key: cord-0940557-qspu9v34
authors: Shi, Shihua; Wang, Fei; Li, Jiang; Li, Yulong; Li, Weihao; Wu, Xiaoping; Kou, Shuo; Wu, Yongcan; Wang, Xiaomin; Pei, Caixia; Huang, Demei; Qiu, Heng; Wang, Peili; Wang, Zhenxing
title: The effect of Chinese herbal medicine on digestive system and liver functions should not be neglected in COVID‐19: An updated systematic review and meta‐analysis
date: 2021-04-02
journal: IUBMB Life
DOI: 10.1002/iub.2467
sha: d4f434cdb5366a9a9bd413fdbb2a1946da6b4d2c
doc_id: 940557
cord_uid: qspu9v34

Gastrointestinal symptoms and liver injury are common in patients with coronavirus disease 2019 (COVID‐19). However, profiles of different pharmaceutical interventions used are relatively underexplored. Chinese herbal medicine (CHM) has been increasingly used for patients with COVID‐19, but the efficacy of CHM used in COVID‐19 on gastrointestinal symptoms and liver functions has not been well studied with definitive results based on the updated studies. The present study aimed at testing the efficacy of CHM on digestive symptoms and liver function (primary outcomes), the aggravation of COVID‐19, and the time to viral assay conversion (secondary outcomes), among patients with COVID‐19, compared with standard pharmacotherapy. The literature search was undertaken in 11 electronic databases from December 1, 2019 up to November 8, 2020. Appraisal of the evidence was conducted with Cochrane risk of bias tool or Newcastle Ottawa Scale. A random‐effects model or subgroup analysis was conducted when significant heterogeneity was identified in the meta‐analysis. The certainty of the evidence was assessed with the grading of recommendations assessment, development, and evaluation approach. Forty‐eight included trials involving 4,704 participants were included. Meta‐analyses favored CHM plus standard pharmacotherapy for COVID‐19 on reducing the aggravation of COVID‐19 and the time to viral assay conversion compared with standard pharmacotherapy. However, the present CHM as a complementary therapy for treating COVID‐19 may not be beneficial for improving most gastrointestinal symptoms and liver function based on the current evidence. More well‐conducted trials are warranted to confirm the potential efficacy of CHM furtherly.

, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly around the world with substantial mortality since December 2019. 1 To date, the potential treatment options to contain the disease include antiviral medications, steroids, antibacterial medications, human immunoglobulin, and so on. Chinese herbal medicine (CHM), as recommended in national treatment guidelines in China, 2 has been increasingly used, and might pose a promising therapy for COVID-19. [3] [4] [5] [6] [7] Some evidence of the efficacy of CHM for COVID-19 has emerged, suggesting that CHM may be used for COVID-19 in improving clinical symptoms, length of hospital stay, lung CT, and inflammatory biomarkers with fewer adverse events than conventional treatments. 8, 9 It was believed that CHM was an effective treatment for COVID-19 in Chinese health care system. However, the previous meta-analysis studying CHM for COVID-19 paid attention to respiratory tract manifestations and fever, without enough consideration on digestive symptoms and liver function. It was understandable that digestive symptoms and liver function were neglected in the previous COVID-19 studies since it was a race to find effective measures and it was of utmost necessity to control the most commonly depicted symptoms due to the sheer magnitude of the COVID-19 pandemic. However, the goal of evidence-based medicine is to provide comprehensive clinical practice suggestions, and the digestive symptoms and liver injury are not uncommon in patients with COVID-19. 10 Emerging data have illustrated that the gastrointestinal tract and liver also represented target organs of SARS-CoV-2, according to the findings that angiotensin-converting enzyme 2, the major receptor of SARS-CoV-2, was also found in liver and gastrointestinal tract. 11 Increased attention should be paid to digestive symptoms and liver function in COVID-19 patients.

CHM as an adjuvant for COVID-19 on gastrointestinal symptoms and liver functions has not been studied with definitive results based on the latest evidence assessment. Whether CHM may constitute a basis of drug treatment for COVID-19 patients with gastrointestinal symptoms and liver dysfunctions remains unclear.

Although empirical use of CHM shows potential improvement, supporting evidence remains limited. We conducted a systematic review and meta-analysis of emerging studies reporting gastrointestinal symptoms and liver function in COVID-19 patients treated with CHM plus standard pharmacotherapy. As for the followup of adverse events that have been studied, 8, 9 we would not study it again.

