Clinical efficacy and safety evaluation of favipiravir in treating patients with severe fever with thrombocytopenia syndrome.

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).

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

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 <26). The T-705-treated group showed shorter viral clearance, lower incidence of hemorrhagic signs, and faster recovery of laboratory abnormities compared with the controls. The in vitro and animal experiments demonstrated that the antiviral efficacies of T-705 were proportionally induced by SFTSV mutation rates, particularly from two transition mutation types. The mutation analyses on T-705-treated serum samples disclosed a partially consistent mutagenesis pattern as those of the in vitro or animal experiments in reducing the SFTSV viral loads, further supporting the anti-SFTSV effect of T-705, especially for the low-viral loads.

Clinical and Virological Characteristics of Ebola Virus Disease Patients Treated With Favipiravir (T-705)-Sierra Leone, 2014.

BACKGROUND: During 2014-2015, an outbreak of Ebola virus disease (EVD) swept across parts of West Africa. No approved antiviral drugs are available for Ebola treatment currently. METHODS: A retrospective clinical case series was performed for EVD patients in Sierra Leone-China Friendship Hospital. Patients with confirmed EVD were sequentially enrolled and treated with either World Health Organization (WHO)-recommended supportive therapy (control group) from 10 to 30 October, or treated with WHO-recommended therapy plus favipiravir (T-705) from 1 to 10 November 2014. Survival and virological characteristics were observed for 85 patients in the control group and 39 in the T-705 treatment group. RESULTS: The overall survival rate in the T-705 treatment group was higher than that of the control group (56.4% [22/39] vs 35.3% [30/85]; P = .027). Among the 35 patients who finished all designed endpoint observations, the survival rate in the T-705 treatment group (64.8% [11/17]) was higher than that of the control group (27.8% [5/18]). Furthermore, the average survival time of the treatment group (46.9 ± 5.6 days) was longer than that of the control group (28.9 ± 4.7 days). Most symptoms of patients in the treatment group improved significantly. Additionally, 52.9% of patients who received T-705 had a >100-fold viral load reduction, compared with only 16.7% of patients in the control group. CONCLUSIONS: Treatment of EVD with T-705 was associated with prolonged survival and markedly reduced viral load, which makes a compelling case for further randomized controlled trials of T-705 for treating EVD.

[Biodiversity of mesophilic microbial community BYND-8 capability of lignocellulose degradation and its effect on biogas production].

The biodiversity of a mesophilic microbial community BYND-8 capable of degrading lignocellulose at 30 degrees C was detected using denaturing gradient gel electrophoresis (DGGE) and the isolation of pure cultures, and the effect of the liquid of rice straw degradation by BYND-8 on biogas production was measured. Six bacterial strains were isolated using peptone cellulose solution medium, and the highest similarities of their 16S rDNA gene sequences to Serratia sp. PSGB 13, S. marcescens strain UFLA-25LS, S. marcescens strain DAP33, Alcaligenes sp. YcX-20, Stenotrophomonas maltophilia strain C6, Bacillus cereus isolate BRL02-71 were 99%, 100%, 96%, 100%, 100% and 99%, respectively. In addition, one band was detected besides six bands of cultured isolates on the DGGE gel, and it showed 100% sequence similarity to uncultured bacterium clone ATB-KS-1446. The cumulative biogas and methane productions of biogas fermentation system added with the liquid of rice straw degraded by BYND-8 were 13 167 mL and 7 248 mL, 44.5% and 95.3% higher than those of the control, respectively, in the early 15 days of fermentation. The results showed that the biodiversity of microbial community BYND-8 was very high, and the time of producing biogas was put forward and biogas production was increased with application of microbial community for rice straw pretreatment during the biogas fermentation.