SARS-CoV-2 spike epitopes as a novel clinically-relevant biomarker for post-COVID syndrome 3558

Abstract Description Persistent symptoms following SARS-CoV-2 infection, known as post-COVID syndrome (PCS), severely affect patients’ quality of life. Despite its prevalence, the underlying mechanisms and reliable biomarkers remain elusive. We investigated the antibody response and epitope recognition patterns in PCS to uncover potential biomarkers and pathophysiological links to immune dysregulation. Humoral immune responses were analyzed in PCS patients (n = 64) and convalescent controls (n = 64), matched for sex, age, and time since acute infection, further corroborated in three independent PCS validation cohorts (n = 420). PCS was associated with significantly elevated levels of neutralizing IgG, IgA and IgM antibodies targeting the SARS-CoV-2 receptor-binding domain and spike subdomains, but not against nucleocapsid or seasonal coronaviruses. Next, we identified three discriminatory PCS-specific spike epitopes, primarily located in the membrane-proximal region, as demonstrated by customized peptide microarray, ELISA and luminex methods. Binary logistic regression analysis revealed 82.8% specificity and 60.0% sensitivity for PCS diagnosis in seropositive patients. PCS-specific antibody levels correlated directly (D-Dimers) or inversely (6 min-walk distance, diffusion capacity) with clinical markers. These findings highlight enhanced spike-specific humoral responses in PCS and propose novel epitope-based biomarkers for PCS diagnosis and mechanistic insights. Funding Sources This project was supported by the German Ministry of Education and Research (BMBF; grant no. 01EP2105A). Topic Categories Viral Immunology (VIR)