MicroRNAs in Acute COVID-19 and Long COVID: Dysregulation, Pathogenic Roles, and Clinical Implications

MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression with central roles in immune responses, inflammation, and viral pathogenesis. Increasing evidence indicates that severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection induces marked dysregulation of host and viral miRNAs (v-miRNAs), contributing to disease severity during acute COVID-19 and to the persistent manifestations observed in long COVID (LC). This narrative review critically synthesizes current evidence on miRNA dysregulation across the acute and post-acute phases of COVID-19, highlighting their pathogenic roles, clinical relevance, and existing knowledge gaps. During acute infection, altered miRNA profiles-including those associated with immune activation, endothelial dysfunction, and immunothrombosis-reflect both host responses and viral strategies of immune modulation, including miRNAs carried by extracellular vesicles (EVs) and SARS-CoV-2-derived v-miRNAs. In LC, emerging data suggest that persistent miRNA alterations are associated with unresolved inflammation, pulmonary dysfunction, neurological symptoms, and vascular injury, although available studies remain limited and heterogeneous. Overall, miRNAs represent promising biomarkers and potential therapeutic targets in COVID-19; however, robust longitudinal and mechanistic studies are urgently needed to clarify their causal roles and translational utility in post-acute disease.