MicroRNAs in SARS-CoV-2 infection: emerging modulators of inflammation, pathogenesis, and therapeutic potential

Since the onset of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), elucidating the molecular regulators of viral pathogenesis and host response has been a critical international research objective. Among these, microRNAs (miRNAs), small non-coding RNAs, that modulate gene expression post-transcriptionally-have emerged as central orchestrators of host-virus interactions. This review exhaustively examines the roles of host-derived miRNAs in SARS-CoV-2 infection, including their roles in viral entry, replication, immune evasion, inflammation, and tissue injury. Dysregulation of certain miRNAs, such as miR-155, miR-146a, and miR-21, has been implicated in disease severity, comorbidities (such as diabetes, obesity), neurological complications, and pregnancy complications. In long COVID (PASC), chronic miRNA changes are linked to persistent inflammation, fibrosis, and cardiometabolic impairment. We emphasize current breakthroughs in miRNA research, including machine learning algorithms for miRNA-based disease stratification, CRISPR-engineered miRNA modulation, exosomal miRNA delivery platforms, and miRNA-adjuvanted vaccines. These advances highlight the potential of miRNAs as diagnostic biomarkers and therapeutic targets. Nevertheless, shortcomings persist in clinical validation, delivery optimization, and tissue-specific miRNA function elucidation. These gaps must be addressed to involve miRNAs in controlling current and future viral infections. This review consolidated differentially expressed miRNAs across disease stages, comorbidities, and clinical settings, providing a valuable resource for translational research and therapeutic innovation.