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

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.

Loss of SPNS1, a lysosomal transporter, in the nervous system causes dysmyelination and white matter dysplasia

“…For detailed metabolomic analysis, metabolites from the brain tissue were extracted using a previously described method with slight modifications (Maeda et al, 2023). Frozen tissue samples were homogenized in 500 μL of ice-cold methanol containing methionine sulfone (L-Met) and 2-morpholinoethanesulfonic acid (MES) as internal standards for cationic and anionic metabolites, respectively, using a Finger Masher manual homogenizer (AM79330; Sarstedt, Tokyo, Japan).…”

Amino Acid Metabolism in Leukocytes Showing In Vitro IgG Memory from SARS-CoV2-Infected Patients

“…Among metabolic reprogramming, amino acid metabolism plays a significant part in the regulation of immune responses and the assembly of progeny viruses, and alternations in amino acid metabolism over the course of SARS-CoV2 infection has become one of the focuses in COVID-19 research [ 31 , 32 , 33 , 34 ].…”

Postnatal xanthine metabolism regulates cardiac regeneration in mammals

“…For NAC or DCA -treated P14 mouse heart, or postnatal mouse hearts (Supplementary Table 3-5), the heart samples were immediately freeze clamped by pre-chilled freezing clamp (Natsume Seisakusho, KN-838-S). Details are described previously 52 . Briefly, metabolites were detected using an orbitrap-type MS instrument (Q-Exactive focus; Thermo Fisher Scientific) connected to a high-performance IC system (ICS-5000 +, Thermo Fisher Scientific) and a triple-quadrupole mass spectrometer (LCMS-8060, Shimadzu Corporation, Kyoto, Japan).…”