Jie; Zheng, Chanfan; Li, Yuping; Li, Chen; Chen, Chengshui; Li, Xiaokun; Gao, Hongchang

doi:10.1016/j.csbj.2021.03.039

Cited by 18 publications

(25 citation statements)

References 80 publications

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“…Because older male COVID-19 patients have a poorer prognosis, as compared to young females [ 3 , 40 , 41 ], and given the large size of our cohorts, we tried identifying metabolic and clinical correlates for these variables ( Figure 3 A–D, Supplementary Figures S4E–J and S5 ). Aging was associated with increased weight, BMI, kidney dysfunction (creatine, creatinine), and tissue damage (creatine kinase), along with markers of hypercoagulability (VWF:AG, FVIII), fibrinolysis (D-dimer), hyperglycemia, hypoxia and mitochondrial dysfunction (2-hydroxyglutarate, lactate, spermidine, acylcarnitines), purine oxidation (urate), inflammation (CRP), proteolysis (albumin), and anemia (hemoglobin levels, RBC counts), especially in COVID-19 patients ( Figure 3 A–D).…”

Section: Resultsmentioning

confidence: 99%

“…As examples, evaluations of biological (e.g., sex [ 54 ], age [ 55 ], ethnicity [ 56 ], body mass index [ 57 ], blood group [ 42 ]) and clinical (e.g., obesity, diabetes, cardiovascular disease, kidney disease) [ 53 ] characteristics are necessary to define independent and overlapping metabolic findings in COVID-19 and other acute diseases. To this end, in some cases, we performed sub-analyses focusing on one variable at a time, such as sex [ 3 , 41 ] or inflammation (e.g., circulating interleukin-6 (IL-6) levels) [ 1 , 4 ].…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, small-molecule metabolites provide the building blocks that fuel viral replication, from nucleic acids to proteins and membrane lipids. SARS-CoV-2 [ 1 , 2 , 3 , 4 , 5 ], like other viral infections [ 6 ], was found to promote the mobilization of free fatty acids to support the formation of viral capsid-associated membranes; a phenomenon that could be explained, at least in part, by activation of phospholipase A2 [ 7 , 8 ], a target amenable to pharmacological intervention.…”

Section: Introductionmentioning

confidence: 99%

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Biological and Clinical Factors Contributing to the Metabolic Heterogeneity of Hospitalized Patients with and without COVID-19

D’Alessandro

Thomas

Akpan

et al. 2021

Cells

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The Corona Virus Disease 2019 (COVID-19) pandemic represents an ongoing worldwide challenge. The present large study sought to understand independent and overlapping metabolic features of samples from acutely ill patients (n = 831) that tested positive (n = 543) or negative (n = 288) for COVID-19. High-throughput metabolomics analyses were complemented with antigen and enzymatic activity assays on plasma from acutely ill patients collected while in the emergency department, at admission, or during hospitalization. Lipidomics analyses were also performed on COVID-19-positive or -negative subjects with the lowest and highest body mass index (n = 60/group). Significant changes in amino acid and fatty acid/acylcarnitine metabolism emerged as highly relevant markers of disease severity, progression, and prognosis as a function of biological and clinical variables in these patients. Further, machine learning models were trained by entering all metabolomics and clinical data from half of the COVID-19 patient cohort and then tested on the other half, yielding ~78% prediction accuracy. Finally, the extensive amount of information accumulated in this large, prospective, observational study provides a foundation for mechanistic follow-up studies and data sharing opportunities, which will advance our understanding of the characteristics of the plasma metabolism in COVID-19 and other acute critical illnesses.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biological and Clinical Factors Contributing to the Metabolic Heterogeneity of Hospitalized Patients with and without COVID-19

D’Alessandro

Thomas

Akpan

et al. 2021

Cells

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“…Proteins could also be biomarkers of respiratory diseases [ 78 , 87 – 89 ]. Optimistically, LC–MS, therefore, have been proposed to COVID-19 diagnosis and research that could bring new insight into biological impact of COVID-19 [ 48 , 60 ]. Various breath sampling systems (Table 3 ) have been successfully developed for collecting EBC [ 90 ].…”

