Amino acid catabolite markers for early prognostication of pneumonia in patients with COVID-19

Author:

Maeda Rae,Seki Natsumi,Uwamino Yoshifumi,Wakui Masatoshi,Nakagama Yu,Kido Yasutoshi,Sasai MiwaORCID,Taira Shu,Toriu Naoya,Yamamoto MasahiroORCID,Matsuura YoshiharuORCID,Uchiyama Jun,Yamaguchi Genki,Hirakawa Makoto,Kim Yun-Gi,Mishima Masayo,Yanagita MotokoORCID,Suematsu MakotoORCID,Sugiura YukiORCID

Abstract

AbstractEffective early-stage markers for predicting which patients are at risk of developing SARS-CoV-2 infection have not been fully investigated. Here, we performed comprehensive serum metabolome analysis of a total of 83 patients from two cohorts to determine that the acceleration of amino acid catabolism within 5 days from disease onset correlated with future disease severity. Increased levels of de-aminated amino acid catabolites involved in the de novo nucleotide synthesis pathway were identified as early prognostic markers that correlated with the initial viral load. We further employed mice models of SARS-CoV2-MA10 and influenza infection to demonstrate that such de-amination of amino acids and de novo synthesis of nucleotides were associated with the abnormal proliferation of airway and vascular tissue cells in the lungs during the early stages of infection. Consequently, it can be concluded that lung parenchymal tissue remodeling in the early stages of respiratory viral infections induces systemic metabolic remodeling and that the associated key amino acid catabolites are valid predictors for excessive inflammatory response in later disease stages.

Funder

Japan Agency for Medical Research and Development

MEXT | Japan Society for the Promotion of Science

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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