Khansaheb, Hamda HAlqassim, Saif SAlsheikh-Ali, Alawi2025-11-212025-11-212025-08-212045-2322https://repository.mbru.ac.ae/handle/1/1930This study aimed to identify miRNA-based biomarkers in a multi-ethnic cohort of SARS-CoV-2-infected individuals to enhance preparedness for future variants of concern. A total of 31 healthy controls and 154 infected patients were enrolled, from which 13 matched controls and 38 infected nasal swab samples were analyzed using miRNA sequencing, followed by qRT-PCR validation. Among the 1788 miRNAs detected, 14 differentially expressed miRNAs and four novel miRNAs were identified, with novel-miR-264-5p showing a ≥ 2-fold change. Correlation with clinical markers highlighted several miRNAs as potential prognostic biomarkers. Seven miRNAs, including miR-146b-3p, miR-154-5p, miR- 5010-3p, miR-127-3p, miR-335-3p, miR-30c-5p, and miR-202-5p, showed strong prognostic potential. Combined ROC analysis demonstrated that a panel of top-performing miRNAs significantly enhanced diagnostic accuracy (AUC 0.939–0.972; p < 0.0001). Moreover, integrating miRNA biomarkers with clinical parameters further improved performance (AUC = 0.982; p < 0.0001). miR-146b-3p, detected exclusively in infected patients, emerged as a highly specific biomarker. Several nasal miRNAs mirrored blood profiles, highlighting the utility of nasal swabs for non-invasive monitoring. Collectively, these findings suggest that miRNA-based biomarkers, alone or combined with clinical markers, offer a promising platform for COVID-19 prognosis and diagnosis, and lay groundwork for future miRNA based antiviral strategies.COVID-19SARS-CoV-2MiRNAsBiomarkersNasopharyngeal swabsMiRNAseqVariantsof- Concern (VOC)Respiratory diseasesInfectious diseasesjournal-article10.1038/s41598-025-15248-6