Proteomic and metabolomic profiling of urine uncovers immune responses in patients with COVID-19
Xiaojie Bi, Wei Liu, Xuan Ding, Shuang Liang, Yufen Zheng, Xiaoli Zhu, Sheng Quan, Xiao Yi, Nan Xiang, Juping Du, Haiyan Lyu, Die Yu, Chao Zhang, Luang Xu, Weigang Ge, Xinke Zhan, Jiale He, Zi Jian Xiong, Shun Zhang, Yanchang Li, Ping Xu, Guangjun Zhu, Donglian Wang, Hongguo Zhu, Shiyong Chen, Jun Li, Haihong Zhao, Yi Zhu, Huafen Liu, Jiaqin Xu, Bo Shen, Tiannan Guo
Abstract
The utility of the urinary proteome in infectious diseases remains unclear. Here, we analyzed the proteome and metabolome of urine and serum samples from patients with COVID-19 and healthy controls. Our data show that urinary proteins effectively classify COVID-19 by severity. We detect 197 cytokines and their receptors in urine, but only 124 in serum using TMT-based proteomics. The decrease in urinary ESCRT complex proteins correlates with active SARS-CoV-2 replication. The downregulation of urinary CXCL14 in severe COVID-19 cases positively correlates with blood lymphocyte counts. Integrative multiomics analysis suggests that innate immune activation and inflammation triggered renal injuries in patients with COVID-19. COVID-19-associated modulation of the urinary proteome offers unique insights into the pathogenesis of this disease. This study demonstrates the added value of including the urinary proteome in a suite of multiomics analytes in evaluating the immune pathobiology and clinical course of COVID-19 and, potentially, other infectious diseases.