Host MiRNA responses during different waves of SARS-CoV-2: diagnostic implications of miR-19a-3p, miR-374b-5p, miR-15b-5p, and miR-320a-5p expression.

BACKGROUND: Given the pivotal roles of miRNAs as regulators of gene expression, circulating miRNAs offer promising non-invasive diagnostic and therapeutic avenues. The evolving landscape of SARS-CoV-2 variants poses challenges for traditional disease detection and control. METHODS: To unveil the specific circulating miRNA profiles linked to COVID-19 and its correlation with severity levels, qPCR was conducted on five potential miRNAs in plasma samples obtained from 112 COVID-19 patients (comprising 58 severe, 50 moderate, and four mild cases) upon hospital admission during two waves (Beta and Delta variants) of the pandemic, alongside samples from 112 healthy controls. Moreover, correlations between miRNA expression and various clinical laboratory parameters were investigated. RESULTS: Two miRNAs, including miR-19a-3p and miR-374b-5p, were upregulated, and two were downregulated (miR-15b-5p and miR-320a-5p), while the miR-423-5p expression was not changed in COVID-19 patients. ROC curve analysis demonstrated that miR-15b-5p and miR-320a-5p showed the highest specificity and sensitivity. In addition, significant correlations were found between miRNA expression and various laboratory parameters, suggesting that these miRNAs may serve as potential biomarkers for disease severity and progression. Further analysis during different COVID-19 waves and severity levels revealed consistent miRNA expression patterns among the two waves of infection, and most importantly, significant changes in expression among the mild/moderate versus severe infected patients, underscoring their diagnostic value upon different virus strain infections. CONCLUSION: While miRNAs do not replace RT-PCR for viral detection, they offer valuable diagnostic insights into host response and disease dynamics, and may enhance early screening, risk stratification, and monitoring in clinical settings. This study highlights the role of miRNAs as non-invasive biomarkers for the diagnosis and monitoring of COVID-19. In conclusion, the SARS-CoV-2 virus is constantly evolving and mutating. The data presented here explores the distinct role of circulating miRNAs within individuals affected by different variants of COVID-19, unveiling their promise as non-invasive diagnostic markers. CLINICAL TRIAL NUMBER: Not applicable.