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. Decrease of urinary ESCRT complex proteins correlates with active SARS-CoV-2 replication. Downregulation of urinary CXCL14 in severe COVID-19 cases positively correlates with blood lymphocyte counts. Integrative multiomic 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 multiomic analytes in evaluating the immune pathobiology and clinical course of COVID-19 and, potentially, other infectious diseases.
Proteomic and metabolomic profiling of urine uncovers immune responses in patients with COVID-19