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| REVIEW ARTICLE |
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| Year : 2022 | Volume
: 6
| Issue : 3 | Page : 105-119 |
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Efficacy and safety of traditional chinese medicine combined with western medicine for the treatment of COVID-19: A systematic review and meta-analysis
Shanshan Tian1, Kai Yuan1, Yongbo Zheng2, Xuejiao Gao1, Xuan Chen3, Yingbo Yang3, Shiqiu Meng4, Lu Cao4, Le Shi1, Wei Yan1, Xiaoxing Liu1, Jie Shi4, Lin Lu5, Jiahui Deng1, Yanping Bao6
1 Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University, Beijing, China
2 Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University; Peking-Tsinghua Center for Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Beijing, China
3 Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University, Beijing; Department of Psychiatry, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China
4 National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China
5 Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University; Peking-Tsinghua Center for Life Sciences, PKU-IDG/McGovern Institute for Brain Research; National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China
6 National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University; School of Public Health, Peking University, Beijing, China
| Date of Submission | 01-May-2022 |
| Date of Acceptance | 02-Sep-2022 |
| Date of Web Publication | 30-Sep-2022 |
Correspondence Address:
Jiahui Deng
Peking University Sixth Hospital, 51 Huayuan Bei Road, Haidian District, Beijing, 100191
China
Prof. Yanping Bao
National Institute on Drug Dependence, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191
China
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/hm.hm_10_22
Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide. Traditional Chinese Medicine (TCM) was considered important by Chinese health authorities in the fight against COVID-19. This review systematically analyzed and evaluated the safety and efficacy of TCM combined with Western Medicine (WM) for the treatment of COVID-19. We sought to provide summary evidence for clinicians when using TCM. We searched for studies in PubMed, Web of Science, Embase, Medline, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data from database inception to June 1, 2021. Overall, 31 studies (14,579 participants) were involved in the final systematic review, including 15 randomized controlled trials and 16 observational studies. TCM combined with WM showed main outcomes of a higher clinical efficacy rate (odds ratio [OR] =2.48, 95% confidence interval [CI] =1.90–3.24, I2 = 4%) and lower case fatality rate (OR = 0.31, 95% CI = 0.19–0.49, I2 = 80%) compared with WM treatment alone. No significant overall adverse events were found between TCM plus WM group and WM group (OR = 1.43, 95% CI = 0.63–2.23, I2 = 75%). Some larger randomized control trials would assist in defining the effect of TCM combined with WM on the treatment of COVID-19 complications such as cardiac injury. TCM combined with WM may be safe and effective for the treatment of COVID-19.
Keywords: COVID-19, efficacy, safety, Traditional Chinese Medicine
How to cite this article:
Tian S, Yuan K, Zheng Y, Gao X, Chen X, Yang Y, Meng S, Cao L, Shi L, Yan W, Liu X, Shi J, Lu L, Deng J, Bao Y. Efficacy and safety of traditional chinese medicine combined with western medicine for the treatment of COVID-19: A systematic review and meta-analysis. Heart Mind 2022;6:105-19 |
How to cite this URL:
Tian S, Yuan K, Zheng Y, Gao X, Chen X, Yang Y, Meng S, Cao L, Shi L, Yan W, Liu X, Shi J, Lu L, Deng J, Bao Y. Efficacy and safety of traditional chinese medicine combined with western medicine for the treatment of COVID-19: A systematic review and meta-analysis. Heart Mind [serial online] 2022 [cited 2023 May 31];6:105-19. Available from: http://www.heartmindjournal.org/text.asp?2022/6/3/105/357540 |
| Introduction | |  |
Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide. Among hospitalized patients, the most common symptoms are fever (up to 90% of patients), cough (60%–86%), shortness of breath (53%–80%), fatigue (38%), nausea/vomiting or diarrhea (15%–39%), and myalgia (15%–44%).[1],[2],[3],[4],[5],[6],[7] Globally, as of January 21, 2022, there have been 340 million confirmed cases of COVID-19, including 5.5 million deaths, according to the official website of World Health Organization (WHO). In the epidemiological context, the public health goal is to prevent the occurrence and deterioration of the disease, and the vaccination campaign is the first-line method to counteract the COVID-19 pandemic. As far, the WHO has already granted several COVID-19 vaccines to prevent COVID-19. However, we have to face numerous challenges, including the delivery of billions of doses to the global public[8],[9] and SARS-CoV-2 variants undermining the effectiveness of all types of vaccines.[10] Although scientists have developed several efficacious and safe COVID-19 vaccines and the general public has a high acceptance of vaccination,[11],[12] we have to face the fact that millions of people are suffering from COVID-19. Those COVID-19 patients should take effective and safe treatment immediately, rather than injecting COVID-19 vaccines. Numerous clinical trials and studies have been conducted to develop and assess various therapeutic options, including pharmacological and non-pharmacological interventions.[13],[14] However, no specific therapy has been developed that treats COVID-19, thus encouraging extensive investigation of drug candidates.
Traditional Chinese Medicine (TCM) could be a potential candidate for treating COVID-19. TCM has played an indispensable role in treating several epidemic disease outbreaks. For example, in 2003, TCM was used to prevent and treat severe acute respiratory syndrome,[15] which had achieved remarkable therapeutic effects. In 2009, TCM had curative effects on the H1N1 influenza pandemic.[16] Similarly, TCM played a significant role in the fight against the COVID-19 pandemic and saved many people's lives in China. TCM is one of the oldest forms of medication in the world, including Chinese herbal medicine (CHM) and Chinese patent medicine (CPM).[17],[18] CHM refers to Chinese botanical medicines (e.g. roots, stems, leaves, and fruit), animal drugs (e.g. internal organs, skin, bones, and organs), and mineral drugs.[17] Based on CHM as raw material, CPM is made from a variety of different dosage forms of TCM products after preparation and processing.[17] To date, the major therapeutic method for COVID-19 patients is still standard care, which consisted of supportive treatments, including supplemental oxygen therapy, daily symptom and vital sign monitoring, clinical laboratory testing, correction of water, electrolyte and acid base imbalances, and administration of antiviral agents and antibiotic agents if a bacterial infection was found. Several medications, including remdesivir, hydroxychloroquine, chloroquine, lopinavir, favipiravir, ribavirin, ritonavir, interferons, azithromycin, capivasertib, and bevacizumab,[9] are currently used in clinical trials for COVID-19. However, because of the lack of convincing evidence, the safety and efficacy of Western Medicine (WM) monotherapy for COVID-19 patients could require further investigation in clinical trials. Hence, TCM may bring hope for the treatment of COVID-19. TCM combined with WM has been widely used in China during the COVID-19 pandemic.[19] Furthermore, some evidence suggests that TCM combined with WM for COVID-19 may have better effects than either treatment modality alone.[20],[21],[22],[23],[24],[25]
Several systematic reviews of the efficacy of TCM for the treatment of COVID-19 have been conducted.[26],[27],[28] However, most of these reviews included incomplete studies and reported various clinical outcomes, thereby providing limited clinical guidance, especially with regard to case fatality rates among severe/critical COVID-19 patients. Therefore, we conducted the present systematic review to comprehensively summarize the safety and efficacy of TCM combined with WM treatment for COVID-19.
