Efficacy and safety of integrated traditional Chinese and Western medicine against COVID‐19: A systematic review and meta‐analysis

Abstract

Although plenty of clinical trials have confirmed the efficacy and safety of integrated traditional Chinese and Western medicine (ITCWM) against COVID‐19, the role of ITCWM remains controversial. So we conducted a systematic review and meta‐analysis of published studies in eight major databases that report the outcomes of interest in COVID‐19 patients receiving ITCWM. RevMan5.4 software was used for meta‐analysis, while the quality of RCTs was assessed by the Cochrane risk of bias tool and the retrospective studies were assessed by Newcastle–Ottawa Scale. Eventually, a total of 53 studies with 5425 COVID‐19 patients was identified. The meta‐analysis results showed that ITCWM was significantly better than western medicine treatment (WMT) alone in the percentage of cases changing to severe/critical [RR = 0.40, 95%CI (0.33, 0.49), p < .00001, I ² = 10%], overall clinical effectiveness [RR = 1.26, 95% CI (1.18, 1.35), p < .00001, I ² = 50%], time to defervescencer [MD = −1.45, 95% CI (−1.82, −1.07), p < .00001, I ² = 83%], disappearing time of cough [MD = −2.11, 95% CI (−2.98, −1.25), p < .00001, I ² = 93%], time of RT‐PCR negativity [MD = −3.35, 95% CI (−4.74, −1.95), p < .00001, I ² = 92%], length of hospital stay [MD = −4.05, 95% CI (−5.24, −2.85), p < .00001, I ² = 91%], improvement in CT scan [RR = 1.22, 95% CI (1.17, 1.28), p < .00001, I ² = 46%], TCM syndrome score [MD = −3.95, 95% CI (−5.07, −2.82), p < .00001, I ² = 92%], disappearance rate of fever [RR = 1.23, 95% CI (1.10, 1.38), p < .00001, I ² = 85%], disappearance rate of cough [RR = 1.43, 95% CI (1.25, 1.63), p < .00001, I ² = 60%], level of CRP [MD = −9.23, 95% CI (−10.94, −7.52), p < .00001, I ² = 97%], and WBC [MD = −9.23, 95% CI (−10.94, −7.52), p < .00001, I ² = 97%]. There is no significant difference between ITCWM and WMT in the adverse reaction rate [RR = 0.85, 95% CI(0.71, 1.03), p = .10, I ² = 25%]. Our results showed evidence of clinical efficacy and safety benefit in COVID‐19 patients treated with ITCWM. In spite of some limitations, the rapidly developing global pandemic warrants further high‐quality and multicenter clinical studies to confirm the contribution of ITCWM.

1. INTRODUCTION

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic, which was declared a Public Health Emergency of International Concern by the World Health Organization (WHO) in 2019, has resulted in high morbidity and mortality with new varieties spread rapidly (JHUCRC, 2021). As of May 1, 2022, it has infected more than 400 million individuals worldwide and caused more than 6 million deaths, making it the fastest and most prevalent infectious disease in a century (Shi Qf & Bj, 2021; Thye, J, Pusparajah, et al., 2021). Due to frequent genetic changes, virus immune evasion, and a variety of other reasons, effective antiviral medications are still scarce, so patients must rely on immunotherapy, symptomatic treatment, and even palliative care around the world (Zhang, S, Liu, et al., 2022).

Patients with advanced age and underlying conditions such as cardiovascular and cerebrovascular disorders, chronic lung diseases or diabetes may suffer a worse treatment outcome and long‐term prognosis once diagnosed with COVID‐19 (China, 2020). If the patient's condition worsens to critical, more problems and sequelae, such as sepsis, physical handicap, cognitive impairment, and additional health deterioration will occur (PrescottHC, 2018).

From the national outbreak in 2019 to the current epidemic in various provinces, China has gained rich experience in the prevention and treatment of COVID‐19 and the guidance of integrated traditional Chinese and Western medicine (ITCWM) is of great importance and significance (Wang, H, Hf, et al., 2021). The National Health Commission and the National Administration of TCM in China have continuously released the Novel Coronavirus Diagnosis and Treatment Guide, which has now been updated to version 8 (China, 2020). Various regions have formulated modified treatment guidance inclining TCM integration according to the local conditions, which is a unique methodology in TCM therapy based on the perspective of harmonization between the environment and the human body. Generally, TCM has fully demonstrated its advantages and characteristics in the treatment of COVID‐19 (China, 2020). Zhang Boli, a Renowned Academician in China, pointed out that TCM has changed from a participant role to an irreplaceable main force in the prevention and treatment of COVID‐19, which could shorten the length of hospital stay, significantly improve clinical symptoms such as fever, cough, fatigue, and pharynx, and be beneficial to human immunity (Li Ly et al., 2020). Up to now, a large number of study conclusions have confirmed that ITCWM does play an important role in improving clinical symptoms, and reducing the incidence of critical illness and mortality (Medicine, 2020). Moreover, the China Clinical Trial Registration Platform shows that there are still numerous clinical trials related to ITCWM in the prevention and treatment of COVID‐19. But due to the limitations of the small sample size and research method in some current published studies, there are still some controversies and doubts about the efficacy of ITCWM against COVID‐19. We, therefore, systematically reviewed and meta‐analyzed the results of relevant literature, so as to provide theoretical basis and therapeutic evidence for the treatment of COVID‐19 by ITCWM.

2. METHODS

This study was guided by the Preferred Reporting Items for Systematic Reviews and Meta‐analysis (PRISMA) statements checklist (Moher, 2009) and Cochrane Handbook for Systematic Reviews (Higgins, 2011). Besides, our study was registered on PROSPERO (No. CRD42022316295).

3. SEARCH STRATEGY

We searched (up to March 1, 2022) EMBASE, PubMed, CENTRAL, Web of Science, the China National Knowledge Infrastructure (CNKI), the Chinese Biomedical Literature Database (CBM), the Wanfang database, and the Chinese Scientific Journals Database (VIP database) without the limitation of language and regions. We also searched the Chinese Clinical Trial Registry (ChiCTR) and ClinicalTrials.gov to identify ongoing and completed trials. Studies included in previously published Systematic Review and Meta‐analysis were additional records in our comprehensive search. Depending on the search database, the following search terms (or Chinese database equivalent to Chinese) are used: “traditional Chinese medicine,” “traditional Chinese medicine decoction,” “Chinese patent medicine,” “Chinese medicine injection,” “Chinese medicine,” “integrated Chinese and Western medicine,” “combination of Chinese traditional and Western medicine,” “Lianhua Qingwen Capsule,” “Lianhua Qingwen Granule,” “Shufeng Jiedu capsules,” “Qingfei Paidu Decoction,” “Huashi Baidu Decoction,” “Maxing Xuanfei Jiedu Decoction,” “Xuebijing Injection,” “Reduning injection,” “Xiyanping injection,” “Jinye Baidu granule,” “New Coronavirus Pneumonia,” “COVID‐19,” “NCP,” “New Coronary Pneumonia,” “Coronavirus,” “corona virus disease 2019,” and “Random,” “retrospective study.”

4. INCLUSION AND EXCLUSION CRITERIA

All included studies must be controlled trials, including randomized controlled trial (RCT) and retrospective cohort studies. Studies with the following conditions will be excluded: (1) duplicate studies: there is duplication in study author, study center, study design, study data, and results; (2) observational and animal studies; (3) non‐controlled trials; (4) there are obvious errors in data incomplete or unable to extract; (5) the outcome do not match; (6) manipulative treatments, such as acupuncture were performed; and (7) full texts were not available.

5. PARTICIPANTS

All participants must comply with the diagnostic criteria of the Diagnosis and Treatment Guidelines of COVID‐19 (Eighth Edition) (China, 2020) or guidelines Published by the NHC PRC (NHC, 2020).

6. INTERVENTIONS

According to the diagnosis and treatment guidelines, all enrolled patients in the control group received conventional WMT (antiviral, antiinfective, supportive therapy, etc.), and the treatment group received WMT plus TCM. TCM is defined as Chinese herbal medicine, including single herbs, proprietary Chinese medicine, or a compound of several herbs irrespective of preparation (decoction, oral liquid, tablet, capsule, powder, or injection). The mode of drug delivery, dosage, and treatment course and regimen were not restricted. Studies that used acupuncture, moxibustion, acupressure, and other nonpharmaceutical TCM therapies as interventions were excluded.

7. OUTCOMES

The outcomes include at least one of the following: percentage of cases changing to severe/critical, overall clinical effectiveness, time to defervescencer, disappearing time of cough, time of RT‐PCR negativity, length of hospital stay, improvement in CT scan, TCM syndrome score, disappearance rate of fever, disappearance rate of cough, adverse reaction rate, and level of CRP and WBC.

8. STUDY SELECTION

Search results were imported to EndNote X9. Two researchers (D.X and Z.W) independently reviewed the literature and deleted duplicates. Articles were first screened based on the title and abstract, and the full texts were obtained in cases of uncertainty. When a disagreement occurs, the third researcher (F.X) joins the negotiation to make the final decision and record the reasons. The process of study selection was documented using a PRISMA flow diagram strictly.

9. DATA COLLECTION

Two researchers (D.X and Z.W) independently extracted data using a pre‐determined extraction table and resolved disagreements by consensus or consulting a third researcher (F.X). We extracted the following data from the included studies: (1) basic information (first author, publication date); (2) baseline characteristics (sample size, gender, age, etc.); (3) research scheme (design type, interventions details, duration, etc.); and (4) outcomes(percentage of cases changing to severe/critical, overall clinical effectiveness, time to defervescencer, disappearing time of cough, time of RT‐PCR negativity, length of hospital stay, improvement in CT scan, TCM syndrome score, disappearance rate of fever, disappearance rate of cough, adverse reaction rate, and level of CRP and WBC, etc.). The composition of formulation and patented drugs will be described as follows: English name (Chinese name, Latin name) to avoid confusion.

10. RISK OF BIAS

The risk of bias in RCTs was assessed according to the “Risk assessment of bias” tool in the Cochrane 5.1 manual consisting of seven domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, and other bias. While the quality of retrospective studies was evaluated by the Newcastle–Ottawa scale (NOS) consisting of three domains (selection of exposure, comparability, and assessment of outcome) (S, A., 2010).

