Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19
Mingxing Huang, Man Li, Fei Xiao, Pengfei Pang, Jiabi Liang, Tiantian Tang, Shaoxuan Liu, Binghui Chen, Jingxian Shu, Yingying You, Yang Li, Meiwen Tang, Jianhui Zhou, Guanmin Jiang, Jingfen Xiang, Wenxin Hong, Songmei He, Zhaoqin Wang, Jianhua Feng, Changqing Lin, Yinong Ye, Zhilong Wu, Yaocai Li, Bei Zhong, Ruilin Sun, Zhongsi Hong, Jing Liu, Huili Chen, Xiaohua Wang, Zhonghe Li, Duanqing Pei, Lin Tian, Jinyu Xia, Shanping Jiang, Nanshan Zhong, Hong Shan
National Science Review, doi:10.1093/nsr/nwaa113
Effective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19. In this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500 mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events. A total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians −6.0 days; 95% CI −6.0 to −4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose. Although randomized trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating the COVID-19 pandemic.
RESEARCH ARTICLE Huang et al. 1435 then double-entered into an electronic database and validated by trial staff. After hospital discharge, patients were followed up once weekly. Patients with 're-positive' viral RNA detection within one week after hospital discharge are defined as having either 2 consecutive RT-PCR positive result from either respiratory tract sample or fecal specimen. In the subgroup of patients in SYSU5, all CT images were reviewed by two fellowship-trained cardio-thoracic radiologists by using a viewing console. Images were reviewed independently, and final decisions were reached by consensus [9] . To fully assess the safety of chloroquine, we monitor the serum concentration of chloroquine at the day 1, 3, 5, 7, 10 during drug administration and day 1 to 7, and day 14, day 21 after treatment completion in a subgroup of samples enrolled from SYSU5 (N = 50). Details about the measurement of serum concentration of chloroquine are described in Supplementary Methods.
Statistical analysis The original plan was to compare the efficacy between three groups, chloroquine only, Lopinavir/Ritonavir only, and chloroquine plus Lopinavor/Ritonavir. At the beginning of the outbreak, different therapies were proposed and tested for the treatment of COVID-19. Therefore, it is challenging to find sufficient patients with unified treatment across all centers. The epidemic in Guangdong had been brought under control rapidly during the study making it difficult to recruit..
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'abstract': '<jats:title>Abstract</jats:title><jats:p>Effective therapies are urgently needed for the '
'SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus '
'in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with '
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