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Published on: August 19, 2025
Plasma proteomics reveal SERPINA1 and CD59 as candidate biomarkers for COVID-19 severity stratification and prognosis
Zizhen Zhou1, Qiwei Liu1, Shuangshuang Ma2
1State Key Laboratory of Respiratory Health and Multimorbidity, Department of Physiology, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Insights
New COVID-19 biomarkers, SERPINA1 and CD59, show promise in predicting patient mortality and thromboembolic complications. These proteomic markers outperform traditional tests like D-dimer for COVID-19 prognosis.
Area of Science:
- Proteomics
- Biomarker Discovery
- COVID-19 Research
Background:
- COVID-19 is linked to coagulation abnormalities.
- Current biomarkers like D-dimer have limited accuracy for severity and prognosis.
Purpose of the Study:
- Identify plasma biomarkers for COVID-19 severity and prognosis using proteomic analysis.
- Validate the predictive utility of identified biomarkers for mortality and thromboembolic complications.
Main Methods:
- Plasma proteomic profiles analyzed across COVID-19 severity classes.
- Differential expression, functional, and clustering analyses performed.
- Candidate biomarkers validated in an independent cohort; predictive performance evaluated using ROC analyses and multivariable regression.
Main Results:
- Proteomic analysis revealed progressive coagulation and complement pathway involvement with disease severity.
- SERPINA1 and CD59 identified as candidate biomarkers with significantly higher levels in severe COVID-19.
- SERPINA1 and CD59 demonstrated strong predictive performance for mortality and sepsis, outperforming D-dimer and FDP.
Conclusions:
- SERPINA1 and CD59 are identified as potential prognostic biomarkers for COVID-19.
- Coagulation and complement pathways play a significant role in COVID-19 severity.
- Further prospective validation of these biomarkers is warranted.
Background:
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.
Objectives:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
