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

Area of Science:

• Biochemistry
• Proteomics
• Medical Diagnostics

Background:

• Post-acute sequelae of SARS-CoV-2 infection (PASC) presents diagnostic and therapeutic challenges, with unclear molecular underpinnings.
• Urinary peptidomics offers a non-invasive approach to identify biomarkers for PASC diagnosis and understand its pathophysiology.

Purpose of the Study:

• To develop a novel, non-invasive diagnostic model for PASC using urinary peptidomics.
• To identify a specific molecular signature indicative of PASC.

Main Methods:

• Capillary electrophoresis-MS was used to analyze urinary peptidomes from 50 PASC patients and 50 controls.
• A support vector machine model was developed based on differential peptide abundance to create the PASC195 classifier.

Main Results:

• A distinct urinary peptide signature, PASC195, comprising 195 peptides (predominantly collagen alpha chains), was identified in PASC patients.
• PASC195 demonstrated high accuracy in distinguishing PASC cases from controls in both training (AUC 0.949) and validation (AUC 0.962) sets.
• The peptide profile suggests altered collagen turnover, inflammation, hemostatic imbalances, and endothelial damage in PASC.

Conclusions:

• The PASC195 classifier represents a promising non-invasive diagnostic tool for PASC.
• This molecular signature provides insights into PASC pathophysiology, potentially guiding therapeutic strategies.
• Further research may explore interventions like GLP-1RAs and MRAs suggested by in silico analysis.