Deciphering the Regulatory Landscape of mRNA-miRNA-lncRNA Interactions in COVID-19 Severity: Insights from Transcriptomic Analysis.

BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has a highly variable clinical course, ranging from mild symptoms to severe systemic complications. Understanding the molecular basis of disease severity is essential for improving diagnostic and therapeutic strategies.

OBJECTIVE In this study, we performed transcriptome analysis of peripheral blood mononuclear cells (PBMCs) from patients with mild and severe COVID-19 to identify differentially expressed mRNAs and long noncoding RNAs (lncRNAs), and to construct a regulatory network including microRNAs (miRNAs).

METHODS Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) from patients with mild and severe COVID-19 was performed to identify differentially expressed mRNAs and long noncoding RNAs (lncRNAs), and to construct a regulatory network including microRNAs (miRNAs) using Cytoscape.

RESULTS A total of 674 mRNAs and 215 lncRNAs were differentially expressed between severe and mild cases, with key pathways enriched in cytokine-cytokine receptor interaction and immunological synapse signaling. The lncRNAs NEAT1 and MALAT1 were identified as regulatory hubs and were broadly expressed across multiple immune and organ tissues. Predicted miRNAs (experimentally supported in interaction databases) were associated with inflammation- and cancer-related signaling pathways, including PI3K-Akt, JAK/STAT, and TNF.

DISCUSSION Our findings are consistent with recent patents (e.g., US2022/0298584A1, EP3892280A3, WO2023147669A1) that propose the use of noncoding RNAs and cytokines as biomarkers for COVID-19 diagnosis and severity assessment.

CONCLUSION Our findings are consistent with recent patents (e.g., "US20220298584A1", "EP3892280A3", "WO2023147669A1") that propose the use of noncoding RNAs and cytokines as biomarkers for COVID-19 diagnosis and severity assessment. This integrative transcriptomic analysis highlights the regulatory role of noncoding RNAs in COVID-19 progression, exemplified by the central hub lncRNAs NEAT1 and MALAT1, which interact with inflammation- associated miRNAs and mRNA targets to modulate cytokine signaling. These findings offer specific transcriptomic biomarkers with potential for clinical application and therapeutic targeting.