A multicenter non-randomized, uncontrolled single arm trial for evaluation of the efficacy and the safety of the treatment with favipiravir for patients with severe fever with thrombocytopenia syndrome

Severe fever with thrombocytopenia syndrome (SFTS) is a bunyavirus infection with high mortality. Favipiravir has shown effectiveness in preventing and treating SFTS virus (SFTSV) infection in animal models. A multicenter non-randomized, uncontrolled single arm trial was conducted to collect data on the safety and the effectiveness of favipiravir in treatment of SFTS patients. All participants received favipiravir orally (first-day loading dose of 1800 mg twice a day followed by 800 mg twice a day for 7-14 days in total). SFTSV RT-PCR and biochemistry tests were performed at designated time points. Outcomes were 28-day mortality, clinical improvement, viral load evolution, and adverse events (AEs). Twenty-six patients were enrolled, of whom 23 were analyzed. Four of these 23 patients died of multi-organ failure within one week (28-day mortality rate: 17.3%). Oral favipiravir was well tolerated in the surviving patients. AEs (abnormal hepatic function and insomnia) occurred in about 20% of the patients. Clinical symptoms improved in all patients who survived from a median of day 2 to day10. SFTSV RNA levels in the patients who died were significantly higher than those in the survivors (p = 0.0029). No viral genomes were detectable in the surviving patients a median of 8 days after favipiravir administration. The 28-day mortality rate in this study was lower than those of the previous studies in Japan. The high frequency of hepatic dysfunction as an AE was observed. However, it was unclear whether this was merely a side effect of favipiravir, because liver disorders are commonly seen in SFTS patients. The results of this trial support the effectiveness of favipiravir for patients with SFTS. Author summary Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne virus infection caused by Dabie bandavirus (formerly SFTS virus, SFTSV), which belongs to the Bandavirus genus of the Phenuiviridae family. The case fatality rate of patients with SFTS is high ranging from 16.2% to 47%. SFTS is endemic to East and Southeast Asia. Favipiravir, an antiviral agent with an inhibitory activity on the RNA-dependent RNA polymerase, inhibited replication of SFTSV in vitro and in vivo. It was suggested that favipiravir treatment lowered the case fatality rate of patients with SFTS by approximately 10% in comparison with those reported so far through epidemiological survey in Japan. People living in the SFTS-endemic regions can not escape from the risk of being infected with SFTSV. Favipiravir might be an effective drug for treatment of patients with SFTS and reduces the mortality and morbidity of patients with SFTS.