Clinical effect and antiviral mechanism of T-705 in treating severe fever with thrombocytopenia syndrome

• Published in: Signal transduction and targeted therapy 2021-04, Vol.6 (1), p.145-13, Article 145
• Main Authors: Li, Hao, Jiang, Xia-Ming, Cui, Ning, Yuan, Chun, Zhang, Shao-Fei, Lu, Qing-Bin, Yang, Zhen-Dong, Xin, Qin-Lin, Song, Ya-Bin, Zhang, Xiao-Ai, Liu, Hai-Zhou, Du, Juan, Fan, Xue-Juan, Yuan, Lan, Yuan, Yi-Mei, Wang, Zhen, Wang, Juan, Zhang, Lan, Zhang, Dong-Na, Wang, Zhi-Bo, Dai, Ke, Bai, Jie-Ying, Hao, Zhao-Nian, Fan, Hang, Fang, Li-Qun, Xiao, Gengfu, Yang, Yang, Peng, Ke, Wang, Hong-Quan, Li, Jian-Xiong, Zhang, Lei-Ke, Liu, Wei
• Format: Article
• Language: English
• Subjects: 631/326; 692/420/254; Administration, Oral; Amides - administration & dosage; Animal research; Animals; Antiviral Agents - administration & dosage; Cancer Research; Cell Biology; Fatalities; Female; Humans; Internal Medicine; Laboratories; Male; Medicine; Medicine & Public Health; Mice; Mice, Knockout; Middle Aged; Mutation; Oncology; Pathology; Phlebovirus - metabolism; Prospective Studies; Pyrazines - administration & dosage; Severe Fever with Thrombocytopenia Syndrome - blood; Severe Fever with Thrombocytopenia Syndrome - drug therapy; Severe Fever with Thrombocytopenia Syndrome - genetics; Severe Fever with Thrombocytopenia Syndrome - mortality; Single-Blind Method; Thrombocytopenia
• ISSN: 2059-3635; 2095-9907; 2059-3635
• DOI: 10.1038/s41392-021-00541-3

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