Front. Pharmacol. Frontiers in Pharmacology Front. Pharmacol. 1663-9812 Frontiers Media S.A. 752978 10.3389/fphar.2022.752978 Pharmacology Systematic Review Clinical Evidence on the Use of Chinese Herbal Medicine for Acute Infectious Diseases: An Overview of Systematic Reviews Luo et al. Chinese Herbal Medicine for Infections Luo Xufei 1 † Zhang Yikai 2 † Li Huishan 2 Ren Mengjuan 1 Liu Yunlan 1 Liu Yunwei 2 Zhang Yilin 3 Kuang Zhuoran 2 Cai Yefeng 2 4 Chen Yaolong 1 5 6 7 8 9 10 11 12 * Ni Xiaojia 2 4 * on behalf of the Evidence-based Traditional and Integrative Medicine Working Group for Public Health Emergency 1 School of Public Health, Lanzhou University, Lanzhou, China 2 Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial, Academy of Chinese Medical Sciences, The Second Clinical School of Guangzhou University of Chinese Medicine, Guangzhou, China 3 The School of Public Health and Management, Guangzhou University of Chinese Medicine, Guangzhou, China 4 Guangdong Provincial Key Laboratory of Research on Emergency in Traditional Chinese Medicine, Guangzhou, China 5 Research Unit of Evidence-Based Evaluation and Guidelines, Chinese Academy of Medical Sciences (2021RU017), School of Basic Medical Sciences, Lanzhou University, Lanzhou, China 6 Institute of Health Data Science, Lanzhou University, Lanzhou, China 7 Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China 8 WHO Collaborating Centre for Guideline Implementation and Knowledge Translation, Lanzhou, China 9 Guideline International Network Asia, Lanzhou, China 10 Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou University, Lanzhou, China 11 Lanzhou University GRADE Center, Lanzhou, China 12 Lanzhou University, An Affiliate of the Cochrane China Network, Lanzhou, China

Edited by: Anthony Booker, University of Westminster, United Kingdom

Reviewed by: Linzi Long, China Academy of Chinese Medical Sciences, China

Hong Li, Southern Medical University, China

 *Correspondence: Xiaojia Ni, grace1984325@126.com; Yaolong Chen, chenyaolong@vip.163.com

These authors have contributed equally to this work

This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

 25 02 2022 2022 13 752978 04 08 2021 24 01 2022 Copyright © 2022 Luo, Zhang, Li, Ren, Liu, Liu, Zhang, Kuang, Cai, Chen and Ni. 2022 Luo, Zhang, Li, Ren, Liu, Liu, Zhang, Kuang, Cai, Chen and Ni

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Background: Acute infectious diseases constitute the most prevalent public health emergency (PHE) in China. Chinese herbal medicine (CHM) has long been used in the treatment of acute infections, but the overall evidence of its benefit and harm has not been comprehensively and systematically evaluated.

Methods: We searched CBM, CNKI, Wanfang, PubMed, Cochrane Library, embase and preprint platforms to retrieve systematic reviews (SRs) on CHM for acute infectious. Participants with COVID-19, SARS, H1N1, tuberculosis, bacillary dysentery, mumps, herpangina, hand-foot-and-mouth disease (HFMD), and other acute infectious diseases were included. Interventional group consisting of patients treated with CHM combined with Western medicine or CHM alone. The AMSTAR 2 tool was used to assess the methodological quality of the retrieved studies. Information on interventions, control measures and outcomes of the included studies was extracted, and meta-analyses were qualitatively synthesized.

Results: A total of 51 SRs and meta-analyses were eligible for this overview, including 19 for COVID-19, 11 for hand-foot-and-mouth disease, 8 for severe acute respiratory syndrome (SARS), 4 for tuberculosis, 3 for mumps, 2 for bacillary dysentery, 2 for H1N1 influenza and 2 for herpangina. Six systematic reviews were of high quality, all of which were on the use of CHM for COVID-19; 24 were of moderate quality; 10 were of low quality; and 11 were of very low quality. CHM appeared to have potential benefits in improving clinical symptoms and signs for most infections with an acceptable safety profile, and the clinical evidence of the benefits of CHM for acute respiratory infections such as COVID-19, SARS and H1N1 seems more sufficient than that for other acute infections.

Conclusion: Overall, CHM, both decoction and Chinese patent medicine, used alone or in combination with conventional medicine may offer potential benefits to relieving symptoms of people with acute respiratory infections. Full reporting of disease typing, staging, and severity, and intervention details is further required for a better evidence translation to the responses for PHE. Future CHM research should focus mainly on the specific aspects of respiratory infections such as its single use for mild infections, and the adjunct administration for sever infections, and individual CHM prescriptions for well-selected outcomes should be prioritized.

 Chinese herbal medicine acute infectious diseases overview of systematic reviews COVID-19 public health emergency Introduction

Public health emergencies (PHEs) are extraordinary events that are determined to constitute public health risks to other states through the international spread of disease and that potentially require a coordinated international response (World Health Organization, 2005). Acute infectious diseases are among the most common PHEs (World Health Organization, 2017). In China, Chinese herbal medicine (CHM) has a long history of treating acute infections such as smallpox, plague, scarlet fever, cholera, typhoid fever, and malaria (Jiang and Wen, 2021). Given the occurrence and epidemics of infectious diseases across different periods, valuable experience has been accumulated in the use of CHM to fight against infectious diseases, which was often documented in classical literature and monographs (Wang W. et al., 2020). Specifically, Yellow Emperor’s Internal Classic, released in approximately 5,000 years ago, was the first publication to find that the occurrence of infectious diseases was closely related to climate change. Treatise on Cold Attack, released in the Eastern Han Dynasty, was written after a large-scale epidemic of acute infectious diseases. Doctor Zhongjing Zhang summarized the development of infectious diseases in the book and recorded many classical formulas such as Xiaochaihu Decoction and Maxing Shigan Decoction, that have been used since then. In late Ming China, with the further deepening of the understanding of infectious diseases in traditional Chinese medicine (TCM), Systematic Differentiation of Warm Pathogen disease authored by Doctor Jutong Wu, systematically expounded the general laws of the occurrence, development, evolution and treatment of infectious diseases, in which, Yinqiao Powder and Sangju Drink, was first documented, and continues to be used for acute upper respiratory disease.

The clinical effectiveness of some classical CHM prescription has been investigated in rigorous randomised controlled trials (RCTs). For example, a single RCT published in Ann Intern Med in 2011 suggested that a CHM formula combining Maxin Shigan Decoction and Yinqiao Power, alone and in combination with an anti-virus pharmacotherapy oseltamivir, can reduce the time for a fever to resolve in patients with H1N1 influenza infection (Wang et al., 2011). Another outstanding example is artemisia annua L., which was recorded in A Handbook of Prescriptions for Emergencies (Doctor Hong Ge, Eastern Jin Dynasty) for treating malaria. Later, this CHM formula has been developed to artemisinin, and transferred to clinical practice of malaria, for which Tu Youyou won the Nobel Prize (Tu, 2016).

In modern China, CHM continues to be applied to a wide range of emergent infectious diseases, such as severe acute respiratory syndrome (SARS), H1N1 influenza, and Coronavirus disease 2019 (COVID-19). And there are many clinical trials and systematic reviews of CHM that have been published. However, there has been no comprehensive study describing the status of the treatment of acute infectious diseases with CHM in the manner of critical appraisal. Therefore, we conducted this study to provide an overview of systematic reviews (SRs) of the treatment of infectious diseases with CHM that could serve as a reference for decision-making in this field.

 Methods

We followed the guidance of overviews of reviews published by Hunt et al. (2018). We also reported this overview according to the PRISMA statement (Moher et al., 2009). We have registered this study with the registration DOI: 10.17605/OSF.IO/VZ4S7.

Inclusion and Exclusion Criteria Study Types Included in This Overview

Systematic reviews (SRs) and meta-analyses, language limited to Chinese and English.

 Participants

Participants with COVID-19, SARS, H1N1, tuberculosis, bacillary dysentery, mumps, herpangina, hand-foot-and-mouth disease (HFMD), and other acute infectious diseases were included, as identified according to the current list of public PHEs in China (Liu et al., 2019).

 Interventions

Interventional group consisting of patients treated with CHM combined with Western medicine or CHM alone, where CHM interventions included proprietary Chinese medicine and traditional Chinese medicine decoction. There was no requirement for what should be included in the control group.

 Outcomes

Outcomes including effectiveness related outcomes which evaluated by the investigator or reported by patients, laboratory tests and radiological imaging, and safety related outcomes such as adverse events, adverse reactions, and toxic scale. The primary outcomes included effectiveness, mortality and adverse events, and secondary outcomes included symptom score, length of stay, laboratory tests and radiological imaging, etc.

 Exclusion Criteria

Studies were excluded from the search when they were conference abstracts, duplicate publications, unpublished data, and those without full details of a SR.

 Literature Search and Screening

We searched the Chinese Biomedical Literature database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database, PubMed, Cochrane Library, embase, medRxiv, bioRxiv, China Association of Chinese Medicine, China Association for Acupuncture and Moxibustion, Chinese Medical Journal Network, and Chinese Medicine Journal Network to retrieve relevant systematic reviews/meta-analyses, and the search time was from the date of database creation to 30 October 2020. Before published of this article, we updated the search time to 31 March 2021. For literature screening, two authors read the title and abstract for the initial screening of the literature, and after downloading the full text, it was read and use to further screen the articles, and the results were submitted to a third author for confirmation and verification. The search strategy was specified in Supplementary 1.

 Methodological Quality and Level of Evidence Assessment

The methodological quality of the included studies was evaluated independently by two authors using A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2) (Shea et al., 2017), and a third author assisted in the judgement in cases of disagreement. The methodological quality of AMSTAR2 for systematic review is divided into 16 entries, among which item 2, item 4, item 7, item 9, item 10, item 11, item 13 and item 15 are recommended critical items for determine methodological quality. Considering the specificity of TCM research, we made the following adjustments to the key items. Since some systematic reviews were published before the establishment of the registration platform and the registration platform does not have a Chinese registration language, it was difficult to obtain the protocols of these previous Chinese systematic reviews, so we did not include item 2 as a key entry. Chinese medicine research is mainly published in Chinese language, and most Chinese journal submission systems do not support the presentation of a list of excluded studies, so item 7 was not considered a key entry.

The final evaluation results were classified as 1) “high quality” when there was no or one non-critical weakness, 2) “medium quality” when there was more than one non-critical weakness, 3) “low quality” when there was one critical flaw with or without non-critical weaknesses, or 4) “very low quality” when there was more than one critical flaw with or without non-critical weaknesses.

We also evaluated the level of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for primary outcomes.

 Data Extraction and Data-Analysis

Two authors independently collected the data on publication information, demographic characteristics, details of the interventions and control measures, outcomes, and statistical results, which were finally checked and confirmed by a third authors. For data analysis, a qualitative integration of the study results was performed for SRs evaluated as having moderate-high quality according to AMSTAR 2.

 Results Results of the Searching and Screening

A total of 46,138 relevant records were obtained from the initial search and 6,468 records were identified from updated search, and after screening, 51 systematic reviews (Liu and Dong, 2021; Liu et al., 2004; Zhang et al., 2004; Zhao et al., 2004; Hao, 2005; Hao et al., 2005; Liu et al., 2005; Chen et al., 2007; Guo et al., 2010; Liu et al., 2012; Ding et al., 2013; Lu et al., 2013; Wang et al., 2013; Xiong et al., 2013; Zhang et al., 2014; Zhang and Wei, 2014; Zhao, 2014; Zhao et al., 2014; Wu et al., 2015; Han, 2016; Li et al., 2016; Liu et al., 2016; Zhang, 2016; Wang et al., 2017; Yan and Gao, 2017; Yue et al., 2017; Jin et al., 2018; Xiong et al., 2019; Ang et al., 2020; Yang et al., 2020a; Yu et al., 2020a; Yang et al., 2020b; Yu et al., 2020b; Fan et al., 2020; Gao et al., 2020; He, 2020; Jin et al., 20201992; Liu et al., 2020; Pang et al., 2020; Qi et al., 2020; Wang et al., 2020; Sun et al., 2020; Wu et al., 2020; Xiong et al., 2020; Yan et al., 2020; Zeng et al., 2020; Zhou et al., 2021a; Zhou et al., 2021b; Luo et al., 2021; Ouyang et al., 2021) were finally included. Among them, 33 (Liu and Dong, 2021; Zhao et al., 2004; Hao, 2005; Hao et al., 2005; Liu et al., 2005; Ding et al., 2013; Lu et al., 2013; Wang et al., 2013; Xiong et al., 2013; Zhang et al., 2014; Zhang and Wei, 2014; Zhao, 2014; Han, 2016; Liu et al., 2016; Zhang, 2016; Wang et al., 2017; Xiong et al., 2019; Yang M. et al., 2020; Yu et al., 2020a; Yang Z. et al., 2020; Yu et al., 2020b; Gao et al., 2020; He, 2020; Qi et al., 2020; Wang S. et al., 2020; Wu et al., 2020; Zhou L. P. et al., 2021; Zhou F. et al., 2021; Ouyang et al., 2021) were written in Chinese, and 18 (Liu et al., 2004; Zhang et al., 2004; Chen et al., 2007; Liu et al., 2012; Zhao et al., 2014; Wu et al., 2015; Li et al., 2016; Ang et al., 2020; Fan et al., 2020; Jin et al., 2020; Liu et al., 2020; Pang et al., 2020; Sun et al., 2020; Xiong et al., 2020; Yan et al., 2020; Zeng et al., 2020; Zhou L. P. et al., 2021; Luo et al., 2021) were written in English. The literature screening process and results are shown in Figure 1. The excluded references are stated in Supplementary 2. The ingredients of the formulas are specified in Supplementary 3.

Flow chart of study search and selection.