In this study, we systematically analyzed the available literature and conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies to evaluate the safety and efficacy of TCM combined with WM for the treatment of COVID-19. Our findings may provide summary evidence for clinicians when using TCM. We also analyzed the efficacy of CHM and CPM. If the hospital does not have CHM, it can be replaced by CPM. Because no effective treatment interventions are available for severe/critical COVID-19 patients, the case fatality rate is still high among these patients. Thus, we performed a subgroup analysis of the case fatality according to disease severity, which may provide clinical evidence for the treatment of severe/critical COVID-19 patients using TCM combined with WM. Finally, we evaluated available and potential therapeutic interventions to control COVID-19 globally.
| Methods | | |
This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) checklist[29] and Cochrane Handbook for Systematic Reviews.[30] The protocol for this study was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42021274619).
Search strategy
We searched PubMed, Web of Science, Embase, Medline, Cochrane library, China National Knowledge Infrastructure, and Wanfang Data for studies from database inception to June 1, 2021. The search was enhanced by scanning the bibliographies of the identified articles using the terms “Traditional Chinese Medicine,” “novel coronavirus pneumonia,” “2019-nCoV,” “COVID-19,” and “SARS-CoV-2.” The search strategy for each database is provided in detail in the Electronic search strategy section in the Supplement.
Eligibility criteria
Study selection was based on a PRISMA flow diagram[31] [Supplementary Table 1]. Articles were retained if they met the following inclusion criteria: (1) the study population included COVID-19 confirmed patients who had been diagnosed according to guidelines that were published by the National Health Commission People's Republic of China,[32] (2) the intervention was CPM or CHM combined with baseline medication or standard treatment, (3) the control group consisted of baseline medication or standard treatment, such as oxygen therapy, antiviral medications, and symptomatic therapies, and (4) the study types were RCTs, cohort studies, or case–control studies.
Two of the authors (TSS and DJH) independently reviewed all of the identified titles and abstracts for eligibility. Articles were first screened based on the title and abstract. When uncertainty occurred, the full texts were reviewed. If disagreement existed between these two authors, two other authors (CX and YYB) were consulted. The same author performed the full article reviews. Reasons for these excluded studies were recorded.
Data extraction and quality appraisal
Data were extracted and recorded from all studies that met the inclusion criteria. Any disagreements were resolved by consensus. Each study was read in full to extract and record study details on a standardized extraction form, including the following information: (1) basic information (e.g. first author, year published, title, study type, location of study, and language), (2) participants' baseline characteristics (e.g. sample size, age, gender distribution, and disease severity), (3) details of intervention and control group (e.g. treatment prescription and treatment duration), and (4) clinical efficacy outcomes (e.g. clinical effective rate, improvements in chest computed tomography [CT] manifestations, rate and time of major symptom disappearance, negative conversion rate and time of viral test, and day of discharge) and clinical safety outcomes (e.g. rate of adverse events and case fatality rate).
Outcomes
The primary outcomes were the overall clinical efficacy rate, overall adverse events, and overall case fatality rate. Secondary outcomes included (1) improvements in chest CT manifestations (e.g. number of patients for whom CT lesions disappeared or were reduced after treatment), (2) negative conversion rate and time of viral test, (3) disappearance rate and time of common symptoms (e.g. fever, cough, and fatigue), (4) day of discharge, (5) rate of major adverse events (e.g. nausea, vomiting, diarrhea, and liver damage), and (6) case fatality rate among severe/critical patients.
Risk of bias assessment
Two reviewers independently assessed the risk of bias for all included studies. The risk of bias assessment tool from the Cochrane Handbook was used to assess the methodological quality of RCTs,[33] and the Newcastle-Ottawa Scale was used to assess the quality of case–control studies and cohort studies.[34] For RCTs, the Cochrane Risk of Bias assessment tool[33] was used, consisting of seven domains: selection bias (random sequence generation and allocation concealment), performance bias (blinding of participants and personnel), detection bias (blinding of outcome assessment), attrition bias (incomplete outcome data), reporting bias (selective reporting), and other sources of bias (baseline imbalance). A global score was assigned to each study (sum of domains with “low risk of bias”). Scores ranged from 0 to 7. Higher scores indicated a lower risk of bias and better quality of the study. For cohort and case–control studies, the Newcastle-Ottawa Scale consisted of three domains: selection of exposure, comparability, and assessment of outcome.[31],[34] The maximum score was 9. Studies with scores ≥7 were graded as high quality. Studies with scores <7 were considered low quality.
Statistical analysis
Procedures and formulas for conducting the meta-analysis were based on recommendations by Lipsey and Wilson.[35] Review Manager 5.4.1 software was used to perform the statistical analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for dichotomous data. Weighted mean differences and 95% CIs were calculated for continuous variables to determine effect sizes. Statistical heterogeneity was assessed using the I2 statistic. Values of <25%, 25%–50%, and >50% indicated low, moderate, and high levels of heterogeneity, respectively.[36] Because of the heterogeneity of drugs that were used in different studies, a random effect model was adopted to analyze these results. We performed subgroup analyses if sufficient data were available, based on the study design, TCM type, and level of severity of COVID-19 patients, which may affect overall clinical safety and efficacy outcomes. Funnel plots were generated to assess publication bias. Statistical significance was set at P < 0.05.
| Results | | |
This section may be divided by subheadings. However, it should provide a concise and precise description of the experimental results, their interpretation, as well as the experimental conclusions that can be drawn.
Eligible studies
A total of 11,554 records were generated from the database searches. After eliminating duplicates, the titles and abstracts of 9158 records were screened. We retrieved and reviewed 96 full-text articles, 31 of which met all of the eligibility criteria for inclusion, including 15 RCTs, 13 case–control studies, and three cohort studies. The detailed results of the selection process for studies that were included in the meta-analyses are shown in [Figure 1].
The 31 studies reported data from 14,579 participants (1697 from RCTs, 10,674 from case–control studies, and 2208 from cohort studies). Of the 31 studies that were included in the systematic review, 15 reported on CPM combined with WM in the intervention group, and the remaining studies reported on CHM plus WM. These medications that were used in the control group were usually antiviral agents, such as lopinavir, ribavirin, and arbidol, combined with antibiotic drugs or corticosteroids when bacterial infection or a cytokine storm occurred. Details of the sample size, study design, and TCM intervention of these included 31 studies are provided in [Table 1], and the composition of TCM in each trial is summarized in Supplementary [Table 2]. | Table 2: Subgroup analysis of clinical efficacy rate and case fatality rate in Traditional Chinese Medicine plus Western Medicine group versus control group
Click here to view |
Publication bias
We used Review Manager 5.4.1 software to test publication bias. The low or mild risk of publication bias is provided in [Supplementary Figure 1], [Supplementary Figure 2], [Supplementary Figure 3], [Supplementary Figure 4], [Supplementary Figure 5], [Supplementary Figure 6], [Supplementary Figure 7], [Supplementary Figure 8], [Supplementary Figure 9], [Supplementary Figure 10], [Supplementary Figure 11], [Supplementary Figure 12], [Supplementary Figure 13], [Supplementary Figure 14], [Supplementary Figure 15], [Supplementary Figure 16], [Supplementary Figure 17], [Supplementary Figure 18].