This systematic review and meta-analysis, registered with the Open Science Framework (DOI: 10.17605/OSF. IO/8QCVP), was performed and reported in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (Appendix S1). 12 

A systematic literature search of the PubMed, ScienceDirect, Web of Science, Scopus, Google Scholar, WorldCat Dissertations database and Index to Theses, PsycINFO, ProQuest, the Chinese National Knowledge Infrastructure, the VIP Information Database, and the Wanfang Database was conducted on November 8, 2020 (updated February 9, 2021) for relevant articles including accepted pre-proof publications in the last 1 year, to identify the latest information on COVID-19. The following grouped terms were used as search strategy and modified to suit each database to screen publications that might be valuable for the present review: ("coronavirus disease 2019" OR "COVID-19" OR "severe acute respiratory syndrome coronavirus 2" OR "SARS-CoV-2" OR "coronavirus" OR "novel coronavirus" OR "nCoV" OR "2019-nCoV") AND ("Medicine, Chinese Traditional" OR "Traditional Medicine, Chinese" OR "Chinese herbal medicine" OR "traditional Chinese medicine" OR "Chinese Traditional Medicine" OR "Chinese Medicine, Traditional" OR "Chinese medicine formulae" OR "Chinese medicine formulations" OR "Chinese herb" OR "Chinese herb therapy" OR "herbal medicine" OR "herb remedy" OR "herb therapy" OR "Zhong Yi Xue" OR "Chung I Hsueh" OR "Hsueh, Chung I"). Given the urgency of treating COVID-19, a gray literature search was also performed. Furthermore, COVID-19 articles in the WHO database and some key journals in this field including the New England Journal of Medicine, BMJ, the Lancet COVID-19 Resource Centre, and JAMA were searched manually for potentially relevant publications. Additional articles were retrieved by hand based on the reference lists of relevant papers. Search strategies were attached in the supplementary (Appendix S2).

Application of CHM in COVID-19 patients was less evaluated through COVID-19 randomized controlled trials (RCTs), due to ethic, feasibility, and methodology issues. Observational studies were common sources of the literature evaluating the efficacy of CHM, considering the urgency of the topic. Accordingly, we included studies on humans, which were RCTs or observational studies with a control arm.

Only patients with COVID-19 were considered in this study. To ensure that all relevant articles were included, we did not set any specifications for the ages, sexes, and ethnic origin of participants.

Participants in the treatment group should receive CHM as a co-intervention with standard pharmacotherapy. Participants in the control group should be treated by standard pharmacotherapy alone or standard pharmacotherapy plus placebo.

The definition of CHM was herbal agents and materials, that originated from botanical herbal products, mineral and animal sources, based on the Pharmacopoeia of the People's Republic of China. 13 Standard pharmacotherapy, namely the standard treatment, consisted of symptomatic control and supportive care for COVID-19, such as antiviral medications, antibacterial medications, steroids, and human immunoglobulin, mostly according to the evolving Chinese national COVID-19 treatment guidelines and hospital practice. 2 

The primary outcome measures were defined as gastrointestinal symptoms and liver functions. The main outcomes of gastrointestinal symptoms included the rate of nausea remission, remission of vomiting, rate of anorexia remission, and rate of diarrhea remission. The improvement rate of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as the main outcomes, represented liver function. The secondary outcome measures were defined as the aggravation of COVID-19, and the time to viral assay conversion.

The following studies were excluded: duplicate publications; review articles; editorials; case series without control group; viewpoints; commentaries; experimental in vitro studies; animal studies; expert opinions; studies pertaining to the suspected cases of COVID-19; and other complementary and alternative therapies beyond CHM, like massage, acupuncture, moxibustion, cupping, and music therapy, were contained in either CHM or control group; studies that did not report indicators to be discussed in this study.

Two investigators (Shihua Shi and Jiang Li) independently searched the databases and screened the titles and abstracts. Disagreements about the eligibility and exclusion of a study were resolved via consensus or resolved by an arbitral reviewer (Zhenxing Wang). The following variables were independently extracted by two reviewers (Yulong Li and Xiaoping Wu) and crosschecked by another reviewer (Fei Wang): author; date; study design; patient demographics; severity of illness; interventions, and outcome parameters. We contacted the corresponding authors to resolve the incomplete data or data failed, attempting for more information, if possible.