 Basic Characteristics of the Included Literature

The disease with the largest proportion in the of systematic reviews was COVID-19, with 19 articles (Liu and Dong, 2021; Ang et al., 2020; Yang M. et al., 2020; Fan et al., 2020; Gao et al., 2020; Jin et al., 2020; Liu et al., 2020; Pang et al., 2020; Qi et al., 2020; Wang S. et al., 2020; Sun et al., 2020; Wu et al., 2020; Xiong et al., 2020; Zeng et al., 2020; Zhou L. P. et al., 2021; Zhou F. et al., 2021; Luo et al., 2021; Ouyang et al., 2021), followed by 11 articles on HFMD (Ding et al., 2013; Wang et al., 2013; Xiong et al., 2013; Zhang et al., 2014; Zhang and Wei, 2014; Xiong et al., 2019; Yu et al., 2020a; Yang Z. et al., 2020; Yu et al., 2020b; He, 2020; Yan et al., 2020), 8 for SARS (Liu et al., 2004; Zhang et al., 2004; Zhao et al., 2004; Hao, 2005; Hao et al., 2005; Liu et al., 2005; Chen et al., 2007; Liu et al., 2012), 4 for tuberculosis (Guo et al., 2010; Yan and Gao, 2017; Yue et al., 2017; Jin et al., 2018), 3 for mumps (Zhao, 2014; Wu et al., 2015; Zhang, 2016), 2 for bacterial dysentery (Han, 2016; Wang et al., 2017), 2 for H1N1 (Zhao et al., 2014; Li et al., 2016), and 2 for herpes pharyngitis (Lu et al., 2013; Liu et al., 2016).

The number of RCTs included in each systematic review ranged from 2 to 45. Regarding the type of intervention in the intervention group, TCM combined with Western medicine accounted for the greatest proportion (n = 43, 84.31%) (Liu and Dong, 2021; Fan et al., 2020; Pang et al., 2020; Jin et al., 20201992; Luo et al., 2021; Sun et al., 2020; Zeng et al., 2020; Wang S. et al., 2020; Yang et al., 2020a; Ang et al., 2020; Xiong et al., 2020; Liu et al., 2020; Gao et al., 2020; Qi et al., 2020; Wu et al., 2020; Chen et al., 2007; Liu et al., 2004; Liu et al., 2012; Zhang et al., 2004; Hao, 2005; Hao et al., 2005; Liu et al., 2005; Zhao et al., 2004; Zhao et al., 2014; Li et al., 2016; Jin et al., 2018; Yan and Gao, 2017; Yue et al., 2017; Guo et al., 2010; Wang et al., 2017; Han, 2016; Wu et al., 2015; Zhang, 2016; Zhao, 2014; Lu et al., 2013; Liu et al., 2016; Zhang and Wei, 2014; Zhang et al., 2014; Xiong et al., 2013; Wang et al., 2013; Ding et al., 2013; Yu et al., 2020a; Yang et al., 2020b), with two SRs (3.92%) including studies with CHM alone (Zhao et al., 2014; Yu et al., 2020b) and 6 SRs (11.76%) including studies investigating CHM alone and CHM in combination with Western medicine (Lu et al., 2013; Zhang and Wei, 2014; Zhao, 2014; Liu et al., 2016; Zhang, 2016; Xiong et al., 2019). The most frequently studied herbal preparations were proprietary CHM drugs (n = 37, 80.43%), followed by CHM decoction (n = 20.43.48%). In terms of pre-defined outcomes, the most used for all diseases were the rate of improvement of clinical symptoms or signs such as fever and cough (n = 47, 92.16%), followed by overall effectiveness (n = 25, 49.02%), adverse events (n = 16, 31.37%), mortality (n = 11, 21.57%), and the proportion of lung X-ray shadows absorbed (n = 11, 21.57%). Detailed data are shown in Table 1.

Basic characteristics of included literature.