11. DATA SYNTHESIS AND ANALYSES

We used RevMan5.4 software for the meta‐analysis of the data. For dichotomous data, relative ratio (RR) was used as the effect indicator. And for continuous data, mean difference (MD) was used to evaluate. The effect size of both variables was represented by a 95% confidence interval (95% CI). A heterogeneity test was performed on the included studies. If I ² < 50%, the fixed effect model was selected for meta‐analysis. Otherwise, random effects model was performed. Subgroup and sensitivity analyses were performed to explore the source of heterogeneity if substantial heterogeneity existed. We conducted a subgroup analysis of RCTs and non‐RCTs in this study. The existence of publication bias was judged by drawing a funnel plot and the Egger method to detect the symmetry.

12. RESULTS

12.1. Results of study selection

A total of 11,254 related literature were preliminarily obtained through database retrieval, and 53 literature were finally included for meta‐analysis after screening out duplicates and unqualified studies. The screening process is detailed in Figure 1.

FIGURE 1.

The process of studies and identification

12.2. Characteristics of included studies

A total of 53 peer‐reviewed articles (Ai Xy, Lp, et al., 2020; Chen Cw, Yf, et al., 2021; Chen Ling, Wu, et al., 2020; Chen Lz & Gl, 2020; Cheng Dz, Li, et al., 2020; Dai Gc, Ww, et al., 2020; Ding Xj, Dc, et al., 2020; Duan, Cj, et al., 2020; Fu Xx & Tan, 2020; He Qing, Xw, et al., 2021; He & Z., 2021; Hu et al., 2021; Ji & P, 2020; Jin, L, Zhao, et al., 2020; Li, A, Jk, et al., 2021; Li Qj, Wang, et al., 2021; Lian, S, Gl, et al., 2020; Liu, 2020; Liu, 2021; Liu Ap, Jw, et al., 2021; Liu Kf, Zp, et al., 2020; Luo, K, Yl, et al., 2022; Lv Rb & Li, 2020; Qian Yj, Wang, et al. 2020; Qin Yl, Zhou, et al., 2020; Qiu, Q, Dp, et al., 2020; Qu Xk, Ma Jing, et al., 2020; Shi Sf, Xiong, et al., 2021; Shi, Z, Ye, et al., 2020; Song Yy, Zhou, et al., 2020; Su Qw, Tao, et al., 2020; Sun Hm, Zhang, et al., 2020; Wang, C, Zheng, et al., 2021; Wang, G, Xy, et al., 2021; Wang Xl, Zhao, et al., 2020; Wang Yj, Yan, et al., 2020; Xia Wg, Cj, et al., 2020; Xiao, J, Ss, et al., 2020; Xiao Mz, 2020; Xiao, X, Wk, et al., 2021; Xin Sy et al., 2020; Xu, D, Sh, et al., 2020; Yang Mf, Huang, et al., 2020; Yao Kt, Li, et al., 2020; Yu, L, Sb, et al., 2020; Yu Xy, Ff, et al., 2020; Zeng, M, & Wang, 2020; Zhang Cy, Zhang, et al., 2020; Zhang Jy, Xj, et al., 2021; Zhang Xy et al., 2021; Zhang Yl, Xu, et al., 2020; Zhou et al., 2021) were included for qualitative and quantitative analysis, including 20 retrospective cohort study(RCS) and 33 RCTs, 41 single center studies and 12 multi‐center studies. Of the 5425 included patients, 2828 were in the experimental group and 2597 were in the control group. Basic characteristics are detailed in Table 1. The intervention measures in all experimental groups were ITCWM, and the components of all Chinese medicine used in the included studies are shown in Table 2.

TABLE 1.

Basic characteristics of included studies

Studies	Study design	Original place of patients	Numbers (T/C)	T intervention	C intervention	Course (d)	Outcomes
Cheng Dz et al. (2020)	Multicenter, RCS	Hubei	51/51	LQ + WMT	WMT	7	①②③④⑦⑨⑩
Lv Rb and Li (2020)	Multicenter, RCS	Hubei	63/38	LQ + WMT	WMT	10	①⑨⑩⑪
Yao Kt et al. (2020)	Multicenter, RCS	Hubei	21/21	LQ + WMT	WMT	N	③⑨⑩
Chen Cw et al. (2021)	RCT	Shenzhen	28/29	LQ + CT	WMT	N	①③④⑤⑪⑫
Yu et al. (2020)	RCT	Hubei	147/148	LQ + WMT	WMT	7	①②⑦⑪⑫⑬
Ding Xj et al. (2020)	RCT	Hubei	51/49	TCMD+WMT	WMT	10	①⑦⑨⑩⑪⑫
Shi et al. (2020)	RCS	Shanghai	49/18	TCMD+WMT	WMT	6	①⑥⑦
Xia Wg et al. (2020)	RCS	Hubei	34/18	TCMD+WMT	WMT	N	①③⑥⑦⑧⑨⑩⑪
Fu Xx and Tan (2020)	RCT	Guangzhou	37/36	TQG + WMT	WMT	15	①②⑪⑫⑬
Duan et al. (2020)	RCT	Hubei	82/41	JQG + WMT	WMT	5	①⑧⑨⑩⑪
Yang Mf et al. (2020)	Multicenter, RCT	Hubei，Shanxi	26/23	RM + WMT	WMT	7	①⑦⑪⑫⑭
Xiao et al. (2020)	RCT	Hubei	100/100	SJC + WMT	WMT	14	②③④⑦⑩⑪⑬
Qu Xk et al. (2020)	RCS	Anhui	40/40	SJC + WMT	WMT	10	③④⑦⑪⑫⑬
Wang Yl, Yp, et al. (2020)	RCT	Hubei	10/10	TCMD+WMT	WMT	7	⑦
Qiu et al. (2020)	RCT	Chongqing	25/25	TCMD+WMT	WMT	10	①③④⑦⑧
Sun Hm et al. (2020)	Multicenter, RCT	Hebei	32/25	LQG + WMT	WMT	14	①⑦⑨⑩
Hu et al. (2021)	Multicenter, RCT	Nine provinces	142/142	LQ + WMT	WMT	14	①②⑦⑪
Zhang Jy et al. (2021)	Multicenter, RCT	Beijing	71/147	JQG + WMT	WMT	3	①⑤⑥⑨⑩⑪
Luo Zh et al. (2022)	RCS	Hubei	26/26	TCMD+WMT	WMT	7	③④⑥⑦⑧⑨⑩⑫⑬
Liu Ap et al. (2021)	RCT	Hubei	15/15	TCMD+WMT	WMT	10	⑦⑧⑩⑪⑫
Li et al. (2021)	RCS	Hubei	50/46	JOL + WMT	WMT	15	④⑤⑨⑩
Wang, L, Bt, et al. (2021)	RCT	Hubei	47/22	TCMD+WMT	WMT	10	②⑫⑬
Liu (2021)	RCT	Hubei	25/25	TCMD+WMT	WMT	30	②⑪⑫⑬
He and Z. (2021)	RCT	Hubei	34/30	TCMD+WMT	WMT	7	⑦⑧⑪⑫
He Qing et al. (2021)	RCT	Hubei	36/36	TCMD+WMT	WMT	10	②⑧⑪⑫
Yu Xy et al. (2020)	RCS	Hubei	43/46	QPD + WMT	WMT	10–14	⑤⑥⑪⑫
Song Yy et al. (2020)	RCS	Chongqing	15/16	TCMD+WMT	WMT	7–14	⑥⑬
Shi et al. (2020)	Multicenter, RCT	Hubei、Jiangsu	51/51	YYG + WMT	WMT	14	②⑧⑪
Jin et al. (2020)	Multicenter, RCT	Sichuang	18/20	TCMD+WMT	WMT	N	①②⑦⑨⑩⑫⑬
Chen Lz and Gl (2020)	RCS	Hubei	115/115	TCMD+WMT	WMT	7–14	①②③④⑥⑦⑨⑩⑪⑫⑬
Yu Hy, Xx, et al. (2020)	RCS	Hubei	64/38	QPD + WMT	WMT	N	①②
			85/38	LQ + WMT	WMT	N	①②
			27/38	JBG + WMT	WMT	N	①②
Qian Yl et al. (2020)	RCT	Hubei	170/130	TCMD+WMT	WMT	N	③⑫⑬
Ji and P (2020)	RCT	Hubei	28/22	TCMD+WMT	WMT	10	①③⑨⑩
Chen Ling et al. (2020)	RCS	Hubei	34/34	SJC + WMT	WMT	7	②③④⑥⑦⑨⑩⑪⑫⑬
Liu (2020)	RCT	Hubei	42/42	TCMD+WMT	WMT	N	①②③⑥⑪
Zhang Yl et al. (2020)	RCT	Hubei	80/40	JL + WMT	WMT	10	⑨⑩⑪
Dai Gc et al. (2020)	RCS	Jiangsu	20/16	TCMD+WMT	WMT	7	②⑦⑧⑪
Ai Xy et al. (2020)	RCT	Guangzhou	55/43	TCMD + WMT	WMT	12	②⑥⑧⑭
Su Qw et al. (2020)	RCS	Hubei	75/75	TCMD+WMT	WMT	N	①③④⑥⑦⑫⑬
Lian et al. (2020)	RCS	Hubei	38/26	TCMD+WMT	WMT	N	①③⑧⑪
Wang, L, et al. (2021)	RCT	Hubei	70/70	QPD + WMT	WMT	10	②⑥⑦⑧⑪⑫ ⑬
Zeng et al. (2020)	RCT	Beijing	104/125	QPD + WMT	WMT	N	⑤⑥⑦
Li Qj et al. (2021)	RCT	Henan	38/38	LQ + WMT	WMT	10	⑨⑩
Xu, D, et al. (2020)	RCS	Hubei	26/26	LQ + WMT	WMT	7	③⑤⑥⑦⑪
			26/26	JBG + WMT	WMT	7	③⑤⑥⑦⑪
Xiao Mz (2020)	RCT	Hubei	58/63	LQ + WMT	WMT	14	①⑨⑩
Zhou et al. (2021)	Multicenter, RCT	Hubei	57/54	SHG + WMT	WMT	14	①②
Xin Sy et al. (2020)	RCS	Hubei	37/26	QPD + WMT	WMT	14	①
Qin Yl et al. (2020)	RCS	Chongqing	21/26	RDN + WMT	WMT	5–7	①⑤⑥⑫⑬
Liu Kf et al. (2020)	RCT	Guizhou	10/10	XBJ + WMT	WMT	3	⑪⑫⑬
Zhang Cy et al. (2020)	RCS	Hubei	22/22	XBJ + WMT	WMT	7	②⑦⑪
Chen Lz and Gl (2020)	RCT	Jiangxi	15/15	XBJ + WMT	WMT	14	②⑪⑫
Xu, D, et al. (2020)	Multicenter, RCT	Multicenter	77/80	RDN + WMT	WMT	14	①⑪
Zhang Xy et al. (2021)	Multicenter, RCT	Jiangxi	65/65	XYP + WMT		7–14	①③⑤

