Plasma Nucleocapsid Protein: A Potential Beacon for COVID-19 Severity Prediction and Prognostic Insight in Severe Patients with Comorbidities

Objectives: The COVID-19 pandemic poses ongoing challenges to global public health systems, emphasizing the critical necessity for efficient diagnostic and prognostic markers. This study evaluates the MAGLUMI® SARS-CoV-2 Ag N protein chemiluminescent immunoassay (MAG-CLIA) for its analytical performance and its role in predicting disease severity and prognosis among severe COVID-19 patients with comorbidities. Methods: Analytical validation of plasma MAG-CLIA SARS-CoV-2 Ag N protein encompassed precision, interference, LoQ and linearity. Plasma N protein concentrations and other biomarkers were measured within 48 hours of admission, tracked until discharge or death. The Mann-Whitney U test explored the association between plasma N protein and COVID-19 severity or prognosis. Longitudinal monitoring of plasma N protein dynamics was conducted in representative patients. Results: MAG-CLIA demonstrated precise quantification of plasma N protein with a CV below 10% and minimal interference. The LoQ was 0.88 ng/L, with a broad linear range. Plasma N protein showed high diagnostic accuracy for COVID-19, achieving 95.42% sensitivity and 78.32% specificity at 2.388 ng/L. Plasma N protein emerged as a valuable prognostic indicator, correlating with mechanical ventilation need and patient survival. Plasma N protein concentrations ≥ 424.3 ng/L (AUC 0.8102, sensitivity 78.38%, specificity 85.48%) were associated with poor prognosis in severe COVID-19 patients with comorbidities. Conclusions : MAG-CLIA's SARS-CoV-2 N protein detection in plasma demonstrates both analytical reliability and clinical relevance in our inaugural evaluation. As a promising prognostic biomarker for severe COVID-19 patients, it offers crucial insights into disease severity and progression, emphasizing the significance of early monitoring and intervention, especially for patients with comorbidities.