Urinary Peptidomic Profiling in Post-Acute Sequelae of SARS-CoV-2 Infection: A Case-Control Study

Background: Post-acute sequelae of severe acute respiratory syndrome coronavirus 2-infection (PASC) is challenging to diagnose and treat, and its molecular pathophysiology remains unclear. Urinary peptidomics can provide valuable information on urine peptides that may enable improved and specified PASC diagnosis. Methods: Using standardized capillary electrophoresis-MS, we examined the urinary peptidomes of 50 patients with PASC 10 months after COVID-19 and 50 controls including healthy individuals (n = 42) and patients with non-COVID-19-associated myalgic encephalomyelitis/chronic fatigue syndrome (n = 8). Based on peptide abundance differences between cases and controls, we developed a diagnostic model using a support vector machine. Results: The abundance of 195 urine peptides among PASC patients significantly differed from that in controls, with a predominant abundance of collagen alpha chains. This molecular signature (PASC195), effectively distinguished PASC cases from controls in the training set [AUC of 0.949 (95% CI 0.900-0.998; p < 0.0001)] and independent validation set [AUC of 0.962 (95% CI 0.897-1.00); p < 0.0001)]. In silico assessment suggested exercise, GLP1-RA and MRA as potentially efficacious interventions. Conclusions: We present a novel and non-invasive diagnostic model for PASC. Reflecting its molecular pathophysiology, PASC195 has the potential to advance diagnostics and inform therapeutic interventions.