Abbreviations: ①, Percentage of cases changing to severe/critical; ②, Overall clinical effectiveness; ③, Time to defervescencer; ④, Disappearing time of cough; ⑤, Time of RT‐PCR negativity; ⑥, length of hospital stay; ⑦, Improvement in CT scan; ⑧, TCM syndrome score; ⑨, Recovery rate of fever; ⑩, Recovery rate of cough; ⑪, Adverse reaction rate; ⑫, CRP; ⑬, WBC,C, The Control Group; ITCWM, Integrated Traditional Chinese and Western Medicine; JBG, Jinye Baidu Granules; JL, Jinyinhua liquid; JOL, Jinbei Oral Liquid; JQG, Jinhua Qinggan Granules; LQ, Lianhua Qingwen Granules or Capsules; LQG, Lianhua Qingke Granules; N, Not clear; QPD, Qingfei Paidu Decoction; RCS, Retrospective cohort study; RDN, Reduning injection; RM, Reyanning Mixture; SHG, Shenhuang Granules; SJC, Shufeng Jiedu Capsule; T, The Treatment Group; TCMD, Traditional Chinese Medicine Decoction; TQG, Toujie Quwen Granules; WMT, Western medicine treatment; XBJ, Xuebijing Injection; XYP, Xiyanping injection; YYG, Yiqi Yangying Granules.

TABLE 2.

