Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: a multicenter, open-label, randomized trial

Zhao, Hong; Zhang, Chi; Zhu, Qi; Chen, Xianxiang; Chen, Guilin; Sun, Wenjin; Xiao, Zuohan; Du, Weijun; Yao, Jing; Li, Guojun; Ji, Yanhua; Li, Niuniu; Jiang, Yujin; Wang, Ying; Zeng, Qingjin; Li, Wei; Gong, Beilei; Chang, Xianyou; Zhu, Feng; Jiang, Xiufeng; Li, Jiawen; Wu, Zhao; Liu, Yingxia; Peng, Peng; Wang, Guiqiang

Background The clinical characteristics and treatment of patients who tested positive for COVID-19 after recovery remained elusive. Effective antiviral therapy is important for tackling these patients. We assessed the efficacy and safety of favipiravir for treating these patients. Methods This is a multicenter, open-label, randomized controlled trial in SARS-CoV-2 RNA re-positive patients. Patients were randomly assigned in a 2:1 ratio to receive either favipiravir, in addition to standard care, or standard care alone. The primary outcome was time to achieve a consecutive twice (at intervals of more than 24 hours) negative RT-PCR result for SARS-CoV-2 RNA in nasopharyngeal swab and sputum sample. Results Between March 27 and May 9 2020, 55 patients underwent randomization; 36 were assigned to the favipiravir group and 19 were assigned to the control group. Favipiravir group had a significantly shorter time from start of study treatment to negative nasopharyngeal swab and sputum than control group (median 17 vs. 26 days); hazard ratio 2.1 (95% CI [1.1 - 4.0], p=0.038). The proportion of virus shedding in favipiravir group was higher than control group (80.6% [29/36] vs. 52.6% [10/19], p=0.030, respectively). C-reactive protein decreased significantly after treatment in the favipiravir group (p=0.016). The adverse events were generally mild and self-limiting. Conclusion Favipiravir was safe and superior to control in shortening the duration of viral shedding in SARS-CoV-2 RNA recurrent positive after discharge. However, a larger scale and randomized, double-blind, placebo-controlled trial is required to confirm our conclusion.