Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction

COVID-19 virus infection can cause disorders of the endocrine system. The aim of this study was to characterize the alterations of nucleotide metabolomic patterns in patients with post-COVID-19 condition (PCC). The study population included 18 patients with PCC alone (PCC-A), 31 patients with PCC combined with type 2 diabetes mellitus (PCC-DM), 20 healthy volunteers (HV), and 20 patients with type 2 diabetes mellitus (DM). Ultraperformance liquid chromatography-mass spectrometry was conducted on plasma metabolites. A total of 116, 178, and 163 differential metabolites were identified in PCC-DM vs PCC-A, PCC-A vs HV groups, and PCC-DM vs DM groups, respectively. Adenine was significantly down-regulated, and purine, thymine, and uracil were significantly up-regulated in the PCC-A group compared with the HV group, and the same results were observed in the PCC-DM group compared with the DM group. Differential metabolites were mainly involved in nucleotide metabolism, especially pyrimidine metabolism in PCC patients. After the arginine stimulation test, cortisol and adrenocorticotropic hormone secretion were reduced in PCC patients. In conclusion, the nucleotide <i>de novo</i> synthesis pathway and the remedial synthesis pathway are seriously damaged in patients with PCC-A, especially in patients with PCC-DM, which leads to the disorder and imbalance of the body cell metabolism pathway.