Components of TCM used in the treatment group

Studies	TCM (usage)	Components (Chinese name and Latin name were used in the bracket)
Cheng Dz et al. (2020)	Lianhua Qingwen granules (6 g/bag, Po, 1 bag/time, Tid)	Forsythia fruit (Lianqiao, Fructus Forsythiae Suspensae), honeysuckle bud and flower (Jinyinhua, Flos Lonicerae), ephedra (Mahuang, Herba Ephedrae), bitter apricot seed (Kuxingren, semen Armeniacae Amarum), gypsum (Shigao, gypsum Fibrosum), Indigowoad root (Banlangen, radix Isatidis), male fern rhizome (Mianma Guanzhong, Rhizoma Dryopteris Crassirhizomae), heartleaf houttuynia herb (Yuxingcao, Herba Houttuyniae), Cablin patchouli herb (Huoxiang, Herba Pogostemonis), rhubarb root and rhizome (Dahuang, radix et Rhizoma Rhei), rose‐boot (Hongjingtian, Herba Rhodiolae), menthol, and Liquoric root (Gancao, radix Glycyrrhizae).
Lv Rb and Li (2020)	Lianhua Qingwen granules (6 g/bag, Po,1 bag/time, Tid)	The same as the components of TCM used in Cheng Dz et al. (2020)
Yao Kt et al. (2020)	Lianhua Qingwen granules (6 g/bag, Po,1 bag/time, Tid)	The same as the components of TCM used in Cheng Dz et al. (2020)
Chen Cw et al. (2021)	Lianhua Qingwen granules (6 g/bag, Po,1 bag/time, Tid)	The same as the components of TCM used in Cheng Dz et al. (2020)
Yu et al. (2020)	Lianhua Qingwen granules (6 g/bag, Po, 1 bag/time, Tid)	The same as the components of TCM used in Cheng Dz et al. (2020)
Ding Xj et al. (2020)	Qingfei Touxie Fuzheng decoction (water decoction, Po, bid)	Ephedra (Mahuang, Herba Ephedrae) 6 g, gypsum (Shigao, gypsum Fibrosum) 20 g, bitter apricot seed (Kuxingren, semen Armeniacae Amarum) 10 g, honeysuckle bud and flower (Jinyinhua, Flos Lonicerae) 30 g, forsythia fruit (Lianqiao, Fructus Forsythiae Suspensae) 15 g, reed rhizome (Lugen, Rhizoma Phragmitis) 30 g, Coix seed (Yiyiren, semen Coicis) 30 g, body of sick silkworm (Jiangcan, Bombyx Batryticatus) 10 g, Circada Moulting (Chantui, Periostracum cicadae) 10 g, Giant knotweed rhizome (Huzhang, Rhizoma Polygoni Cuspidati) 15 g, turmeric (Jianghuang, Rhizoma Curcumae Longae) 10 g, white Peony root (Baishaoyao, radix Albus Paeoniae Lactiflorae) 10 g, Pseudostellaria root (Taizishen, Pseudostellariae radix) 20 g, and Liquoric root (Gancao, radix Glycyrrhizae) 15 g. If dampness is severe, Atractylodes rhizome (Cangzhu, Rhizoma Atractylodis) was added. If abdominal distention and diarrhea are obvious, Poria (Fuling, Scierotium Poriae Cocos) and Dioscorea root (Shanyao, Dioscoreae Rhizoma) were added. If high fever was identified, gypsum (Shigao, gypsum Fibrosum) and Thorowax root (Chaihu, radix Bupleuri) were added. If cough and phlegm were identified, Pinellia rhizome (Banxia, Rhizoma Pinelliae Tematae) and Tendrilleaf fritillary bulb (Chuanbeimu, Bulbus Fritillariae Cirrhosae) were added. If chest tightness was identifed, Snakegourd fruit (Gualou, Fructus Trichosanthis) was added.
Shi et al. (2020)	Chinese patent medicine or TCM decoction were given according to syndrome differentiation	Shufeng Jiedu capsules: Giant knotweed rhizome (Huzhang, Rhizoma Polygoni Cuspidati), forsythia fruit (Lianqiao, Fructus Forsythiae Suspensae), Indigowoad root (Banlangen, radix Isatidis), Thorowax root (Chaihu, radix Bupleuri), Atrina glass(Baijiangcao, Herba Patriniae), European verbena herb (Mabiancao, Herba Verbenae), reed rhizome (Lugen, Rhizoma Phragmitis), and Liquoric root (Gancao, radix Glycyrrhizae).Lianhua Qingwen granules; Xuanfei Zhisou mixture: Fineleaf schizonepeta herb (Jingjie, Herba Schizonepetae), Hogfennel root (Qianhu, radix Peucedani), root of the balloon flower (Jiegeng, Platycodi radix), Stemona root (Baibu, radix Stemonae), honey‐fried Tatarian Aster root (Ziwan, radix Asteris Tatarici), tangerine Peel (Chenpi, Pericarpium Citri Reticulatae), heartleaf houttuynia herb (Yuxingcao, Herba Houttuyniae), field mint (Bohe, Herba Menthae Haplocalycis), poppy capsule (Yingsuke, Pericarpium Papaveris), and Liquoric root (Gancao, radix Glycyrrhizae). Shuanghuanglian oral liquids: Honeysuckle bud and flower (Jinyinhua, Flos Lonicerae), Baical skullcap root (Huangqin, radix Scutellariae Baicalensis), and forsythia fruit (Lianqiao, Fructus Forsythiae Suspensae). Yupingfeng granules: Astragalus (Huangqi, radix Astragali Membranacei), white Atractylodes rhizome (Baizhu, Rhizoma Atractylodis Macrocephalae), and Ledebouriella root (Fangfeng, radix Ledebouriellae Divaricatae).
Xia Wg et al. (2020)	TCM were given according to syndrome differentiation	Damp‐toxin obstructing lung formula;toxin blocking lung formula;Ganlu Xiaodu pills;Mangxing Shigan decoction;Chailing Pingwei decoction;Haoqin Qingdan decoction;Huopu Xialing decoction;Lianhua Qingwen granules;Huoxiang Zhengqi liquids;Xuebijing injection;Shengmai injection;Shenfu injection
Fu Xx and Tan (2020)	Toujie Quwen granules (take it in hot water, bid)	Forsythia fruit (Lianqiao, Fructus Forsythiae Suspensae) 30 g, Appendiculate Cremastra Pseudobulb (Shancigu, Pseudobulbus Cremastrae seu Pleiones) 20 g, honeysuckle bud and flower (Jinyinhua, Flos Lonicerae) 15 g, Baical skullcap root (Huangqin, radix Scutellariae Baicalensis) 10 g, dyers Woad leaf (Daqingye, folium Isatidis) 10 g, Thorowax root (Chaihu, radix Bupleuri) 5 g, sweet wormwood (Qinghao, Artemisiae Apiaceae seu Annuae Herba) 10 g, Circada Moulting (Chantui, Periostracum cicadae) 10 g, Hogfennel root (Qianhu, radix Peucedani) 5 g, Tendrilleaf fritillary bulb (Chuanbeimu, Bulbus Fritillariae Cirrhosae) 10 g, Thunberbg fritillary bulb (Zhebeimu, Bulbus Fritillariae Thunbergii) 10 g, smoked plum (Wumei, Fructus Mume) 30 g, Ningpo figwort root (Xuanshen, radix Scrophulariae Ningpoensis) 10 g, Astragalus (Huangqi, radix Astragali Membranacei) 45 g, Poria (Fuling, Scierotium Poriae Cocos)30 g, and Pseudostellaria root (Taizishen, Pseudostellariae radix) 15 g.
Duan et al. (2020)	Jinhua Qinggan granule (5 g/bag, Po, 2 bag/time, Tid)	Honeysuckle bud and flower (Jinyinhua, Flos Lonicerae), gypsum (Shigao, gypsum Fibrosum), ephedra (Mahuang, Herba Ephedrae), bitter apricot seed (Kuxingren, semen Armeniacae Amarum), Baical skullcap root (Huangqin, radix Scutellariae Baicalensis), forsythia fruit (Lianqiao, Fructus Forsythiae Suspensae), Thunberbg fritillary bulb (Zhebeimu, Bulbus Fritillariae Thunbergii). Anemarrhena rhizome (Zhimu, Rhizoma Anemarrhenae Aspheloidis), great burdock achene (Niubangzi, Fructus Arctii), sweet wormwood (Qinghao, Artemisiae Apiaceae seu Annuae Herba), field mint (Bohe, Herba Menthae Haplocalycis), and Liquoric root (Gancao, radix Glycyrrhizae).
Yang Mf et al. (2020)	Reyanning mixture (100 ml/bottle, Po, 10–20 ml/time, bid‐Qid)	Mongolian dandelion herb (Pugongying, Herba Taraxaci), Giant knotweed rhizome (Huzhang, Rhizoma Polygoni Cuspidati), Atrina glass (Baijiangcao, Herba Patriniae), Barbated Skullcup herb (Banzhilian, Herba Scutellariae Barbatae), et al.
Xiao et al. (2020)	Shufeng Jiedu capsules (0.52 g/table, Po, 4 tablets/time, Tid)	Giant knotweed rhizome (Huzhang, Rhizoma Polygoni Cuspidati), forsythia fruit (Lianqiao, Fructus Forsythiae Suspensae), Indigowoad root (Banlangen, radix Isatidis), Thorowax root (Chaihu, radix Bupleuri), Atrina glass (Baijiangcao, Herba Patriniae), European verbena herb (Mabiancao, Herba Verbenae), reed rhizome (Lugen, Rhizoma Phragmitis), and Liquoric root (Gancao, radix Glycyrrhizae).
Qu Xk et al. (2020)	Shufeng Jiedu capsules (0.52 g/table, Po, 4 tablets/time, Tid)	The same as the components of TCM used in Xiao et al. (2020)
Wang Yl et al. (2020)	TCM were given according to syndrome differentiation	Modified Buzhong Yiqi decoction: Astragalus (Huangqi, radix Astragali Membranacei) 30 g, ginseng (Renshen, radix ginseng) 15 g, Liquoric root (Gancao, radix Glycyrrhizae) 15 g, white Atractylodes rhizome (Baizhu, Rhizoma Atractylodis Macrocephalae) 10 g, tangerine Peel (Chenpi, Pericarpium Citri Reticulatae) 6 g, Chinese Angelica root (Danggui, radix Angelicae Sinensis) 10 g, Chinese date (Dazao, Fructus Zizyphi Jujubae) 6, fresh ginger rhizome (Shengjiang, fresh Rhizoma Zingiberis) 9 slices, Thorowax root (Chaihu, radix Bupleuri) 12 g, and Largetrifoliolious bugbane rhizome (Shengma, Rhizoma Cimicifugae) 6 g. CHM 2: Coptis rhizome (Huanglian, Rhizoma Coptidis) 20 g, rhubarb root and rhizome (Dahuang, radix et Rhizoma Rhei) 10 g, Baical skullcap root (Huangqin, radix Scutellariae Baicalensis) 10 g, Atractylodes rhizome (Cangzhu, Rhizoma Atractylodis) 10 g, honey‐fried Tatarian Aster root (Ziwan, radix Asteris Tatarici) 10 g, heartleaf houttuynia herb (Yuxingcao, Herba Houttuyniae) 10 g, Mongolian dandelion herb (Pugongying, Herba Taraxaci) 10 g, Giant knotweed rhizome (Huzhang, Rhizoma Polygoni Cuspidati)10 g, and Astragalus (Huangqi, radix Astragali Membranacei) 20 g. CHM 3: Pueraria (Gegen, radix Puerariae) 15 g, Dahurian Angelica root (Baizhi, radix Angelicae Dahuricae) 12 g, Magnolia flower (Xinyi, Flos Magnoliae Lilliflorae) 9 g, Indigowoad root (Banlangen, radix Isatidis) 30 g, forsythia fruit (Lianqiao, Fructus Forsythiae Suspensae) 15 g, and Thunberbg fritillary bulb (Zhebeimu, Bulbus Fritillariae Thunbergii) 12 g.
Qiu et al. (2020)	Maxing Xuanfei Jiedu decoction (water decoction, Po, bid)	Ephedra (Mahuang, Herba Ephedrae) 9 g, bitter apricot seed (Kuxingren, semen Armeniacae Amarum) 12 g, gypsum (Shigao, gypsum Fibrosum) 15‐30 g, Thunberbg fritillary bulb (Zhebeimu, Bulbus Fritillariae Thunbergii) 12 g, Circada Moulting (Chantui, Periostracum cicadae) 10 g, body of sick silkworm (Jiangcan, Bombyx Batryticatus) 15 g, turmeric (Jianghuang, Rhizoma Curcumae Longae) 12 g, root of the balloon flower (Jiegeng, Platycodi radix) 12 g, Orange fruit (Zhike, Fructus Aurantii) 12 g, fruit of Caoguo (Caoguo, Fructus Tsaoko) 9 g, and Cardamon fruit (Baidoukou, Fructus Ammomi Rotundus) 12 g.
Sun Hm et al. (2020)	Lianhua Qingke granule (1 bag/time, Po, Tid)	EEphedra (Mahuang, Herba Ephedrae), mulberry root bark (Sangbaipi, Mori Radicis cortex), bitter apricot seed (Kuxingren, semen Armeniacae Amarum), forsythia fruit (Lianqiao, Fructus Forsythiae Suspensae), honeysuckle bud and flower (Jinyinhua, Flos Lonicerae), rhubarb root and rhizome (Dahuang, radix et Rhizoma Rhei), et al.
Hu et al. (2021)	Lianhua Qingwen capsules (4 capsules/time, Po, Tid)	The same as the components of TCM used in Cheng Dz et al. (2020)
Zhang Jy et al. (2021)	Jinhua Qinggan granule (5 g/bag, Po, 2 bag/time, Tid)	The same as the components of TCM used in Duan et al. (2020)
Luo Zh et al. (2022)	Sanxiaoyin decoction (water decoction, Po, bid)	Betel nut (Binglang, Areca catechu) 10 g, Tsaoko Amomum fruit (Caoguo, Amomum) 10 g, Scutellaria baicalensis georgi (Huangqin, Scutellaria baicalensis) 10 g, Angelica dahurica (Baishao, Radix paeoniae alba) 10 g, Anemarrhena rhizome (Zhimu, Rhizoma Anemarrhenae Aspheloidis) 10 g, Liquoric root (Gancao, radix Glycyrrhizae) 10 g, Rhubarb root and rhizome (Dahuang, radix et Rhizoma Rhei) 10 g, Circada Moulting (Chantui, Periostracum cicadae) 10 g, Stiff silkworm (Jiangchan, bombyx batryticatus) 10 g, Microcos paniculata (Buzhaye, Microcos folium) 10 g, Commen Bomhax flower (Mumianhua, Bombax ceiba Linn) 10 g, Common Achyranthes herb (Tuniuxi, Achyranthes aspera L) 10 g, Syconium Fici Caricae (Wuhuaguo, Ficus caricaLinn) 10 g.
Liu Ap et al. (2021)	Sangju drink (water decoction, Po, bid)	Mulberry leaf (Sangye, folium mori) 20 g, chrysanthemum (Juhua, Dendranthema Morifolium) 6 g, Bitter apricot seed (Kuxingren, semen Armeniacae Amarum) 20 g, Honeysuckle bud and flower (Jinyinhua, Flos Lonicerae) 15 g, forsythia fruit (Lianqiao, Fructus Forsythiae Suspensae) 15 g, Platycodonis radix (Jiegeng, Platycodon grandiflorum)10 g, Anemarrhena rhizome (Zhimu, Rhizoma Anemarrhenae Aspheloidis) 6 g, Thunberbg fritillary bulb (Beimu, Bulbus Fritillariae Thunbergii)15 g, Field mint (Bohe, Herba Menthae Haplocalycis) 6 g, and Liquoric root (Gancao, radix Glycyrrhizae) 6 g, Reed rhizome (Lugen, Rhizoma Phragmitis)10 g, Jobstears seed (Yiyiren, Semen coicis) 10 g, et al.
Li et al. (2021)	Jinbei oral liquid (4 tablets [40 ml]/time, Tid)	Astragalus (Huangqi, radix Astragali Membranacei), Liquoric root (Gancao, radix Glycyrrhizae), Pinellia rhizome (Banxia, Rhizoma Pinelliae Tematae), Chinese Angelica root (Danggui, radix Angelicae Sinensis), forsythia fruit (Lianqiao, Fructus Forsythiae Suspensae), honeysuckle bud and flower (Jinyinhua, Flos Lonicerae), Tendrilleaf fritillary bulb (Chuanbeimu, Bulbus Fritillariae Cirrhosae), et al.
Wang, L, et al. (2021)	Feipi Qixu Decpction (water decoction, Po, bid)	Pinellia rhizome (Banxia, Rhizoma Pinelliae Tematae) 9 g, Astragalus (Huangqi, radix Astragali Membranacei) 30 g, Poria (Fuling, Scierotium Poriae Cocos) 15 g, Tangerine Peel (Chenpi, Pericarpium Citri Reticulatae) 10 g, Herba Agastaches (Huoxiang, Agastache rugosa) 10 g.
