1. Understanding COVID-19 outcome: Exploring the prognostic value of soluble biomarkers indicative of endothelial impairment.
- Author
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Mariappan, Vignesh, Adla, Deepthi, Jangili, Shraddha, Ranganadin, Pajanivel, Green, Siva Ranaganthan, Mohammed, Salma, Mutheneni, Srinivasa Rao, and Pillai, Agieshkumar Balakrishna
- Subjects
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PROGNOSIS , *MACHINE learning , *COVID-19 , *BIOMARKERS , *CYTOKINE release syndrome - Abstract
• Proteins released by activated endothelial cells due to SARS-CoV2 infections are implicated COVID-19 severity. • The levels of BK, KLK, SERPIN A, IL-18, and ACE2 are directly linked to D-dimer, ferritin, CTSS, and the WHO clinical progression score. • Increased shedding of study proteins, along with D-dimer and ferritin, could be beneficial indicator of COVID-19 pathogenesis. • Machine model analysis demonstrated that SERPIN A could serve as a robust prognostic biomarker for COVID-19 disease severity. • The study supports the idea that COVID-19 is a vascular disease that involves endothelial impairment due to bradykinin/cytokine storm. Host proteins released by the activated endothelial cells during SARS-CoV-2 infection are implicated to be involved in coagulation and endothelial dysfunction. However, the underlying mechanism that governs the vascular dysfunction and disease severity in COVID-19 remains obscure. The study evaluated the serum levels of Bradykinin, Kallikrein, SERPIN A, and IL-18 in COVID-19 (N-42 with 20 moderate and 22 severe) patients compared to healthy controls (HC: N-10) using ELISA at the day of admission (DOA) and day 7 post-admission. The efficacy of the protein levels in predicting disease severity was further determined using machine learning models. The levels of bradykinins and SERPIN A were higher (P ≤ 0.001) in both severe and moderate cases on day 7 post-admission compared to DOA. All the soluble proteins studied were found to elevated (P ≤ 0.01) in severe compared to moderate in day 7 and were positively correlated (P ≤ 0.001) with D-dimer, a marker for coagulation. ROC analysis identified that SERPIN A, IL-18, and bradykinin could predict the clinical condition of COVID-19 with AUC values of 1, 0.979, and 1, respectively. Among the models trained using univariate model analysis, SERPIN A emerged as a strong prognostic biomarker for COVID-19 disease severity. The serum levels of SERPIN A in conjunction with the coagulation marker D-dimer, serve as a predictive indicator for COVID-19 clinical outcomes. However, studies are required to ascertain the role of these markers in disease virulence. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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