Risk of bias
Of the 15 RCTs,[20],[23],[39],[41],[44],[47],[51],[52],[56],[57],[58],[60],[61],[62],[65] three[39],[51],[62]had a score of 3 for risk of bias [Supplementary Table 3]. Thirteen case–control and cohort studies[37],[40],[42],[43],[45],[48],[49],[50],[53],[54],[55],[59],[63] and three cohort studies[38],[46],[64] were assessed for quality using the Newcastle-Ottawa Scale. The maximum quality score was 9, ranging from 6 to 8. The median score was 6.9 [Supplementary Table 4]. These studies had high or moderate quality.
Primary outcome
Eleven studies reported the overall clinical efficacy rate of TCM combined with WM.[20],[40],[42],[51],[52],[54],[56],[57],[59],[60] The overall clinical efficacy rate of the TCM plus WM group was better than the control group, and the difference was statistically significant [OR = 2.48, 95% CI = 1.90–3.24, I2 = 4%; [Figure 2]]. There was no significant difference in overall adverse events between TCM plus WM group and the control group among eight studies[20],[39],[42],[47],[56],[57],[61],[65] [OR = 1.43, 95% CI = 0.63-3.23, I2 = 75%; [Figure 3]]. Eleven studies compared the case fatality rate for COVID-19 between TCM plus WM group and the control group.[38],[43],[44],[48],[49],[54],[55],[56],[59],[64] Outcomes indicated that the case fatality rate in the TCM plus WM group was significantly lower than the control group [OR = 0.31, 95% CI = 0.19-0.49, I2 = 80%; [Figure 4]]. | Figure 2: The clinical efficacy rate, the improvement in chest CT manifestations, the negative conversion rate of viral test and the major symptoms disappearance rate in the TCM combined with WM group versus WM group
Click here to view |
 | Figure 3: The overall and major adverse events and the case fatality rate in the TCM combined with WM group versus WM group
Click here to view |
 | Figure 4: The negative conversion day of viral test, the day of discharge and the overall and major symptoms disappearance time in the TCM combined with WM group versus WM group
Click here to view |
Secondary outcomes
Symptom disappearance rate and time
This meta-analysis compared the effects of TCM combined with WM on clinical symptoms, including fever, cough, and fatigue. Eight studies reported rates of fever disappearance,[37],[39],[41],[45],[47],[58],[63],[65] and seven studies reported rates of cough and fatigue disappearance.[37],[39],[41],[47],[58],[63],[65] These results showed that rates of fever disappearance [OR = 3.41, 95% CI = 2.10-5.56, I2 = 0%; [Figure 2]], cough disappearance [OR = 3.33, 95% CI = 2.14-5.17, I2 = 0%; [Figure 2]], and fatigue disappearance [OR = 3.01, 95% CI = 1.84-4.93, I2 = 0%; [Figure 2]] were higher in the TCM plus WM group compared with the control group. Five studies compared disappearance time of overall symptoms between TCM plus WM group and control group.[20],[47],[51],[59],[61] [SMD = −0.53, 95% CI = −1.24–0.17, I2 = 96%; [Figure 4]]. Seven studies,[20],[37],[44],[45],[59],[61],[63] four studies,[20],[37],[42],[61] and three studies[20],[37],[42] reported the time of disappearance of fever, cough, and fatigue, respectively. Although the difference in disappearance time of cough and fatigue was not statistically significant, TCM plus WM decreased the disappearance time of fever in COVID-19 patients [SMD = −0.70, 95% CI = −1.12–−0.28, I2 = 83%; [Figure 4]]. TCM combined with WM improved the rate of symptom disappearance and shortened the time of fever disappearance compared with WM monotherapy.
Improvements in chest CT manifestations
Thirteen studies evaluated improvements in chest CT manifestations.[20],[37],[41],[42],[44],[52],[59],[60],[62] The meta-analysis revealed significant improvements in CT findings in the TCM plus WM group [OR = 2.21, 95% CI = 1.75–2.80, I2 = 0%; [Figure 2]].
Negative conversion rate and time of viral test
This meta-analysis compared the negative conversion rate[23],[40],[46],[47],[50] and time of viral test[20],[44],[61],[63] between TCM plus WM group and control group. These results suggested that TCM combined with WM improved the negative conversion rate (OR = 2.84, 95% CI = 1.70–4.74, I2 = 23%; [Figure 2]) and reduced the negative conversion time of viral test [SMD = −0.59, 95% CI = -0.85 to -0.33, I2 = 41%; [Figure 4]].
Day of discharge
Six studies recorded the day of discharge among COVID-19 patients.[37],[51],[54],[55],[59] The meta-analysis showed no significant difference in the length of hospitalization of COVID-19 patients between TCM plus WM group and control group [SMD = 0.26, 95% CI = -0.72–1.25, I2 = 96%; [Figure 4]].
Rate of adverse effects (nausea, vomiting, diarrhea, and liver damage)
In addition to overall adverse effects, the meta-analysis evaluated the rate of some common adverse effects, including nausea, vomiting, diarrhea, and liver damage, which were reported in six,[20],[42],[44],[47],[56],[61] three,[20],[47],[56] nine,[20],[42],[44],[47],[56],[57],[61],[63] and three[20],[49],[63] studies, respectively. No significant difference in nausea, vomiting, diarrhea, or liver damage was found between TCM plus WM group and control group [Figure 3].
Subgroup analysis of clinical effective rate and case fatality rate
The subgroup analysis evaluated the clinical efficacy rate and case fatality rate based on study type (RCTs vs. non-RCTs), TCM type (CPM vs. CHM), and COVID-19 patient type (severe/critical patients vs. mixed patients). The result revealed a larger effect size in non-RCTs (case–control studies and cohort studies) than in RCTs (OR = 3.12, 95% CI = 1.61-6.06 vs. OR = 2.35, 95% CI = 1.75-3.15, P = 0.17). Similarly, compared with CPM, CHM had a larger effect size with regard to the overall clinical efficacy rate (OR = 3.52, 95% CI = 1.78–6.95 vs. OR = 2.31, 95% CI = 1.75–3.06, P = 0.06). Furthermore, TCM combined with WM in severe/critical patients decreased the case fatality rate more than in mixed patients (OR = 0.31, 95% CI = 0.15–0.63 vs. OR = 0.19, 95% CI = 0.11–0.33, P = 0.40). However, no significant difference was found among these subgroups. Detailed results of these analyses are shown in [Table 2].
| Discussion | | |
The present systematic review demonstrated that TCM combined with WM therapy may be more effective than WM monotherapy for COVID-19 patients, especially with regard to improving clinical efficacy and lowering the case fatality rate. Our results also showed no significant difference in overall adverse events between TCM plus WM therapy and WM monotherapy in these included studies. Our study could provide evidence of additional treatment options during the COVID-19 pandemic.