Liu (2021)	Huashi Baidu decoction (water decoction, Po, Qd ~ bid)	Gypsum (Shigao, gypsum Fibrosum) 15 g, ephedra (Mahuang, Herba Ephedrae) 6 g, bitter apricot seed (Kuxingren, semen Armeniacae Amarum) 9 g, Liquoric root (Gancao, radix Glycyrrhizae) 3 g, Herba Agastaches (Huoxiang, Agastache rugosa) 10 g, Pinellia rhizome (Banxia, Rhizoma Pinelliae Tematae) 9 g, Poria (Fuling, Scierotium Poriae Cocos) 15 g, Peony root (Cishaoyao, radix Albus Paeoniae Lactiflorae) 10 g, Tsaoko Amomum fruit (Caoguo, Amomum) 10 g, Rhubarb root and rhizome (Dahuang, radix et Rhizoma Rhei) 5 g, Magnolia‐bark (Houpu, Magnolia officinalis) 10 g, Rhizoma Atractylodis (Cangshu, Atractylodis Rhizoma) 15 g, Pepperweed seed (Tinglizi, Semen Lepidii) 10 g.
He and Z. (2021)	Shengmai san (water decoction, Po, bid)	Ginseng (Renshen, radix ginseng), dwarf lilyturf tuber (Maidong, Ophiopogonis radix), Chinese Magnolcavine fruit (Wuweizi, Schisandrae Chinensis Fructus)
He Qing et al. (2021)	Buzhong Yiqi decoction (water decoction, Po, bid)	Astragalus (Huangqi, radix Astragali Membranacei) 10 g, ginseng (Renshen, radix ginseng) 3 g, Liquoric root (Gancao, radix Glycyrrhizae) 5 g, white Atractylodes rhizome (Baizhu, Rhizoma Atractylodis Macrocephalae) 3 g, tangerine Peel (Chenpi, Pericarpium Citri Reticulatae) 3 g, Chinese Angelica root (Danggui, radix Angelicae Sinensis) 3 g, Thorowax root (Chaihu, radix Bupleuri) 3 g, Largetrifoliolious bugbane rhizome (Shengma, Rhizoma Cimicifugae) 3 g.
Yu Xy et al. (2020)	Qingfei Paidu decoction (water decoction, Po, bid)	Ephedra (Mahuang, Herba Ephedrae) 9 g, gypsum (Shigao, gypsum Fibrosum) 15 ~ 30 g, bitter apricot seed (Kuxingren, semen Armeniacae Amarum) 9 g, Liquoric root (Gancao, radix Glycyrrhizae) 6 g, Pinellia rhizome (Banxia, Rhizoma Pinelliae Tematae) 9 g, Poria (Fuling, Scierotium Poriae Cocos) 9 g, horowax root (Chaihu, radix Bupleuri) 16 g, Scutellaria baicalensis georgi (Huangqin, Scutellaria baicalensis) 6 g, Dioscorea root (Shanyao, Dioscoreae Rhizoma)12 g, Tangerine Peel (Chenpi, Pericarpium Citri Reticulatae) 6 g, Herba Agastaches (Huoxiang, Agastache rugosa) 9 g, Fresh ginger rhizome (Shengjiang, fresh Rhizoma Zingiberis) 9 g, White Atractylodes rhizome (Baizhu, Rhizoma Atractylodis Macrocephalae) 9 g, Honey‐fried Tatarian Aster root (Ziwan, radix Asteris Tatarici) 9 g, Cassia twig (Guizhi, Ramulus Cinnamomi), Alisma Orientale (Zexie, Alismatis Rhizoma) 9 g, Common coltsfoot flower (Kuandonghua, Flos Farfarae) 9 g, Blackberrylily rhizome (Shegan, Belamcandae Rhizoma) 9 g, Manchurian wildginger (xixin, Asari radix et Rhizoma) 6 g, Bitter Orange (Zhishi, Citrus X aurantium) 6 g.
Song Yy et al. (2020)	TCM were given according to syndrome differentiation	Prescription no. 1, Prescription no. 2, Prescription no. 3.
Shi et al. (2020)	Yiqi Yangyin granule (water decoction, Po, bid)	Liquoric root (Gancao, radix Glycyrrhizae), Poria (Fuling, Scierotium Poriae Cocos), dwarf lilyturf tuber (Maidong, Ophiopogonis radix), white Atractylodes rhizome (Baizhu, Rhizoma Atractylodis Macrocephalae), tangerine Peel (Chenpi, Pericarpium Citri Reticulatae), Tangshen (Dangshen, Codonopsis Radix), Lili (Baihe, Lilium brownii), cooked grist (Maiya, Fructus hordei germinatus), Chinese wolfberry root‐bark (Digupi, Lycii cortex).
Jin et al. (2020)	(from Day 1 to Day 3 of hospitalization) compound Yinchai granules or Qingqiao Jiedu granules; (from day 4 to day 21 of hospitalization) TCM were given according to syndrome differentiation	Compound Yinchai granules: Honeysuckle stem (Rendongteng, Lonmicera japonica Thunb), Thorowax root (Chaihu, radix Bupleuri), field mint (Bohe, Herba Menthae Haplocalycis), Herba Agastaches (Huoxiang, Agastache rugosa), Fineleaf Schizonepeta herb (Jingjie, Herba Schizonepetae), et al. Qingqiao Jiedu granules: Honeysuckle stem (Rendongteng, Lonmicera japonica Thunb), forsythia fruit (Lianqiao, Fructus Forsythiae Suspensae), Pueraria (Gegen, radix Puerariae), sweet wormwood (Qinghao, Artemisiae Apiaceae Seu Annuae Herba), Thorowax root (Chaihu, radix Bupleuri), Yunnan Manyleaf Paris rhizome (Chonglou, Paridis Rhizoma), Indigowoad root (Banlangen, radix Isatidis), Blackberrylily rhizome (Shegan, Belamcandae Rhizoma), Mongolian dandelion herb (Pugongying, Taraxaci Herba), Indigowoad leaf (Daqingye, Isatidis folium), et al.
Chen Lz and Gl (2020)	Ganlu Xiaodu Dan (water decoction, Po, Tid)	Talc (Huashi, talcum), 45 g, Capillary wormwood herb (Yinchen, Artemisiae Scopariae Herba) 30 g, Baical skullcap root (Huangqin, radix Scutellariae Baicalensis) 30 g, Acorus Tatarinowii (Shichangpu, Acori Tatarinowii Rhizoma) 18 g, Blackberrylily rhizome (Shegan, Belamcandae Rhizoma) 12 g, Forsythia fruit (Lianqiao, Fructus Forsythiae Suspensae) 12 g, Fritillary bulb (Chuanbeimu, Bulbus Fritillariae Cirrhosae) 15 g, Liquoric root (Gancao, radix Glycyrrhizae) 10 g, Common yam rhizome (Shanyao, Dioscoreae Rhizoma) 30 g.
Yu Hy et al. (2020)	Qingfei Paidu decoction (water decoction, Po, bid)	The same as the components of TCM used in Yu Xy et al. (2020)
	Lianhua Qingwen capsules(4 capsules/time, Po, Tid)	The same as the components of TCM used in Cheng Dz et al. (2020)
	Jinye Baidu granule (10 g/bag, Po, 1 bag/time, Tid)	Mongolian dandelion herb (Pugongying, Taraxaci Herba), honeysuckle bud and flower (Jinyinhua, Flos Lonicerae), Indigowoad leaf (Daqingye, Isatidis folium), heartleaf Houttuynia herb (Yuxincao, Houttuyniae Herba), et al.
Qian Yj et al. (2020)	TCM (water decoction, Po, bid)	Ginseng (Renshen, radix ginseng) 30 g, Fresh ginger rhizome (Shengjiang, fresh Rhizoma Zingiberis) 45 g, Atractylodes rhizome (Cangzhu, Rhizoma Atractylodis) 20 g, Ephedra (Mahuang, Herba Ephedrae) 10 g, Bitter apricot seed (Kuxingren, semen Armeniacae Amarum) 15 g, Poria (Fuling, Scierotium Poriae Cocos) 50 g, Cassia twig (Guizhi, Ramulus Cinnamomi) 40 g, Pinellia rhizome (Banxia, Rhizoma Pinelliae Tematae) 40 g, Chinese Magnolcavine fruit (Wuweizi, Schisandrae Chinensis Fructus) 20 g, red paeony root (Cishao, Paeoniae radix Rubra) 40 g, Alisma Orientale (Zexie, Alismatis Rhizoma) 30 g, Tsaoko Amomum fruit (Caoguo, Amomum) 20 g, Alisma Orientale (Zexie, Alismatis Rhizoma) 30 g, et al.
Ji and P (2020)	COVID‐19 decoction (water decoction, Po, bid)	Betel nut (Binglang, Areca catechu) 6 g, Tsaoko Amomum fruit (Caoguo, Amomum) 10 g, Ephedra (Mahuang, Herba Ephedrae), bitter apricot seed (Kuxingren, semen Armeniacae Amarum), great burdock achene (Niubangzi, Fructus Arctii) 9 g, Root of the balloon flower (Jiegeng, Platycodi radix) 10 g, Scutellaria baicalensis georgi (Huangqin, Scutellaria baicalensis) 6 g, Forsythia fruit (Lianqiao, Fructus Forsythiae Suspensae) 9 g, Atractylodis (Cangshu, Atractylodis Rhizoma) 10 g, Liquoric root (Gancao, radix Glycyrrhizae) 6 g, Circada Moulting (Chantui, Periostracum cicadae) 9 g, Atractylodes rhizome (Cangzhu, Rhizoma Atractylodis) 10 g
Chen Ling et al. (2020)	Shufeng Jiedu capsules	The same as the components of TCM used in Xiao et al. (2020)
Liu (2020)	TCM were given according to syndrome differentiation (water decoction, Po, bid)	Pneumonia no.1 ~ 5 formula given according to syndrome differentiation
Zhang Yl et al. (2020)	Honeysuckle oral liquid (20 mg/branch, Po, 3 branchs/time, Tid)	Extracts of honeysuckle bud and flower (Jinyinhua, Flos Lonicerae)
Dai Gc et al. (2020)	Yinqiao SAN combined with Sanren soup (water decoction, Po, bid)	Mongolian dandelion herb (Pugongying, Taraxaci Herba) 30 g, Reed rhizome (Lugen, Rhizoma Phragmitis) 30 g, Ma ‐ yuen Jobstears seed (Yiyiren, Coicis semen) 30 g, Herba Agastaches (Huoxiang, Agastache rugosa) 10 g, Bitter apricot seed (Kuxingren, semen Armeniacae Amarum) 10 g, forsythia fruit (Lianqiao, Fructus Forsythiae Suspensae) 15 g, honeysuckle bud and flower (Jinyinhua, Flos Lonicerae) 15 g, Baical skullcap root (Huangqin, radix Scutellariae Baicalensis) 10 g, Thorowax root (Chaihu, radix Bupleuri) 10 g, Platycodonis radix (Jiegeng, Platycodon grandiflorum) 10 g.
Ai Xy et al. (2020)	Pneumonia no.1 formula (water decoction, Po, bid)	Artemisia annua L. (Qinghao; Artemisiae annuae herba)10 g, Astragalus mongholicusBunge (Huangqi; Astragali radix) 45 g, Cremastra appendiculata (D. Don) Makino (Shancigu, Cremastrae pseudobulbus pleiones pseudobulbus) 20 g, forsythia fruit (Lianqiao, Fructus Forsythiae Suspensae) 30 g, Circada Moulting (Chantui, Periostracum cicadae) 10 g, Pseudostellaria root (Taizishen, Pseudostellariae radix) 15 g. Tendrilleaf fritillary bulb (Chuanbeimu, Bulbus Fritillariae Cirrhosae) 10 g, Thunberbg fritillary bulb (Zhebeimu, Bulbus Fritillariae Thunbergii) 10 g, Ningpo figwort root (Xuanshen, radix Scrophulariae Ningpoensis) 15 g, Honeysuckle bud and flower (Jinyinhua, Flos Lonicerae) 15 g, ndigowoad root (Banlangen, radix Isatidis) 10 g, Poria (Fuling, Scierotium Poriae Cocos) 30 g.
Su Qw et al. (2020)	TCM were given according to syndrome differentiation (water decoction, Po, bid)	Pneumonia no.1 formula(Yinqiao SAN combined with Sangju yin): Fagopyri Dibotryis Rhizoma (Jinqiaomai, Fagopyrum dibotrys) 30 g, Forsythia fruit (Lianqiao, Fructus Forsythiae Suspensae) 15 g, honeysuckle bud and flower (Jinyinhua, Flos Lonicerae) 30 g, Great burdock achene (Niubangzi, Fructus Arctii) 10 g, Mulberry leaf (Sangye, foliummori) 10 g, chrysanthemum (Juhua, Dendranthema Morifolium) 30 g, Balloon flower (Jiegeng, Platycodi radix) 10 g, Indigowoad root (Banlangen, radix Isatidis) 30 g, Liquoric root (Gancao, radix Glycyrrhizae) 6 g, Fineleaf Schizonepeta herb (Jingjie, Schizonepetae Herba) 10 g. Pneumonia no.2 formula(Xuanmai Ganjie decoction combined with Xiaoxianxiong decoction): Ningpo figwort root (Xuanshen, radix Scrophulariae Ningpoensis) 30 g, Balloon flower (Jiegeng, Platycodi radix) 10 g, Indigowoad root (Banlangen, radix Isatidis) 30 g, Liquoric root (Gancao, radix Glycyrrhizae) 10 g, Dwarf lilyturf tuber (Maidong, Ophiopogonis radix) 15 g, Pinellia rhizome (Banxia, Rhizoma Pinelliae Tematae) 10 g, Coptis Root, Chinese goldthread (Huanglian, Coptidis Rhizoma) 10 g. Pneumonia no.3 formula(Shengmai san combined with Qianjin WeijingDecoction): Milkvetch root (Huangqi, Astragali radix) 30 g, American genseng (Xiyangshen, Panacis Quinquefolii radix) 6 g, Coastal Glehnia root (Shashen, Glehniae radix) 15 g, Ningpo figwort root (Xuanshen, radix Scrophulariae Ningpoensis) 30 g, Reed rhizome (Lugen, Rhizoma Phragmitis) 30 g, Ma ‐ yuen Jobstears seed (Yiyiren, Coicis semen) 30 g, Dwarf lilyturf tuber (Maidong, Ophiopogonis radix) 15 g, Peach seed (Taoren, Persicae semen) 6 g.
Lian et al. (2020)	TCM were given according to syndrome differentiation (water decoction, Po, bid)	—
Wang, L, et al. (2021)	Qingfei Paidu decoction (water decoction, Po, bid)	The same as the components of TCM used in Yu Xy et al. (2020)
Zeng et al. (2020)	Qingfei Paidu decoction (water decoction, Po, bid)	The same as the components of TCM used in Yu Xy et al. (2020)
Li Qj et al. (2021)	Lianhua Qingwen granules (6 g/bag, Po, 1 bag/time, Tid)	The same as the components of TCM used in Cheng Dz et al. (2020)
Xu, D, et al. (2020)	Lianhua Qingwen capsules (4 capsules/time, Po, Tid)	The same as the components of TCM used in Cheng Dz et al. (2020)
	Jinye Baidu granule (10 g/bag, Po, 1 bag/time, Tid)	The same as the components of TCM used in Yu Hy et al. (2020)
Xiao Mz (2020)	Lianhua Qingwen capsules (4 capsules/time, Po, Tid)	The same as the components of TCM used in Cheng Dz et al. (2020)
Zhou et al. (2021)	Shenhuang granule	Panax ginseng C. A. Mey (Renshen) root 50 g, Rheum palmatum L. stem (Dahuang) 40 g, Sargentodoxa cuneata stem (Hongteng) 30 g, Taraxacum mongolicum whole plant (Pugongying) 30 g, Aconiti Lateralis radix Praeparata stem (Fuzi) 30 g, Whitmania pigra Whitman (Shuizhi) 6 g. after a series of extraction and manufacturing processes, the final product is a concentrated granule which is 1:5 of the raw herbs. The granules were packaged into two sachets before serving. The SHG was provided and manufactured by Beijing Tcmages Pharma‐ceutical Co., Ltd. The product was approved by the National Medical Product Administration (China) (approval number: Jing 20180032).
Xin Sy et al. (2020)	Qingfei Paidu decoction (water decoction, Po, bid)	The same as the components of TCM used in Yu Xy et al. (2020)
Qin Yl et al. (2020)	Reduning injection (10 ml/tablet, 20 ml/time, Ivd, Qd)	Extracts of Artemisia annua, Lonicera japonica Thunb, and Gardenia jasminoides Ellis.
Liu Kf et al. (2020)	Xuebijing injection (50 ml/time, Ivd, bid)	Safflower flower (Honghua, Flos Carthami Tinctorii), red Peony root (Chishao, radix Rubrus Paeoniae Lactiflorae), Szechuan Lovage root (chuanxiong, Rhizoma Ligustici chuanxiong), salvia root (Danshen, radix Salviae Miltiorrhizae), and Chinese Angelica root (Danggui, radix Angelicae Sinensis).
Zhang Cy et al. (2020)	Xuebijing injection (50 mL/time, Ivd, bid)	The same as the components of TCM used in Liu (2020)
Chen Lz and Gl (2020)	Xuebijing injection (50 ml/time, Ivd, bid)	The same as the components of TCM used in Liu (2020)
Xu, D, et al. (2020)	Reduning injection (10 ml/tablet, 20 ml/time, Ivd, Qd)	The same as the components of TCM used in Qin Yl et al. (2020))
Zhang Xy et al. (2021)	Xiyanping injection (250 ml/time, Ivd, Qd)	Extracts of common Andrographis herb (Chuanxinlian, Andrographis Herba)