The Modification of Cochrane Tool 14 to assess the risk of bias in randomized trials was used, in which the response options for each of the domains included "definitely or probably yes" (assigned a low risk of bias) and "definitely or probably no" (assigned a high risk of bias). 15, 16 The Newcastle Ottawa Scale (NOS) 17 was used to assess the risk of bias of observational studies that met the inclusion criteria. The quality of enrolled studies was independently rated by two reviewers (Yongcan Wu and Xiaomin Wang). Any disagreements were resolved by discussion or resolved by a senior reviewer (Weihao Li).

The gastrointestinal symptoms including the remission rate of diarrhea, anorexia, nausea, and vomiting; liver function parameters including the improvement rate of ALT and AST; the rate of aggravation of COVID-19 and time to viral assay conversion were evaluated and merged. Meta-analysis of the outcomes above was conducted using the Cochrane Collaboration Review Manager software (RevMan, Version 5.3). The relative treatment effects of dichotomous data and continuous data were measured using risk ratio (RR) and mean difference (MD), respectively. The standard error was calculated from the 95% confidence interval (CI). Heterogeneity was explored using the Mantel-Haenszel χ 2 -test and I 2 statistic. 18 The random-effects model was utilized to address the variation across the included studies, since the pooled studies may differ in study design, duration, disease type, severity, or others. Subject to the availability of a sufficient number of studies, subgroup analyses were performed according to the study design, specific prescriptions of interventions, disease type, severity, or duration to explain the heterogeneity issues identified before data analyses. We assessed publication bias using the funnel plot 19 and the certainty of the evidence using the GRADEpro software.

Searches in the 11 databases yielded a total of 19,614 potential publications initially. 3,921 records remained after the removal of duplicates. The titles and abstracts of these papers were screened and 3,501 studies were dropped at this stage. The 420 studies, deemed to meet the criteria for full-text review, were retrieved for further eligibility assessment. Then, 375 of them failed to meet the inclusion criteria for various reasons (see Figure 1 ). Additional potentially relevant papers (n = 3) were identified through searches by hand in reference lists of reviews and included studies. Finally, 48 papers were appraised in the final stage (Table 1 ).

In total, we analyzed 48 studies 3-7,20-60 recruiting 4,704 patients with COVID-19. Of these, 29 20,22-29,31,34-36,39,40,49-62 were observational studies with a control group, and 19 [3] [4] [5] [6] [7] 30, 32, 33, 37, 38, [41] [42] [43] [44] [45] [46] [47] [48] 63 were RCTs included in the final analysis. Of these participants, 2,696 had been assigned to receive CHM as an adjuvant medicine, and 2,008 receive standard pharmacotherapy. CHM in most enrolled trials was orally administered. Other details were described in Table 1 . Table 2 summarized the risk of bias for the 19 RCTs. [3] [4] [5] [6] [7] 30, 32, 33, 37, 38, [41] [42] [43] [44] [45] [46] [47] [48] 63 Sixteen studies described the method of randomization, employing computer software, 4,6,7,63 random number tables, 3, 5, 30, 33, 37, 38, 41, 42, 44, 46, 48 or tossing a coin 47 for randomization. Six RCTs 3, 4, 30, 47, 48, 63 were open-label studies because of the urgency of major public health events, subject to the risk of performance bias owing to the lack of placebo control. The other 13 studies 5-7,32,33,37,38,41-46 did not mention the blinding of patients and personnel. Table 3 showed the NOS details for 29 observational studies. 20, [22] [23] [24] [25] [26] [27] [28] [29] 31, [34] [35] [36] 39, 40, [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] [62] Eight observational studies 20, 22, 24, 26, 34, 49, 50, 57 were judged to be of moderate methodologic quality, subject to the unsatisfying risk of bias mostly owing to the lack of adequacy of follow up and completing accounting for observational studies.

Of the 48 studies, six studies 20, 25, [27] [28] [29] 47 reported CHM on the rate of nausea remission in ordinary cases. No significant difference was found in the rate of nausea remission between the users and non-users of CHM (RR 1.04; 95% CI 0.83-1.30), and the heterogeneity was not significant (I 2 = 0, p = .92) ( Figure 2a ). We conducted subgroup analysis by study design, disease type, prescriptions of interventions, and duration. Similar result was found in observational trials, ordinary cases, Lianhua Qingwen group and subgroup with treatment course ≤7 days.

