Targeting the lethal weakness of SFTSV: Latest advances in antiviral strategies and immune prevention

In recent years, severe fever with thrombocytopenia syndrome (SFTS), caused by the SFTS virus (SFTSV), has a fatality rate ranging from 12% to 50%, but there are currently no approved therapies to effectively treat the infection. Host cell receptors CCR2 and LRP1 have been identified as key entry points for viral invasion, and viral non-structural proteins evade the host innate immune response through multiple mechanisms. Several clinical studies have demonstrated that inflammatory markers (such as, IL-6, TNF-α, etc.), lipid metabolites, and ferritin are reliable prognostic indicators, aiding in early risk stratification. Favipiravir was associated with approximately a 10% reduction in mortality in clinical trials, while JAK inhibitors have shown efficacy in managing cytokine storms in critically ill patients. Recent drug repurposing studies have identified several FDA-approved compounds that show promise in combating SFTSV, potentially accelerating the development of therapeutic options. The comprehensive management of critically ill patients integrates multiple approaches, including antiviral therapy, immunomodulation, and organ function support, significantly improving clinical outcomes. Vaccine development has progressed across several platforms, including live attenuated and mRNA-based technologies. Several candidates have shown protective effects in animal studies, with improved formulations for high-risk elderly individuals. However, challenges remain in establishing protective immunity, ensuring long-term safety, and scaling up production for clinical use. This review summarizes recent progress in the transmission, pathogenesis, clinical features, immune response, prognosis, treatment, and vaccine development for SFTSV. It also identifies knowledge gaps and research limitations, proposing key areas for future focus to improve the management of this emerging infectious disease.