12.3. Risk of bias

The bias risk evaluation of 33 RCTs is shown in Figure 2, among which seven studies have relatively high bias risk. While the bias risk evaluation of 20 RSs is listed in Table 3, with NOS scores ranging from 7 to 8. Bias risk assessment results of included retrospective cohort study are shown in Table 3.

FIGURE 2.

Bias risk assessment results of included RCT

TABLE 3.

Bias risk assessment results of included retrospective studies

Studies	Score								Total score
	①	②	③	④	⑤	⑥	⑦	⑧
Cheng Dz et al. (2020)	1	1	1	1	2	1	0	1	8
Lv Rb and Li (2020)	1	1	1	1	1	1	0	1	7
Yao Kt et al. (2020)	1	1	1	1	2	1	0	1	8
Shi et al. (2020)	1	1	1	1	1	1	0	1	7
Xia Wg et al. (2020)	1	1	1	1	1	1	1	1	8
Qu Xk et al. (2020)	1	1	1	1	1	1	0	1	7
Luo Zh (2021)	1	1	1	1	2	1	0	1	8
Li et al. (2021)	1	1	1	1	2	1	0	1	8
Yu Xy et al. (2020)	1	1	1	1	1	1	0	1	7
Song Yy et al. (2020)	1	1	1	1	1	1	0	1	7
Chen, Zq, et al. (2020)	1	1	1	1	2	1	0	1	8
Yu Hy et al. (2020)	1	1	1	1	1	1	0	1	7
Chen Ling et al. (2020)	1	1	1	1	2	1	0	1	8
Dai Gc et al. (2020)	1	1	1	1	2	1	0	1	8
Su Qw et al. (2020)	1	1	1	1	2	1	0	1	8
Lian et al. (2020)	1	1	1	1	2	1	0	1	8
Xu, D, et al. (2020)	1	1	1	1	2	1	0	1	8
Xin Sy et al. (2020)	1	1	1	1	1	1	0	1	7
Qin Yl et al. (2020)	1	1	1	1	1	1	0	1	7
Zeng et al. (2020)	1	1	1	1	2	1	0	1	8

Note: ①, Representativeness of the exposed group; ②, Representativeness of the non‐exposed group; ③, Identification of exposure factors; ④, Confirmation of no outcome indicators to be observed at the beginning of the study; ⑤, Comparability of the exposed and unexposed groups was considered in the design and statistical analysis; ⑥, Evaluation of outcome indicators; ⑦, Sufficient follow‐up time; ⑧, Completeness of follow‐up between the exposed and unexposed groups.

13. OUTCOMES

13.1. Percentage of cases changing to severe/critical

A total of 29 studies (Chen Cw et al., 2021; Chen Ling et al., 2020; Cheng Dz et al., 2020; Ding Xj et al., 2020; Duan et al., 2020; Fu Xx & Tan, 2020; Hu et al., 2021; Ji & P, 2020; Jin et al., 2020; Lian et al., 2020; Liu, 2020; Lv Rb & Li, 2020; Qin Yl et al., 2020; Qiu et al., 2020; Shi et al., 2020; Su Qw et al., 2020; Sun Hm et al., 2020; Xia Wg et al., 2020; Xiao et al., 2021; Xiao Mz, 2020; Xin Sy et al., 2020; Yang Mf et al., 2020; Yu et al., 2020; Yu Hy et al., 2020; Zhang Jy et al., 2021; Zhang Xy et al., 2021; Zhou et al., 2021) reported the percentage of cases changing to severe/critical in COVID‐19, among which Yu Hy et al. (2020) published three groups of data (WMT group, WMT group+QPD group, WMT group + LQ group, and WMT group + JBG group). There was no significant heterogeneity among the studies (I ² = 10%, p = .31), so a fixed‐effect model was used for meta‐analysis. The results (Figure 3) showed that ITCWM could significantly improve the percentage of cases changing to severe/critical in COVID‐19 patients compared with WMT alone [RR = 0.40, 95%CI (0.33, 0.49), p < .00001]. And the RCT subgroup analysis showed the same results [RR = 0.49, 95% CI (0.39, 0.63), p < 0.00001].

FIGURE 3.