COVID-19 has become a severe public health issue, one of the leading causes of death worldwide. Researchers and scientists have tried their best to discover therapeutic and preventive measures, including drugs and vaccines. In fact, several types of vaccines, which could confer protection against COVID-19 in different ways, were already administrated all over the world. However, SARS-CoV-2 variants compromised the effectiveness of all types of vaccines. Nowadays, millions of confirmed cases need to get effective treatment at once. COVID-19 treatment is still solely based on clinical management through supportive care, which encourages extensive investigation of therapeutic and methodological candidates. TCM combined with WM may be one of these promising candidates. Our findings are consistent with previously published systematic reviews and meta-analyses.[26],[27],[28],[66] Du et al. showed that CHM combined with conventional therapy may be safe and effective for the treatment of mild to moderate COVID-19,[26] but this previous study only included 12 RCTs and reported only a few outcomes. Luo et al. performed a systematic review and meta-analysis of add-on effects of CHM on COVID-19,[28] but this previous study did not report the effect of CHM on the case fatality rate or symptom disappearance time. Liu et al. reported that integrated medicine could have better effects and did not increase adverse drug reactions for COVID-19,[27] but the result of this study included few clinical outcomes. Luo et al. suggested that a Chinese herbal formula could be an alternative approach for the prevention of COVID-19 in high-risk populations,[66] but the conclusion of this study was only based on indirect evidence (from SARS and H1N1). The present study included 31 studies, 15 of which were RCTs, which had more RCTs and represented more reliable evidence than other systematic reviews and meta-analyses. Moreover, many clinical efficacy outcomes were more systematically and comprehensively analysed in our study, which included the clinical efficacy rate, adverse effects, case fatality rate, and symptom disappearance time. We examined the quality of these included studies based on the risk of bias assessment tool. We also compared the case fatality rate between severe/critical patients and mixed (mild/common/moderate) patients, showing that TCM combined with WM may be more effective for severe/critical patients. Among severe/critical patients with COVID-19, organ failure and acute respiratory distress syndrome (ARDS) occurred rapidly, which could cause death in a short period. Cytokine storm plays a significant role in disease aggravation, which is considered to be the major reason of ARDS and organ failure. Clinical studies have confirmed the presence of cytokine storm in severe/critical patients with COVID-19. Therefore, suppressing the cytokine storm is an important therapy for the treatment of severe/critical patients. TCM drugs consisted of many active ingredients that can target various pathways for the treatment of cytokine storm. In addition, the network pharmacological results demonstrated that TCM played some important roles in the management of COVID-19, including anti-virus and anti-inflammation. Above all, TCM combined with WM may be an effective treatment option for severe/critical patients.
In the CPM studies, five[20],[37],[45],[46],[52] reported evidence that could support the safety and efficacy of Lianhuaqingwen granules or capsules combined with WM as a method for improving clinical efficacy in COVID-19 patients. The remaining studies[23],[41],[42],[43],[50],[56],[60],[61],[65] involved Lianhuaqingke granules, Jinhuaqingke granules, Reyanning mixture, Xiyanping injection, Xuebijing injection, Shuanghuanlian oral liquids, Shufengjiedu capsules, and Shenhuang granules. The preparations of CHM in our included studies were Qingfeipaidu tang (two studies), Xuanfeipaidu tang, Mahuangliujun tang, and so on.[38],[39],[40],[44],[48],[51],[53],[54],[55],[56],[57],[58],[62],[63],[64]
With regard to the possible mechanism of TCM for the treatment of COVID-19, one study showed that Lianhuaqingwen capsules could inhibit the cytokine storm induced by SARS-COV-2 by inhibiting the expression of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), C-C motif chemokine ligand 2 (CCL-2)/monocyte chemoattractant protein 1 (MCP-1), and C-X-C motif chemokine 10 (CXCL-10)/interferon-induced protein 10 (IP-10).[22] Lianhuaqingwen capsules were also reported to have antiviral activity in vitro and inhibited the replication of SARS-COV-2 in cells. Xuebijing exerted a good downregulating effect on inflammatory reactions. For example, one animal study found that Xuebijing downregulated the expression of inflammatory cytokines, such as IL-6, TNF-α, MCP-1, macrophage chemoattractant protein 2 (MIP-2), and IL-10.[67] Ren et al. suggested that the mechanism of action of Qingfeipaidu Decoction involved the inhibition of arachidonic acid metabolism and regulation of cytokine levels.[21] In the study, the Toll-like receptor signaling pathway was shown to play an important role in the therapeutic effect of Qingfeipaidu Decoction against COVID-19.[68] In the present review, we found no significant difference between the CPM and CHM subgroups, although CHM treatment was reported to result in more effective improvements in the overall clinical efficacy rate compared with CPM treatment. Thus, hospitals may be able to take CPM combined with WM for the treatment of COVID-19, if without CHM. To our knowledge, the present study was the first to analyze clinical efficacy according to TCM type.
In addition, apart from pneumonia and ARDS, COVID-19 could also cause several complications, including acute liver injury, cardiac injury, kidney injury, and secondary inflammatory response.[69] Among these complications, COVID-19 confirmed patients who suffer from cardiac injury seem to be associated with higher mortality.[70] Approximately 12% of COVID-19-hospitalized patients could be accompanied by the myocardial injury.[71] Compared with those without myocardial injury, COVID-19 patients with myocardial injury presented higher mortality (51.2% vs. 4.5%; P < 0.001).[72] In fact, myocardial injury has been an independently risk factor for mortality.[72] In addition, Shi et al. reported that myocardial injury was associated with a higher need for ventilations, namely non-invasive (46.3% vs. 3.9%) or invasive ventilation (22.0% vs. 4.2%).[72] Meanwhile, COVID-19 confirmed patients, who suffered from myocardial injury, had a higher incidence of ARDS (58.5% vs. 14.7%) and complications, including acute kidney injury and coagulopathy, 8.5% and 7.3%, respectively.[72]
We recorded and discussed the safety and efficacy of TCM combined with WM for COVID-19 patients with myocardial injury, in those studies which reported the plasma markers of myocardial injury at the before and after treatment. At last, we found that eight included studies reported the recovery of laboratory indicators, such as creatine kinase (CK), CK-myocardial band (CK-MB), cardiac troponin I (cTnI), myoglobin (MYO) and lactate dehydrogenase (LDH), or the complications of cardiac injury between two groups of patients on discharge. At endpoints, in terms of LDH, Xin et al.,[55] Xia et al.[59] and Guo et al.[40] found that the recovery rate was higher in TCM combined with WM group than WM group (P < 0.05). Xin et al.[55] also found that CK and CK-MB levels declined only in the TCM plus WM group (P < 0.05) and Xia et al.[59] showed that the recovery rate of CK-MB level was higher in the TCM combined with WM group than the control group (P < 0.05). In addition, Feng et al.[43] found that, compared with the control group, treatment group patients were less likely to develop cardiac injury (P < 0.05) and Zhou et al.[56] also found that some adverse events, such as cardiopulmonary failure and cardiac arrest, D-dimer was lower after administration of TCM (P < 0.05). However, no significant difference was found in three studies,[47],[51],[61] which only examined serum markers of myocardial injury at the portion of patients or had an imbalance in baseline characteristics. In the future, some larger randomized control trials would assist in defining the effect of TCM combined with WM on the treatment of cardiac injury caused by COVID-19.