Study Disease type Disease stage Disease classification Number of included studies Intervention types Traditional Chinese medicine treatment Outcomes Frequency of the formulas Adverse event
Fan et al. (2020) COVID-19 NS NS 7 Traditional Chinese + H2:H44 medicine + western medicine conventional treatment VS Western medicine treatment Qingfeitouxiefuzheng decoction (10) (44) (19) Qingfeitouxiefuzheng decoction; bid for 10 days; Jinhua Qinggan granules: 15 g tid for 5 days; Toujieqingwen granule: bid for 10 days–15 days; CHM formulae: 200 ml, bid for 7 days; Jiaweidayu granule: tid for 7 days NS
Jinhuaqinggan granule
Qingfeipaidu decoction
Toujieqingwen granule
Jiaweidayu granule
Shengfutang decoction/Maxinshigan-dayuan decoction
Pang et al. (2020) COVID-19 NS NS 11 Traditional Chinese medicine + western medicine conventional treatment VS Western medicine treatment Qingfeitouxiefuzheng decoction (21) (29) (44) (31) (56) (19) NS Y
Jinhuaqinggan granule
Toujiequwen granule
Qingfeipaidu decoction
Maxingxuanfeijiedu Decoction
Sufengjiedu capsule
Chinese patent medicine + Chinese herbal medicine
Jin et al. (2020) COVID-19 NS NS 5 Traditional Chinese medicine + western medicine conventional treatment VS Western medicine treatment Qingfeitouxiefuzheng decoction/Lianhuaqingwen granule/Lianhuaqingke granule/Xuebijing injection (10) 150 ml each time, 2 times a day for 10 days; 6 g each time, 3 times a day for 7 days; 1 bag each time, 3 times a day for 14 days; 50 ml each time, 2 times a day for 7 days NS
Luo et al. (2021) COVID-19 NS NS RCT:6 CCT:13 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment/Western medicine treatment + Traditional Chinese medicine placebo Lianhuaqingwen granule (10) (18) (45) (51) (44) (21) (19) NS Y
Shufengjiedu capsule
Touxiequwen granule
Reyanning mixture
Jinhuaqinggan granule
Jiaweidayuan decoction
Pneumonia No. 1 formula
Modified Qingfeipaidu decoction
Sun et al. (2020) COVID-19 NS NS 7 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment Shufengjiedu capsule (10) (19) (29) (18) (25) TouxieQuwen prescription (2 dose/d); Reyanning mixture (10–20 ml, bid-q6h); Shufengjiedu capsule (2.08 g, tid); Qingfeitouxiefuzheng prescription (1 dose/d); Shufengjiedu capsule (2.08 g, tid); Feiyanyihao prescription or feiyanerhao prescription (1 dose/d); Jinhuaqinggan granule (10 g, tid) Y
Touxiequwen granule
Reyanning mixture
Qingfeixiejiefuzheng formula
Feidian No.1 formula/Feidian No.2 formula
Jinhuaqinggan granule
Zeng et al. (2020) COVID-19 NS NS 2 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment Lianhuaqingwen granule (6) (10) (11) (12) (13) (14) (15) (16) (17) (18) (22) NS NS
Wang S. et al. (2020) COVID-19 NS NS 7 Traditional Chinese medicine + western medicine conventional treatment VS Western medicine treatment Lianhuaqingwen granule (12) (62) (18) (26) Lianhuaqingwen granule: 6g/bag, 1 bag each time, 3 times a day; 4 tablets/day, tid; 6 g tid NS
Yang M. et al. (2020) COVID-19 NS Ordinary type RCT:2 NRCT:1 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment Lianhuaqingwen granule (3) (25) (19) (36) (48) NS N
Ang et al. (2020) COVID-19 NS NS 7 Traditional Chinese medicine + western medicine conventional treatment/Traditional Chinese medicine vs Western medicine treatment Lianhuaqingwen granule (1) (5) (9) (10) (13) (18) (26) (31) (41) (45) Lianhua Qingke granules, 1 packet for 3 times daily for 14 days; Shufeng Jiedu capsule, 4 capsules for 3 times daily for 2 weeks; Jinhua Qinggan granules, 2 packets for 3 times daily for 5 days; Toujie Quwen granules, 1 packet per time for 2 times daily for 10–15 days Y
Shufengjiedu capsule
Touxiequwen granule
Jinhuaqinggan granule
Xiong et al. (2020) COVID-19 NS Minor illnesses, major illnesses 18 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine treatment/Western medicine treatment + Traditional Chinese medicine placebo Maxingshigan decoction/Chailingpingwei decoction/Haoqinqingdan decoction/Huopuxialing decoction/Modified Buzhongyiqi decoction/Pneumonia No. 1 formula/Powerful Pneumonia No. 1 formula/Pneumonia No. 2 formula/Qingfeitouxiefuzheng formula/Shiduyufei formula/Yidubifei formula/Qiwei decoction/Toujiequwen granule/Shufengjiedu capsule/Lianhuaqingwen granule and capsule/Xuanfeizhisou mixture/Shuanghuanglian oral liquid/Yupingfeng granule/Ganluxiaodu decoction/Huoxiangzhengqi liquid/Reyanning mixture/Jinhuaqinggan granule/Xuebijing injection/Tanreqing injection/Shengmai injection/Shenfu injection/Lianhuaqingke granule/Maxingxuanfeijiedu Decoction (2) (11) (29) (41) (44) (21) (45) (30) (13) (27) (18) CHM(1dose/d, 10 days); Qingfei Touxie Fuzheng recipe (1dose/d, 10 days); Toujie Quwen granules (1dose/d, 15 days); Jihua Qinggan granules (10 g, tid, 5 days); Reyanning mixture (10–20 ml, bid- q6 h, 7 days); Shufeng Jiedu capsules (2.08g, tid, 10-14 days); Lianhua Qingwen granules (6 g, tid, 7-14 days); Lianhua Qingke granules (1 bag, tid, 14 days); Lianhua Qingwen capsules (1.4 g, tid, 14 days) Y
Liu et al. (2020) COVID-19 NS NS RCT:4 NRCT:7 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment Lianhuaqingwen granule (10) (19) (62) (54) (16) (64) Diammonium glycyrrhizinate enteric coated capsules (150 mg,tid); Qingfeitouxie fuzhengfang (150 ml,bid); Shufeng Jiedu Capsule (2.08 g,tid); Lianhua Qingwen granules (6 g,tid); Reyanning mixture (10–20 ml,bid); Tongjiequwen granule formula (150 ml,bid); Jinhua Qinggan granules (10 g,tid) Y
Shufengjiedu capsule
Touxiequwen granule
Jinhuaqinggan granule
Qingfeitouxiefuzheng decoction
Gao et al. (2020) COVID-19 NS NS RCT:4 NRCT:8 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment Lianhuaqingwen granule (10) (61) (5) (18) (11) (12) (29) (45) NS NS
Shufengjiedu capsule
Touxiequwen granule
Jinhuaqinggan granule
Qingfeixiejiefuzheng decoction
Pneumonia 1/pneumonia 2 + conventional treatment
Liu et al. (2020) COVID-19 Medical Observation Period Minor illness, general type RCT:1 NRCT:6 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment NS (12) (25) (26) (29) (41) NS NS
Qi et al. (2020) COVID-19 NS Ordinary type RCT:2 NRCT:3 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment Lianhuaqingwen granule (10) (36) (5) (6) (11) (12) (36) (44) (19) Lianhuaqingwen granule: 1 bag per time (6 g), tid NS
Wu et al. (2020) COVID-19 NS Minor/general/severe/critical illnesses RCT:1 NRCT:7 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment Lianhuaqingwen granule Shufengjiedu capsule (12) (13) (18) (26) (27) (29) (25) NS NS
Zhou L. P. et al. (2021) COVID-19 NS NS 10 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine treatment Jinhua Qinggan granule (5) (12) (13) (18) (19) Jinhua Qinggan granule (3 times a day, once 10 g); Qingfei Touxie Fuzheng recipe (one dose a day, 2 times a day, in the morning and in the evening); Toujie Quwen granules (2 times a day); Lianhua Qingke granule (once 1 bag, 3 times a day); FeiyanYihao Chinese Medicine granules (one dose a day, 2 times a day); Jinyinhua oral liquid (once 60 ml, 3 times a day); Diammonium glycyrrhizinate entericcoated capsule (once 150 mg, 3 times a day); Lianhua Qingwen capsule (once 6 g, 3 times a day); Lianhua Qingwen capsule (4 capsules thrice daily) Y
Qingfei Touxie Fuzheng recipe
Toujie Quwen granule
Lianhua Qingke granule
FeiyanYihao Chinese Medicine granule self-made decoction
Jinyinhua oral liquid
Diammonium glycyrrhizinate enteric-coated capsule
Lianhua Qingwen capsule
Liu et al. (2020) COVID-19 Medical Observation Period Minor illness, general type RCT:1 NRCT:6 Traditional Chinese medicine + western medicine conventional treatment/Traditional Chinese medicine vs Western medicine conventional treatment Jinhua Qinggan granule (5) (6) (10) (11) (12) (18) (44) NS Y
Shufeng jiedu granule
Jinhua qinggan granule
Xuebijing injuction
Zhou F. et al. (2021) COVID-19 NS Minor illness, general type 6 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine treatment Xuanfei Baidu decoction (5) (6) (10) (11) (13) (18) (19) (21) (27) (62) CHM: 1 dose of 300 ml/day, 100ml/time; CHM: 1dose/day, 250 ml/time. bid, 10 days; CHM: 19.4 g, bid; CHM: 200 ml/bag/time, bid Y
Maxing Shigan Decoction
Keguan⁃1
No.1 prescription for pneumonia
Hema xingren shigan decoction
Qushi Paidu fuzheng decoction
Sanreng decoction
Xiaochaihu decoction
Ouyang et al. (2021) COVID-19 NS Minor illness, general type RCT:6 NRCT:4 Western medicine conventional treatment + Traditional Chinese medicine/Western medicine conventional treatment + Placebo + Traditional Chinese medicine vs Western medicine conventional treatment/Western medicine conventional treatment + Placebo Reyanning mixture (5) (6) (10) (11) (12) (18) (19) (24) (29) (64) NA Y
Jinhua Qinggan granule
Toujie Quwen granule
Lianhua Qingwen granule
Shufeng Jiedu Capsule
Chen et al. (2007) SARS NS NS RCT:15; NRCT:9 Traditional Chinese medicine + western medicine conventional treatment VS Western medicine treatment NS (1) (2) (5) (8) (9) (12) NS NS
Liu et al. (2004) SARS NS NS RCT:8; NRCT:8 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment Feidian No.1/2/3 formula (2) (3) (4) (5) (9) (11) (14) TCM: decoction, one dosage daily, for treatment of 21 days; Qiankunning: 6 tablets/time, 4 times daily, for 14 days NS
Feidian No.4 formula
Guoyao No.2/3 formula
Yiqiyang formula/Bufeijianpi formula/Yangyinqingre formula Qianlunning capsule
Chuanhuning injection, Shenmai injection, hufeiqingsha decoction/Jieduzhitong capsule/Zhuyinsan capsule
Liu et al. (2012) SARS NS NS 12 Traditional Chinese medicine + western medicine conventional treatment VS Western medicine treatment Feidian No.1/2 formula (2) (3) (5) (6) (7) (8) (9) (13) (14) (15) National drug No. 2.3 and 4, 2 times/d, 200 ml, for 7–9 days; Kangfeidian No. 1, 2, 3, 2 times/d, 200 ml; potenili 3 times/d, 300 ml NS
Feidian No.1 formula
Hufeiqingsha decoction
Jieduzhitong capsule
Zhuyinsanjie capsule
Qingshaling spra
Feidian No.2/3/4 formula
Zhang et al. (2004) SARS NS NS 6 Traditional Chinese medicine + western medicine conventional treatment/Traditional Chinese medicine vs Western medicine treatment Feidian No.1/2/3/4 formula (2) (6) (7) (8) (9) (16) NS NS
Hao et al. (2005) SARS NS NS RCT:5 CCT:6 Traditional Chinese medicine + western medicine conventional treatment/Traditional Chinese medicine vs Western medicine treatment Feidian No.1/2/3/4 formula (12) (27) (63) NS NS
Guoyao No.2/3/4 formula
Chuanhupo injection/Shenmai injection/hufeiqingsha decoction Shufengxuanfei formula
Xingnaojing injection + Shenmai injection
HOUTTUYNIA CORDATA (Chinese pinyin: yuxingcao) injection + Qingkailing injection
Hao et al. (2005) SARS NS NS RCT:5 CCT:4 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment NS (27) NS NS
Liu 2005 SARS NS NS RCT:8 NRCT:8 Traditional Chinese medicine + western medicine conventional treatment/Traditional Chinese medicine vs Western medicine treatment Yiqiyang formula (27) (12) (18) (20) (19) (63) Yiqiyang formula: 1dose/d, 3 weeks; CHM 1 d0se/d, 12 days; Qiankunning 6 tables, 4 times/days, 2 weeks; Guoyao No.2/3/4 formula: 1dose/d; Traditional Chinese medicine SARS No.4 formula: 1 bag, bid; Feidian No.1/2/3/4 formula: 1dose, 2–3 weeks NS
Chuanhuning injection/Shenmai injection/Hufeiqingsha decoction/Jieduzhitong capsule
Qiankunning capsule
Bufeijianpi formula
Yangyinqingre formula
Guoyao No.2/3/4 formula
Feidian No.1/2/3/4 formula
Traditional Chinese medicine SARS No.4 formula
Zhao et al. (2004) SARS NS NS RCT:5 NRCT:4 Traditional Chinese medicine + western medicine conventional treatment VS Western medicine treatment Shenmai injection/Hufeiqingsha decoction/Jieduzhitong capsule/Zhuyinsanjie capsule/Qingshaling spray (27) (4) (12) (18) (5) (23) (19) (63) NS NS
Guoyao No.2/3/4 formula
Feidian No.1/2/3/4 formula
Zhao et al. (2004) H1N1 NS NS 5 Traditional Chinese medicine + western medicine conventional treatment VS Western medicine treatment Lianhuaqingwen granule (2) (3) (4) (5) (6) NS NS
Li et al. (2016) H1N1 NS NS 30 Traditional Chinese medicine + western medicine conventional treatment VS Western medicine treatment Fanggan decoction (1) (6) (7) NS NS
Lianhuaqingwen capsule
Yinqiao decoction
Maxingshigan decoction
RADIX ISATIDIS(Chinese pinyin:Banlangen) granule
Qingkailing injection + Tanreqing injection
Jin et al. (2018) Tuberculosis NS NS 45 Traditional Chinese medicine + western medicine conventional treatment VS Western medicine treatment NS (29) (22) (41) (15) (19) NS Y
Yan and Gao (2017) Tuberculosis NS NS 16 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment Tuberculous pill (29) (22) (61) NS NS
Yue et al. (2017) Tuberculosis NS NS 20 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment ASTRAGALUS MONGHOLICUS (Chinese pinyin: Huangqi) related Chinese patent medicine, including Feining pill, Jianfeirunpi pill, Yupingfeng Oral liquid, Shuangbai oral liquid, Baidiziyin pill, Buzhongyiqi pill, Zhenqifuzheng granule, Qianggan capsule, Qingjin granule, Bufeihuoxue capsule and Huangqi granule (39) (18) (15) (61) (19) NS Y
Guo et al. (2010) Tuberculosis NS NS 6 Traditional Chinese medicine + western medicine conventional treatment/Traditional Chinese medicine vs Western medicine treatment Feitai capsule (29) (39) (22) NS NS
Tuberculin tablet
Qibaihe tablet
Modified Huangqijianzhong decoction
Baozhen decoction
Self-made decoction
Wang et al. (2017) Bacterial dysentery Acute phase NS 12 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment Modified Baitouweng decoction (10) (12) (40) (19) NS Y
Zhili decoction
Yuli decoction
Modified Dachaihu decoction
Modified Shaoyao decoction
Zhili formula
Shaoyao decoction/Baitouweng decoction
Dima mixture
Gancaozaolian porridge
Self-made decoction
Han (2016) Bacterial dysentery Acute phase Minor, General, Major 28 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment NS (10) (50) NS NS
Wu et al. (2015) Mumps NS NS 11 Traditional Chinese medicine + western medicine conventional treatment/Traditional Chinese medicine vs Western medicine treatment ANDROGRAPHIS PANICULATA (Chinese pinyin: chuanxinlian) injection (4) (12) (10) (9) Potassium Dehydroandrographolide Succinate Injection: 5–30 mg/(kg.d) Y
Zhang (2016) Mumps NS NS 7 Traditional Chinese medicine + western medicine conventional treatment VS Western medicine treatment NS (10) NS NS
Zhao (2014) Mumps NS NS 33 Traditional Chinese medicine + western medicine conventional treatment VS Western medicine treatment Modified Pujixiaodu decoction + External application of Chinese herbal medicine including RHUBARB(Chinese pinyin: Shengdahuang), TETRADIUM RUTICARPUM(Chinese pinyin: Wuzhuyu), MIRABILITE(Chinese pinyin: Mangxiao) External application of Chinese herbal medicine including CORTEX PHELLODENDRI(Chinese pinyin: Huangbai) and GYPSUM(Chinese pinyin: Shigao) + RADIX ISATIDIS(Chinese pinyin: Banlangen) granule (10) NS Y
Self-made Fuhuang ointment
Reduning injection
Shuanghuanglian injection
Acupuncture
Compound oral mixture of Folium Isatidis (Chinese pinyin: Daqingye) and external application of Cactus
Xianfanghuoming decoction + Zijin Cube with vinegar
External application of Zhitongxiaoyan ointment + Conventional treatment
Shuanghuanglian injection
Self-made decoction
External application of Wanyin ointment
External application of Quzhaling ointment
Lu et al. (2013) Mumps Acute phase NS 12 Traditional Chinese medicine + western medicine conventional treatment VS Western medicine treatment Pudilanxiaoyan oral liquid (10) (19) (44) NS Y
Liu et al. (2016) Herpangina NS NS 17 Traditional Chinese medicine + western medicine conventional treatment VS Western medicine treatment Modified Yinqiao decoction (10) (19) (12) NS NS
Qingjieliyan decoction
Modified Xiexindaochi decoction
Self-made Qingjiexiehuang decoction
Mixture of Yinqiao decoction
Self-made QingQinYinqiao decoction
Qingrejieduliyan formula
Jieduqinghuo formula
Self-made Jieduliyan decoction
Self-made Kouchangjing formula
Yinqiaohaihe decoction
Self-made decoction
Self-made Zhitongyanyan decoction
Qingyan decoction
Niuhuangtianmaliyan powder
Qingyanjiedu decoction
Zhang et al. (2014) Hand foot mouth disease NS Ordinary type 21 Traditional Chinese medicine + western medicine conventional treatment/Traditional Chinese medicine vs Western medicine treatment Chaihuang granule (10) (12) (30) NS NS
Modified Gegenqilian decoction
Modified Jidaiyu decoction
Jieduqingre decoction
Jinlan mixture
Kangfuxin liquid + Qingrejiedu oral liquid
Pudilanxiaoyan oral liquid + Yanhuning injection
Qingrexiehuo decoction
Sandouyinqiao decoction
Yinqiaohuojun decoction
Modified Yinqiaomabo decoction
Self-made Yinqiaoxiaodu decoction
Jinlianqingre granule
Self-made Dazi formula
Self-made Baidu decoction
Zhang et al. (2014) Hand foot mouth disease NS Normal type, heavy duty 11 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment —— (12) (14) (13) NS Y
Xiong et al. (2013) Hand foot mouth disease NS NS 6 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment Xiyanping injection (10) (14) NS Y
Wang et al. (2013) Hand foot mouth disease NS NS 24 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment Xiyanping injection (10) (14) (19) (12) Xiyanping injection: 1–10 mg/kg, iv, qd Y
Ding et al. (2013) Hand foot mouth disease NS NS 11 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment Xiyanping injection (12) (14) (19) (23) NS Y
Yu et al. (2020a) Hand foot mouth disease NS NS 17 Traditional Chinese medicine + western medicine conventional treatment vs Western Medicine/Traditional Chinese medicine Reduning injection/Tanreqing injection/Xiyanping injection/Yanhuning injection (10) (12) (14) (19) (23) Reduning injection: 0.3–15 ml/kg, qd; Tanreqing injection: 0.3–0.5 ml/kg, qd; Xiyanping injection: 0.2–10 ml/kg, qd; Yanhuning injection: 5–10 ml/kg, qd Y
Yang Z. et al. (2020) Hand foot mouth disease NS NS 24 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment Lanqin oral liquid (10) (12) (14) (19) (23) NS Y
Yan et al. (2020) Hand foot mouth disease NS NS 5 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment Jinlianqingre effervescent tablets/Jinzhen oral liquid/Kangbingdu oral liquid/Reduning injection/Xiyanping injection (12) (26) (14) (19) NS Y
Xiong et al. (2019) Hand foot mouth disease NS NS 11 Traditional Chinese medicine + western medicine conventional treatment VS Western medicine treatment Tanreqing injection/Xiyanping injection/Reduning Injection (10) (12) (26) (14) (19) Tanreqing injection: 0.3–0.5 ml/kg, 5-10 days; Xiyanping injection: 5–10 mg/kg, 3-10 days; Reduning Injection: 1-5 years, 0.5 ml/kg; 6–10 years, 10 ml; 11–13 years 15ml, 3-10 d Y
He (2020) Hand foot mouth disease NS NS 14 Traditional Chinese medicine + western medicine conventional treatment VS Western medicine treatment Xiyanping injection + Chinese patent medicine (Lanqin oral liquid/Kangfuxin liquid/Pudilan oral liquid/Jinhoujian spray/Tanreqing injection) (10) (12) (14) (19) (37) NS NS
Yu et al. (2020b) Hand foot mouth disease NS NS 26 Traditional Chinese medicine vs Western medicine treatment/Traditional Chinese medicine Lanqin oral liquid (10) (12) (14) (19) (30) (57) Fuganlin oral liquid: 10 ml, tid; Huangzhihua oral liquid:10 ml, tid or 5–20 ml, bid; Kangbingdu oral liquid: 10 ml tid; Huangqin oral liquid:10 ml, tid; Pudilan oral liquid:5–10 ml, tid Y
PU Di LAN Xiaoyan oral liquid
Yellow Gardenia liquid
Fuganlin oral liquid
Kangbindu oral liquid
Huangqing oral liquid
Shuanghuanglian oral liquid
Outcomes:(1) Anxiety relief
(2) C reaction protein levels
(3) Chest tightness disappearance rate
(4) Complications due to hormone use (secondary bleeding, infection, diabetes, hypertension)
(5) Cough improvement (cough symptom score, cough disappearance time, cough disappearance rate, number of cough disappearance cases, difference in points before and after cough, cough relief rate, cough duration)
(6) Cough sputum disappearance rate
(7) D-di-concentration level
(8) Diarrhea improvement (diarrhoea disappearance rate, diarrhea remission rate)
(9) Discharge rate
(10) Efficiency
(11) Fatigue improvement (weak disappearance time, fatigue disappearance rate, fatigue improvement rate, fatigue improvement case count, fatigue duration, fatigue symptom integration)
(12) Fever mitigation (number of cases of fever, fever symptom score, fever disappearance rate, fever time, fever control rate)
(13) Healing rate
(14) Healing time for rashes or mouth ulcers
(15) Hollow improvement (shrink rate, close rate)
(16) IFN-α
(17) IL-6 level
(18) Improvement of pulmonary CT (rate of improvement of CT in the lungs, effective rate of improvement in CT in the lungs, absorption rate of pneumonia, improvement rate of imagery of the lungs, lesions absorption)
(19) Incidence of adverse reactions (liver damage, diarrhea, nausea and vomiting...)
(20) Incidence of secondary fungal infections following the use of hormones
(21) Length of stay
(22) Lesions absorption rate
(23) Lung immersion absorption (lung immersion absorption time, lung immersion absorption score, number of cases of lung immersion absorption, pulmonary immersion absorption rate)
(24) Lymphocyte improvement (number of lymphocytes, lymphocyte toxicity, percentage of lymphocytes)
(25) Major symptoms and inflammatory markers integral
(26) Mild to severe (severe conversion rate, number of cases of severe illness) (hand, foot and mouth disease)
(27) Mortality
(28) Nausea disappearance rate
(29) Nucleic acid to negative
(30) Oral ulcers are cured
(31) Oxygenation index
(32) Percentage of neutrophils
(33) Points for dry throat symptoms
(34) Progress rate of hand, foot and mouth disease
(35) Quality of life
(36) Respiratory Difficulty Disappearance Rate
(37) Resume feeding time
(38) Secondary infection rate
(39) Sputum bacteria turn negative
(40) Stop the time
(41) TCM Certificate Improvement
(42) The duration of the sore throat
(43) The duration of the virus shedding
(44) The main clinical symptoms are efficient (fever, fatigue and cough)
(45) The number of cases of severe to mild illness
(46) The number of CD4 plus (47) The rate of disappearance of shortness of breath
(48) The rate of loss of appetite
(49) The rate of muscular aches and pains disappeared
(50) The time at which the feces was transferred to Yin
(51) The time of the nucleic acid cathodic turn
(52) The time when herpes disappeared
(53) The time when the snot disappeared
(54) The time when the symptoms disappear
(55) Time for cheek swelling
(56) Time of physical pain
(57) Time of the disappearance of rash and herpes
(58) Time when nasal congestion disappears
(59) Total calcitonin levels
(60) Total medical journey time
(61) Total remission of clinical symptoms (main symptom disappearance rate, other symptom disappearance rate, total clinical symptom score, difference before and after total clinical symptom score, symptom integral/clinical symptom disappearance time)
(62) Total remission of clinical symptoms of COVID-19 (main symptom disappearance rate, other symptom disappearance rate, total clinical symptom score, difference before and after total clinical symptom score, symptom score/clinical symptom disappearance time)
(63)The use of hormone (average hormone dosage, treatment course, average use time, end-of-treatment hormone dosage)
(64) White blood cell count

NS: not stated; Y: yes.

