Plasma proteomics reveal SERPINA1 and CD59 as candidate biomarkers for COVID-19 severity stratification and prognosis prediction.

Authors

Zizhen Zhou, Qiwei Liu, Shuangshuang Ma, Anke Shi, Yuzhi Tao, Tianpeng Hu, Shengtao Yan, Yinong Chen, Xiaofan Ji, Lu Sun, Hong Zhang, Wanlu Song, Zhu Zhang, Peiran Yang, Zhenguo Zhai

Published in

Annals of medicine. Volume 58. Issue 1. Pages 2688626. Epub Jun 21, 2026.

Abstract

COVID-19 has been closely associated with coagulation abnormalities. However, existing biomarkers, including D-dimer and fibrin degradation products (FDP), exhibit limited accuracy in stratifying disease severity and predicting long-term clinical outcomes.
This study aimed to use proteomic analysis to identify plasma biomarkers associated with COVID-19 severity and prognosis, and validate their predictive utility for mortality and thromboembolic complications.
Plasma proteomic profiles were analyzed across three COVID-19 severity classes. Differential expression analysis and functional analysis were performed. Clustering analysis was used to identify proteins correlated with disease severity. Candidate biomarkers were validated in an independent cohort. Predictive performance of the biomarkers for mortality, sepsis and venous thromboembolism was evaluated using bootstrap-corrected ROC analyses and multivariable regression analyses.
Proteomic analysis revealed progressive involvement of the coagulation and complement pathway with increasing disease severity. SERPINA1 and CD59 were identified as candidate biomarkers and exhibited significantly higher plasma levels in severe cases. Bootstrap-corrected ROC analyses demonstrated strong predictive performance: SERPINA1 achieved AUCs of 0.775 and 0.924 for 30-day and 12-month mortality, and CD59 achieved AUCs of 0.720 for sepsis; the combined model further improved prediction of 12-month mortality (AUC 0.946) and sepsis (AUC 0.904), outperforming D-dimer and FDP. Multivariable regression confirmed their independent prognostic value.
This exploratory study identifies SERPINA1 and CD59 as candidate prognostic biomarkers in COVID-19, highlighting the role of coagulation and complement-related pathways in disease severity and warranting further prospective validation.

PMID:
42323884
Bibliographic data and abstract were imported from PubMed on 22 Jun 2026.

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