Bioinformatics analysis of the proteome in the pathway of complement and coagulation cascades in COVID-19: discovering potential biomarkers of FGB and SERPINA5

The complement system, a key innate immunity component, is implicated in COVID-19 pathogenesis. Proteomic studies reveal dysregulated complement and coagulation cascades (CCC) proteins in COVID-19, yet comprehensive analyses remain limited. This bioinformatics study analyzed proteomic data (from inception to January 13, 2025) across Web of Science, PubMed, EMBASE, and Wiley Online Library using keywords "complement and coagulation cascades", "COVID-19", and "proteomics". Included studies compared differentially expressed proteins (DEPs) in COVID-19 patients versus healthy controls. Two reviewers independently extracted data. DEPs were analyzed via R (v4.4.2), Stata (v14), and STRING (v12.0). Twenty studies identified 3,018 DEPs, including 58 CCC-related genes (e.g., FGB, SERPINA5, FGG, F2). Hub genes were identified using MCODE and cytohubba in Cytoscape, and 16 hub genes (e.g., FGB, SERPINA5) were found. Stata confirmed consistent expression of FGB, SERPINA5, FGG, and F2. All of them are the biomarkers of diseases, and are the drug targets except SERPINA5 according to the reports from OpenTargets database. Immunohistochemistry validated FGB upregulation and SERPINA5 downregulation. In summary, CCC pathway proteins are extensively dysregulated in COVID-19. FGB and SERPINA5 are potential diagnostic biomarkers and therapeutic targets, offering insights into severe COVID-19 mechanisms and guiding novel treatment strategies.