Eighteen systematic reviews on COVID-19 that reported on specific drugs showed that the most used proprietary CHM drugs were Lianhua Qingwen Granule/Capsule (n = 14, 77.78%) and Shufeng Jiedu Capsule (n = 10, 55.56%), and the most used CHM decoction were Qingfei Touxie Fuzheng Decoction (n = 7, 38.89%). Six studies that reported specific drugs for SARS showed that the most used prescription was SARS No.2 formula (n = 6, 75.00%), SARS No.1 formula (n = 5, 62.50%), SARS No.3 formula (n = 5, 62.50%) and SARS No.4 formula (n = 5, 62.50%). The two H1N1 SRs used Lianhua Qingwen Capsule (n = 2,100.00%). The three tuberculosis studies that reported specific drugs showed common use of Astragalus Membranaceus (Chinese pinyin: Huangqi) preparations (n = 2). One SR for bacillary dysentery reported the use of CHM decoctions such as Baitouweng Decoction, Shaoyao Decoction, and Jiawei Dachaihu Decoction. The two SRs for mumps that reported specific drugs used Chuanxinlian injections, externally applied Fuhuang ointment, and Pujixiaodu Decoction. The two SRs for herpangina reported specific drugs, including Pudilan Xiaoyan Oral Solution and Yinqiao Decoction. Ten SRs that reported on specific drugs for HFMD most used herbal injections, such as Xiyanping Injection (n = 7, 70.00%), Reduning Injection (n = 3, 30.00%) and Tanreqing Injection (n = 3, 30.00%). Twenty-three SRs reported safety issues, among which one SR concluded that there were no adverse reactions to CHM. Twenty-one SRs reported adverse events, the most common of which were abdominal distension, diarrhoea, nausea, and vomiting, and poor appetite. Detailed data are shown in Table 1.

 Results of AMSTAR2 Quality Assessment

The results of the AMSTAR2 evaluation showed that of the 51 systematic reviews, three (6.52%) were of high quality (Wang S. et al., 2020; Zeng et al., 2020; Luo et al., 2021), 22 (47.83%) were of moderate quality (Zhang et al., 2004; Zhao et al., 2004; Hao, 2005; Hao et al., 2005; Liu et al., 2005; Zhao, 2014; Zhao et al., 2014; Wu et al., 2015; Wang et al., 2017; Yan and Gao, 2017; Yue et al., 2017; Jin et al., 2018; Xiong et al., 2019; Yang M. et al., 2020; Yu et al., 2020a; Yang Z. et al., 2020; Fan et al., 2020; Gao et al., 2020; Jin et al., 2020; Pang et al., 2020; Sun et al., 2020; Xiong et al., 2020), ten (21.74%) were of low quality (Liu et al., 2004; Chen et al., 2007; Guo et al., 2010; Liu et al., 2012; Han, 2016; Li et al., 2016; Ang et al., 2020; Liu et al., 2020; Qi et al., 2020; Wu et al., 2020), and 11 (23.91%) were of very low quality (Liu and Dong, 2021; Zhao et al., 2004; Lu et al., 2013; Liu et al., 2016; Zhang and Wei, 2014; Zhang et al., 2014; Xiong et al., 2013; Wang et al., 2013; Ding et al., 2013; Yan et al., 2020; He, 2020).

Six of the high-quality SRs were on TCMs against COVID-19 (Wang S. et al., 2020; Zeng et al., 2020; Zhou L. P. et al., 2021; Zhou F. et al., 2021; Luo et al., 2021; Ouyang et al., 2021). Most of the medium-quality SRs were on COVID-19 (n = 8, 42.11%) (Liu and Dong, 2021; Fan et al., 2020; Pang et al., 2020; Jin et al., 2020; Sun et al., 2020; Yang M. et al., 2020; Xiong et al., 2020; Gao et al., 2020), followed by SARS (n = 5, 62.50%) (Zhang et al., 2004; Zhao et al., 2004; Hao, 2005; Hao et al., 2005; Liu et al., 2005), HFMD (n = 4, 36.36%) (Xiong et al., 2019; Yu et al., 2020a; Yang Z. et al., 2020; Yu et al., 2020b), tuberculosis (n = 3, 75.00%) (Yan and Gao, 2017; Yue et al., 2017; Jin et al., 2018), mumps (n = 2, 66.67%) (Zhao, 2014; Wu et al., 2015), H1N1 (n = 1, 50.00%) (Zhao et al., 2014) and bacillary dysentery (n = 1, 50.00%) (Wang et al., 2017). Among the lower-quality SRs, COVID-19 was also the most frequent disease (n = 4, 21.05%) (Ang et al., 2020; Liu et al., 2020; Qi et al., 2020; Wu et al., 2020), followed by SARS (n = 3, 37.50%) (Liu et al., 2004; Chen et al., 2007; Liu et al., 2012), H1N1 (n = 1, 50.00%) (Li et al., 2016), tuberculosis (n = 1, 25.00%) (Guo et al., 2010) and bacillary dysentery (n = 1.50.00%) (Han, 2016). The highest number of very low-grade SRs reported on HFMD (n = 7, 63.64%) (Ding et al., 2013; Wang et al., 2013; Xiong et al., 2013; Zhang et al., 2014; Zhang and Wei, 2014; He, 2020; Yan et al., 2020), followed by herpangina (n = 2, 100.00%) (Lu et al., 2013; Liu et al., 2016), COVID-19 (n = 1, 5.26%) (Liu and Dong, 2021), and mumps (n = 1, 33.33%) (Zhang, 2016). The summary of AMSTAR 2 assessment is shown in Figure 2. The details of each evaluation item are shown in Supplementary 4.

Results of the AMSTAR2 methodological quality evaluation. Abbreviations: AMSTAR2: A MeaSurement Tool to Assess Systematic Reviews 2; COVID-19: Coronavirus disease 2019; HFMD: Hand-foot-and-mouth disease; H1N1: Influenza A subtype H1N1; SARS: Severe Acute Respiratory Syndromes.

 Qualitatively Analysis of Medium- And-High-Quality Systematic Reviews

The only two SRs on herpangina was excluded from the data-synthesis due to very low quality. SRs of medium- and high-quality for COVID-19, SARS, H1N1 type influenza, tuberculosis, bacillary dysentery, mumps, and HFMD were included to qualitative data-synthesis. Detailed data are shown in Table 2.

Medium and high-quality literature details.

