连花清瘟制剂治疗病毒性疾病的Meta分析再评价

Overview of Meta-analysis of Lianhua Qingwen preparations in treatment of viral diseases

为了对连花清瘟制剂治疗流行性感冒、新型冠状病毒肺炎、手足口病等病毒性疾病的Meta分析再评价,得到更高等级的循证证据,检索中国知网(CNKI)、万方(Wanfang)、维普(VIP)、中国临床试验注册中心、PubMed、EMbase、Web of Science、Cochrane Library等数据库,收集连花清瘟制剂治疗病毒感染性疾病的Meta分析,检索时间均为建库至2022年4月1日。根据纳入、排除标准筛选及提取文献内容后,使用AMSTAR2量表评价纳入的Meta分析质量,使用GRADE系统评价各结局指标质量,并汇总连花清瘟制剂治疗病毒感染性疾病的疗效及安全性。在最终纳入的13篇Meta分析中,3篇AMSTAR2评分为低级,10篇为极低级。共得到75个结局指标,涉及流行性感冒、新型冠状病毒肺炎、手足口病,GRADE评分结果为高级证据5个(6.7%),中级证据18个(24.0%),低级证据25个(33.3%),极低级证据27个(36.0%)。结果显示,(1)在治疗流行性感冒方面,临床疗效显愈率连花清瘟制剂优于其他中成药和利巴韦林,而与奥司他韦差异无统计学意义;改善临床症状指标连花清瘟制剂优于其他中成药、奥司他韦与利巴韦林;病毒核酸转阴时间与转阴率连花清瘟制剂与奥司他韦或中西医抗流感常规治疗差异无统计学意义。(2)在治疗新型冠状病毒肺炎方面,连花清瘟制剂联合或不联合常规治疗在总有效率、主要症状消退率、次要症状消退率及主要症状消退时间均优于常规治疗,并在改善发热好转率、发热持续时间、发热消退时间、咳嗽消退率、咳嗽消退时间、乏力消退率、乏力消退时间、肌痛消退率、咯痰消退率、胸闷消退率等优于常规治疗;而在咽痛消退率、恶心消退率、腹泻消退率、食欲下降消退率、头痛消退率、呼吸困难消退率、气短消退率等方面,连花清瘟制剂与常规治疗差异无统计学意义;在胸部CT改善率、临床转重症率、治愈时间及住院时间方面,连花清瘟单用或联合常规治疗均优于常规治疗。(3)在治疗手足口病方面,连花清瘟颗粒在总有效率、平均退热时间、疱疹消退时间及病毒核酸转阴时间优于常规治疗。(4)安全性方面,连花清瘟制剂组不良反应发生率较低且均为轻症,可随停药痊愈。现有证据表明,连花清瘟制剂能减轻流行性感冒、新型冠状病毒肺炎及手足口病患者的临床症状,缩短住院时间并改善胸部CT指标,在治疗病毒感染性疾病时有一定疗效,并且安全性佳。但由于原始研究的质量偏低,仍需开展更多高质量的临床试验支持以上结论。

This study aims to obtain higher-level evidence by overviewing the Meta-analysis of Lianhua Qingwen preparations in the treatment of viral diseases including influenza, coronavirus disease 2019(COVID-19), and hand, foot and mouth disease(HFMD). CNKI, Wanfang, VIP, China Clinical Trial Registry(ChiCTR), PubMed, EMbase, Web of Science, and Cochrane Library were searched for the Meta-analysis about the treatment of viral diseases with Lianhua Qingwen preparations from the database establishment to April 1, 2022. After literature screening and data extraction, AMSTAR2 and the grading of recommendations assessment, development and evaluations(GRADE) system were used to assess the methodological quality and evidence quality, respectively, and then the efficacy and safety outcomes of Lianhua Qingwen preparations in the treatment of viral diseases were summarized. Thirteen Meta-analysis were finally included, three of which were rated as low grade by AMSTAR2 and ten as very low grade. A total of 75 outcome indicators were obtained, involving influenza, COVID-19, and HFMD. According to the GRADE scoring results, the 75 outcome indicators included 5(6.7%) high-level indicators, 18(24.0%) mediate-level indicators, 25(33.3%) low-level evidence indicators, and 27(36.0%) very low-level indicators.(1)In the treatment of influenza, Lianhua Qingwen preparations exhibited better clinical efficacy than other Chinese patent medicines and Ribavirin and had similar clinical efficacy compared with Oseltamivir. Lianhua Qingwen preparations were superior to other Chinese patent medicines, Oseltamivir, and Ribavirin in alleviating clinical symptoms. They showed no significant differences from Oseltamivir or conventional anti-influenza treatment in terms of the time to and rate of negative result of viral nucleic acid test.(2)In the treatment of COVID-19, Lianhua Qingwen preparation alone or combined with conventional treatment was superior to conventional treatment in terms of total effective rate, main symptom subsidence rate and time, fever clearance rate, duration of fever, time to fever clearance, cough subsidence rate, time to cough subsidence, fatigue subsidence rate, time to fatigue subsidence, myalgia subsidence rate, expectoration subsidence rate, chest tightness subsidence rate, etc. Lianhua Qingwen preparations no difference from conventional treatment in terms of subsiding sore throat, nausea, diarrhea, loss of appetite, headache, and dyspnea. In terms of chest CT improvement rate, rate of progression to severe case, cure time, and hospitalization time, Lianhua Qingwen alone or in combination with conventional treatment was superior to conventional treatment.(3)In the treatment of HFMD, Lianhua Qingwen Granules was superior to conventional treatment in terms of total effective rate, average fever clearance time, time to herpes subsidence, and time to negative result of viral nucleic acid test.(4)In terms of safety, Lianhua Qingwen preparations led to low incidence of adverse reactions, all of which were mild and disappeared after drug withdrawal. The available evidence suggests that in the treatment of influenza, COVID-19, and HFMD, Lianhua Qingwen preparations can relieve the clinical symptoms, shorten the hospitalization time, and improve the chest CT. They have therapeutic effect and good safety in the treatment of viral diseases. However, due to the low quality of available studies, more high-quality clinical trials are needed to support the above conclusions.