Proteomic and Metabolomic Profiling of Plasma Uncovers Immune Responses in Patients with Long COVID-19

Long COVID is an often-debilitating condition with severe, multisystem symptoms that can persist for weeks or months and increase the risk of various diseases. Currently, there is a lack of diagnostic tools for Long COVID in clinical practice. Therefore, this study utilizes plasma proteomics and metabolomics technologies to understand the molecular profile and pathophysiological mechanisms of Long COVID, providing clinical evidence for the development of potential biomarkers. This study included three age- and gender-matched cohorts: healthy controls ( = 18), COVID-19 recovered patients ( = 17), and Long COVID patients ( = 15). The proteomics results revealed significant differences in proteins between Long COVID-19 patients and COVID-19 recovered patients, with dysregulation mainly focused on pathways such as coagulation, platelets, complement cascade reactions, GPCR cell signal transduction, and substance transport, which can participate in regulating immune responses, inflammation, and tissue vascular repair. Metabolomics results showed that Long COVID patients and COVID-19 recovered patients have similar metabolic disorders, mainly involving dysregulation in lipid metabolites and fatty acid metabolism, such as glycerophospholipids, sphingolipid metabolism, and arachidonic acid metabolism processes. In summary, our study results indicate significant protein dysregulation and metabolic abnormalities in the plasma of Long COVID patients, leading to coagulation dysfunction, impaired energy metabolism, and chronic immune dysregulation, which are more pronounced than in COVID-19 recovered patients.