Study Diagnosis Comparison (T vs C) Outcomes Estimate (95% CI) Model I2 No. participants No. controlled trials Level of evidence
Fan 2020 COVID-19 Traditional Chinese medicine + western medicine vs Western medicine Symptom and inflammatory markers scores SMD = -1.30 (-2.43, -0.16) Random 94% 261 3 Low
C-reactive protein MD = -11.82 (-17.95, -5.69) Random 97% 325 5 Low
Improvement of lung CT RR = 1.34 (1.19, 1.51) Random 0% 489 4 Moderate
Pang 2020 COVID-19 Traditional Chinese medicine + western medicine vs Western medicine Number of severe cases transferred RR = 0.47 (0.32, 0.69) Random 0% 989 8 High
Mortality RR = 0.50 (0.08, 3.00) Random 0% 337 2 Moderate
Length of stay MD = -7.95 (-14.66, -1.24) Fixed —— 12 1 Very Low
Nucleic acid negative conversion rate (%) RR = 1.08 (0.94, 1.24) —— —— 284 2 Low
Total score of clinical symptoms MD = -0.84 (-2.15, 0.47) Random 92% 250 2 Very Low
Time of heat removal MD = -1.20 (-2.03, -0.38) Random 77% 250 2 Low
Antipyretic rate (%) RR = 1.18 (0.88, 1.60) Random 69% 232 3 Low
Cough disappearance time MD = -1.57 (-4.17, 1.03) Random 94% 250 2 Very Low
Cough disappearance rate (%) RR = 1.37 (1.15, 1.64) Random 0% 264 3 Low
Weakness disappearance time MD = -0.33 (-0.78, 0.12) —— —— 200 1 Low
Weakness disappearance rate (%) RR = 1.37 (1.02, 1.83) Random 11% 147 2 Low
Shortness of breath disappearance rate (%) RR = 2.20 (1.11, 4.39) —— —— 35 1 Very Low
Diarrhea remission rate (%) RR = 0.32 (0.01, 15.49) Random 87% 30 2 Very Low
Physical pain disappearance rate (%) RR = 1.17 (0.73, 1.87) —— —— 30 1 Very Low
Adverse event incidence rate RD = 0.03 (-0.02, 0.08) Random 83% 1,152 8 Moderate
Jin 2020 COVID-19 Qingfeitouxiefuzheng prescription + symptomatic support treatment vs Symptomatic support treatment Effective rate of pulmonary CT improvement OR = 2.25 (1.01, 5.01) —— —— 100 —— Very Low
Lianhuaqingwen granule + symptomatic support treatment vs Symptomatic support treatment OR = 1.38 (0.91, 2.08) —— —— 397 —— Low
Lianhuaqingwen granule + symptomatic support treatment vs Symptomatic support treatment OR = 12.06 (1.37, 106.04) —— —— 57 —— Very Low
Xuebijing injection + symptomatic support treatment vs Symptomatic support treatment OR = 9.80 (1.09, 88.23) —— —— 44 —— Very Low
Lianhuaqingwen granule + symptomatic support treatment vs Qingfei xiefuzheng prescription + symptomatic support treatment OR = 0.61 (0.25, 1.51) —— —— 249 —— Low
Lianhuaqingwen granule + symptomatic support treatment vs Qingfei xiefuzheng prescription + symptomatic support treatment OR = 5.37 (0.53, 54.48) —— —— 83 —— Very Low
Xuebijing injection + symptomatic support treatment vs Qingfei xiefuzheng prescription + symptomatic support treatment OR = 4.36 (0.42, 45.27) —— —— 73 —— Very Low
Lianhuaqingwen granule + symptomatic support treatment vs Lianhuaqingwen granule + symptomatic support treatment OR = 8.75 (0.96, 79.95) —— —— 230 —— Low
Xuebijing injection + symptomatic support treatment vs Lianhuaqingwen granule + symptomatic support treatment OR = 7.11 (0.76, 66.50) —— —— 220 —— Low
Xuebijing injection + symptomatic support treatment vs Lianhuaqingwen granule + symptomatic support treatment OR = 0.81 (0.04, 17.89) —— —— 54 —— Very Low
Luo 2020 COVID-19 Traditional Chinese medicine + western medicine vs Western medicine Cure rate (%) OR = 2.67 (1.83, 3.89) Random 0% 792 CCT:7 RCT:3 Moderate
Improvement of lung CT OR = 2.43 (1.80, 3.29) Random 0% 985 CCT:9 RCT:4 Moderate
Conversion rate of severe cases (%) OR = 0.40 (0.24, 0.67) Random 17.1% 840 CCT:8 RCT:3 Moderate
Nucleic acid negative conversion rate (%) OR = 2.55 (1.06, 6.17) Random 56.4% 311 CCT:5 Low
Cough disappearance rate (%) OR = 2.95 (1.88, 4.63) Random 0% 468 CCT:3 RCT:2 Moderate
Weakness disappearance rate (%) OR = 2.61 (1.56, 4.34) Random 0% 368 CCT:3 RCT:1 Moderate
Fever disappearance rate (%) OR = 3.17 (1.95, 5.15) Random 0% 468 CCT:3 RCT:2 Moderate
Length of stay MD = -0.46 (-3.87, 2.95) Random 99.5% 326 CCT:5 Low
Adverse reactions incidence rate (%) OR = 1.21 (0.48, 3.07) Random 43.5% 1,233 CCT:10 RCT:5 Moderate
Sun 2020 COVID-19 Traditional Chinese medicine + western medicine vs Western medicine Clinical effective rate RR = 1.21 (1.08, 1.36) Fixed 0% 273 RCT:2 Low
Adverse event incidence rate RR = 1.17 (0.39, 3.52) Random 62% 681 RCT:7 Low
Nucleic acid negative conversion rate RR = 1.49 (1.13, 1.97) Fixed 0% 185 RCT:3 Low
Pneumonia Remission rate RR = 1.27 (1.12, 1.44) Fixed 0% 415 RCT:4 Low
White blood cell count MD = 0.92 (0.07, 1.76) Random 87% 339 RCT:3 Low
Lymphocyte count MD = 0.33 (0.08, 0.57) Random 76% 188 RCT:3 Low
Percentage of lymphocytes MD = 2.90 (2.09, 3.71) Fixed 0% 273 RCT:2 Low
C-reactive protein MD = -12.66 (-24.40, -0.92) Random 97% 288 RCT:4 Very Low
IL-6 level MD = -8.17 (-22.40, 6.06) Random 73% 166 RCT:2 Very Low
Zeng 2020 COVID-19 Lianhuaqingwen granule + western medicine vs Western medicine Other symptoms disappearance rate (%) OR = 6.54 (3.59, 11.90) Fixed 0% 142 2 Low
Heating time OR = -1.04 (-1.60, -0.49) Random 0% 142 2 Low
Main symptoms disappearance rate (%) OR = 3.34 (2.06, 5.44) Fixed 0% 142 2 Low
Fever (Main symptoms disappearance rate (%)) OR = 3.64 (1.57, 8.47) Fixed 0% 142 2 Low
Cough (Main symptoms disappearance rate (%)) OR = 4.22 (1.73, 10.26) Fixed 37.9% 142 2 Low
Weakness (Main symptoms disappearance rate (%)) OR = 2.53 (2.06, 5.44) Fixed 0% 142 2 Low
Muscle soreness (Main symptoms/Secondary symptoms disappearance rate (%)) OR = 6.97 (1.47, 33.01) Random 0% 142 2 Low
Sputum (Main symptoms/Secondary symptoms disappearance rate (%)) OR = 8.82 (2.48, 31.41) Random 0% 142 2 Low
Shortness of breath (Main symptoms/Secondary symptoms disappearance rate (%)) OR = 13.08 (2.60, 65.91) Random 0% 142 2 Low
Chest tightness (Main symptoms/Secondary symptoms disappearance rate (%)) OR = 7.17 (1.83, 28.12) Random 0% 142 2 Low
Dyspnea (Main symptoms/Secondary symptoms disappearance rate (%)) OR = 2.82 (0.27, 29.18) Random 0% 142 2 Low
Nausea (Main symptoms/Secondary symptoms disappearance rate (%)) OR = 1.21 (0.19, 7.81) Random 0% 142 2 Low
Loss of appetite (Main symptoms/Secondary symptoms disappearance rate) OR = 18.07 (0.33, 997.88) Random 79% 142 2 Low
Wang 2020 COVID-19 Lianhuaqingwen granule + western medicine vs Western medicine Effective rate of main clinical symptoms RR = 1.24 (1.12, 1.38) Fixed 0% 576 5 Moderate
CT improvement RR = 1.14 (1.02, 1.28) Random 53.9% 403 5 Low
Clinical conversion to severe RR = 0.48 (0.31, 0.72) Fixed 10.8% 439 4 Moderate
Duration of fever SMD = -0.87 (-1.22, -0.52) Fixed 0% 186 3 Low
Clinical symptoms disappearance time SMD = -0.19 (-1.56, -0.82) Fixed 0% 151 3 Low
Length of stay SMD = -0.61 (-0.91, -0.30) Fixed 19.6% 416 4 Moderate
Yang 2020 COVID-19 Lianhuaqingwen granule + western medicine vs Western medicine Fever disappearance rate (%) RR = 1.76 (1.05, 2.96) Random 82.8% 197 3 Very Low
Cough disappearance rate (%) RR = 1.96 (1.43, 2.68) Fixed 24.0% 197 3 Low
Weakness disappearance rate (%) RR = 1.77 (1.36, 2.30) Fixed 49.2% 197 3 Low
Chest tightness disappearance rate (%) RR = 2.19 (0.89, 5.40) Fixed 82.8% 197 3 Very Low
Dyspnea disappearance rate (%) RR = 4.58 (2.39, 8.79) Fixed 35.5% 197 3 Low
Loss of appetite disappearance rate (%) RR = 1.36 (1.00, 1.84) Fixed 1.9% 197 3 Low
Xiong 2020 COVID-19 Traditional Chinese medicine + western medicine vs Western medicine/Traditional Chinese medicine placebo + western medicine Lung CT improved RR = 1.23 (1.15, 1.32) Fixed —— 1,402 13 High
Mortality (%) RR = 0.34 (0.05, 2.18) Fixed 0% 463 4 Moderate
Cure rate (%) RR = 1.18 (1.13, 1.24) Fixed 24% 1,523 7 High
The number of severe to mild cases RR = 1.34 (0.47, 3.80) Fixed 0% 167 2 Low
The number of cases from mild to severe RR = 0.40 (0.29, 0.56) Fixed 0% 1,246 11 High
Length of stay (d) MD = -1.99 (-3.28, -0.70) Fixed —— 119 2 Low
Total score of clinical symptoms MD = -1.84 (-3.10, -0.58) Fixed 0% 133 2 Low
Antipyretic cases RR = 1.28 (0.98, 1.67) Random 66% 388 5 Low
Time of heat removal (d) MD = -1.36 (-1.8, -0.93) Random 58% 1,017 10 Low
Fever symptom score MD = -0.6 (-0.69, -0.50) Random 61% 885 3 Low
Number of cases with cough disappeared RR = 1.50 (1.26, 1.78) Fixed 0% 422 6 Low
Cough symptom score MD = -0.78 (-1.32, -0.24) Random 99% 934 4 Low
Cough disappearance time MD = -1.42 (-2.82, -0.01) Random 90% 698 6 Low
Weakness Number of improved cases RR = 1.73 (1.39, 2.16) Fixed 0% 307 5 Moderate
Weakness Symptom score MD = -0.70 (-0.98, -0.42) Random 97% 934 4 Low
Weakness disappearance time (d) MD = -1.13 (-2.22, -0.04) Random 93% 585 4 Low
Improvement of TCM syndromes (%) MD = -3.67 (-6.6, -0.73) Random 86% 225 5 Low
Nucleic acid negative conversion rate (%) RR = 1.18 (1.04, 1.34) Fixed 41% 469 4 Low
WBC count (109 cell/L) MD = 0.27 (-0.22, 0.76) Random 95% 1,151 5 Low
Lymphotoxicity MD = 0.24 (-0.04, 0.51) Random 97% 483 4 Low
C-reactive protein level (mg/L) MD = -8.91 (-12.56, -5.27) Random 97% 1,100 6 Low
Adverse reactions RR = 0.93 (0.49, 1.75) Random 46% 1,069 9 Low
Guo 2020 COVID-19 Traditional Chinese medicine + western medicine vs Western medicine Total effective rate (%) RR = 1.31 (1.11, 1.56) Fixed 0% 138 RCT:2 Very Low
Difference of total score of clinical symptoms before and after treatment SMD=0.82 (0.03, 1.61) Random 84.9% 240 Prospective NRCT:2 RCT:1 Very Low
Difference of total score of clinical symptoms before and after treatment (RCT subgroup) SMD=0.20 (-0.17, 0.58) Random —— 123 RCT:1 Very Low
Difference of total score of clinical symptoms before and after treatment (RCT subgroup) SMD=1.17 (0.41, 1.92) Random 66.6% 117 Prospective NRCT:2 Very Low
Fever control rate (%) RR = 1.30 (1.16, 1.45) Fixed 42.9% 536 Prospective NRCT:3 Retrospective NRCT:1 RCT:2 Low
Fever integral SMD=0.76 (-0.57, 2.10) Random 94.4% 187 Prospective NRCT:1 RCT:2 Very Low
Fever score (RCT subgroup) SMD = 1.46 (1.08, 1.83) Fixed 0% 138 RCT:2 Very Low
Fever score (NRCT subgroup) SMD = -0.64 (-1.21, -0.06) Random —— 49 Prospective NRCT:1 Very Low
Uration of fever MD = -1.58 (-1.98, -1.17) Fixed 9.2% 333 Prospective NRCT:1 Retrospective NRCT:1 Moderate
Weakness Improvement rate (%) RR = 1.55 (1.21, 1.99) Fixed 0% 368 Prospective NRCT:2 Retrospective NRCT:3 Moderate
Weakness Symptom score SMD = 1.49 (0.68, 2.30) Random 83.3% 187 Prospective NRCT:1 RCT:2 Very Low
Weakness symptom score (RCT subgroup) SMD = 1.43 (0.14, 2.73) Random 91.3% 138 RCT:2 Very Low
Weakness symptom score (NRCT subgroup) SMD = 1.62 (0.97, 2.27) Random —— 49 Prospective NRCT:1 Very Low
Weakness duration MD=-1.74 (-2.01, -1.48) Fixed 0% 172 Prospective NRCT:1 Retrospective NRCT:1 Low
Cough Improvement rate (%) RR = 1.65 (1.34, 2.04) Fixed 42.20% 468 Prospective NRCT:2 Retrospective NRCT:1 RCT:2 Low
Cough Integral difference before and after SMD=1.95 (1.13, 2.77) Random 81.40% 187 Prospective NRCT:1 RCT:2 Very Low
Cough duration MD=-1.71 (-2.30, -1.12) Fixed 0% 172 Prospective NRCT:2 Low
Improvement rate of lung CT RR = 1.28 (1.04, 1.57) Random 68.30% 526 Prospective NRCT:2 Retrospective NRCT:3 RCT:2 Low
Nucleic acid negative conversion rate (%) RR = 1.43 (0.94, 2.16) Fixed 0% 138 Prospective NRCT:2 Very Low
Conversion rate of severe cases (%) RR = 0.44 (0.26, 0.67) Fixed 10.30% 842 Prospective NRCT:3 Retrospective NRCT:3 RCT:4 Moderate
Zhou F. et al. (2021) COVID-19 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment Adverse reaction RR = 0.87 (0.67.1.14) —— —— —— —— Low
Mortality RR = 0.33 (0.08.1.34) —— —— —— —— Low
Cure rate RR = 1.15 (CI 1.04.1.26) Random 60% 976 6 Low
Lowering body temperature RR = 1.10 (0.94.1.29) —— 85% —— 9 Low
Relieving cough —— —— —— —— 9 ——
Improvement in chest CT images —— —— —— —— 5 ——
Deterioration of condition RR = 0.58 (0.43, 0.77) —— 0% —— 6 Low
Adverse effects RR = 0.81 (0.42, 1.57) —— 56% —— 9 Low
Liu 2021 COVID-19 Traditional Chinese medicine + western medicine conventional treatment/Traditional Chinese medicine vs Western medicine conventional treatment Severe conversion rate OR = 0.35 (0.18.0.69) Fixed 0% 326 3 High
Total effective rate OR = 2.50 (1.46.4.29) Fixed 0% 346 3 High
Pulmonary imaging (CT) improvement rate OR = 2.27 (1.37.3.77) Fixed 33% 346 3 Moderate
Heating duration SMD = -0.81 (-1.25,-0.38) Random 75% 414 4 Low
Fever disappearance rate OR = 3.05 (1.85.5.01) Fixed 0% 343 4 Moderate
Disappearance rate of cough OR = 2.99 (1.84.4.85) Fixed 0% 322 4 Moderate
Disappearance rate of fatigue OR = 2.60 (1.56.4.33) Fixed 0% 283 4 Moderate
Disappearance rate of expectoration OR = 1.94 (1.19.3.18) Fixed 56% 315 4 Low
Zhou L. P. et al. (2021) COVID-19 Traditional Chinese medicine + western medicine conventional treatment vs Western medicine conventional treatment Healing time of oral ulcer —— —— —— 1,133 7 ——
Adverse reaction RR = 0.87 (0.67, 1.14) —— —— 812 5 Low
Cure rate RR = 1.63 (0.36.7.30) —— —— —— —— Low
Total effective rate RR = 1.25 (0.94.1.67) —— —— —— —— Low
Ouyang 2021 COVID-19 Western medicine conventional treatment + Traditional Chinese medicine/Western medicine conventional treatment + Placebo + Traditional Chinese medicine vs Western medicine conventional treatment/Western medicine conventional treatment + Placebo Total effective rate RR = 1.26 (1.14, 1.40) Fixed 0% 427 4 Moderate
Heating duration WMD = -1.21 (-1.71, -0.71) Random 55% 414 2 Low
Disappearance rate of novel coronavirus pneumonia related symptoms RR = 1.25 (0.88, 1.80) Random —— —— 5 Moderate
Pneumonia absorption rate RR = 1.15 (0.93, 1.43) Random 84% —— 6 Low
Disapperance rate of weakness RR = 1.36 (0.71, 2.62) Random 75% —— —— Low
Disapperance rate of cough RR = 1.87 (0.58, 6.08) Random 97% —— —— Low
Virus nucleic acid negative rate RR = 1.47 (1.05, 2.05) Fixed 0% —— 3 High
Leukocyte count RR = 0.74 (0.26, 1.22) Random 75% —— 2 Low
Lymphocyte count RR = 0.21 (0.15, 0.27) Fixed 0% —— 2 High
Percentage of lymphocytes RR = 2.69 (1.92, 3.47) Fixed 31% —— 2 High
Zhang 2004 SARS Combination of Chinese and Western medicine vs Western medicine Mortality (%) RR = 0.86 (0.22, 3.29) Random —— 139 6 Low
GuoYaoNO.2.3.4 formula + westernmedicine vsWestern medicine Mortality (%) RR = 0.41 (0.04, 4.78) Fixed —— 53 6 Very Low
GuoYaoNO.2.3.4 formula + western medicine vs Western medicine Secondary infection rate RR = 0.42 (0.11, 1.62) Fixed —— 53 6 Very Low
GuoYaoNO.2.3.4 formula + western medicine vs Western medicine Lung infiltration and absorption (%) RR = 5.45 (1.54, 19.26) Fixed —— 53 6 Very Low
FeidianNO.1.2.3 formula + western medicine vs Western medicine Lung infiltration and absorption (%) RR = 6.68 (2.93, 15.24) Random —— 139 6 Low
FufangNo.1 formula + western medicine vs Western medicine Lung infiltration and absorption (%) MD = 0.24 (0.02, 0.46) Fixed —— 40 6 Very Low
Combination of Chinese and western medicine vs Western medicine Lung infiltration and absorption (%) RR = 8.06 (0.4, 163.21) Fixed —— 59 5 Very Low
FeidianNo2.3.4 formula + western medicine vs Western medicine Dyspnea disappearance RR = 1.50 (0.41, 5.43) Fixed —— 38 1 Very Low
FeidianNo.4 formula + western medicine vs Western medicine Cough disappearance RR = 1.29 (0.30, 5.43) Fixed —— 30 1 Very Low
Combination of Chinese and western medicine vs Western medicine Average total dosage of hormone (mg) MD = -39.65 (-116.84, 37.54) Fixed —— 98 2 Very Low
Hao 2005 SARS Traditional Chinese medicine + western medicine vs Western medicine Mortality (%) RR = 0.24 (0.13, 0.42) Random 0% 697 9 High
Average dosage of hormone (mg) SMD = -1.40 (-2.58, -0.23) Fixed 95.30% 175 5 Very Low
Mean heating time RD = -0.65 (-1.45, -0.15) Random 21.10% 73 4 Very Low
Hao, Hong 2005 SARS Traditional Chinese medicine + western medicine vs Western medicine Mortality (%) RR = 0.24 (0.13, 0.43) Random —— 599 9 High
Liu 2005 SARS Traditional Chinese medicine + western medicine vs Western medicine/p lacebo Mortality (%) RCT:RR = 0.32 (0.12, 0.91) NRCT:RR = 0.27 (0.12, 0.61) Random —— RCT:294 NRCT:486 RCT:5 NRCT:6 High
Time of heat removal(d) MD = -0.83 (-1.3, -0.35) Fixed —— 182 3 Low
Symptom relief time (d) MD = -1.23 (-2.9, -0.37) Fixed —— 119 2 Low
Abnormal chest X-ray RR = 0.29 (0.15, 0.56) Random —— 126 2 Low
Average total dosage of hormone (mg) RR = -770.45 (-1798.47,257.58) Random 99.20% 109 2 Low
Daily average total dosage of hormone (mg) RR = -54.13 (-120.63, 12.38) Random —— 126 2 Low
Recovery time of chest X-ray (d) MD = -2.27 (-3.16, -1.39) Fixed —— 175 2 Low
Secondary fungal infection incidence rate (%) RR = 0.35 (0.14, 0.90) Random —— 128 2 Low
Zhao 2004 SARS Traditional Chinese medicine + western medicine vs Western medicine Mortality (%) OR = 0.32 (0.14, 0.71) Random 9.80% 333 4 Low
Complications caused by hormone use (%) OR = 0.29 (0.13, 0.65) Random 0% 33 3 Low
Time of heat removal (d) MD = -1.17 (-1.83, -0.5) Fixed 11.00% —— 5 Low