The strength of the present study is to help us understand safety and efficacy of TCM combined with WM for the treatment of COVID-19. Although some articles have been published on the topic of TCM in the treatment of COVID-19, the present article included more RCTs and represented more reliable evidence than other systematic reviews and meta-analyses. Meanwhile, the review made subgroup analysis to evaluate the efficacy and safety of TCM in the treatment of COVID-19. We compared the case fatality rate between severe/critical patients and mixed patients, showing that TCM combined with WM may be more effective for severe/critical patients. When treating severe/critical patients, TCM combined with WM may be an important treatment option for doctors. We also compared the clinical efficacy rate between CPM and CHM subgroup, which was the first to analyze clinical efficacy according to TCM type.
The present review and meta-analysis has some limitations. First, we found substantial heterogeneity among the included studies. TCM and WM that were used in the intervention group and control group involved many different medications and treatments. Although we performed subgroup analyses and used a random effect model to mitigate potential bias, the large heterogeneity of these studies and results required careful interpretation. Second, our review only included the Chinese and English literature, which could introduce bias that arose from language. Third, the reported effect sizes were biased toward higher numbers, because investigators were more likely to publish positive results. Fourth, most of RCTs in our study had only low or medium quality. Therefore, further large-sample clinical studies and multicenter RCTs are needed. Further updates are expected to complement the results of the present systematic review at the end of the COVID-19 era. Despite these limitations, the present systematic review and meta-analysis could provide useful information about the safety and efficacy of TCM combined with WM for the treatment of COVID-19.
| Conclusions | | |
The present systematic review and meta-analysis showed that TCM combined with WM could have better effects than monotherapy for the treatment of COVID-19. Future studies with larger samples, high-quality multicenter RCTs, and research on mechanisms of action are still needed, which will likely clarify the safety, efficacy, and mechanism of action of TCM both alone and combined with WM. Some larger randomized control trials would assist in defining the effect of TCM combined with WM on the treatment of COVID-19 complications such as cardiac injury. Additional research is also needed to evaluate the potential of TCM for improving sequelae after hospital discharge.
Supplementary materials
Supplementary material associated with this article can be found in the online version. [Supplementary Table 1]. PRISMA checklist. [Supplementary Table 3]. Risk of bias of included randomized controlled trials. [Supplementary Table 4]. Quality of included case–control and cohort studies. [Supplementary Figure 1], [Supplementary Figure 2], [Supplementary Figure 3], [Supplementary Figure 4], [Supplementary Figure 5], [Supplementary Figure 6], [Supplementary Figure 7], [Supplementary Figure 8], [Supplementary Figure 9], [Supplementary Figure 10], [Supplementary Figure 11], [Supplementary Figure 12], [Supplementary Figure 13], [Supplementary Figure 14], [Supplementary Figure 15], [Supplementary Figure 16], [Supplementary Figure 17], [Supplementary Figure 18]. Publication bias.
Financial support and sponsorship
This research was partly supported by Natural Science Foundation of China (no. 81761128036, 82171514, 81821092, and 31900805), the National Key Research and Development Program of China (no. 2021YFC0863700 and 2019YFA0706200), the PKU-Baidu Fund (no. 2020BD011), and National Programs for Brain Science and Brain-like Intelligence Technology of China (2021ZD0200800, 2021ZD0200700).
Conflicts of interest
Prof. Lin Lu is the Editor-in-Chief of the Heart and Mind journal. The article was subject to the journal's standard procedures, with peer review handled independently of Prof. Lin Lu and the research groups. There are no conflicts of interest.
| Electronic Search Strategy | | |
Electronic search strategy in PubMed, Web of Science, Embase, Medline, Cochrane library, China National Knowledge Infrastructure, and Wanfang
Search date: June 1, 2021
PubMed: 2366
((((((((((((((((((((((((((((((((((((((COVID-19[MeSH]) OR (COVID-19)) OR (COVID 19)) OR (COVID-19 Virus Disease)) OR (COVID 19 Virus Disease)) OR (COVID-19 Virus Diseases)) OR (Disease, COVID-19 Virus)) OR (Virus Disease, COVID-19)) OR (COVID-19 Virus Infection)) OR (COVID 19 Virus Infection)) OR (COVID-19 Virus Infections)) OR (Infection, COVID-19 Virus)) OR (Virus Infection, COVID-19)) OR (2019-nCoV Infection)) OR (2019 nCoV Infection)) OR (2019-nCoV Infections)) OR (Infection, 2019-nCoV)) OR (Coronavirus Disease-19)) OR (Coronavirus Disease 19)) OR (2019 Novel Coronavirus Disease)) OR (2019 Novel Coronavirus Infection)) OR (2019-nCoV Disease)) OR (2019 nCoV Disease)) OR (2019-nCoV Diseases)) OR (Disease, 2019-nCoV)) OR (COVID19)) OR (Coronavirus Disease 2019)) OR (Disease 2019, Coronavirus)) OR (SARS Coronavirus 2 Infection)) OR (SARS-CoV-2 Infection)) OR (Infection, SARS-CoV-2)) OR (SARS CoV 2 Infection)) OR (SARS-CoV-2 Infections)) OR (COVID-19 Pandemic)) OR (COVID 19 Pandemic)) OR (COVID-19 Pandemics)) OR (Pandemic, COVID-19))) AND (((((((((((((((((((Medicine, Chinese Traditional[MeSH]) OR (Traditional Chinese Medicine)) OR (Chung I Hsueh)) OR (Hsueh, Chung I)) OR (Traditional Medicine, Chinese)) OR (Zhong Yi Xue)) OR (Chinese Traditional Medicine)) OR (Chinese Medicine, Traditional)) OR (Traditional Tongue Diagnosis)) OR (Tongue Diagnoses, Traditional)) OR (Tongue Diagnosis, Traditional)) OR (Traditional Tongue Diagnoses)) OR (Traditional Tongue Assessment)) OR (Tongue Assessment, Traditional)) OR (Traditional Tongue Assessments)) OR (((((((((((((((((((((((((((((Medicine, East Asian Traditional[MeSH]) OR (Oriental Medicine, Traditional)) OR (Medicine, Traditional Oriental)) OR (Traditional Oriental Medicine)) OR (Traditional Oriental Medicines)) OR (Traditional Medicine, Oriental)) OR (Traditional East Asian Medicine)) OR (Medicine, Traditional, East Asia)) OR (Traditional Medicine, East Asia)) OR (Traditional Far Eastern Medicine)) OR (East Asian Traditional Medicine)) OR (Oriental Traditional Medicine)) OR (Medicine, Oriental Traditional)) OR (East Asian Medicine)) OR (East Asian Medicines)) OR (Medicine, East Asian)) OR (Oriental Medicine)) OR (Medicine, Far East)) OR (East Medicine, Far)) OR (East Medicines, Far)) OR (Far East Medicine)) OR (Far East Medicines)) OR (Medicines, Far East)) OR (Medicine, East Asia)) OR (Asia Medicines, East)) OR (East Asia Medicine)) OR (East Asia Medicines)) OR (Medicines, East Asia)) OR (Medicine, Oriental))) OR (((((((((((((((((Medicine, Traditional[MeSH]) OR (Traditional Medicine)) OR (Home Remedies)) OR (Home Remedy)) OR (Remedies, Home)) OR (Remedy, Home)) OR (Medicine, Primitive)) OR (Primitive Medicine)) OR (Medicine, Folk)) OR (Folk Medicine)) OR (Medicine, Indigenous)) OR (Indigenous Medicine)) OR (Folk Remedies)) OR (Folk Remedy)) OR (Remedies, Folk)) OR (Remedy, Folk)) OR (Ethnomedicine))) OR (((((((Drugs, Chinese Herbal[MeSH]) OR (Chinese Drugs, Plant)) OR (Chinese Herbal Drugs)) OR (Herbal Drugs, Chinese)) OR (Plant Extracts, Chinese)) OR (Chinese Plant Extracts)) OR (Extracts, Chinese Plant))) OR ((((((((Medicine, Tibetan Traditional[MeSH]) OR (Tibetan Traditional Medicine)) OR (Tibetan Medicine, Traditional)) OR (Medicine, Traditional Tibetan)) OR (Traditional Tibetan Medicine)) OR (Tibetan Medicine)) OR (Medicine, Tibetan)) OR (Traditional Medicine, Tibetan)))
Web of science: 5563
TS=((((((((((((((((((((((((((((((((((((((COVID-19[Mesh]) OR (COVID-19)) OR (COVID 19)) OR (COVID-19 Virus Disease)) OR (COVID 19 Virus Disease)) OR (COVID-19 Virus Diseases)) OR (Disease, COVID-19 Virus)) OR (Virus Disease, COVID-19)) OR (COVID-19 Virus Infection)) OR (COVID 19 Virus Infection)) OR (COVID-19 Virus Infections)) OR (Infection, COVID-19 Virus)) OR (Virus Infection, COVID-19)) OR (2019-nCoV Infection)) OR (2019 nCoV Infection)) OR (2019-nCoV Infections)) OR (Infection, 2019-nCoV)) OR (Coronavirus Disease-19)) OR (Coronavirus Disease 19)) OR (2019 Novel Coronavirus Disease)) OR (2019 Novel Coronavirus Infection)) OR (2019-nCoV Disease)) OR (2019 nCoV Disease)) OR (2019-nCoV Diseases)) OR (Disease, 2019-nCoV)) OR (COVID19)) OR (Coronavirus Disease 2019)) OR (Disease 2019, Coronavirus)) OR (SARS Coronavirus 2 Infection)) OR (SARS-CoV-2 Infection)) OR (Infection, SARS-CoV-2)) OR (SARS CoV 2 Infection)) OR (SARS-CoV-2 Infections)) OR (COVID-19 Pandemic)) OR (COVID 19 Pandemic)) OR (COVID-19 Pandemics)) OR (Pandemic, COVID-19))) AND
TS=(((((((((((((((((((Medicine, Chinese Traditional[MeSH]) OR (Traditional Chinese Medicine)) OR (Chung I Hsueh)) OR (Hsueh, Chung I)) OR (Traditional Medicine, Chinese)) OR (Zhong Yi Xue)) OR (Chinese Traditional Medicine)) OR (Chinese Medicine, Traditional)) OR (Traditional Tongue Diagnosis)) OR (Tongue Diagnoses, Traditional)) OR (Tongue Diagnosis, Traditional)) OR (Traditional Tongue Diagnoses)) OR (Traditional Tongue Assessment)) OR (Tongue Assessment, Traditional)) OR (Traditional Tongue Assessments)) OR (((((((((((((((((((((((((((((Medicine, East Asian Traditional[MeSH]) OR (Oriental Medicine, Traditional)) OR (Medicine, Traditional Oriental)) OR (Traditional Oriental Medicine)) OR (Traditional Oriental Medicines)) OR (Traditional Medicine, Oriental)) OR (Traditional East Asian Medicine)) OR (Medicine, Traditional, East Asia)) OR (Traditional Medicine, East Asia)) OR (Traditional Far Eastern Medicine)) OR (East Asian Traditional Medicine)) OR (Oriental Traditional Medicine)) OR (Medicine, Oriental Traditional)) OR (East Asian Medicine)) OR (East Asian Medicines)) OR (Medicine, East Asian)) OR (Oriental Medicine)) OR (Medicine, Far East)) OR (East Medicine, Far)) OR (East Medicines, Far)) OR (Far East Medicine)) OR (Far East Medicines)) OR (Medicines, Far East)) OR (Medicine, East Asia)) OR (Asia Medicines, East)) OR (East Asia Medicine)) OR (East Asia Medicines)) OR (Medicines, East Asia)) OR (Medicine, Oriental))) OR (((((((((((((((((Medicine, Traditional[MeSH]) OR (Traditional Medicine)) OR (Home Remedies)) OR (Home Remedy)) OR (Remedies, Home)) OR (Remedy, Home)) OR (Medicine, Primitive)) OR (Primitive Medicine)) OR (Medicine, Folk)) OR (Folk Medicine)) OR (Medicine, Indigenous)) OR (Indigenous Medicine)) OR (Folk Remedies)) OR (Folk Remedy)) OR (Remedies, Folk)) OR (Remedy, Folk)) OR (Ethnomedicine))) OR (((((((Drugs, Chinese Herbal[MeSH]) OR (Chinese Drugs, Plant)) OR (Chinese Herbal Drugs)) OR (Herbal Drugs, Chinese)) OR (Plant Extracts, Chinese)) OR (Chinese Plant Extracts)) OR (Extracts, Chinese Plant))) OR ((((((((Medicine, Tibetan Traditional[MeSH]) OR (Tibetan Traditional Medicine)) OR (Tibetan Medicine, Traditional)) OR (Medicine, Traditional Tibetan)) OR (Traditional Tibetan Medicine)) OR (Tibetan Medicine)) OR (Medicine, Tibetan)) OR (Traditional Medicine, Tibetan)))
