Association between Early Treatment and Favorable Clinical Outcomes of COVID-19: Evidence from Nine Provinces in China

• DOI: 10.2139/ssrn.3619794
• Publication Date: 2020-07-31T11:41:06Z
• Authors: Nannan Shi; Bin Liu; Ning Liang; Yan Ma; Youwen Ge; Hongmei Wo; Honggang Yi; Heng Gu; Yuan Kuang; Shaowen Tang; Yang Zhao; Lin Tong; Sihong Liu; Chen Zhao; Renbo Chen; Weiguo Bai; Yipin Fan; Zhan Shi; Li Li; Jia Liu; Hao Gu; Yingjie Zhi; Zhifei Wang; Yuanyuan Li; Huizhen Li; Liwen Jiao; Yaxin Tian; Yibai Xiong; Ruili Huo; Jiangfeng Bai; Hong Chen; Liying Chen; Qiao Feng; Tuanmao Guo; Yong Hou; Guifen Hu; Xiaomei Hu; Yunhong Hu; Jin Huang; Qiuhua Huang; Shaozhen Huang; Liang Ji; Haihao Jin; Xiao Lei; Chunyan Li; Guihui Wu; Jike Li; Minqing Li; Quntang Li; Xianyong Li; Hongde Liu; Jinping Liu; Zhang Liu; Yuting Ma; Ya Mao; Liufen Mo; Hui Na; Jingwei Wang; Fangli Song; Sheng Sun; Dongting Wang; Mingxuan Wang; Xiaoyan Wang; Yinzhen Wang; Yudong Wang; Wei Wu; Lanping Wu; Yanhua Xiao; Haijun Xie; Hongming Xu; Shoufang Xu; Ruixia Xue; Chun Yang; Kaijun Yang; Puye Yang; Shengli Yuan; Gongqi Zhang; Jinbo Zhang; Linsong Zhang; Shusen Zhao; Wanying Zhao; Kai Zheng; Yingchun Zhou; Junteng Zhu; Guangxi Li; Tianqing Zhu; Wei Wang; Huamin Zhang; Yanping Wang; Yongyan Wang

Background: Few studies have examined the association between treatment given time and clinical outcomes, which is indeed of great importance to clinical management of coronavirus disease 2019 (COVID-19). We performed this study to explore whether early treatment brings favorable clinical outcomes. Methods: In this retrospective multicenter study, we included patients aged 18 to 87 years with confirmed COVID-19 on admission from 54 hospitals in nine provinces of China from 21 January to 10 March, 2020. Final date of follow-up was March 17, 2020. All patients were treated by Lung cleansing & detoxifying decoction combined with western medicine. Patients were divided into four groups according to the interval from the first date of onset of symptoms to the date of starting a treatment, i.e., ≤1 week group (≤7 days), 1-2 weeks group (>7 days and ≤14 days), 2-3 weeks group (>14 days and ≤21 days) and >3 weeks group (>21 days). Multivariable Cox proportional hazard ratio (HR) models were used to estimate unadjusted and adjusted HRs and 95% confidence intervals (CIs) for the association between the treatment given time and clinical outcomes (time to recovery, days of viral shedding, duration of hospital stay, course of disease, fever and CT images). Findings: Of the 782 patients (median age was 46 years old, and 405 (52%) were male), there were 321 (41%) patients in ≤1 week group, 221 (28%) in 1-2 weeks group, 123 (16%) in 2-3 weeks group and 117 (15%) in >3 weeks group. Compared to patients in later treatment group (greater than 3 weeks), patients in earlier treatment groups of less than 1 week, 1 to 2 weeks, or 2 to 3 weeks had higher likelihood of recovery, with adjusted HR (95% CI) of 3.81 (2.65-5.48), 2.63 (1.86-3.73) and 1.92 (1.34-2.75), respectively. The median days of viral shedding was 13 days and 12 days in 2-3 weeks group and 3 weeks group (P=0.0137). The median course of disease decreased from 34 days to 24 days, 21 days and 18 days when treatment was given every one week in advance compared to that was given later than 3 weeks from the onset of symptoms (P<0.0001). Treatment within 1 week since onset of symptoms was related with a decrease of 1 to 4 days in terms of median duration of hospital stay compared to later treatment (P<0.0001). Interpretation: Earlier treatment was associated with favorable outcomes, including sooner recovery, shorter time to viral shedding, and shorter duration of hospital stay. This paper demonstrated that early treatment could be an effective strategy in the epidemic control, and can provide evidence for government and international organizations to develop the policy of COVID-19. Funding Statement: This study was supported by “National Science and Technology Major Project” (2018ZX10101001-005-003, 2018ZX10101001-005-004). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study was approved by National Administration of Traditional Chinese Medicine, Administration of Traditional Chinese Medicine of nine provinces and the institutional board of 54 participating setting. Due to the urgency of the treatment of COVID-19, the requirement for informed consent from study participants was replaced by verbal consent.