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)

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Publication Details

Journal
The Journal of Immunology
Published
2025-11-01
DOI
https://doi.org/10.1093/jimmun/vkaf283.1349
Primary Topic
Long-Term Effects of COVID-19
Type
article
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article

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

Philipp Schuster, Martina Sester, David Peterhoff, Daniel Schmalenberger et al.
The Journal of Immunology
Long-Term Effects of COVID-19
article

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

Philipp Schuster, Martina Sester, David Peterhoff, Daniel Schmalenberger, Clara Luzia Magnus, Thilo Hinterberger, Romina Kardashi, Jonas Abel, Tina Schmidt, Verena Klemis, Robert Bals, Christian Lensch, Thomas Loew, André Gessner, Arno Mohr, Ida Montanari, Stefan Blaas, Katja de With, Bernd Salzberger, Jan Medenbach, Michael T Koller, Annelie Plentz, Annika Walter, Maximilian Malfertheiner, Matthias Mack, Bárbara Schmidt, Vivian Glück, Roman Pfeifer, Kerstin Renner, Thomas Glück, Lars Klaphecke, Sandra Schaubschläger, Tabea Gerschütz
article en

Abstract

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)

The Journal of ImmunologyVol. 214(Supplement_1)
University Hospital Regensburg (DE), Kreisklinik Trostberg (DE), Klinik Donaustauf (DE), Institute of Medical Microbiology and Hygiene (DE), University of Regensburg (DE), Technische Universität Dresden (DE), Saarland University (DE)
Openalex Percentile: Top 51%
Long-Term Effects of COVID-19
DOIOpen Access PDFOpenAlex
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