Absorption time of lung shadow on chest X-ray MD = 0.63 (-1.33, 2.59) Fixed 0% —— —— Low
Absorption ratio of lung shadow on chest X-ray OR = 2.16 (1.22, 3.84) Random —— —— —— Low
Remission time of lower respiratory tract infection MD = -1.47 (-1.96, -0.98) Fixed 53.40% —— —— Low
Average total dosage of hormone (mg) MD = -207.19 (-334.98, -69.00) Fixed —— —— —— Very Low
Average time of hormone use (d) MD = -1.67 (-3.3, -0.03) Fixed —— —— —— Low
Pan 2014 H1N1 Chinese patent medicine vs Western medicine Fever duration(d) MD = -4.65 (-8.91, -0.38) Fixed 71.8% —— 5 Low
Cough duration (d) MD = -9.79 (-14.61, -4.98) Fixed 11.2% 320 4 Low
Sore throat duration (d) MD = -13.01 (-21.76, -4.27) Fixed 87.1% 321 4 Low
Physical pain time (d) MD = -16.68 (-32.33, -1.03) Fixed 89.7% 137 3 Very Low
Nucleic acid negative conversion time (H) MD = -0.24 (-4.97, 4.31) Fixed 49.6% —— 5 Low
Jin 2018 Tuberculosis Traditional Chinese medicine + chemotherapy vs Chemotherapy Sputum negative conversion rate (%) RR = 1.30 (1.22, 1.39) Fixed 35% 2,479 21 High
Sputum negative conversion rate (%) (after 3 months of treatment) RR = 1.41 (1.28.1.55) Fixed 0% 1784 21 High
Sputum negative conversion rate (%) (after 6months of treatment) RR = 1.30 (1.22, 1.39) Fixed 35% 2,479 21 High
Sputum negative conversion rate (%) (after 9 months of treatment) RR = 1.35 (1.24, 1.46) Fixed 40% 1,060 11 High
Sputum negative conversion rate (%) (after 12 months of treatment) RR = 1.31 (1.22, 1.42) Fixed 76% 1,137 12 Moderate
Sputum negative conversion rate (%) (after 18 months of treatment) RR = 1.23 (1.14, 1.33) Fixed 0% 1,461 10 High
Sputum negative conversion rate (%) (after 24 months of treatment) RR = 1.32 (1.10, 1.59) Fixed 0% 252 4 High
Absorption rate of lesions (%) RR = 1.08 (1.01, 1.14) —— —— —— 36 Moderate
Absorption rate of lesions (%) (after 3 months of treatment) RR = 1.20 (1.10, 1.31) —— —— —— —— Low
Absorption rate of lesions (%) (after 6 months of treatment) RR = 1.08 (1.01, 1.14) —— 59% —— —— Low
Absorption rate of lesions (%) (after 9 months of treatment) RR = 1.29 (1.14, 1.46) —— —— —— —— Low
Absorption rate of lesions (%) (after 12 months of treatment) RR = 1.28 (1.18, 1.40) —— —— —— —— Low
Absorption rate of lesions (%) (after 18 months of treatment) RR = 1.16 (1.09, 1.25) —— —— —— —— Low
Absorption rate of lesions (%) after 24 months of treatment) RR = 1.24 (1.08, 1.43) —— —— —— —— Low
Absorption rate of lesions (%) (after 3 months of treatment) RR = 1.07 (0.85, 1.33) —— —— —— —— Low
Absorption rate of lesions (%) (after 6 months of treatment) RR = 1.11 (0.92, 1.34) —— —— —— —— Low
Absorption rate of lesions (%) (after 9 months of treatment) RR = 1.86 (1.43, 2.42) —— 69% —— —— Very Low
Absorption rate of lesions (%) (after 12 months of treatment) RR = 1.60 (1.25, 2.04) —— —— —— —— Low
Absorption rate of lesions (%) (after 18 months of treatment) RR = 1.16 (1.06, 1.27) —— —— —— —— Low
Absorption rate of lesions (%) (after 24 months of treatment) RR = 1.28 (1.09, 1.51) —— —— —— —— Low
Improvement of TCM syndromes (%) RR = 1.23 (1.17, 1.29) —— —— —— 7 Low
Improvement of TCM syndromes (%) (after 3 months of treatment) RR = 1.53 (1.25, 1.87) —— —— —— —— Low
Improvement of TCM syndromes (%) (after 6months of treatment) RR = 1.19 (1.04, 1.36) —— —— —— —— Low
Improvement of TCM syndromes (%) (after 9 months of treatment) RR = 1.19 (1.06, 1.32) —— >50% —— —— Low
Improvement of TCM syndromes (%) (after 12months of treatment) RR = 1.17 (1.06, 1.29) —— >50% —— —— Low
Improvement of TCM syndromes (%) (after 18 months of treatment) RR = 1.24 (1.11, 1.37) —— >50% —— —— Low
Improvement of TCM syndromes (%) (after 24 months of treatment) RR = 1.18 (1.05, 1.32) —— —— —— —— Low
Total effective rate (%) RR = 1.30 (1.21, 1.39) —— 29% —— 10 Moderate
Adverse reactions incidence rate (%) RR = 0.65 (0.58, 0.74) —— —— —— 23 Low
Yan 2017 Tuberculosis Chinese patent medicine + chemotherapy vs Chemotherapy Sputum negative conversion rate (%) (after 2 months of treatment) OR = 2.75 (2.10, 3.62) Fixed 26% 1,316 10 High
Sputum negative conversion rate (%) (after 3 months of treatment) OR = 1.70 (1.20, 2.41) Fixed 0% 914 7 High
Sputum negative conversion rate (%) (after 6months of treatment) OR = 1.71 (1.08, 2.70) Fixed 1% 671 5 High
Absorption rate of lesions (%) (after 2months of treatment) OR = 2.19 (1.32, 1.61) Random 72% 1,424 9 Moderate
Absorption rate of lesions (%) (after 3 months of treatment) OR = 1.94 (1.30, 2.90) Fixed 36% 558 7 Moderate
Absorption rate of lesions (%) (after 6months of treatment) OR = 2.06 (1.29, 3.27) Fixed 43% 457 5 Moderate
Symptom remission rate (%) OR = 2.10 (1.52, 2.92) Fixed 0% 1,128 9 Moderate
Relief of gastrointestinal tract adverse reactions incidence rate (%) OR = 0.25 (0.10, 0.62) Fixed 0% 92 2 Very Low
Yue 2017 Tuberculosis Coptis chinensis combination Chinese patent medicine + chemotherapy vs Chemotherapy Sputum negative conversion rate (%) RR = 1.35 (1.21, 1.50) Random 82% 3,484 16 Moderate
Absorption rate of lesions (%) RR = 1.21 (1.10, 1.32) Random 88% 2049 15 Moderate
Void reduction rate (%) RR = 1.19 (1.08, 1.31) Random 70% 1,301 11 Moderate
Improvement rate of clinical symptoms and signs (%) RR = 1.12 (1.07, 1.16) Fixed 36% 877 7 Moderate
Adverse reactions incidence rate (%) (Gastrointestinal reaction incidence rate) RR = 0.32 (0.24, 0.43) Fixed 42% 885 6 Moderate
Adverse reactions incidence rate (%) (Liver function damage incidence rate) RR = 0.35 (0.25, 0.49) Fixed 24% 1,044 7 High
Adverse reactions incidence rate (%) (rash incidence rate) RR = 0.31 (0.11, 0.87) Fixed 0% 430 3 High
Wang 2017 Bacterial dysentery Traditional Chinese medicine + Western medicine vs Western medicine Total effective rate (%) OR = 6.87 (3.68, 12.81) Fixed 0% 1,143 12 High
Time of heat removal (d) MD = -1.58 (-1.77, -1.38) Fixed 92% 454 6 Moderate
Antidiarrheal time (d) MD = -1.58 (-1.81, -1.33) Fixed 94% 429 5 Moderate
Wu 2015 Mumps Andrographis injection + symptomatic treatment vs Ribavirin + symptomatic treatment Total effective rate (%) (no antibiotics) RR = 1.30 (1.12, 1.50) Fixed 34% 155 3 Low
Total effective rate (%) (The use of antibiotics was not mentioned) RR = 1.19 (1.09, 1.31) Fixed 0% 230 3 Low
Total effective rate (%) RR = 1.23 (1.14, 1.33) Fixed 0% 448 6 Low
Time of heat removal (no antibiotics) MD = -1.64 (-1.89, -1.39) Fixed 40% 446 6 Low
Time of heat removal (Use of antibiotics) MD = -0.86 (-1.06, -0.66) Random —— 60 1 Very Low
Time of heat removal (The use of antibiotics was not mentioned) MD = -1.28 (-2.28, -0.29) Random 99% 312 4 Very Low
Detumescence time of cheek (no antibiotics) MD = -2.20 (-2.72, -1.69) Random 67% 446 6 Low
Detumescence time of cheek (Use of antibiotics) MD = -1.60 (-1.87, -1.33) Random —— 60 1 Very Low
Detumescence time of cheek (The use of antibiotics was not mentioned) MD = -2.09 (-3.51, -0.67) Random 99% 312 4 Very Low
Detumescence time of cheek MD = -2.10 (-2.78, -1.41) Random 97% 818 11 Low
Zhao 2014 Mumps Traditional Chinese medicine vs Western medicine Total effective rate (%) OR = 6.36 (4.85, 8.34) Fixed 21.6% 2,913 21 Moderate
Traditional Chinese medicine vs Chinese patent medicine Total effective rate (%) OR = 7.93 (3.25, 19.39) Fixed 0% 432 6 Low
Traditional Chinese medicine vs Western medicine (Traditional Chinese medicine、western medicine、western medicine) Total effective rate (%) OR = 9.94 (5.44, 18.17) Fixed 20.4% 4,505 6 Moderate
Yu 2020 Hand, foot and mouth disease in children Ribavirin vs Reduning Total effective rate (%) OR = 11.9 (4.64, 3.71) —— Existence of heterogeneity 1,421 —— Moderate
Time of heat removal (d) MD = -2.47 (-4.67, -0.19) —— Existence of heterogeneity 82 —— Very Low
Skin rash regression time (d) MD = -2.83 (-4.25, -1.52) —— Existence of heterogeneity 160 —— Low
Healing time of oral ulcer (d) MD = -1.76 (-3.23, -0.24) —— Existence of heterogeneity 204 —— Low
Adverse reactions incidence rate (%) OR = 0.20 (0.01, 1.64) —— Existence of heterogeneity 170 —— Low
Length of stay (d) MD = -5.88 (-10.80, -0.82) —— Existence of heterogeneity —— —— Low
Ribavirin vs Tanreqing Total effective rate (%) OR = 3.21 (0.73, 5.29) —— Existence of heterogeneity 147 —— Low
Time of heat removal (d) MD = -0.99 (-3.03, 1.08) —— —— 63 —— Very Low
Skin rash regression time (d) MD = -0.52 (-1.85, 0.88) —— —— 63 —— Very Low
Healing time of oral ulcer (d) MD = -1.59 (-3.72, 0.56) —— —— 63 —— Very Low
Length of stay (d) MD = -0.76 (-4.04, 2.39) —— —— 63 —— Very Low
Ribavirin vs Xiyanping Total effective rate (%) OR = 6.17 (2.39, 5.72) —— Existence of heterogeneity 550 —— Low
Time of heat removal (d) MD = -1.47 (-2.91, -0.05) —— Existence of heterogeneity 264 —— Low
Skin rash regression time (d) MD = -1.99 (-2.80, -1.18) —— Existence of heterogeneity 414 —— Low
Healing time of oral ulcer (d) MD = -3.58 (-6.52, -0.58) —— Existence of heterogeneity —— —— Low
Adverse reactions incidence rate (%) OR = 1.29 (0.03, 3.81) —— Existence of heterogeneity —— —— Low
Length of stay (d) MD = -2.53 (-5.14, 0.18) —— —— 150 —— Low
Ribavirin vs Yanhuning Total effective rate (%) OR = 2.28 (0.72, 5.43) —— Existence of heterogeneity 86 —— Very Low
Healing time of oral ulcer (d) MD = -2.21 (-4.40, -0.07) —— Existence of heterogeneity 86 —— Very Low
Length of stay (d) MD = -1.57 (-5.80, 2.70) —— —— 86 —— Very Low
Reduning vs Tanreqing Total effective rate (%) OR = 3.70 (0.60, 2.24) —— Existence of heterogeneity —— —— Very Low
Time of heat removal (d) MD = -1.48 (-4.35, 1.39) —— —— —— —— Very Low
Skin rash regression time (d) MD = -2.30 (-4.29, -0.50) —— Existence of heterogeneity —— —— Very Low
Healing time of oral ulcer (d) MD = -0.17 (-2.80, 2.51) —— —— —— —— Very Low
Length of stay (d) MD = -5.12 (-10.16, 0.27) —— —— —— —— Very Low
Reduning vs Xiyanping Total effective rate (%) OR = 1.92 (0.58, 7.02) —— Existence of heterogeneity 64 —— Very Low
Time of heat removal (d) MD = -0.98 (-3.14, 1.12) —— —— 64 —— Very Low
Skin rash regression time (d) MD = -0.84 (-2.29, 0.45) —— —— 64 —— Very Low
Healing time of oral ulcer (d) MD = 1.83 (-1.47, 5.17) —— —— 64 —— Very Low
Length of stay (d) MD = -3.38 (-7.44, 0.86) —— —— 64 —— Very Low
Adverse reactions incidence rate (%) OR = 0.15 (0.01, 1.82) —— Existence of heterogeneity 64 —— Very Low
Reduning vs Yanhuning Total effective rate (%) OR = 0.96 (0.02, 9.78) —— Existence of heterogeneity —— —— Low
Healing time of oral ulcer (d) MD = 0.44 (-2.13, 3.15) —— —— —— —— Low
Length of stay (d) MD = -4.32 (-10.63, 2.44) —— —— —— —— Low
Tanreqing vs Yanhuning Total effective rate (%) OR = 0.52 (0.11, 2.65) —— Existence of heterogeneity —— —— Low
Time of heat removal (d) MD = 0.48 (-1.58, 2.54) —— —— —— —— Low
Skin rash regression time (d) MD = 1.46 (0.10, 2.88) —— Existence of heterogeneity —— —— Low
Healing time of oral ulcer (d) MD = 1.99 (-0.08, 4.07) —— —— —— —— Low
Length of stay (d) MD = 1.76 (-1.57, 4.91) —— —— —— —— Low
Tanreqing vs Xiyanping Total effective rate (%) OR = 0.25 (0.01, 6.76) —— Existence of heterogeneity 80 —— Very Low
Healing time of oral ulcer (d) MD = 0.62 (-2.35, 3.66) —— —— 80 —— Very Low
Length of stay (d) MD = 0.82 (-4.43, 6.14) —— —— 80 —— Very Low
Xiyanping vs Yanhuning Total effective rate (%) OR = 0.50 (0.01, 1.83) —— Existence of heterogeneity —— —— Low
Healing time of oral ulcer (d) MD = -1.37 (-5.00, 2.32) —— —— —— —— Low
Length of stay (d) MD = -0.94 (-5.84, 4.10) —— —— —— —— Low
Yang 2020 Hand, foot and mouth disease in children Chinese patent medicine/Chinese patent medicine + Western medicine vs Western medicine Total effective rate (%) RR = 1.20 (1.16, 1.23) Fixed 45% 3,311 23 Moderate
Time of heat removal (d) MD = -1.20 (-1.44, -0.95) Random 94% 2,708 19 Low
Herpes disappearance time (d) MD = -1.78 (-2.10, -1.46) Random 95% 2,743 19 Low
Healing time of oral ulcer (d) MD = -1.45 (-1.62, -1.27) Random 95% 553 7 Low
Total duration of disease (d) MD = -2.22 (-2.39, -2.04) Random 76% 943 9 Low
Adverse reactions incidence rate (%) RR = 1.16 (0.79, 1.70) Fixed 22% 92 16 Low
Xiong et al. (2019) Hand, foot and mouth disease in children Tanreqing + conventional therapy vs Conventional therapy of western medicine Total effective rate (%) OR = 2.88 (1.62, 5.10) Fixed —— 400 3 Low
Xiyanping injection、Reduning injection/Xiyanping injection、Reduning injection + traditional treatment of western medicine vs Traditional treatment of western medicine Time of rash regression (H) MD = -29.57 (-47.18, -11.95) Random 98% 1,029 9 Low
Xiyanping injection/Reduning injection vs Conventional therapy of western medicine Time of rash regression (H) (Traditional Chinese medicine group vs western medicine group) MD = -27.20 (-50.35, -4.04) Random 98% 691 5 Low
Xiyanping injection/Reduning injection + traditional treatment of western medicine vs Traditional treatment of western medicine Time of rash regression (H) (Integrated traditional Chinese and Western medicine group vs western Medicine group) MD = -29.57 (-47.28, -11.85) Random 98% 338 4 Low
Xiyanping injection、Reduning injection/Xiyanping injection、Reduning injection + conventional therapy of western medicine vs Conventional therapy of western medicine Antipyretic onset time (H) MD = -8.10 (-11.77, -4.42) Fixed 2% 162 4 Low
Xiyanping injection/Reduning injection vs Traditional treatment of western medicine Antipyretic onset time (H) (Traditional Chinese medicine group vs western Medicine group) MD = -9.77 (-18.48, -1.06) Random 51% 81 2 Very Low
Xiyanping injection/Reduning injection + Traditional treatment of western medicine vs Traditional treatment of western medicine Antipyretic onset time (H) (Integrated traditional Chinese and Western medicine group vs Western medicine group) MD = -7.86 (-13.26, -2.47) Random 0% 79 2 Very Low
Xiyanping injection/Reduning injection + Traditional treatment of western medicine vs Traditional treatment of western medicine Time of heat removal (h) (Subgroup analysis was performed according to the combination of western medicine) MD = -16.63 (-22.68, -10.59) Random 98% 1,320 10 Moderate
Xiyanping injection/Reduning injection/Tanreqing injection vs Traditional treatment of western medicine Time of heat removal (h) (Subgroup analysis according to the combination of western medicine, traditional Chinese medicine group vs Western medicine group) MD = -21.91 (-33.61, -10.22) Random 84% 445 4 Moderate
Xiyanping injection/Reduning injection/Tanreqing injection + Traditional treatment of western medicine vs Traditional treatment of western medicine Time of heat removal (h) (Subgroup analysis was performed according to the combined use of western medicine, and the combination group of western medicine and Chinese medicine was compared with the western medicine group) MD = -13.51 (-21.24, -5.77) Random 98% 875 5 Low
Xiyanping injection, Reduning injection, Tanreqing injection Time of heat removal (h) (Subgroup analysis by traditional Chinese medicine injection) MD = -18.26 (-27.34, -9.17) Random 89% 1,326 8 Low
Tanreqing injection/Tanreqing injection + Traditional treatment of western medicine vs Traditional treatment of western medicine Time of heat removal (h) (Subgroup analysis according to traditional Chinese medicine injection variety, Tanreqing) MD = -2.30 (-17.17, 12.56) Random 81% 323 2 Low
Xiyanping injection/Xiyanping injection + Traditional treatment of western medicine vs Traditional treatment of western medicine Time of heat removal (h) (Subgroup analysis by traditional Chinese medicine injection, Xiyanping) MD = -12.02 (-15.47, -8.56) Random 0 413 4 Low
Reduning injection/Reduning injection + Traditional treatment of western medicine vs Traditional treatment of western medicine Time of heat removal (h) (Subgroup analysis by traditional Chinese medicine injection, Reduning) MD = -30.48 (-51.95, -9.01) Random 91% 590 5 Low
Xiyanping injection, Reduning injection/Xiyanping injection, Reduning injection, Tanreqing injection + Traditional treatment of western medicine vs Traditional treatment of western medicine Conversion rate of severe cases (%) OR = 0.83 (0.45, 1.53) Fixed 0% 1,331 8 High
Xiyanping injection、Reduning injection/Xiyanping injection、Reduning injection、 Tanreqing injection + Traditional treatment of western medicine vs Traditional treatment of western medicine Adverse reactions incidence rate (%) OR = 2.37 (0.39, 14.40) Fixed 0% 1815 10 Moderate
Yu 2020 Hand, foot and mouth disease Traditional Chinese medicine vs Western medicine treatment/Traditional Chinese medicine Disappearance rate of other symptoms OR = 6.54 (3.59.11.90) Fixed 0% 142 2 Low
Duration of fever OR = -1.04 (-1.60, -0.49) Random 0% 142 2 Low
Efficiency —— —— —— 3,925 26 ——
Regression time of hand foot rash —— —— —— 2,262 17 ——
Antipyretic time —— —— —— 2086 16 ——

