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National Science Review, Volume 7 , Issue 7 : 1157-1168(2020) https://doi.org/10.1093/nsr/nwaa086

Plasma metabolomic and lipidomic alterations associated with COVID-19

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  • ReceivedApr 1, 2020
  • AcceptedApr 23, 2020
  • PublishedApr 28, 2020

Abstract

The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. The symptoms of COVID-19 range from mild to severe, but the physiological changes associated with COVID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of patients with COVID-19 who had experienced different symptoms. We found that metabolite and lipid alterations exhibit apparent correlation with the course of disease in these patients, indicating that the development of COVID-19 affected their whole-body metabolism. In particular, malic acid of the TCA cycle and carbamoyl phosphate of the urea cycle result in altered energy metabolism and hepatic dysfunction, respectively. It should be noted that carbamoyl phosphate is profoundly down-regulated in patients who died compared with patients with mild symptoms. And, more importantly, guanosine monophosphate (GMP), which is mediated not only by GMP synthase but also by CD39 and CD73, is significantly changed between healthy subjects and patients with COVID-19, as well as between the mild and fatal cases. In addition, dyslipidemia was observed in patients with COVID-19. Overall, the disturbed metabolic patterns have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about plasma biomarkers associated with COVID-19 and potential therapeutic targets, as well as an important resource for further studies of the pathogenesis of COVID-19.


Funded by

Strategic Priority Research Program of CAS(XDB29010300 to X.Z.)

National Science and Technology Major Project(2020ZX09201-001 to D.-Y.Z.)

National Science and Technology Major Project(2018ZX10101004 to X.Z.)

National Natural Science Foundation of China(81971818)

National Natural Science Foundation of China(81772047 to Y.S.)

National Natural Science Foundation of China(81873964 to Y.Q.)

National Natural Science Foundation of China(31670161 to X.Z.)

Fundamental Research Funds for the Central Universities(20720200013 to S-H.L.)

a grant from Clinical Research Center for Anesthesiology of Hubei Province(2019ACA167)


References

[1] The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) - China, 2020. China CDC Weekly 2020; 2: 113-22. Google Scholar

[2] WHO. Coronavirus disease 2019 (COVID-19) Situation Report-71. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200331-sitrep-71-covid-19.pdf?sfvrsn=4360e92b_8 (31 March 2020, date last accessed). Google Scholar

[3] Wang D, Hu B, Hu C et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020; 323: 1061-9. CrossRef Google Scholar

[4] Huang C, Wang Y, Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497-506. CrossRef Google Scholar

[5] Chen N, Zhou M, Dong X et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395: 507-13. CrossRef Google Scholar

[6] Zhang C, Shi L, Wang FS . Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol 2020; 5: 428-30. CrossRef Google Scholar

[7] Yang X, Yu Y, Xu J et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med 2020; 8: 475-81. CrossRef Google Scholar

[8] Eisfeld AJ, Halfmann PJ, Wendler JP et al. Multi-platform 'omics analysis of human Ebola virus disease pathogenesis. Cell Host Microbe 2017; 22: 817-29. CrossRef Google Scholar

[9] Kyle JE, Burnum-Johnson KE, Wendler JP et al. Plasma lipidome reveals critical illness and recovery from human Ebola virus disease. Proc Natl Acad Sci USA 2019; 116: 3919-28. CrossRef Google Scholar

[10] National Health Commission of China. Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia, 6th edn (in Chinese). http://www.nhc.gov.cn/yzygj/s7653p/202002/8334a8326dd94d329df351d7da8aefc2/files/b218cfeb1bc54639af227f922bf6b817.pdf (18 February 2020, date last accessed). Google Scholar

[11] Sigoillot FD, Kotsis DH, Serre V et al. Nuclear localization and mitogen-activated protein kinase phosphorylation of the multifunctional protein CAD. J Biol Chem 2005; 280: 25611-20. CrossRef Google Scholar

[12] Struck J, Uhlein M, Morgenthaler NG et al. Release of the mitochondrial enzyme carbamoyl phosphate synthase under septic conditions. Shock 2005; 23: 533-8. Google Scholar

[13] Schnater JM, Bruder E, Bertschin S et al. Subcutaneous and intrahepatic growth of human hepatoblastoma in immunodeficient mice. J Hepatol 2006; 45: 377-86. CrossRef Google Scholar

[14] Chen KF, Lai YY, Sun HS et al. Transcriptional repression of human cad gene by hypoxia inducible factor-1alpha. Nucleic Acids Res 2005; 33: 5190-8. CrossRef Google Scholar

[15] Chi Z, Wang ZP, Wang GY et al. Microbial biosynthesis and secretion of l-malic acid and its applications. Crit Rev Biotechnol 2016; 36: 99-107. CrossRef Google Scholar

[16] Qiang F . Effect of Malate-oligosaccharide Solution on antioxidant capacity of endurance athletes. Open Biomed Eng J 2015; 9: 326-9. CrossRef Google Scholar

[17] Veech RL . A humble hexose monophosphate pathway metabolite regulates short- and long-term control of lipogenesis. Proc Natl Acad Sci USA 2003; 100: 5578-80. CrossRef Google Scholar

[18] Shaeri J, Wright I, Rathbone EB et al. Characterization of enzymatic D-xylulose 5-phosphate synthesis. Biotechnol Bioeng 2008; 101: 761-7. CrossRef Google Scholar

[19] Nakayama Y, Kinoshita A, Tomita M . Dynamic simulation of red blood cell metabolism and its application to the analysis of a pathological condition. Theor Biol Med Model 2005; 2: 18. CrossRef Google Scholar

[20] Kabashima T, Kawaguchi T, Wadzinski BE et al. Xylulose 5-phosphate mediates glucose-induced lipogenesis by xylulose 5-phosphate-activated protein phosphatase in rat liver. Proc Natl Acad Sci USA 2003; 100: 5107-12. CrossRef Google Scholar

[21] Jacobs BAW, Snoeren N, Samim M et al. The impact of liver resection on the dihydrouracil:uracil plasma ratio in patients with colorectal liver metastases. Eur J Clin Pharmacol 2018; 74: 737-44. CrossRef Google Scholar

[22] Antonioli L, Pacher P, Vizi ES et al. CD39 and CD73 in immunity and inflammation. Trends Mol Med 2013; 19: 355-67. CrossRef Google Scholar

[23] Glycerol-3-phosphate cytidylyltransferase. In: Schomburg D, Schomburg I, Chang A (eds). Springer Handbook of Enzymes. Berlin & Heidelberg: Springer, 2007, 404-11. Google Scholar

[24] Chanda B, Xia Y, Mandal MK et al. Glycerol-3-phosphate is a critical mobile inducer of systemic immunity in plants. Nat Genet 2011; 43: 421-7. CrossRef Google Scholar

[25] Thaker SK, Ch'ng J, Christofk HR . Viral hijacking of cellular metabolism. BMC Biol 2019; 17: 59. CrossRef Google Scholar

[26] Yan CH, Faraji F, Prajapati DP et al. Association of chemosensory dysfunction and Covid‐19 in patients presenting with influenza‐like symptoms. Int Forum Allergy Rhinol 2020; doi: 10.1002/alr.22579. Google Scholar

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