Proteomic and metabolomic profiling of plasma reveals physiologic changes in patients with convalescent COVID-19.

BACKGROUND: This study aimed to analyze the molecular composition and physiological changes in the plasma of patients with convalescent coronavirus disease 2019 (COVID-19). METHODS: Plasma samples from 29 hospitalized patients recovering from COVID-19 and 30 uninfected controls were analyzed using untargeted metabolomics and data-independent acquisition mass spectroscopy proteomic analyses. Integrative metabolomic-proteomic analysis was then conducted to construct a protein-metabolite interaction network. RESULTS: Untargeted metabolomic profiles revealed 415 differential metabolites, with 28.05% of the metabolites belonging to lipids and lipid-like molecules, most of which were upregulated in patients with convalescent COVID-19, such as sphingolipids. Differential metabolites were involved in taste transduction, thermogenesis, and sphingolipid metabolism. Proteomic analysis identified 947 differentially expressed proteins, which were mainly involved in immunoinflammation-related pathways, such as complement and coagulation cascades, neutrophil extracellular trap formation, and platelet activation. Several significant pathways were influenced by differential metabolites and proteins, such as estrogen signaling, ferroptosis, and neurodegeneration-associated pathways. CONCLUSION: This study revealed differential metabolite and protein compositions in the plasma of patients with convalescent COVID-19 compared with uninfected controls. The main physiological changes were associated with the pathology of this disease, suggesting that the phenotype of patients with convalescent COVID-19 did not return to a phenotype similar to that of uninfected controls.