Embase: 1558
('COVID-19'/exp OR 'COVID-19':ti, ab OR 'COVID 19':ti, ab OR 'COVID-19 Virus Disease':ti, ab OR 'COVID 19 Virus Disease':ti, ab OR 'COVID-19 Virus Diseases':ti, ab OR 'Disease, COVID-19 Virus':ti, ab OR 'Virus Disease, COVID-19':ti, ab OR 'COVID-19 Virus Infection':ti, ab OR 'COVID 19 Virus Infection':ti, ab OR 'COVID-19 Virus Infections':ti, ab OR 'Infection, COVID-19 Virus':ti, ab OR 'Virus Infection, COVID-19':ti, ab OR '2019-nCoV Infection':ti, ab OR '2019 nCoV Infection':ti, ab OR '2019-nCoV Infections':ti, ab OR 'Infection, 2019-nCoV':ti, ab OR 'Coronavirus Disease-19':ti, ab OR 'Coronavirus Disease 19':ti, ab OR '2019 Novel Coronavirus Disease':ti, ab OR '2019 Novel Coronavirus Infection':ti, ab OR '2019-nCoV Disease':ti, ab OR '2019 nCoV Disease':ti, ab OR '2019-nCoV Diseases':ti, ab OR 'Disease, 2019-nCoV':ti, ab OR 'COVID19':ti, ab OR 'Coronavirus Disease 2019':ti, ab OR 'Disease 2019, Coronavirus':ti, ab OR 'SARS Coronavirus 2 Infection':ti, ab OR 'SARS-CoV-2 Infection':ti, ab OR 'Infection, SARS-CoV-2':ti, ab OR 'SARS CoV 2 Infection':ti, ab OR 'SARS-CoV-2 Infections':ti, ab OR 'COVID-19 Pandemic':ti, ab OR 'COVID 19 Pandemic':ti, ab OR 'COVID-19 Pandemics':ti, ab OR 'Pandemic, COVID-19':ti, ab) AND
('Medicine, Chinese Traditional'/exp OR 'Traditional Chinese Medicine':ti, ab OR 'Chung I Hsueh':ti, ab OR 'Hsueh, Chung I':ti, ab OR 'Traditional Medicine, Chinese':ti, ab OR 'Zhong Yi Xue':ti, ab OR 'Chinese Traditional Medicine':ti, ab OR 'Chinese Medicine, Traditional':ti, ab OR 'Traditional Tongue Diagnosis':ti, ab OR 'Tongue Diagnoses, Traditional':ti, ab OR 'Tongue Diagnosis, Traditional':ti, ab OR 'Traditional Tongue Diagnoses':ti, ab OR 'Traditional Tongue Assessment':ti, ab OR 'Tongue Assessment, Traditional':ti, ab OR 'Traditional Tongue Assessments':ti, ab OR 'Medicine, East Asian Traditional'/exp OR 'Oriental Medicine, Traditional':ti, ab OR 'Medicine, Traditional Oriental':ti, ab OR 'Traditional Oriental Medicine':ti, ab OR 'Traditional Oriental Medicines':ti, ab OR 'Traditional Medicine, Oriental':ti, ab OR 'Traditional East Asian Medicine':ti, ab OR 'Medicine, Traditional, East Asia':ti, ab OR 'Traditional Medicine, East Asia':ti, ab OR 'Traditional Far Eastern Medicine':ti, ab OR 'East Asian Traditional Medicine':ti, ab OR 'Oriental Traditional Medicine':ti, ab OR 'Medicine, Oriental Traditional':ti, ab OR 'East Asian Medicine':ti, ab OR 'East Asian Medicines':ti, ab OR 'Medicine, East Asian':ti, ab OR 'Oriental Medicine':ti, ab OR 'Medicine, Far East':ti, ab OR 'East Medicine, Far':ti, ab OR 'East Medicines, Far':ti, ab OR 'Far East Medicine':ti, ab OR 'Far East Medicines':ti, ab OR 'Medicines, Far East':ti, ab OR 'Medicine, East Asia':ti, ab OR 'Asia Medicines, East':ti, ab OR 'East Asia Medicine':ti, ab OR 'East Asia Medicines':ti, ab OR 'Medicines, East Asia':ti, ab OR 'Medicine, Oriental':ti, ab OR 'Medicine, Traditional'/exp OR 'Traditional Medicine':ti, ab OR 'Home Remedies':ti, ab OR 'Home Remedy':ti, ab OR 'Remedies, Home':ti, ab OR 'Remedy, Home':ti, ab OR 'Medicine, Primitive':ti, ab OR 'Primitive Medicine':ti, ab OR 'Medicine, Folk':ti, ab OR 'Folk Medicine':ti, ab OR 'Medicine, Indigenous':ti, ab OR 'Indigenous Medicine':ti, ab OR 'Folk Remedies':ti, ab OR 'Folk Remedy':ti, ab OR 'Remedies, Folk':ti, ab OR 'Remedy, Folk':ti, ab OR 'Ethnomedicine':ti, ab OR 'Drugs, Chinese Herbal'/exp OR 'Chinese Drugs, Plant':ti, ab OR 'Chinese Herbal Drugs':ti, ab OR 'Herbal Drugs, Chinese':ti, ab OR 'Plant Extracts, Chinese':ti, ab OR 'Chinese Plant Extracts':ti, ab OR 'Extracts, Chinese Plant':ti, ab OR 'Medicine, Tibetan Traditional'/exp OR 'Tibetan Traditional Medicine':ti, ab OR 'Tibetan Medicine, Traditional':ti, ab OR 'Medicine, Traditional Tibetan':ti, ab OR 'Traditional Tibetan Medicine':ti, ab OR 'Tibetan Medicine':ti, ab OR 'Medicine, Tibetan':ti, ab OR 'Traditional Medicine, Tibetan':ti, ab)
Medline: 833
((((((((((((((((((((((((((((((((((((((COVID-19[MeSH]) OR (COVID-19)) OR (COVID 19)) OR (COVID-19 Virus Disease)) OR (COVID 19 Virus Disease)) OR (COVID-19 Virus Diseases)) OR (Disease, COVID-19 Virus)) OR (Virus Disease, COVID-19)) OR (COVID-19 Virus Infection)) OR (COVID 19 Virus Infection)) OR (COVID-19 Virus Infections)) OR (Infection, COVID-19 Virus)) OR (Virus Infection, COVID-19)) OR (2019-nCoV Infection)) OR (2019 nCoV Infection)) OR (2019-nCoV Infections)) OR (Infection, 2019-nCoV)) OR (Coronavirus Disease-19)) OR (Coronavirus Disease 19)) OR (2019 Novel Coronavirus Disease)) OR (2019 Novel Coronavirus Infection)) OR (2019-nCoV Disease)) OR (2019 nCoV Disease)) OR (2019-nCoV Diseases)) OR (Disease, 2019-nCoV)) OR (COVID19)) OR (Coronavirus Disease 2019)) OR (Disease 2019, Coronavirus)) OR (SARS Coronavirus 2 Infection)) OR (SARS-CoV-2 Infection)) OR (Infection, SARS-CoV-2)) OR (SARS CoV 2 Infection)) OR (SARS-CoV-2 Infections)) OR (COVID-19 Pandemic)) OR (COVID 19 Pandemic)) OR (COVID-19 Pandemics)) OR (Pandemic, COVID-19))) AND (((((((((((((((((((Medicine, Chinese Traditional[MeSH]) OR (Traditional Chinese Medicine)) OR (Chung I Hsueh)) OR (Hsueh, Chung I)) OR (Traditional Medicine, Chinese)) OR (Zhong Yi Xue)) OR (Chinese Traditional Medicine)) OR (Chinese Medicine, Traditional)) OR (Traditional Tongue Diagnosis)) OR (Tongue