Of the 48 studies, four studies 28, 29, 34, 47 reported CHM on the remission of vomiting. As shown in Figure 2b , there was no significant difference in the remission of vomiting between users and non-users of CHM (RR 1; 95% CI 0.77-1.29), and heterogeneity was almost non-existent (I 2 = 0%, p = 1.00). Similar result was observed in subgroup analysis conducted by study design, disease type, severity, or duration.

Of the 48 studies, three controlled observational studies 20, 25, 27 and three RCTs 37,47,63 reported the rate of anorexia remission. Of the total 160 COVID-19 patients with anorexia, 75 received CHM along with standard pharmacotherapy and 85 received only standard pharmacotherapy. Three studies 25, 27, 47 reported a reduction in the rate of anorexia and three 20,37,63 did not report any benefit with the use of CHM compared with the controls. The heterogeneity was significant (I 2 = 87%, p < 0.00001), which was likely due to variations across studies, and random-effects model was used to accommodate statistical heterogeneity.

As shown in Figure 2c , in the rate of anorexia remission, the combined treatment group outperformed standard pharmacotherapy alone (RR 2.09; 95% CI 1.04-4.19), with an improved disappearance rate of anorexia. We conducted subgroup analysis when ≥2 studies could be pooled, and a similar result was observed in the subgroup of observational studies.

Twelve studies explored the rate of diarrhea remission after the use of CHM for COVID-19. Six of them 6 The effective rate of ALT returning to normal was examined by three controlled observational studies, 22,24,60 and one RCT. 44 As shown in Figure 3a , there was no significant difference in the effective rate of ALT returning to normal between the users and non-users of CHM (RR 1.23; 95% CI 0.91-1.65; I 2 = 54%). Subgroup analysis could not be conducted since the number of studies was limited.

The effective rate of AST returning to normal was examined by three controlled observational studies, 22,24,60 and one RCT. 44 As shown in Figure 3b, (Figure 4b) . These results were consistent with those in the subgroups conducted by study design, duration, disease type, and severity.

Potential publication bias was found by the visual inspection of the funnel plot in the meta-analysis of CHM's effects on the aggravation of COVID-19. The funnel plot was asymmetric, suggesting a mild publication bias of this meta-analysis ( Figure 5 ).

The certainty of evidence relevant to the aggravation of COVID-19 in RCTs had high quality. Diarrhea remission in RCTs, anorexia remission in observational trials, and the aggravation of COVID-19 in observational trials had a moderate quality of evidence. The certainty of evidence relevant to the following outcomes was low: the rate of nausea remission, anorexia remission, and vomiting remission in RCTs; the effective rate of ALT and AST returning to normal in RCT; the rate of nausea remission, and diarrhea remission in observational trials. Additionally, the quality of findings relevant to the time to viral assay conversion, the remission of vomiting in observational trials, and the effective rate of ALT and AST returning to normal in observational trials, was very low, suggesting that those outcomes should be interpreted carefully and may be changed after future researches (Table 4 ). Several initial observational studies were reported in rapid succession with poor methodologic quality, and most did not report outcomes of gastrointestinal symptoms and liver function. Nevertheless, COVID-19 patients experienced gastrointestinal symptoms, such as anorexia, nausea, vomiting, and diarrhea; they may also present with abnormal liver functions, which manifested as an increase in ALT and AST; digestive symptoms and liver F I G U R E 2 Forest plot of the comparison of CHM versus standard pharmacotherapy for the outcome of gastrointestinal symptoms injury became more pronounced as the severity of the disease increased. 65 Hence, identifying the efficacy of potential therapeutics not only on COVID-19 but also on gastrointestinal symptoms and liver function, needed to be considered. Among the various medications tried, CHM has received noticeable attention. Traditional Chinese medicine believed patients can be diagnosed and generalized into certain patterns according to clinical manifestations, and treated with herbal medicine. With the increasing relevant evidence including RCTs, we investigated the pooled efficacy of CHM on gastrointestinal symptoms and liver function in patients with COVID-19, and found that CHM plus standard pharmacotherapy may reduce the rate of COVID-19 aggravation and the nucleic acidnegative conversion time, but did not improve liver functions, compared with standard pharmacotherapy. In addition, the present CHM aimed at COVID-19 had no advantages on most gastrointestinal symptoms compared with standard pharmacotherapy, which may be caused by the large number of applications of cold-natured herbs with the function of clearing away heat and removing toxins to treat the emergency symptoms of COVID-19. symptoms and liver injury, which may inspire future COVID-19 studies. Besides, we conducted subgroup analysis according to study design, duration, prescriptions of interventions, disease type, and severity to rule out the influence of variations and eliminate heterogeneity. In addition, we evaluated the current results based on the grading of recommendations assessment, development, and evaluation (GRADE) assessment, which may be beneficial to the revision and promotion of the new diagnosis and treatment guidelines in the later stage.