Section: Ms-based Multidimensional Breath Analysismentioning

confidence: 99%

Mass Spectrometry-Based Human Breath Analysis: Towards COVID-19 Diagnosis and Research

Yuan

2021

J. Anal. Test.

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COVID-19 is a highly contagious respiratory disease that can be infected through human exhaled breath. Human breath analysis is an attractive strategy for rapid diagnosis of COVID-19 in a non-invasive way by monitoring breath biomarkers. Mass spectrometry (MS)-based approaches offer a promising analytical platform for human breath analysis due to their high speed, specificity, sensitivity, reproducibility, and broad coverage, as well as its versatile coupling methods with different chromatographic separation, and thus can lead to a better understanding of the clinical and biochemical processes of COVID-19. Herein, we try to review the developments and applications of MS-based approaches for multidimensional analysis of COVID-19 breath samples, including metabolites, proteins, microorganisms, and elements. New features of breath sampling and analysis are highlighted. Prospects and challenges on MS-based breath analysis related to COVID-19 diagnosis and study are discussed.

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“…An additional unbiased strategy for defining circulating factors useful for risk stratification is mass spectrometric metabolomics, a technique that requires a minimum of initial sample preparation (snap freezing of serum or heparin serum and its storage at -80° C), is entirely automatable and yields accurate information on hundreds of known metabolites (i.e. a combination of chromatographic retention times and masses that allow for the >bona fide identification of the corresponding chemical compound) as well as thousands of unknown metabolites [ 21 – 32 ].…”

Section: Introductionmentioning

confidence: 99%

Circulating acetylated polyamines correlate with Covid-19 severity in cancer patients

Bourgin

Derosa

Silva

et al. 2021

Aging

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Cancer patients are particularly susceptible to the development of severe Covid-19, prompting us to investigate the serum metabolome of 204 cancer patients enrolled in the ONCOVID trial. We previously described that the immunosuppressive tryptophan/kynurenine metabolite anthranilic acid correlates with poor prognosis in non-cancer patients. In cancer patients, we observed an elevation of anthranilic acid at baseline (without Covid-19 diagnosis) and no further increase with mild or severe Covid-19. We found that, in cancer patients, Covid-19 severity was associated with the depletion of two bacterial metabolites, indole-3-proprionate and 3-phenylproprionate, that both positively correlated with the levels of several inflammatory cytokines. Most importantly, we observed that the levels of acetylated polyamines (in particular N 1 -acetylspermidine, N 1 ,N 8 -diacetylspermidine and N 1 ,N 12 -diacetylspermine), alone or in aggregate, were elevated in severe Covid-19 cancer patients requiring hospitalization as compared to uninfected cancer patients or cancer patients with mild Covid-19. N 1 -acetylspermidine and N 1 ,N 8 -diacetylspermidine were also increased in patients exhibiting prolonged viral shedding (>40 days). An abundant literature indicates that such acetylated polyamines increase in the serum from patients with cancer, cardiovascular disease or neurodegeneration, associated with poor prognosis. Our present work supports the contention that acetylated polyamines are associated with severe Covid-19, both in the general population and in patients with malignant disease. Severe Covid-19 is characterized by a specific metabolomic signature suggestive of the overactivation of spermine/spermidine N 1 -acetyl transferase-1 (SAT1), which catalyzes the first step of polyamine catabolism.

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Metabolomics reveals sex-specific metabolic shifts and predicts the duration from positive to negative in non-severe COVID-19 patients during recovery process

Abstract: Graphical abstract

Cited by 18 publications

References 80 publications

Biological and Clinical Factors Contributing to the Metabolic Heterogeneity of Hospitalized Patients with and without COVID-19

Biological and Clinical Factors Contributing to the Metabolic Heterogeneity of Hospitalized Patients with and without COVID-19

Mass Spectrometry-Based Human Breath Analysis: Towards COVID-19 Diagnosis and Research

Circulating acetylated polyamines correlate with Covid-19 severity in cancer patients

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