Diagnoses, Traditional)) OR (Tongue Diagnosis, Traditional)) OR (Traditional Tongue Diagnoses)) OR (Traditional Tongue Assessment)) OR (Tongue Assessment, Traditional)) OR (Traditional Tongue Assessments)) OR (((((((((((((((((((((((((((((Medicine, East Asian Traditional[MeSH]) OR (Oriental Medicine, Traditional)) OR (Medicine, Traditional Oriental)) OR (Traditional Oriental Medicine)) OR (Traditional Oriental Medicines)) OR (Traditional Medicine, Oriental)) OR (Traditional East Asian Medicine)) OR (Medicine, Traditional, East Asia)) OR (Traditional Medicine, East Asia)) OR (Traditional Far Eastern Medicine)) OR (East Asian Traditional Medicine)) OR (Oriental Traditional Medicine)) OR (Medicine, Oriental Traditional)) OR (East Asian Medicine)) OR (East Asian Medicines)) OR (Medicine, East Asian)) OR (Oriental Medicine)) OR (Medicine, Far East)) OR (East Medicine, Far)) OR (East Medicines, Far)) OR (Far East Medicine)) OR (Far East Medicines)) OR (Medicines, Far East)) OR (Medicine, East Asia)) OR (Asia Medicines, East)) OR (East Asia Medicine)) OR (East Asia Medicines)) OR (Medicines, East Asia)) OR (Medicine, Oriental))) OR (((((((((((((((((Medicine, Traditional[MeSH]) OR (Traditional Medicine)) OR (Home Remedies)) OR (Home Remedy)) OR (Remedies, Home)) OR (Remedy, Home)) OR (Medicine, Primitive)) OR (Primitive Medicine)) OR (Medicine, Folk)) OR (Folk Medicine)) OR (Medicine, Indigenous)) OR (Indigenous Medicine)) OR (Folk Remedies)) OR (Folk Remedy)) OR (Remedies, Folk)) OR (Remedy, Folk)) OR (Ethnomedicine))) OR (((((((Drugs, Chinese Herbal[MeSH]) OR (Chinese Drugs, Plant)) OR (Chinese Herbal Drugs)) OR (Herbal Drugs, Chinese)) OR (Plant Extracts, Chinese)) OR (Chinese Plant Extracts)) OR (Extracts, Chinese Plant))) OR ((((((((Medicine, Tibetan Traditional[MeSH]) OR (Tibetan Traditional Medicine)) OR (Tibetan Medicine, Traditional)) OR (Medicine, Traditional Tibetan)) OR (Traditional Tibetan Medicine)) OR (Tibetan Medicine)) OR (Medicine, Tibetan)) OR (Traditional Medicine, Tibetan)))
Cochrane Library: 157
#1 (((((((((((((((((((((((((((((((COVID-19)) OR (COVID 19)) OR (COVID-19 Virus Disease)) OR (COVID 19 Virus Disease)) OR (COVID-19 Virus Diseases)) OR (Disease, COVID-19 Virus)) OR (Virus Disease, COVID-19)) OR (COVID-19 Virus Infection)) OR (COVID 19 Virus Infection)) OR (COVID-19 Virus Infections)) OR (Infection, COVID-19 Virus)) OR (Virus Infection, COVID-19)) OR (2019 nCoV Infection)) OR (Coronavirus Disease-19)) OR (Coronavirus Disease 19)) OR (2019 Novel Coronavirus Disease)) OR (2019 Novel Coronavirus Infection)) OR (2019 nCoV Disease)) OR (COVID19)) OR (Coronavirus Disease 2019)) OR (Disease 2019, Coronavirus)) OR (SARS Coronavirus 2 Infection)) OR (SARS-CoV-2 Infection)) OR (Infection, SARS-CoV-2)) OR (SARS CoV 2 Infection)) OR (SARS-CoV-2 Infections)) OR (COVID-19 Pandemic)) OR (COVID 19 Pandemic)) OR (COVID-19 Pandemics)) OR (Pandemic, COVID-19))
AND
#2 (((((((((((((((((((Medicine, Chinese Traditional) OR (Traditional Chinese Medicine)) OR (Chung I Hsueh)) OR (Hsueh, Chung I)) OR (Traditional Medicine, Chinese)) OR (Zhong Yi Xue)) OR (Chinese Traditional Medicine)) OR (Chinese Medicine, Traditional)) OR (Traditional Tongue Diagnosis)) OR (Tongue Diagnoses, Traditional)) OR (Tongue Diagnosis, Traditional)) OR (Traditional Tongue Diagnoses)) OR (Traditional Tongue Assessment)) OR (Tongue Assessment, Traditional)) OR (Oriental Medicine, Traditional)) OR (Medicine, Traditional Oriental)) OR (Traditional Oriental Medicine)) OR (Traditional Oriental Medicines)) OR (Traditional Medicine, Oriental)) OR (Traditional East Asian Medicine)) OR (Medicine, Traditional, East Asia)) OR (Traditional Medicine, East Asia)) OR (Traditional Far Eastern Medicine)) OR (East Asian Traditional Medicine)) OR (Oriental Traditional Medicine)) OR (Medicine, Oriental Traditional)) OR (East Asian Medicine)) OR (East Asian Medicines)) OR (Medicine, East Asian)) OR (Oriental Medicine)) OR (Medicine, Far East)) OR (East Medicine, Far)) OR (East Medicines, Far)) OR (Far East Medicine)) OR (Far East Medicines)) OR (Medicines, Far East)) OR (Medicine, East Asia)) OR (Asia Medicines, East)) OR (East Asia Medicine)) OR (East Asia Medicines)) OR (Medicines, East Asia)) OR (Medicine, Oriental))) OR (((((((((((((((((Medicine, Traditional) OR (Traditional Medicine)) OR (Home Remedies)) OR (Home Remedy)) OR (Remedies, Home)) OR (Remedy, Home)) OR (Medicine, Primitive)) OR (Primitive Medicine)) OR (Medicine, Folk)) OR (Folk Medicine)) OR (Medicine, Indigenous)) OR (Indigenous Medicine)) OR (Folk Remedies)) OR (Folk Remedy)) OR (Remedies, Folk)) OR (Remedy, Folk)) OR (Ethnomedicine))) OR (((((((Drugs, Chinese Herbal) OR (Chinese Drugs, Plant)) OR (Chinese Herbal Drugs)) OR (Herbal Drugs, Chinese)) OR (Plant Extracts, Chinese)) OR (Chinese Plant Extracts)) OR (Extracts, Chinese Plant))) OR ((((((((Medicine, Tibetan Traditional) OR (Tibetan Traditional Medicine)) OR (Tibetan Medicine, Traditional)) OR (Medicine, Traditional Tibetan)) OR (Traditional Tibetan Medicine)) OR (Tibetan Medicine)) OR (Medicine, Tibetan)) OR (Traditional Medicine, Tibetan)))
CNKI: 705
TI=’中药’ AND SU=’新冠’+’新型冠状病毒’+’冠状病毒肺炎’+’COVID‑19’+’coronavirus‘+’2019‑nCOV’+’SARS‑COV‑2’+‘ SARS COV 2’+’COV‑19’+’CORONA’+’COVID’
Wanfang: 372
题名:(中药) and 主题:(新冠 OR 新型冠状病毒 OR 冠状病毒肺炎 OR COVID‑19 OR coronavirus OR 2019‑nCOV OR SARS‑COV‑2 OR SARS COV 2 OR COV‑19 OR CORONA OR COVID)
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]
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