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Leveraging metabolic modeling to identify functional metabolic alterations associated with COVID-19 disease severity

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July 12 2022
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Metabolomics. 2022 Jul 11;18(7):51. doi: 10.1007/s11306-022-01904-9.

ABSTRACT

OBJECTIVE: Since the COVID-19 pandemic began in early 2020, SARS-CoV2 has claimed more than six million lives world-wide, with over 510 million cases to date. To reduce healthcare burden, we must investigate how to prevent non-acute disease from progressing to severe infection requiring hospitalization.

METHODS: To achieve this goal, we investigated metabolic signatures of both non-acute (out-patient) and severe (requiring hospitalization) COVID-19 samples by profiling the associated plasma metabolomes of 84 COVID-19 positive University of Virginia hospital patients. We utilized supervised and unsupervised machine learning and metabolic modeling approaches to identify key metabolic drivers that are predictive of COVID-19 disease severity. Using metabolic pathway enrichment analysis, we explored potential metabolic mechanisms that link these markers to disease progression.

RESULTS: Enriched metabolites associated with tryptophan in non-acute COVID-19 samples suggest mitigated innate immune system inflammatory response and immunopathology related lung damage prevention. Increased prevalence of histidine- and ketone-related metabolism in severe COVID-19 samples offers potential mechanistic insight to musculoskeletal degeneration-induced muscular weakness and host metabolism that has been hijacked by SARS-CoV2 infection to increase viral replication and invasion.

CONCLUSIONS: Our findings highlight the metabolic transition from an innate immune response coupled with inflammatory pathway inhibition in non-acute infection to rampant inflammation and associated metabolic systemic dysfunction in severe COVID-19.

PMID:35819731 | DOI:10.1007/s11306-022-01904-9

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Computational Systems Biology Laboratory; The research group of Dr. Jason Papin in the Department of Biomedical Engineering at the University of Virginia.

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The research group of Dr. Jason Papin in the Department of Biomedical Engineering at the University of Virginia

  • Email: papinlab@virginia.edu
  • Phone (434) 924-8195

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  • Meet Our Team
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