Clinical efficacy and safety evaluation of favipiravir in treating patients with severe fever with thrombocytopenia syndrome
Yang Yuan,
Qing-Bin Lu,
Wen-Si Yao,
Jing Zhao,
Xiao-Ai Zhang,
Ning Cui,
Chun Yuan,
Tong Yang,
Xue-Fang Peng,
Shou-Ming Lv,
Jia-Chen Li,
Ya-Bin Song,
Dong-Na Zhang,
Li-Qun Fang,
Hong-Quan Wang,
Hao Li,
Wei Liu
Affiliations
Yang Yuan
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China
Qing-Bin Lu
Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing 100191, PR China
Wen-Si Yao
The 990th Hospital of Joint Logistic Support Force of Chinese People's Liberation Army, Xinyang, Henan 464000, PR China
Jing Zhao
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China
Xiao-Ai Zhang
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China
Ning Cui
The 990th Hospital of Joint Logistic Support Force of Chinese People's Liberation Army, Xinyang, Henan 464000, PR China
Chun Yuan
The 990th Hospital of Joint Logistic Support Force of Chinese People's Liberation Army, Xinyang, Henan 464000, PR China
Tong Yang
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China
Xue-Fang Peng
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China
Shou-Ming Lv
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China; Graduate School of Anhui Medical University, Hefei 230601, PR China
Jia-Chen Li
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China
Ya-Bin Song
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China
Dong-Na Zhang
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China
Li-Qun Fang
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China
Hong-Quan Wang
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China; Corresponding authors at: Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, 20 Dong-Da Street, Fengtai District, Beijing 100071, China.
Hao Li
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China; Graduate School of Anhui Medical University, Hefei 230601, PR China; Corresponding authors at: Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, 20 Dong-Da Street, Fengtai District, Beijing 100071, China.
Wei Liu
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, PR China; Department of Laboratorial Science and Technology, School of Public Health, Peking University, Beijing 100191, PR China; Graduate School of Anhui Medical University, Hefei 230601, PR China; Beijing Key Laboratory of Vector Borne and Natural Focus Infectious Diseases, Beijing 100191, PR China; Corresponding authors at: Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, 20 Dong-Da Street, Fengtai District, Beijing 100071, China.
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).
