A Multivariable Plasma Extracellular Vesicle Surface Profile Associated with Post-COVID-19 Syndrome
- 1Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstr. 1, 89081 Ulm, Germany
Abstract
Post-COVID-19 syndrome (PCS) is characterized by fatigue, neurological impairment and systemic symptoms. This heterogeneity of symptoms hinders biomarker development. Here, we profiled extracellular-vesicle (EV) surface markers in plasma and CSF from 61 participants with PCS (COVIDpost), 80 recovered controls (COVIDreco), and 10 participants with non-SARS-CoV-2 post-viral syndromes. EVs were analysed by bead-based multiplex flow cytometry using tetraspanin-directed (TSPN) and phosphatidylserine-directed lactadherin (PS) detection. Amongst 37 targets covering tetraspanins and vasculature-, immunity- and stemness-associated markers, none met a 1% false-discovery-rate threshold. However, L1-regularized logistic regression under fully nested 5x5 cross-validation identified a distributed plasma EV profile, with mean out-of-fold areas under the receiver operating characteristic curve (AUCs) of 0.788 (95% CI 0.715-0.852) for TSPN and 0.716 (95% CI 0.636-0.792) for PS detection. Across the pooled COVIDpost and COVIDreco population, EV classification scores covaried with clinical group differences, but did not track clinical severity within either cohort. These PCS-EV classification scores decreased at one-year follow-up in COVIDpost participants. Our findings identify an internally cross-validated multivariable EV surface profile associated with COVIDpost versus COVIDreco status and support independent validation and exploration of EV-based biomarkers in post-viral fatigue syndromes.
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BibTeX
@misc{erhart2026multivariable,
title = {{A Multivariable Plasma Extracellular Vesicle Surface Profile Associated with Post-COVID-19 Syndrome}},
author = {D. K. Erhart and H. Ressin and L. T. Balz and S. Chatterjee and D. Lule and S. Mueller and J. Lewerenz and J. Muench and H. Tumani and R. M. Gross},
howpublished = {medRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.27.26361498},
url = {https://www.medrxiv.org/content/10.64898/2026.08.27.26361498v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - A Multivariable Plasma Extracellular Vesicle Surface Profile Associated with Post-COVID-19 Syndrome
AU - D. K. Erhart
AU - H. Ressin
AU - L. T. Balz
AU - S. Chatterjee
AU - D. Lule
AU - S. Mueller
AU - J. Lewerenz
AU - J. Muench
AU - H. Tumani
AU - R. M. Gross
PY - 2026
DA - 2026/08/27
PB - medRxiv
DO - 10.64898/2026.08.27.26361498
UR - https://www.medrxiv.org/content/10.64898/2026.08.27.26361498v1
AB - Post-COVID-19 syndrome (PCS) is characterized by fatigue, neurological impairment and systemic symptoms. This heterogeneity of symptoms hinders biomarker development. Here, we profiled extracellular-vesicle (EV) surface markers in plasma and CSF from 61 participants with PCS (COVIDpost), 80 recovered controls (COVIDreco), and 10 participants with non-SARS-CoV-2 post-viral syndromes. EVs were analysed by bead-based multiplex flow cytometry using tetraspanin-directed (TSPN) and phosphatidylserine-directed lactadherin (PS) detection. Amongst 37 targets covering tetraspanins and vasculature-, immunity- and stemness-associated markers, none met a 1% false-discovery-rate threshold. However, L1-regularized logistic regression under fully nested 5x5 cross-validation identified a distributed plasma EV profile, with mean out-of-fold areas under the receiver operating characteristic curve (AUCs) of 0.788 (95% CI 0.715-0.852) for TSPN and 0.716 (95% CI 0.636-0.792) for PS detection. Across the pooled COVIDpost and COVIDreco population, EV classification scores covaried with clinical group differences, but did not track clinical severity within either cohort. These PCS-EV classification scores decreased at one-year follow-up in COVIDpost participants. Our findings identify an internally cross-validated multivariable EV surface profile associated with COVIDpost versus COVIDreco status and support independent validation and exploration of EV-based biomarkers in post-viral fatigue syndromes.
ER -