The Role of lncRNAs in the TNF Pathway in Patients with COVID-19: A Narrative Review

Abstract

Context: SARS-CoV-2 infection can trigger a severe inflammatory response and, in critical cases, cytokine storm syndrome. Tumor necrosis factor-alpha (TNF-α) is a key cytokine involved in this process. Long non-coding RNAs (lncRNAs), which regulate gene expression and immune responses, may modulate TNF-α-related inflammatory pathways in COVID-19. Evidence Acquisition: This review examined the role of lncRNAs involved in the TNF pathway in patients with COVID-19, focusing on their regulatory mechanisms, associations with disease severity, and potential clinical applications. Results: Several lncRNAs, including NEAT1 (Nuclear Enriched Abundant Transcript 1), MALAT1 (Metastasis-Associated Lung Adenocarcinoma Transcript 1), THRIL (TNF-alpha and hnRNPL Related Immunoregulatory LncRNA), GAS5 (Growth Arrest-Specific 5), TUG1 (Taurine Up-Regulated 1), and HULC (Highly Upregulated in Liver Cancer), were found to modulate TNF-α and other inflammatory cytokines via mechanisms such as microRNA sponging, epigenetic regulation, and transcriptional control. Evidence from immune interventions, including BCG vaccination and immunonutrition, as well as bioinformatics-based network analyses, further supports the involvement of lncRNAs in the regulation of the TNF pathway. Altered expression of these lncRNAs was associated with COVID-19 severity, prognosis, and treatment response. Conclusions: LncRNAs involved in the TNF signaling pathway may contribute to the inflammatory response and clinical severity of COVID-19. Accordingly, they may serve as potential diagnostic and prognostic biomarkers and as promising therapeutic targets for the management of COVID-19.