Percentage of cases changing to severe or critical

13.2. Overall clinical effectiveness

Twenty‐three studies (Ai Xy et al., 2020; Chen et al., 2020; Chen Ling et al., 2020; Chen Lz & Gl, 2020; Cheng Dz et al., 2020; Dai Gc et al., 2020; Fu Xx & Tan, 2020; He Qing et al., 2021; Hu et al., 2021; Jin et al., 2020; Liu, 2020; Liu, 2021; Shi Sf et al., 2021; Wang, G, et al., 2021; Wang, L, et al., 2021; Xiao et al., 2020; Yang Mf et al., 2020; Yu et al., 2020; Yu Hy et al., 2020; Zhang Cy et al., 2020; Zhou et al., 2021) evaluated the overall clinical effectiveness in the ITCWM and WMT group, among which Yu Xy et al. (2020) published the same three sets of data as before. The meta‐analysis revealed a significantly increasing improvement in the overall clinical effectiveness in the ITCWM group compared with WMT alone (RR = 1.26, 95% CI (1.18, 1.35), p < .00001, I ² = 50%, random‐effect model, Figure 4). And the RCT subgroup analysis showed the same results (RR = 1.23, 95%CI (1.13, 1.33), p < .00001).

FIGURE 4.

Overall clinical effectiveness

13.3. Time to defervescence

Eighteen studies (Chen Cw et al., 2021; Chen Ling et al., 2020; Chen Lz & Gl, 2020; Cheng Dz et al., 2020; Ji & P, 2020; Lian et al., 2020; Liu, 2020; Luo et al., 2022; Qian Yj, Wang, et al. 2020; Qiu et al., 2020; Qu Xk et al., 2020; Su Qw et al., 2020; Wang Yj et al., 2020; Xia Wg et al., 2020; Xiao et al., 2020; Xiao Mz, 2020; Xu, D, et al., 2020; Yao Kt et al., 2020; Zhang Xy et al., 2021) reviewed the time to defervescence of patients with COVID‐19, among which Xu Xh et al. (Yu Hy et al., 2020) published two groups of data (WMT group, WMT group+ LQ, and WMT group + JBG group). The results of the meta‐analysis showed that there was a significant difference in the time to defervescence between the ITCWM group and WMT group (MD = −1.45, 95% CI (−1.82, −1.07), p < .00001, I ² = 83%, random‐effect model, Figure 5). And the RCT subgroup analysis showed the same results (MD = −1.00, 95% CI (−1.52, −0.49), p = .0001).

FIGURE 5.

Time to defervescence

13.4. Disappearing time of cough

Ten studies (Chen et al., 2020; Chen Cw et al., 2021; Chen Ling et al., 2020; Cheng Dz et al., 2020; Li et al., 2021; Luo et al., 2022; Qiu et al., 2020; Qu Xk et al., 2020; Su Qw et al., 2020; Xiao et al., 2020) reported on the disappearing time of cough. The meta‐analysis suggested that the disappearing time of cough was significantly lower in the ITCWM group than in the WMT group (MD = −2.11, 95% CI [−2.98, −1.25], p < .00001, I ² = 93%, random‐effect model, Figure 6). And the RCT subgroup analysis showed the same results (MD = −1.32, 95% CI [−2.34, −0.30], p = .01).

FIGURE 6.

Disappearing time of cough

13.5. Time of RT‐PCR negativity

Seven studies (Chen Cw et al., 2021; Li et al., 2021; Qin Yl et al., 2020; Xu, D, et al., 2020; Zeng et al., 2020; Zhang Jy et al., 2021; Zhang Xy et al., 2021) reported on the time of RT‐PCR negativity, among which Xu, D, et al. (2020) published the same two sets of data as before. The meta‐analysis showed that the ITCWM group could significantly reduce the time of RT‐PCR negativity compared with WMT alone (MD = −3.35, 95%CI (−4.74, −1.95), p < .00001, I ²  = 92%, random‐effect model, Figure 7). And the RCT subgroup analysis showed the same results (MD = −3.46, 95% CI (−6.13, −0.79), p = .01).

FIGURE 7.

Time of RT‐PCR negativity

13.6. Length of hospital stay

Fifteen studies (Ai Xy et al., 2020; Chen Ling et al., 2020; Chen Lz & Gl, 2020; Liu, 2020; Luo et al., 2022; Qin Yl et al., 2020; Shi et al., 2020; Song Yy et al., 2020; Su Qw et al., 2020; Wang, L, et al., 2021; Xia Wg et al., 2020; Xu, D, et al., 2020; Yu Hy et al., 2020; Zeng et al., 2020; Zhang Jy et al., 2021) reported on the length of hospital stay, among which Xu, D, et al. (2020) published the same two sets of data as before. The meta‐analysis showed that the ITCWM could significantly reduce the length of hospital stay better than WMT alone (MD = −4.05, 95% CI (−5.24, −2.85), p < .00001, I ² = 91%, random‐effect model, Figure 8). And the RCT subgroup analysis showed the same results (MD = −4.14, 95% CI (−5.78, −2.51), p < .00001).

FIGURE 8.

Length of hospital stay

13.7. Improvement in CT scan

Twenty‐four studies (Chen Ling et al., 2020; Chen Lz & Gl, 2020; Cheng Dz et al., 2020; Dai Gc et al., 2020; Ding Xj et al., 2020; He & Z., 2021; Hu et al., 2021; Jin et al., 2020; Liu, 2021; Luo et al., 2022; Qiu et al., 2020; Qu Xk et al., 2020; Shi et al., 2020; Su Qw et al., 2020; Sun Hm et al., 2020; Wang, L, et al., 2021; Wang Yj et al., 2020; Xia Wg et al., 2020; Xiao et al., 2020; Xu, D, et al., 2020; Yang Mf et al., 2020; Yu et al., 2020; Zeng et al., 2020; Zhang Cy et al., 2020) reported on the improvement in CT scan, among which Xu, D, et al. (2020) published the same two sets of data as before. The meta‐analysis showed that there was a significant difference in the improvement in CT scan between the ITCWM group and WMT group (RR = 1.22, 95% CI (1.17, 1.28), p < .00001, I ² = 46%, fix‐effect model, Figure 9). And the RCT subgroup analysis showed the same results (RR = 1.24, 95% CI (1.17, 1.32), p < .00001).

FIGURE 9.

Improvement in CT scan

13.8. TCM syndrome score

Twelve studies (Ai Xy et al., 2020; Dai Gc et al., 2020; Duan et al., 2020; He Qing et al., 2021; He & Z., 2021; Lian et al., 2020; Liu Ap et al., 2021; Luo et al., 2022; Qiu et al., 2020; Shi Sf et al., 2021; Wang, L, et al., 2021; Xia Wg et al., 2020) reported on the TCM syndrome score. The meta‐analysis showed significant improvement by ITCWM on TCM syndrome score compared with WMT alone (MD = −3.95, 95% CI [−5.07, −2.82], p < .00001, I ² = 92%, random‐effect model, Figure 10). And the RCT subgroup analysis showed the same results (MD = −4.15, 95% CI [−5.65, −2.66], p < .00001).

FIGURE 10.

TCM syndrome score

13.9. Disappearance rate of fever

Seventeen studies (Chen et al., 2020; Chen Ling et al., 2020; Cheng Dz et al., 2020; Ding Xj et al., 2020; Duan et al., 2020; Ji & P, 2020; Jin et al., 2020; Li et al., 2021; Li Qj et al., 2021; Luo et al., 2022; Lv Rb & Li, 2020; Sun Hm et al., 2020; Xia Wg et al., 2020; Xiao Mz, 2020; Yao Kt et al., 2020; Zhang Jy et al., 2021; Zhang Yl et al., 2020) reported on the disappearance rate of fever. The meta‐analysis suggested that the rates of disappearance of fever were higher in the ITCWM group compared to the WMT group (RR = 1.23, 95% CI (1.10, 1.38), p < .00001, I ² = 85%, random‐effect model, Figure 11). But the RCT subgroup analysis showed the different results (RR = 1.13, 95% CI (0.99, 1.28), p < .00001).

FIGURE 11.

Disappearance rate of fever

13.10. Disappearance rate of cough

Eighteen studies (Chen Ling et al., 2020; Chen Lz & Gl, 2020; Cheng Dz et al., 2020; Ding Xj et al., 2020; Duan et al., 2020; Ji & P, 2020; Jin et al., 2020; Li et al., 2021; Li Qj et al., 2021; Liu Ap et al., 2021; Luo et al., 2022; Lv Rb & Li, 2020; Sun Hm et al., 2020; Xia Wg et al., 2020; Xiao et al., 2020; Xiao Mz, 2020; Yao Kt et al., 2020; Zhang Jy et al., 2021; Zhang Yl et al., 2020) reported on the disappearance rate of cough. The meta‐analysis suggested that the rates of disappearance of cough were higher in the ITCWM group compared to the WMT group (RR = 1.43, 95% CI (1.25, 1.63), p < .00001, I ² = 60%, random‐effect model, Figure 12). And the RCT subgroup analysis showed the same results (RR = 1.39, 95% CI (1.14, 1.70), p = .001).

FIGURE 12.

Disappearance rate of cough

13.11. Adverse reaction rate

Thirty‐one studies (Chen Cw et al., 2021; Chen Ling et al., 2020; Chen Lz & Gl, 2020; Dai Gc et al., 2020; Ding Xj et al., 2020; Duan et al., 2020; Fu Xx & Tan, 2020; He Qing et al., 2021; He & Z., 2021; Hu et al., 2021; Lian et al., 2020; Liu, 2020; Liu, 2021; Liu Ap et al., 2021; Liu Kf et al., 2020; Lv Rb & Li, 2020; Qu Xk et al., 2020; Shi Sf et al., 2021; Wang, L, et al., 2021; Xia Wg et al., 2020; Xiao et al., 2020; Xiao et al., 2021; Xu, D, et al., 2020; Yang Mf et al., 2020; Yu et al., 2020; Yu Xy et al., 2020; Zhang Cy et al., 2020; Zhang Jy et al., 2021; Zhang Yl et al., 2020) reported on the adverse reaction rate. The meta‐analysis indicated no significant difference in adverse reaction rate between COVID‐19 patients in the ITCWM and WMT groups (RR = 0.85, 95% CI (0.71, 1.03), p = .10, I ² = 25%, Fix‐effect model, Figure 13). And the RCT subgroup analysis showed the same results (RR = 0.93, 95% CI (0.75, 1.16), p = .54).

FIGURE 13.