——: Not Reported.

 COVID-19

Six high-quality SRs (Wang S. et al., 2020; Zeng et al., 2020; Zhou L. P. et al., 2021; Zhou F. et al., 2021; Luo et al., 2021; Ouyang et al., 2021) and eight moderate-quality SRs (Liu and Dong, 2021; Fan et al., 2020; Pang et al., 2020; Jin et al., 2020; Sun et al., 2020; Yang M. et al., 2020; Xiong et al., 2020; Gao et al., 2020) evaluated the efficacy and safety of conventional therapy combined with CHM decoction/proprietary CHM drugs and the results all suggested that this combination therapy was better than conventional therapy alone in improving the overall treatment efficiency for COVID-19 patients.

One single high-quality SR including 19 controlled trials (Luo et al., 2021) identified the efficacy and safety of conventional therapy combined with TCM/tonics, the results showed that the combined with TCM/tonics could improve the appearance of pulmonary CT lesions and the nucleic acid conversion rate, improve the alleviation of symptoms such as fever, cough, malaise, reduce hospitalization time and the rate of clinical cases from mild to severe. However, there was no difference in the incidence of adverse events between the treatments.

Specific to Lianhuaqingwen Capsule, a proprietary CHM drug, a moderate quality SR involving seven RCTs (Wang S. et al., 2020) identified the CHM combined with conventional therapy vs. conventional therapy to treat the COVID-19 patients, and the results suggested that the CHM combined with conventional therapy could improve the appearance of pulmonary CT lesions, shorten the fever duration and the time in hospital, and reduce the possibility being worsening. As for safety, no adverse events were reported.

One moderate quality SR including 12 RCTs with mild and ordinary COVID-19 patients (Gao et al., 2020) suggested that the combined with CHM decoction/proprietary CHM drugs could reduce the duration of fever, fatigue, and cough, improve the appearance of pulmonary CT lesions and the nucleic acid conversion rate, and reduce the rate of clinical cases from mild to severe. However, another high-quality systematic review (Ouyang et al., 2021) including six RCTs and four cohort studies identified the efficacy and safety of TCM in the treatment of common or mild COVID-19 patients, showing that TCM was superior to the control group in improving efficiency and reducing the duration of fever, but there was no difference in the relief of related symptoms such as fever and malaise and the incidence of adverse effects between the two groups.

One moderate quality SR involving seven RCTs (Fan et al., 2020) identified the CHM combined with conventional therapy vs. conventional therapy to treat the COVID-19 patients ranging from being mild to severe, and the results suggested that the CHM combined with conventional therapy could improve the appearance of pulmonary CT lesions and reduce C-reactive protein. As for safety, no adverse events were reported.

One single moderate-quality SR including three RCTs (Yang M. et al., 2020) evaluated the efficacy and safety of Lianhuaqingwen capsule, and the results suggested that in combination with conventional treatment, they could improve the alleviation of symptoms such as fever, cough, fatigue, and chest tightness, dyspnoea, and loss of appetite in ordinary COVID-19 patients better than conventional treatment alone. Regarding safety, there was no difference in the incidence of adverse events between the treatments.

One high-quality network meta-analysis including five RCTs (Jin et al., 2020) evaluated the efficacy of four CHM prescripts, namely, Qingfei Touxie Fuzheng Decoction, Lianhua Qingwen Granule, Lianhua Qingke Granule, and Xuebijing Injections, and the results suggested that the combination of symptomatic and supportive treatment with either one of four prescriptions could better improve the appearance of the lungs on pulmonary CT than symptomatic treatment alone. Among them, the combination of symptomatic and supportive care with Lianhua Qingke Granule had the highest surface under the cumulative ranking (SUCRA) value, suggesting it had the highest overall effectiveness.

Two high-quality systematic reviews (Zhou L. P. et al., 2021; Zhou F. et al., 2021) identified the add-on effect of TCM for COVID-19. One included 10 RCTs and the other included 6 RCTs, and both studies suggested that TCM may be an effective auxiliary treatment for COVID-19 patients, which is likely to help improve the main symptoms, such as fever, cough, and fatigue, shorten the hospital stay and reduce disease progression.

 SARS

Five moderate-quality SRs (Zhang et al., 2004; Zhao et al., 2004; Hao, 2005; Hao et al., 2005; Liu et al., 2005) evaluated the effectiveness of CHM combined with Western medicine for SARS, and the results all suggested that the combination better improved the clinical progression of SARS patients; however, the benefits to specific outcomes varied across SRs.

One moderate-quality SR including eight controlled trials (Liu et al., 2005) suggested that the additional use of CHM reduced the mortality, the incidence of secondary fungal infections in the lungs, shorten the duration of fever, the persisting clinical symptoms and the time for Chest X-ray to return normal appearance. There were no adverse events for the combination treatments.

Another moderate-quality SR including six RCTs with mild-to-sever patients (Zhang et al., 2004) showed that the improvement of the appearance of abnormal chest X-ray shadows was better in the group treated with CHM decoction and conventional medicine than the conventional treatment alone. However, there was no statistical difference in the reduction of mortality, and dose of corticosteroids, and the alleviation of cough and dyspnoea between two groups.

Two other moderate-quality SR (Hao, 2005; Hao et al., 2005) supported the conclusion the combination of CHM and conventional medicine was better in reducing the duration of fever and mortality among the patients with SARS; however, the use of corticosteroids had not been reduced due to the additional use of CHM.

Another moderate-quality SR (Zhao et al., 2004) did not support the benefits to improving Chest X-ray imaging among the SARs patients when CHM was used alongside conventional medicine; it confirmed the superiority of CHM in reducing the duration of fever, mortality dose of corticosteroids and complications due to overuse of corticosteroids as well as improving clinical symptoms.

 H1N1 Influenza

One moderate-quality SR including five RCTs (Zhao et al., 2014) suggested that the use of Lianhua Qingwen Capsule was better at reducing the duration of symptoms such as fever, cough, sore throat, and body pain in H1N1 patients compared with the use of ooseltamivir. However, there was no statistical difference of the time to conversion to nucleic acid negativity between two treatments. Regarding safety, no details of adverse events were reported.

