Integrative hematological and transcriptomic analysis reveals monocyte alterations and molecular signatures of inflammatory-coagulation crosstalk in long COVID.

Long COVID has complicated immunological and coagulation dysregulations. The study explores the pathophysiological pathways by integrating clinical hematological characteristics with transcriptome bioinformatics. In a comparison of 45 patients (21 with Long COVID and 24 asymptomatic controls), the Long COVID cohort demonstrated significantly reduced total WBC counts (p = 0.031) and circulating monocytes (p = 0.008), as well as reduced platelet counts (p = 0.040) and prolonged APTT (p = 0.016). To better understand these findings, transcriptome analysis of the public dataset GSE251849 was performed applying DESeq2, Gene Set Enrichment Analysis (GSEA), and a Protein-Protein Interaction (PPI) network assessed through the Maximal Clique Centrality (MCC) algorithm. Transcriptomic profiling demonstrated significant enrichment of inflammation, cellular stress, and coagulation pathways. The MCC analysis identified IL6, MYC, CDKN1A, SERPINE1, CD44, and PLAUR as the key hub genes. The significant decrease in circulating monocytes, along with upregulation of CD44, indicates monocyte depletion due to enhanced endothelium adherence. Furthermore, the significant upregulation of SERPINE1 and PLAUR underscores the important connection between chronic vascular inflammation and severe fibrinolysis resistance (hypofibrinolysis). These findings establish a strong biological basis for the clinical features of Long COVID, highlighting an immunothrombosis proposed mechanistic model driven by cellular stress and hypofibrinolysis, thus pinpointing prospective targets for future diagnostics and therapeutics.