Introduction:
COVID-19 and venous thrombosis pose significant global health challenges. Recent studies suggest a potential overlap in their underlying molecular mechanisms, particularly immune responses and inflammation. This study aims to elucidate shared molecular pathways between COVID-19 and venous thrombosis, identify common biomarkers, and propose potential therapeutic targets through a comprehensive multi-dataset analysis.

Material and Methods:
Public datasets (GSE171110, GSE189990, GSE178246, GSE48000, and GSE19151) were analyzed using the “Limma” package in R for differential gene expression analysis. Functional enrichment (GO, KEGG) was conducted via the “ClusterProfiler” package. Protein-protein interaction (PPI) networks, transcription factor (TF)-target, and miRNA-target networks were constructed using TRRUST and miRDB databases. Drug sensitivity was assessed using CellMiner, and feature genes were identified using LASSO regression. Immune infiltration analysis was performed with CIBERSORT, and key genes were validated using qRT-PCR and animal models.

Results:
Key differentially expressed genes (DEGs), including SELP and CLEC4D, were identified, highlighting their roles in immune regulation and thrombosis. Drug sensitivity analysis revealed correlations with specific chemotherapeutic agents. Immune infiltration analysis demonstrated increased expression of SELP and CLEC4D in certain immune cells, confirmed by qRT-PCR and in animal models.

Conclusions:
This study uncovered shared molecular mechanisms between COVID-19 and venous thrombosis, identifying potential biomarkers and therapeutic targets such as SELP and CLEC4D. These findings provide new insights into the diagnosis and treatment of both conditions.