Plasma Metabolomic Profiles in Recovered COVID-19 Patients without Previous Underlying Diseases 3 Months After Discharge

Shujing Zhang,1,2,* Ping Luo,3,* Juanjuan Xu,1,* Lian Yang,4,* Pei Ma,1,* Xueyun Tan,1,* Qing Chen,5,* Mei Zhou,1 Siwei Song,1 Hui Xia,1 Sufei Wang,1 Yanling Ma,1 Fan Yang,4 Yu Liu,5 Yumei Li,1 Guanzhou Ma,1 Zhihui Wang,6 Yanran Duan,7 Yang Jin1 1Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 2Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 3Department of Translational Medicine Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 4Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 5Health Checkup Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 6Department of Scientific Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 7School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang JinDepartment of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, People’s Republic of ChinaEmail whuhjy@126.comBackground: It remains unclear whether discharged COVID-19 patients have fully recovered from severe complications, including the differences in the post-infection metabolomic profiles of patients with different disease severities.Methods: COVID-19-recovered patients, who had no previous underlying diseases and were discharged from Wuhan Union Hospital for 3 months, and matched healthy controls (HCs) were recruited in this prospective cohort study. We examined the blood biochemical indicators, cytokines, lung computed tomography scans, including 39 HCs, 18 recovered asymptomatic (RAs), 34 recovered moderate (RMs), and 44 recovered severe/ critical patients (RCs). A liquid chromatography-mass spectrometry-based metabolomics approach was employed to profile the global metabolites of fasting plasma of these participants.Results: Clinical data and metabolomic profiles suggested that RAs recovered well, but some clinical indicators and plasma metabolites in RMs and RCs were still abnormal as compared with HCs, such as decreased taurine, succinic acid, hippuric acid, some indoles, and lipid species. The disturbed metabolic pathway mainly involved the tricarboxylic cycle, purine, and glycerophospholipid metabolism. Moreover, metabolite alterations differ between RMs and RCs when compared with HCs. Correlation analysis revealed that many differential metabolites were closely associated with inflammation and the renal, pulmonary, heart, hepatic, and coagulation system functions.Conclusion: We uncovered metabolite clusters pathologically relevant to the recovery state in discharged COVID-19 patients which may provide new insights into the pathogenesis of potential organ damage in recovered patients.Keywords: COVID-19, recovery, metabolomics