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Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus with high fatality and an expanding endemic. Currently, effective anti-SFTSV intervention remains unavailable. Favipiravir (T-705) was recently reported to show in vitro and in animal model antiviral efficacy against SFTSV. Here, we conducted a single-blind, randomized controlled trial to assess the efficacy and safety of T-705 in treating SFTS (Chinese Clinical Trial Registry website, number ChiCTR1900023350). From May to August 2018, laboratory-confirmed SFTS patients were recruited from a designated hospital and randomly assigned to receive oral T-705 in combination with supportive care or supportive care only. Fatal outcome occurred in 9.5% (7/74) of T-705 treated patients and 18.3% (13/71) of controls (odds ratio, 0.466, 95% CI, 0.174–1.247). Cox regression showed a significant reduction in case fatality rate (CFR) with an adjusted hazard ratio of 0.366 (95% CI, 0.142–0.944). Among the low-viral load subgroup (RT-PCR cycle threshold ≥26), T-705 treatment significantly reduced CFR from 11.5 to 1.6% (P = 0.029), while no between-arm difference was observed in the high-viral load subgroup (RT-PCR cycle threshold

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality, however with no effective therapy available. Methods The effect of favipiravir (FPV) in treating SFTS was evaluated by an integrated analysis on data collected from a single-arm study (n=428), a surveillance study (n=2350) and published data from a randomized controlled trial study (n=145). A 1:1 propensity score matching was performed to include 780 patients: 390 received FPV and 390 received supportive therapy only. Case fatality rates (CFRs), clinical progress, and adverse effects were compared. Findings FPV treatment had significantly reduced CFR from 20.0% to 9.0% (odds ratio 0.38, 95% confidence interval 0.23-0.65), however showing heterogeneity when patients were grouped by age, onset-to-admission interval, initial viral load and therapy duration. The effect of FPV was significant only among patients aged ≤70 years, with onset-to-admission interval ≤5 days, therapy duration ≥5 days or baseline viral load ≤1 × 106 copies/mL. Age-stratified analysis revealed no benefit in the aging group >70 years, regardless of their sex, onset-to-admission interval, therapy duration or baseline viral load. However, for both ≤60 and 60-70 years groups, therapy duration and baseline viral load differentially affected FPV therapy efficiency. Hyperuricemia and thrombocytopenia, as the major adverse response of FPV usage, were observed in >70 years patients. Interpretation FPV was safe in treating SFTS patients but showed no benefit for those aged >70 years. Instant FPV therapy could highly benefit SFTS patients aged 60-70 years. Funding China Natural Science Foundation (No. 81825019, 82073617 and 81722041) and China Mega-project for Infectious Diseases (2018ZX10713002 and 2015ZX09102022).