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

Rae Maeda, Natsumi Seki, Yoshifumi Uwamino, Masatoshi Wakui, Yu Nakagama, Yasutoshi Kido, Miwa Sasai, Shu Taira, Naoya Toriu, Masahiro Yamamoto, Yoshiharu Matsuura, Jun Uchiyama, Genki Yamaguchi, Makoto Hirakawa, Yun-Gi Kim, Masayo Mishima, Motoko Yanagita, Makoto Suematsu and Yuki Sugiura ()
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Rae Maeda: Kyoto University Graduate School of Medicine
Natsumi Seki: Kyoto University Graduate School of Medicine
Yoshifumi Uwamino: Keio University School of Medicine
Masatoshi Wakui: Keio University School of Medicine
Yu Nakagama: Osaka Metropolitan University
Yasutoshi Kido: Osaka Metropolitan University
Miwa Sasai: Osaka University
Shu Taira: Fukushima University
Naoya Toriu: Kyoto University
Masahiro Yamamoto: Osaka University
Yoshiharu Matsuura: Osaka University
Jun Uchiyama: Keio University
Genki Yamaguchi: Keio University
Makoto Hirakawa: Keio University
Yun-Gi Kim: Keio University
Masayo Mishima: Keio University School of Medicine
Motoko Yanagita: Kyoto University
Makoto Suematsu: Keio University School of Medicine
Yuki Sugiura: Kyoto University Graduate School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Effective 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.

Date: 2023
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DOI: 10.1038/s41467-023-44266-z

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