Towards risk stratification and prediction of disease severity and mortality in COVID-19: Next generation metabolomics for the measurement of host response to COVID-19 infection

被引:10
|
作者
D'Amora, Paulo [1 ,2 ,3 ]
Silva, Ismael Dale C. G. [1 ,4 ]
Budib, Maria Auxiliadora [5 ]
Ayache, Ricardo [5 ]
Siufi Silva, Rafaela Moraes [5 ]
Silva, Fabricio Colacino [5 ]
Appel, Robson Mateus [5 ]
Sarat Junior, Saturnino [5 ]
Dorsa Pontes, Henrique Budib [5 ]
Alvarenga, Ana Carolina [5 ]
Arima, Emilli Carvalho [5 ]
Martins, Wellington Galhano [5 ]
Silva, Nakal Laurenco F. [5 ]
Diaz, Ricardo Sobhie [6 ]
Salzgeber, Marcia B. [1 ]
Palma, Anton M. [7 ]
Evans, Steven S. [2 ,3 ,4 ]
Nagourney, Robert A. [2 ,3 ,4 ,8 ,9 ]
机构
[1] Fed Univ Sao Paulo EPM UNIFESP, Dept Gynecol, Mol Gynecol & Metabol Lab, Coll Med, Sao Paulo, SP, Brazil
[2] Nagourney Inst, Long Beach, CA 90806 USA
[3] Metabolomycs Inc, Long Beach, CA 90806 USA
[4] Nagourney Canc Inst, Long Beach, CA USA
[5] CASSEMS Hosp, Dept Emergency & Intens Care Unit, Campo Grande, MS, Brazil
[6] Fed Univ Sao Paulo EPM UNIFESP, Dept Med, Infect Dis Div, Retrovirol Lab,Coll Med, Sao Paulo, SP, Brazil
[7] Univ Calif Irvine, Inst Clin & Translat Sci, Irvine, CA USA
[8] Mem Med Ctr Long Beach, Todd Canc Inst, Long Beach, CA USA
[9] Univ Calif Irvine, Dept Obstet & Gynecol, Orange, CA 92668 USA
来源
PLOS ONE | 2021年 / 16卷 / 12期
基金
美国国家卫生研究院;
关键词
D O I
10.1371/journal.pone.0259909
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
This study investigated the association between COVID-19 infection and host metabolic signatures as prognostic markers for disease severity and mortality. We enrolled 82 patients with RT-PCR confirmed COVID-19 infection who were classified as mild, moderate, or severe/critical based upon their WHO clinical severity score and compared their results with 31 healthy volunteers. Data on demographics, comorbidities and clinical/laboratory characteristics were obtained from medical records. Peripheral blood samples were collected at the time of clinical evaluation or admission and tested by quantitative mass spectrometry to characterize metabolic profiles using selected metabolites. The findings in COVID-19 (+) patients reveal changes in the concentrations of glutamate, valeryl-carnitine, and the ratios of Kynurenine/Tryptophan (Kyn/Trp) to Citrulline/Ornithine (Cit/Orn). The observed changes may serve as predictors of disease severity with a (Kyn/Trp)/(Cit/Orn) Receiver Operator Curve (ROC) AUC = 0.95. Additional metabolite measures further characterized those likely to develop severe complications of their disease, suggesting that underlying immune signatures (Kyn/Trp), glutaminolysis (Glutamate), urea cycle abnormalities (Cit/Orn) and alterations in organic acid metabolism (C5) can be applied to identify individuals at the highest risk of morbidity and mortality from COVID-19 infection. We conclude that host metabolic factors, measured by plasma based biochemical signatures, could prove to be important determinants of Covid-19 severity with implications for prognosis, risk stratification and clinical management.
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页数:16
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