Preprint Urinary Peptidomic Profiling in Post-Acute Sequelae of SARS-CoV-2 Infection: A Case-Control Study, 2025,

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

Dilara Guelmez, Justyna Siwy, Katharina Kurz, Ralph Wendt, Miroslaw Banasik, Bjorn Peters, Emmanuel Dudoignon, Francois Depret, Mercede Salgueira, Elena Nowacki, Amelie Kurnikowski, Sebastian Mussnig, Simon Krenn, Samuel Gonos, Judith Loffler-Ragg, Guenter Weiss, Harald Mischak, Manfred Hecking, Eva Schernhammer, Joachim Beige

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.

Web | PDF | Preprint: MedRxiv | Open Access
 
Competing Interest Statement
H.M. is the co-founder and co-owner of Mosaiques Diagnostics. J.S. is employed by Mosaiques Diagnostics GmbH.

Funding Statement
This project was supported by the Federal Ministry of Health (BMG) via grant number 2523FSB114; by the German Ministry for Education and Science (BMBF) via grant 01KU2309; by the Province of Tyrol via grant number GZ 75759; by Fisser Bergbahnen through a benefit gala donation (2022) under the project name: Projekt ME/CFS-Forschung; by the Province of Tyrol and the WE & ME Foundation (Scientific Commitment & Myalgic Encephalomyelitis Foundation) via grant number GZ 86686; by the Swedens innovation agency (Vinnova) via grant 2022-00542; by the National Centre for Research and Development (Narodowe Centrum Badan i Rozwoju) via grant number: PerMed/V/80/UriCov/2023; by the Austrian Science Fund (FWF) via Project number I 6464, Grant-DOI 10.55776/I6464; by the French National Research Agency-Agence Nationale de la Recherche (ANR)-under the grant ANR-22-PERM-0014; and in part by the Austrian Science Fund (FWF) via Project number I 6471, Grant-DOI 10.55776/I6471 under the frame of ERA PerMed. The funders were not involved in the study design, data collection, data analysis, interpretation of results, or manuscript preparation.
 
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