Immune-regulatory vault RNAs are associated with molecular signatures in COVID-19

Abstract

Background: Vault RNAs (vtRNAs), a group of small non-coding RNAs, are recognized to regulate host immune responses, mainly through the NF-kappa B/PKR signaling pathway. Viral recruitment of vtRNAs has been described in numerous infections, but their function in COVID-19 is still unclear. Objective: To examine the expression profiles of vtRNAs (vtRNA1-1, vtRNA1-2, vtRNA1-3, and vtRNA2-1) in individuals with severe COVID-19 and evaluate their potential clinical implications. Methods: Peripheral blood mononuclear cells were isolated from 50 patients diagnosed with severe COVID-19 and 50 matched healthy controls. Expression levels of vtRNAs were quantified using real-time PCR, normalized to ACTB, and analyzed through non-parametric statistical analyses. Associations with demographic and clinical features were calculated. Diagnostic performance was evaluated using ROC curve analysis. Results: Expression of vtRNA1-2, vtRNA1-3, and vtRNA2-1 was significantly upregulated in COVID-19 patients compared with controls (p < 0.05). vtRNA1-1 expression showed no meaningful difference. Notably, vtRNA2-1 expression correlated with specific blood groups. ROC curve analysis showed statistically significant but modest discriminatory performance for vtRNA1-2 (AUC = 0.615), vtRNA1-3 (AUC = 0.622), and vtRNA2-1 (AUC = 0.673), indicating limited diagnostic utility when considered as individual markers. Conclusion: This study provides preliminary evidence that vtRNAs are dysregulated in PBMCs from patients with severe COVID-19. The observed upregulation of vtRNA1-2, vtRNA1-3, and vtRNA2-1 suggests that these noncoding RNAs may be involved in host molecular responses associated with severe SARS-CoV-2 infection. However, their diagnostic and mechanistic relevance requires validation in larger cohorts, including patients with different disease severities and appropriate disease-control groups.