Longitudinal multi-omics analysis of convalescent individuals with respiratory sequelae 6–36 months after COVID-19

作者：Huqin Yang, Lujia Guan, Yi Xue, Xuyan Li, Leyi Gao, Zhijin Zhang, Haifan Zhang, Haomiao Ma, Fengjiao Liu, Xuan Huang, Zhaohui Tong, Jieqiong Li · 发表于：BMC Medicine · 年份：2025 · DOI：10.1186/s12916-025-03971-w · 被引用次数：12 · 研究领域：Long-Term Effects of COVID-19、Heme Oxygenase-1 and Carbon Monoxide、COVID-19 Clinical Research Studies

BACKGROUND: Approximately 10-30% of individuals continue to experience symptoms classified as post-acute sequelae of coronavirus disease 2019 (COVID-19 (PASC)). PASC is a multisystem condition primarily characterized by respiratory symptoms, such as reduced diffusing capacity for carbon monoxide (DLco). Although many studies have investigated the pathogenesis of acute COVID-19, the long-term molecular changes in COVID-19 convalescents with PASC remain poorly understood. METHODS: We prospectively recruited 70 individuals who had been diagnosed with COVID-19 from 7 January 2020 to 29 May 2020 (i.e., COVID-19 convalescents); we performed follow-up visits at 6 months, 1 year, 2 years, and 3 years after hospital discharge. Thirty-five healthy controls (CONs), recruited from a physical examination center before the COVID-19 pandemic, served as a comparison group. We explored the proteomic and metabolomic profiles of 174 plasma samples from the 70 COVID-19 convalescents and 35 CONs. RESULTS: We performed a comprehensive molecular analysis of COVID-19 convalescents to investigate host changes up to 3 years after hospital discharge. Our multi-omics analysis revealed activation of cytoskeletal organization and glycolysis/gluconeogenesis, as well as suppression of gas transport and adaptive immune responses, in COVID-19 convalescents. Additionally, metabolites involved in glutathione metabolism; alanine, aspartate, and glutamate metabolism; and ascorbate and aldarate metabolism were sig...