Study of the prognostic significance of microRNA in hemorrhagic fever with renal syndrome

Objective. To evaluate the prognostic potential of exosomal microRNAs (miR-146a-5p, miR-155-5p, miR-126-3p, miR-218-5p, miR-410-3p, miR-503-5p, miR-29a-3p) depending on the severity of HFRS. Patients and methods. We examined 288 patients at the Republican Clinical Infectious Diseases Hospital in Ufa in 2023–2025 with a diagnosis of HFRS: moderate severity (n = 105), severe (n = 99), and severe with complications (n = 84). Blood samples for molecular genetic analysis were taken during the febrile, oliguric, and convalescent periods of HPS. Total RNA was isolated using the exoRNeasy Midi Kit (Qiagen, Germany). Quantitative real-time PCR (qRT-PCR) was performed using the miRCURY LNA SYBR Green PCR Kit (Qiagen, Germany) and the LightCycler96 real-time PCR product detection system (Roche, Switzerland). Results. When comparing groups of patients with varying severity, distinct differences were found in the levels of exosomal microRNAs miR-146a-5p and miR-155-5p. In patients with severe disease with complications, the level of miR-146a-5p was higher than in patients with moderate disease (FC = 2.70, p = 0.0022, q = 0.007). For miR-155-5p, the increase was FC = 1.86 in severe cases (p = 0.049, q = 0.11 – trend) and FC = 1.98 in severe cases with complications (p = 0.001, q = 0.009). For miR‑503-5p, a weak tendency toward a decrease was identified in severe forms (–25–30% of the medium to severe form, p = 0.08), which may have pathogenetic significance. Significant correlations were found between miR-155-5p/miR-503-5p and clinical and laboratory parameters: creatinine, C-reactive protein, and duration of fever. Conclusion. MicroRNA-146a-5p and microRNA-155-5p can be considered as early prognostic biomarkers of HFRS severity. Our findings expand the understanding of the role of microRNAs in the pathogenesis of HFRS and confirm the need for further research to develop microRNA-based prognostic tests and targeted interventions. Key words: hemorrhagic fever with renal syndrome, microRNA severity of HFRS