 Tuberculosis

One moderate-quality SR (Jin et al., 2018) evaluated the efficacy of CHM decoction/proprietary CHM drugs combined with chemotherapy, and the results suggested that the combination better improved the negative conversion rate of sputum bacteria, lesion absorption rate, lung cavity closure rate, clinical symptom improvement rate, and overall effectiveness of patients with multi-drug-resistant tuberculosis over chemotherapy alone. In terms of safety, the incidence of adverse events was more reduced with the combination treatment.

Specifically, a moderate-quality SR including 16 RCTs (Yan and Gao, 2017) suggested that the proprietary CHM drugs Jiehe Pills in combination of chemotherapy better improved the rate of sputum conversion and lesion resorption and alleviated clinical symptoms and signs such as cough, haemoptysis, fever, emaciation, fatigue, and night sweats in tuberculosis patients over chemotherapy alone. In terms of safety, the incidence of digestive discomforts was more reduced with the combination treatment. Another moderate-quality SR including 20 RCTs (Yue et al., 2017) evaluated the efficacy of oral proprietary CHM drugs including Astragalus membranaceus in combination with chemotherapy better improved the rate of sputum conversion and lesion resorption, with less adverse events related to digestive discomforts, liver injury and the occurrence of rash.

 Bacillary Dysentery

One moderate-quality SR (Wang et al., 2017) evaluated the efficacy of the combined use of CHM decoction and Western conventional therapy, and the results suggested that the combination better improved the overall effectiveness and shortened the time to fever and to diarrhoeal alleviation in adults with bacillary dysentery over Western conventional therapy alone; in terms of safety, digestive disorders were observed (intervention: control: 2 cases versus 5 cases).

 Mumps

One moderate-quality SR including 11 RCTs (Wu et al., 2015) evaluated the effectiveness of the combined use of Chuanhuning Injection versus anti-virus pharmacotherapy ribavirin, and the results suggested that the combined use of Chuanhuning Injection and routine care better improved the overall effectiveness, shortened the time to fever and cheek swelling reduction, and reduced the occurrence of complications in children with mumps over ribavirin combined with routine care. In terms of safety, no adverse events occurred in the intervention group compared with the control including 4 cases of adverse events.

Another moderate-quality SR (Zhao, 2014) evaluated the effect of treatment with CHM alone, and the results suggested that internal and external treatment with CHM better improved the overall effectiveness, over proprietary CHM drugs alone; the external use of CHM outperformed the oral treatment. For safety, adverse events were observed, but no details were provided for individual groups.

 Hand-Foot-And-Mouth Disease

A moderate-quality SR (Xiong et al., 2019) evaluated the effectiveness of proprietary CHM injections alone or in combination with conventional treatment, and the results suggested the monotherapy or the adjunct use of CHM injections reduced the time to fever and rash reduction, and improved the overall clinical effectiveness in children with HFMD. However, there was no difference in the incidence of adverse events and severe case conversion rate between treatments.

A moderate-quality SR including 24 RCTs (Yang Z. et al., 2020) evaluated the effectiveness of using oral proprietary CHM drug Lanqin Oral Solution in addition to conventional treatment, and the results suggested that the combination treatment better reduced the time to fever and rash reduction and oral ulcer healing and shortened the total duration of illness in children with HFMD. In terms of safety, there was no difference in the incidence of adverse events between treatments.

One moderate-quality SR including 17 RCTs (Yu et al., 2020a) conducted a network meta-analysis of proprietary CHM drugs for HFMD. The results suggested that the Yanhuning Injection, Reduning Injection, Xiyanping injection and Tanreqing injection were significantly better than Ribavirin in improving the total clinical effectiveness; as for oral ulcer healing time and hospitalization time, Xiyanping and Reduning were significantly shorter than ribavirin; in terms of safety, Reduning and Xiyanping were significantly higher than ribavirin.

Another moderate-quality SR (Yu et al., 2020b) conducted a network meta-analysis to identify the effectiveness and safety of Qingre Jiedu TCM oral liquid in the treatment of HFMD. They concluded that seven TCM oral liquids, including Lanqin oral liquid, Pudilan oral liquid, Yellow Gardenia liquid, Fuganlin oral liquid, Kangbindu oral liquid, Huangqing oral liquid, and Shuanghuanglian oral liquid, had good therapeutic effects in clinical efficacy and recovery time of related symptoms. In the adverse reactions aspect, Pudilan oral liquid had the highest clinical safety.

Supplementary 5 detailed the amount of each drug in a polyherbal preparation, and the complete species and drug name of the included SRs.

 Discussion

This study provides a broad review of the efficacy and safety of CHM in the treatment of acute infectious diseases. After a systematic search and screening, we included 46 systematic reviews, and meta-analysis of moderate-to-high-quality showed that CHM alone or in combination with Western medicine was effective in treating acute and emergent respiratory diseases such as COVID-19, H1N1, and SARS in terms of symptom improvement such as fever, cough and dyspnoea, without serious adverse events. When combined with Western medicine, CHM shows potential in improving certain outcomes, such as mortality, but the evidence is not yet sufficient. In addition, some studies showed that CHM combined with Western medicine can also improve some intermediate outcomes including white blood cell count, nucleic acid negativity conversion rate, lung CT improvement rate. The adjunct use of CHM may be accounted for treating children with acute infections such as HFMD, bacillary dysentery and mumps; however, safety should be closely monitored before and after the treatment.

In the treatment of COVID-19, several moderate-to-high quality systematic reviews and meta-analyses (Yang M. et al., 2020; Fan et al., 2020; Gao et al., 2020; Jin et al., 2020; Pang et al., 2020; Wang S. et al., 2020; Sun et al., 2020; Xiong et al., 2020; Zeng et al., 2020; Luo et al., 2021) showed that combination therapy had a good overall efficiency and nucleic acid negativity conversion rate and alleviated disease symptoms and that CHM may effectively control cytokine storms by inhibiting the excessive activation of immune cells and reducing inflammatory cytokines in relieving COVID-19 symptoms. According to the current overview, the most common drug in the SRs included in this study was Lianhua Qingwen Capsule, a proprietary CHM drug composed of 13 herbs, namely, the dry fruit of Forsythia suspensa (Thunb.) Vahl, the dry buds or with blooming flowers of Lonicera japonica Thunb., the dry caudex of Ephedra sinica Stapf, Ephedra intermedia Schrenk et C.A.Mey. or Ephedra equisetina Bge., the dry matured seeds of Prunus armeniaca L. var.ansu Maxim., Prunus sibirica L. or Prunus mandshurica (Maxim.) Koehne or Prunus armeniaca L., Gypsum Fibrosum, the dry roots of Isatis indigotica Fort., the dry roots of Dryopteris crassirhizoma Nakai., the dry aboveground part of Houttuynia cordata Thunb., the dry aboveground part of Pogostemon cablin (Blanco) Benth, the dry roots of Rheum palmatum L., the dry roots of Rhodiola crenulate (Hook. f. et Thoms.) H. Ohba, the fresh stem of Mentha haplocalyx Briq., and the dry roots and rhizomes of Glycorrhiza uralensis Fisch., Glycorrhiza inflata Bat. or Glycorrhiza glabra L. Its benefits for people infected by H1N1 virus and SARS-CoV-2 has been determined by randomised, large-sample, controlled clinical trials, and explained by its capacity of anti-inflammation and immunoregulation in pharmacological experiments (Duan et al., 2011; Huang et al., 2020; Hu et al., 2021). However, some important CHM interventions, for which no SRs have been published yet, probably due to the urgency of the fight against the epidemic, have been published as original studies, while drugs for which clinical studies have been conducted including Xuebijing Injection, Xuanfeibaidu Decoction, Qinfeipaidu Decoction, and Huashibaidu Decoction (Wang L. et al., 2020; Xiao et al., 2020; Hu et al., 2021). Substantial publications on prospective/retrospective cohort studies for these CHM prescriptions should be included in future updates of SRs on CHM for acute infections.

For other diseases, a moderate-quality systematic review found that CHM combined with Western medicine for epidemic parotitis shortened the time to fever reduction and improved the overall efficiency, with no significant differences in safety. The main modalities of TCM treatment for mumps include both external and internal application, but validation of the efficacy of these regimens is challenging when designing blinded clinical trials. To enhance and promote exploration of this aspect of the study, some objective outcomes can be selected to be measured as much as possible. Additionally, appropriate reporting guidelines can be selected, such as the CONSORT for Non-Pharmacologic Treatment Interventions (Boutron et al., 2017) and the CONSORT for Chinese Herbal Medicine Formulas (Cheng et al., 2017), to enhance the convenience and operability in conducting systematic reviews.

In addition, the systematic reviews included in this study showed that CHM injections improved the overall clinical effectiveness and severe conversion rate, reduced the time to fever and rash remission and the time for healing of oral ulcers, and shortened the total duration of illness in patients with HFMD. However, none of these SRs reported the occurrence of adverse reactions. HFMD is most prevalent in children, who are a vulnerable group, and there are challenges in conducting clinical studies for this population. Overall, the safety of CHM injections, particularly regarding the amounts used, continues to be of concern. When using CHM injections, one needs to determine whether they are worth using, and if so, their safety needs to be monitored closely.

To the best of our knowledge, this study is the first overview to analyse and evaluate CHM for acute infectious diseases. We systematically assessed 46 systematic reviews and meta-analyses to describe the status of CHM in the treatment of acute infectious diseases. However, the systematic reviews and meta-analyses of CHM alone or in combination with Western medicine for acute infectious diseases were generally plagued with several problems. First, many clinical trials and systematic reviews on Chinese medicine for acute infectious diseases have been published, but most of they are lacking rigorous design and strict quality control. Though time is pressed for fighting against public health emergencies, complying with relevant regulations and methodological consensuses such as “Best practice in research–overcoming common challenges in phytopharmacological research”, is necessary for conducting an ethical and high-quality studies. Theses quality-improving issues should be considered in the future research (Heinrich et al., 2020). Second, we only included studies published in Chinese and English, which may lead to publication bias. Last, we are not able to recommend any specific kind of TCM to be used in public health emergencies as the comparative effectiveness between CHM decoction and Chinese patent medicine is to be determined in future studies.

In general, the clinical applicability of existing SRs on the treatment of acute infectious diseases in CHM is not good, and it is suggested that future studies should focus on the staging and typing of diseases, the type of drugs used, and the singularity of interventions. Second, the reporting of outcomes of these systematic reviews is not standardized, and references can be made to the core set of outcomes in TCM for reporting, such as the COVID-19 core outcome set (COS) (Jin et al., 2020; Qiu et al., 2020). In addition, the low quality of reviews can be addressed by strictly following the standards of PRISMA 2020 (Page et al., 2021) and AMSTAR 2 (Shea et al., 2017) when producing future systematic reviews, thus improving the overall quality in the field. Last but not the least, the precise and appropriate use of botanical scientific nomenclature in CHM SRs is further required to avoid ambiguities and error (Rivera et al., 2014).

Although PHEs are a worldwide issue, China has achieved excellent results by applying CHM and Western medicine. For countries that use traditional medicine, there should be more benefits from applying the wisdom of traditional medicine, especially when there is no drug treatment for new and emergency infectious diseases. Moreover, the richness of traditional medicine may also be a source for developing new drugs for emergency infectious diseases, and it would be worthwhile to conduct in-depth research on drugs with a long history of application and clinical effectiveness. However, due to lack of rigorous regulation, the efficacy, safety and quality of some CHM products need to be proved by more high quality, large sample, unbiased randomized trials.

 Conclusion

Overall, CHM, both decoction and Chinese patent medicine, used alone or in combination with conventional medicine may offer potential benefits to relieving symptoms of people with acute respiratory infections. Full reporting of disease typing, staging, and severity, and intervention details is further required for a better evidence translation to the responses for PHE. Future CHM research should focus mainly on the specific aspects of respiratory infections such as its single use for mild infections, and the adjunct administration for sever infections, and individual CHM prescriptions for well-selected outcomes should be prioritized.

 Data Availability Statement

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.

 Authors Contributions

YC and XN conceived the study. XN, XL and YZ drafted the manuscript. XL validated the data and contributed to the methodology. XN designed the study and analyzed the data. YZ, HL, YLL, MR, YWL, YZ, ZK contributed to the literature search, data collection and quality assessment. YC, and XN interpreted the result from the perspective of Chinese medicine practitioner and clinical investigator. XN interpreted the data from the perspective of public health emergency. YC and XL interpreted the result from the perspective of methodology. All authors provided critical review to the manuscript and approved the submission.

 Funding

This study was supported by the internal funding from Guangdong Provincial Key Laboratory of Research on Emergency in TCM (No. 2017B030314176), the external funding from National Natural Science Foundation of China (No. 82104685) and Lanzhou City Talent Innovation and Entrepreneurship Project (Evaluation and Translation of Clinical Evidence of Dominant Diseases of Traditional Chinese Medicine in Gansu Province, No. 2016-RC-1). The funding body was not involved in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

 Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

 Publisher’s Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

We acknowledged the contribution from Jingyan Lin, Yuan Liu, Jiahui Lin, and Yidan Zhang, Ping Zeng, and Sichu Xiong from The Second Clinical School of Guangzhou University of Chinese Medicine for their assistance with the preliminary search and data sorting.

 Supplementary Material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2022.752978/full#supplementary-material

Abbreviations

AMSTAR 2, A MeaSurement Tool to Assess systematic Reviews 2; CBM, Chinese Biomedical Literature database; CD4, Cluster of differentiation 4; CHM, Chinese herbal medicine; COS, Core Outcome Set; CNKI, China National Knowledge Infrastructure; COVID-19, Coronavirus disease 2019; CONSORT, Consolidated Standards of Reporting Trials; H1N1, Influenza A H1N1 influenza; HFMD, Hand-foot-and-mouth disease; IL-6 level, Interleukin-6 level; IFN-α, Interferon-alpha; MD, Mean difference; OR, Odds ratio; PHE, Public health emergency; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RCT, Randomised controlled trial; RD, Rate difference, Risk difference; RoB, Risk of Bias; RR, Relative risk; SARS, Severe Acute Respiratory Syndrome; SMD, Standardized mean difference; SR, Systematic review; SUCRA, Surface under the cumulative ranking; TCM, Traditional Chinese Medicine.

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