Nevertheless, some limitations should be noted in our meta-analysis. First, most of our included studies were conducted in China. Limited information on other ethnic groups may have admission bias and selection bias. Second, as for the controlled observational studies included, some confounding factors may influence the certainty of the evidence. The sample size of some studies was small, so the test efficiency of some outcomes may be insufficient. Third, clinical studies evaluating the efficacy of CHM on COVID-19 usually had several limitations such as no placebo and poor methodologic quality.

In view of the public anxiety on COVID-19 worldwide, this systematic review and meta-analysis, critically appraising CHM and presenting evidence, may provide some evidence on this important issue. CHM achieved synergistic efficacy in reducing the rate of COVID-19 aggravation and the time to viral assay conversion when combined with standard pharmacotherapy, which may give meaningful hints to the clinical practice, and inspiration for the development of new drugs. Our results may allow clinicians and COVID-19 patients to comprehensively understand the efficacy of CHM on the digestive system and liver functions and make informed decisions. Certainly, the CHM that aimed at COVID-19 with a protective effect on the liver and digestive system needs to be investigated furtherly. Due to the limited understanding of the mechanism and precise therapeutic components of CHM, the standardization or evidence-based rationale for CHM used in COVID-19 still needs further studies. Additionally, the relevant placebo-controlled trials with doubleblind are warranted in future COVID-19 researches.

This meta-analysis of CHM on gastrointestinal symptoms and liver function for COVID-19 patients seemingly indicated that although CHM had some benefits in reducing the rate of COVID-19 aggravation and nucleic acid-negative conversion time, the present CHM against COVID-19 showed limited advantages in improving gastrointestinal symptoms and liver function in conjunction with conventional medical care for COVID-19 patients, based on the latest evidence. Further exploration of current findings and well-conducted trials are warranted. 

The authors have declared that no competing interest exists. 

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General Office of National Health Commission of the People's Republic of China Office of National Administration of Traditional Chinese Medicine. Diagnosis and treatment of corona virus disease-19

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Efficacy and safety of Lianhuaqingwen capsules, a repurposed Chinese herb, in patients with coronavirus disease 2019: A multicenter, prospective, randomized controlled trial

Jinyinhua liquid at different dosage combined with western medicine conventional treatment for common type COVID-19: a multicenter trial of 187 cases

Clinical observation on Jinhua Qinggan granule combined with conventional western medicine therapy in treating mild cases of coronavirus disease 2019

Clinical effect and mechanism of Qingfei Touxie Fuzheng recipe in the treatment of COVID-19

Research Group for Evidence-based Chinese M. Chinese herbal medicine for COVID-19: Current evidence with systematic review and meta-analysis

Chinese herbal medicine for coronavirus disease 2019: A systematic review and meta-analysis

Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis

Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

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The Cochrane Collaboration's tool for assessing risk of bias in randomised trials

Specific instructions for estimating unclearly reported blinding status in randomized trials were reliable and valid

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Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses

Measuring inconsistency in meta-analyses

Bias in meta-analysis detected by a simple, graphical test. Asymmetry detected in funnel plot was probably due to true heterogeneity

Retrospective clinical analysis on treatment of coronavirus disease 2019 with traditional Chinese Medicine Lianhua Qingwen

Retrospective clinical study on treatment of COVID-19 patients with integrated traditional Chinese and western medicine

Clinical observation on 34 patients with novel coronavirus pneumonia (COVID-19) treated with intergrated traditional Chinese and Western Medicine

Clinical observation on 49 cases of non-critical COVID-19 in Shanghai treated by integrated traditional Chinese and western medicine

Integrated traditional Chinese and Western Medicine in the Treatment of 40 cases of critical patients with COVID-19

Retrospective study of clinical efficacy of integrated Chinese and Western medicine in treatment of COVID-19

Clinical observation of 31 cases with corona virus disease 2019 treated with Guizhi Erchen decoction based on triple-Jiao sequential therapy

Analysis of curative effect of 51 patients with novel coronavirus pneumonia treated with Chinese medicine Lianhua Qingwen: a multicentre retrospective study