Adverse reaction rate

14. CRP

Twenty‐two studies (Chen et al., 2020; Chen Cw et al., 2021; Chen Ling et al., 2020; Chen Lz & Gl, 2020; Ding Xj et al., 2020; Fu Xx & Tan, 2020; He Qing et al., 2021; He & Z., 2021; Jin et al., 2020; Liu, 2021; Liu Ap et al., 2021; Liu Kf et al., 2020; Luo et al., 2022; Qin Yl et al., 2020; Qu Xk et al., 2020; Su Qw et al., 2020; Wang, G, et al., 2021; Wang, L, et al., 2021; Qian Yj, Wang, et al. 2020; Yang Mf et al., 2020; Yu et al., 2020; Yu Xy et al., 2020) reported on the CRP. The meta‐analysis indicated that the ITCWM group could significantly improved the CRP compared to the WMT group (MD = −9.23, 95% CI (−10.94, −7.52), p < .00001, I ² = 97%, random‐effect model, Figure 14). And the RCT subgroup analysis showed the same results (MD = −10.30, 95% CI (−12.40, −8.19), p < .00001).

FIGURE 14.

CRP

15. WBC

Sixteen studies (Chen Ling et al., 2020; Chen Lz & Gl, 2020; Fu Xx & Tan, 2020; Jin et al., 2020; Liu, 2021; Liu Kf et al., 2020; Luo et al., 2022; Qin Yl et al., 2020; Qu Xk et al., 2020; Song Yy et al., 2020; Su Qw et al., 2020; Wang, G, et al., 2021; Wang, L, et al., 2021; Qian Yj, Wang, et al. 2020; Xiao et al., 2020; Yu et al., 2020) reported on the WBC. The meta‐analysis indicated that the ITCWM group could significantly improved the WBC compared to the WMT group (MD = 0.07, 95% CI (−0.37, −0.51), p < .00001, I ² = 97%, random‐effect model, Figure 15). And the RCT subgroup analysis showed the same results (MD = 0.42, 95% CI (−0.00, 0.85), p < .00001).

FIGURE 15.

WBC

The results of total meta‐analysis and RCT subgroup analysis of all outcomes were shown in the Table 4.

TABLE 4.

Meta‐analysis result of ITCWM for COVID‐19

Outcomes	NS	Meta‐analysis result		NS	Subgroup analysis results
		Effect size(95% CI)	p		Effect size(95% CI)	p
Percentage of cases changing to severe/critical	29	0.40 (0.33, 0.49)	<.00001	17	0.49 (0.39, 0.63)	<.00001
Overall clinical effectiveness	23	1.26 (1.18, 1.35)	<.00001	14	1.23 (1.13, 1.33)	<.00001
Time to defervescence	18	−1.45 (−1.82, −1.07)	<.00001	7	−1.00 (−1.52, −0.49)	.0001
Disappearing time of cough	10	−2.11 (−2.98, −1.25)	<.00001	3	−1.32 (−2.34, −0.30)	.01
Time of RT‐PCR negativity	7	−3.35 (−4.74, −1.95)	<.00001	4	−3.46 (−6.13, −0.79)	.01
Length of hospital stay	15	−4.05 (−5.24, −2.85	<.00001	5	−4.14 (−5.78, −2.51)	<.00001
Improvement in CT scan	24	1.22 (1.17, 1.28)	<.00001	13	1.24 (1.17,1.32)	<.00001
TCM syndrome score	12	−3.95 (−5.07, −2.82)	<.00001	8	−4.15 (−5.65, −2.66)	<.00001
Disappearance rate of fever	17	1.23 (1.10, 1.38)	<.00001	9	1.13 (0.99, 1.28)	<.00001
Disappearance rate of cough	18	1.43 (1.25, 1.63)	<.00001	10	1.39 (1.14, 1.70)	.001
Adverse reaction rate	31	0.85 (0.71, 1.03)	.10	21	0.93 (0.75, 1.16)	.54
CRP	22	−9.23 (−10.94, −7.52)	<.00001	15	−10.30 (−12.40, −8.19)	<.00001
WBC	16	−9.23 (−10.94, −7.52)	<.00001	9	−10.30 (−12.40, −8.19)	<.00001

Abbreviation: NS, number of studies.

16. DISCUSSION

The newly emerged COVID‐19 viral disease caused by the SARS‐CoV‐2 pathogen has not only created severe panic among the people but also challenged the social culture and healthcare infrastructure all over the world. COVID‐19 can bring about a series of clinical symptoms such as fever, cough, chest tightness, and shortness of breath. What's worse, patients with severe conditions may develop dyspnea, acute respiratory failure, kidney failure, and even death (Ralph, J, Zeng, et al., 2020; Xu, Z, Deng, et al., 2020). Unfortunately, a global pandemic situation has been established because of its long incubation period, high infectivity, general susceptibility to infection, and without obvious symptoms in the early stage (Commission, 2020). Plenty of studies have confirmed that the pathology of COVID‐19 is associated with immune disorders and inflammatory responses, which could directly damage deep airways and alveoli and finally brings acute respiratory distress syndrome, hypoxemia, and metabolic acidosis (Liu, R, Gq, et al., 2020; Xu, S, Wang, et al., 2020). Therefore, the rapid elimination of inflammatory response transmitters, blocking inflammatory storms, and regulating immune disorders are of great significance to controlling patients’ conditions and preventing them from developing into severe and critical cases (Han, L., Lb, et al., 2019). However, there are still many problems and challenges in the research and development of clinically approved drugs for COVID‐19. Undoubtedly, China has achieved remarkable results in the past using a combination of traditional Chinese and western medicine in the absence of specific drugs and vaccines.

COVID‐19 is considered a plague by TCM, with the pathogenesis of invasion of the epidemic virus, lung damage, and other organ injury gradually and the characteristics of “Dampness, Heat, Blood stasis, Poison and Deficiency” (Medicine, 2020). TCM has unique advantages of holistic view and dialectical treatment. It has not only the efficacy of multiple targets, multiple approaches, and multiple systems but also the personalized treatment for different physical conditions, different places, and different climates (Zhuo Bw, Mm, et al., 2021). Therefore, a variety of TCM and dosage forms have emerged for COVID‐19. In the past, many studies have shown that TCM such as Qingfei Paidu Decoction, Huashi Baidu Prescription, Xuanfei Baidu Prescription, and so on play an overall therapeutic role in antiviral, antibacterial, antipyretic, and immune regulation (Wang, G, et al., 2021). There was an in vitro study finding that Qingfei Paidu Decoction could dose‐dependently inhibit the replication of coronavirus at the levels of RNA and protein. Furthermore, it has shown that Qingfei Paidu Decoction can not only inhibit the absorption of viruses into cells but also act as an antiviral agent by upregulating the expression of interferon and interferon‐stimulated genes (Wang, Y, Wu, et al., 2021). Other studies have also proved that Lianhua Qingwen Granule can reduce the impact of the virus to host cells by blocking multiple binding sites of angiotensin‐converting enzyme to SARS‐COV‐2 in the human body (Niu M, Wang, et al., 2020). Another external study conducted by the State Key Laboratory of Respiratory Diseases found that Lianhua Qingwen Granule can significantly inhibit novel coronavirus activity, reduce virus content in cell membrane and cytoplasm, and inhibit cytokine overactivation (Jia, H, Chang, et al., 2020). Honeysuckle bud and flower (Jinyinhua, Flos Lonicerae), one of the widely used TCM in COVID‐19, has been confirmed that actually has the therapeutic effects of antiinflammatory, antiviral, regulation of non‐specific immunity (Wang & M, 2022). However, there are great difficulties in the identification and confirmation of the specific active components of TCM (Wang Xl et al., 2020). We also hope that, just like the discovery of Artemisinin for malaria by Nobel Prize winner Tu Youyou, medicines with guaranteed efficacy against COVID‐19 can be found in the treasure house of TCM as soon as possible.

Generally speaking, a large number of studies have confirmed that TCM can provide multi‐component, multi‐channel, multi‐target, and personalized treatment for COVID‐19 (Tao Jl, Cs, et al., 2019). Several previous meta‐studies have also demonstrated that TCM can significantly improve clinical symptoms and reduce the conversion rate of severe cases in the treatment of COVID‐19 (Ming Liu, Yuan, et al., 2020; Xin, F, Wukai, et al., 2020; Xiong, W, Su, Cho, & Xing, 2020). But due to the limitations of the study sample size, we carried out this study for the purpose of more sufficient evidence. By comparison, we did a totally comprehensive review and included more relevant studies with more sample sizes, thoroughly analyzed all the outcomes, and successfully got more evidence. Our study showed that ITCWM could significantly improve the percentage of cases changing to severe/critical, clinical symptoms (fever and cough), time of RT‐PCR negativity, CT scan, and inflammatory reaction in COVID‐19 patients compared with WMT alone.

17. CONCLUSION

Our meta‐analysis results have shown that the ITCWM dose has significant efficacy and safety in COVID‐19 patients. These findings would contribute to providing more evidence of ITCWM for COVID‐19 and accelerating the formation of a more comprehensive consensus on the treatment guidelines for human health. However, from the perspective of research methodology, this meta‐analysis still has the following limitations: (1) the quantity of published RCT literature is relatively few. (2) the quality of some literature research methods is low, and there may be some risk of bias. (3) the prescriptions and dosage forms of TCM used in included studies are not completely consistent, which may lead to information bias. (4)the combined analysis of the RCT study and retrospective study, the inconsistent treatment course of each study, and other factors may also cause bias. (5) most of the included literature are Chinese studies. Moreover, it is a pity that many studies lacked an assessment of long‐term outcomes for treatment. Nevertheless, greater international collaboration, more large‐scale and high‐quality RCTs with good design, and more multicenter studies are expected to effectively enhance the contribution of TCM to global pandemics. We are looking forward to more studies to prove that TCM does play an effective and great role in COVID‐19 and make contributes to human health.

AUTHORS CONTRIBUTIONS

All authors had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Zhuang Jieqin conceived and drafted the study. Dai Xingzhen and Zhang Weizhang were responsible for literature retrieval, data collection, and analysis. Zhang Weizhang and Fu Xue contributed to the revision of the manuscript. All authors contributed to the interpretation of the data and made critical comments on the manuscript to be published.

FUNDING INFORMATION

This meta‐analysis was sponsored by the National Natural Science Foundation of China (82074342).

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Zhuang, J. , Dai, X. , Zhang, W. , Fu, X. , Zhang, G. , Zeng, J. , Zhao, S. , & Chen, B. (2022). Efficacy and safety of integrated traditional Chinese and Western medicine against COVID‐19: A systematic review and meta‐analysis. Phytotherapy Research, 36(12), 4371–4397. 10.1002/ptr.7643

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.