Understanding the molecular underpinnings of disease severity and progression in human studies is necessary to develop metabolism-related preventative strategies for severe COVID-19. Metabolites and metabolic pathways that predispose individuals to severe disease are not well understood. In this study, we generated comprehensive plasma metabolomic profiles in >550 patients from the Longitudinal EMR and Omics COVID-19 Cohort. Samples were collected before (n = 441), during (n = 86), and after (n = 82) COVID-19 diagnosis, representing 555 distinct patients, most of which had single timepoints. Regression models adjusted for demographics, risk factors, and comorbidities, were used to determine metabolites associated with predisposition to and/or persistent effects of COVID-19 severity, and metabolite changes that were transient/lingering over the disease course. Sphingolipids/phospholipids were negatively associated with severity and exhibited lingering elevations after disease, while modified nucleotides were positively associated with severity and had lingering decreases after disease. Cytidine and uridine metabolites, which were positively and negatively associated with COVID-19 severity, respectively, were acutely elevated, reflecting the particular importance of pyrimidine metabolism in active COVID-19. This is the first large metabolomics study using COVID-19 plasma samples before, during, and/or after disease. Our results lay the groundwork for identifying putative biomarkers and preventive strategies for severe COVID-19.

To understand why Procapra przewalskii does not show the same white myopathy as sheep in Se-deficient regions and to provide reference for feeding nutrition level of artificial population and selection of wild reintroduction areas in the later period, a Se-deficient model was established. The mineral elements content, physiological and biochemical parameters in blood and serum metabonomics were determined. In the Se-deficient group compared with the control group, the Se content was highly significantly lower (P < 0·01), and the Cu content was significantly higher (P < 0·05). The activity of glutathione peroxidase was significantly lower (P < 0·05), but total superoxide dismutase was significantly higher (P < 0·05). By matching the mass spectrum data of compounds with the Kyoto Encyclopedia of Genes and Genomes (KEGG database), eighty-six types of differential metabolites in the serum were identified. The main metabolic pathways included secondary bile acid biosynthesis, biosynthesis of unsaturated fatty acids and pyrimidine metabolism. Further analysis showed that there were seven different metabolites in pyrimidine metabolism pathway between the two groups. And there was no significant difference in erythrocyte, Hb and total antioxidant capacity between the two groups (P > 0·05). The above results showed that the differential metabolism of substances exhibited complementary functions, thus alleviating some adverse effects and resulting normal activities of P. przewalskii can be carried out under the condition of dietary Se content lower than 0·05 mg/kg.