Clinical efficacy of Shufeng Jiedu capsule combined with Western medicine in treatment of common COVID-19 patients by retrospective analysis

Retrospective analysis on clinical efficacy of Ganlu Xiaodu decoction combined with Western medicine in treatment of common COVID-19 patients

Study on clinical efficacy of Lianhua Qingke granule in treatment of mild and ordinary COVID-19

Analysis of clinical results of 75 cases of COVID-19 treated by integrated Traditional Chinese and Western medicine-based on the theory of Fengwen Yi

Study on the effect and safety of self-made traditional Chinese medicine decoction in patients with COVID-19

Efficacy observation of maxing Xuanfei Jiedu decoction on moderate COVID-19 patients

Clinical observation on integrated traditional Chinese and western medicine in the treatment of 51 cases of Corona Virus Disease 2019 in Hangzhou area

Analysis of TCM syndrome characteristics and clinical efficacy of 72 patients with COVID-19

Analysis of drug use in 616 patients with coronavirus disease 2019 in a hospital

Effect of integrated traditional Chinese and Western medicine on T lymphocyte subsets of patients with normal type of COVID-19

Effects of Lianhua Qingwen granules plus arbidol on treatment of mild corona virus disease-19

Observation on clinical effect of modified Qingfei Paidu Decoction in treatment of COVID-19

Clinical efficacy of reduning injection combined with methylprednisolone in the treatment of severe coronavirus disease 2019

Clinical study of Lianhua Qingwen capsule in the treatment of corona virus disease 2019

Clinical observation on effect of Toujie Quwen granules in treatment of COVID-19

Clinical efficacy and mechanism of Qushi Paidu Fuzheng Recipe in treatment of corona virus disease 2019 with syndrome of cold dampness lung stagnation and epidemic toxin closing lung

Clinical study on Xuanfei Qingre decoction as an adjuvant treatment for ordinary cases of COVID-19

Clinical observation of Jiawei Yupingfeng powder combined with western medicine in the treatment of the novel coronavirus pneumonia

Clinical study on Shengmai Powder combined with Shenling Baizhu Powder in the treatment of common Corona Virus Disease

Efficacy of herbal medicine (Xuanfei Baidu decoction) combined with conventional drug in treating COVID-19: a pilot randomized clinical trial

Guideline-based Chinese herbal medicine treatment plus standard care for severe coronavirus disease 2019 (G-CHAMPS): Evidence From China

Xuebijing injection in the treatment of COVID-19: a retrospective case-control study

Analysis of curative effect of integrated traditional Chinese and Western medicine on new coronavirus Pneumoni

Clinical study of artesunate in the treatment of coronavirus disease 2019

Clinical study on combined scheme of Lianhuaqingwen Capsules and abidole in the treatment for coronavirus disease 2019

Observation on clinical effect of Shufeng Jiedu Capsule combined with Arbidol Hydrochloride Capsule in treatment of COVID-19

Clinical retrospective study on novel coronavirus pneumonia treated with triple focus treatment

Retrospective analysis of Jinye Baidu Granules and Lianhua Qingwen Capsules in the treatment of ordinary cases of COVID-19

Comparison of clinical efficacy of Qingfei Paidu decoction combined with western medicine in 43 cases and single western medicine in 46 cases in the treatment of COVID-19

Effect of Qingfei Paidu decoction on clinical efficacy of COVID-19 pneumonia with Phlegm heat blocking lung

Evaluation of the adjuvant efficacy of natural herbal medicine on COVID-19: a retrospective matched case-control study

Retrospective study of traditional Chinese Medicine "Ma Xing Shigan decoction" combined with Western Medicine in the treatment of ordinary COVID-19

Retrospective analysis of 38 cases with coronavirus disease 2019 treated by integrated traditional Chinese and Western Medicine

A Retrospective Study on the Treatment of Coronavirus Disease

Effect and safety of Chinese herbal medicine granules in patients with severe coronavirus disease 2019 in Wuhan, China: a retrospective, single-center study with propensity score matching

Efficacy of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in treatment of COVID-19: a randomized controlled trial

COVID-19) outbrake situation

Clinical characteristics of 3062 COVID-19 patients: a meta-analysis

The average NOS score of this outcome was six, and the risk of bias of it was moderate.f RR < 0.5 based on consistent evidence from at least two studies.g Visual inspection of the funnel plot showed an asymmetry in the meta-analysis.