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      Herbal Medicine for the Treatment of Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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          Abstract

          Background: The coronavirus disease 2019 (COVID-19) pandemic has caused a worldwide outbreak of respiratory illness. This review aims to evaluate the effectiveness and adverse events of herbal medicines for the treatment of COVID-19. Methods: Twelve databases were searched through 12 May 2020. Randomized controlled trials (RCTs) and quasi-RCTs assessing the effects of herbal medicines for the treatment of COVID-19 were eligible. The study selection and data extraction were performed by two independent reviewers. The Cochrane risk of bias tool was used for the assessment of the risk of bias in all included RCTs. Mean differences (MDs), risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and the effect sizes of the studies were pooled. Results: Seven RCTs with a total of 855 patients were included. All included trials compared the combined therapy of herbal medicine with Western medicine to Western medicine alone. The combined therapy significantly improved the total effective rate (RR 1.23, 95% CI 1.13 to 1.34, p < 0.001), cough symptom disappearance rate (RR 1.45, 95% CI 1.12 to 1.89, p = 0.005), and sputum production symptom disappearance rate (RR 1.73, 95% CI 1.19 to 2.50, p = 0.004). Beneficial effects of the combined therapy were also seen in TCM syndrome score of cough (MD −1.18, 95% CI −1.34 to −1.03, p < 0.001), fever (MD −0.62, 95% CI −0.79 to −0.45, p < 0.001), dry and sore throat (MD −0.83, 95% CI −1.45 to −0.20, p = 0.009), and fatigue (MD −0.60, 95% CI −1.04 to −0.17, p = 0.007). The overall risk of bias of the included studies was unclear. No serious adverse events were reported. Conclusion: Significant effects of the combined therapy of herbal medicine with Western medicine were found, and revealed the potential role of herbal medicine in treating COVID-19. More high-quality RCTs are needed to further validate the effectiveness and adverse events of herbal medicine in the treatment of COVID-19.

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          Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective

          Currently, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, formerly known as 2019-nCoV, the causative pathogen of Coronavirus Disease 2019 (COVID-19)) has rapidly spread across China and around the world, causing an outbreak of acute infectious pneumonia. No specific anti-virus drugs or vaccines are available for the treatment of this sudden and lethal disease. The supportive care and non-specific treatment to ameliorate the symptoms of the patient are the only options currently. At the top of these conventional therapies, greater than 85% of SARS-CoV-2 infected patients in China are receiving Traditional Chinese Medicine (TCM) treatment. In this article, relevant published literatures are thoroughly reviewed and current applications of TCM in the treatment of COVID-19 patients are analyzed. Due to the homology in epidemiology, genomics, and pathogenesis of the SARS-CoV-2 and SARS-CoV, and the widely use of TCM in the treatment of SARS-CoV, the clinical evidence showing the beneficial effect of TCM in the treatment of patients with SARS coronaviral infections are discussed. Current experiment studies that provide an insight into the mechanism underlying the therapeutic effect of TCM, and those studies identified novel naturally occurring compounds with anti-coronaviral activity are also introduced.
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            Can Chinese Medicine Be Used for Prevention of Corona Virus Disease 2019 (COVID-19)? A Review of Historical Classics, Research Evidence and Current Prevention Programs

            Objective Since December 2019, an outbreak of corona virus disease 2019 (COVID-19) occurred in Wuhan, and rapidly spread to almost all parts of China. This was followed by prevention programs recommending Chinese medicine (CM) for the prevention. In order to provide evidence for CM recommendations, we reviewed ancient classics and human studies. Methods Historical records on prevention and treatment of infections in CM classics, clinical evidence of CM on the prevention of severe acute respiratory syndrome (SARS) and H1N1 influenza, and CM prevention programs issued by health authorities in China since the COVID-19 outbreak were retrieved from different databases and websites till 12 February, 2020. Research evidence included data from clinical trials, cohort or other population studies using CM for preventing contagious respiratory virus diseases. Results The use of CM to prevent epidemics of infectious diseases was traced back to ancient Chinese practice cited in Huangdi’s Internal Classic (Huang Di Nei Jing) where preventive effects were recorded. There were 3 studies using CM for prevention of SARS and 4 studies for H1N1 influenza. None of the participants who took CM contracted SARS in the 3 studies. The infection rate of H1N1 influenza in the CM group was significantly lower than the non-CM group (relative risk 0.36, 95% confidence interval 0.24–0.52; n=4). For prevention of COVID-19, 23 provinces in China issued CM programs. The main principles of CM use were to tonify qi to protect from external pathogens, disperse wind and discharge heat, and resolve dampness. The most frequently used herbs included Radix astragali (Huangqi), Radix glycyrrhizae (Gancao), Radix saposhnikoviae (Fangfeng), Rhizoma Atractylodis Macrocephalae (Baizhu), Lonicerae Japonicae Flos (Jinyinhua), and Fructus forsythia (Lianqiao). Conclusions Based on historical records and human evidence of SARS and H1N1 influenza prevention, Chinese herbal formula could be an alternative approach for prevention of COVID-19 in high-risk population. Prospective, rigorous population studies are warranted to confirm the potential preventive effect of CM. Electronic Supplementary Material Supplementary material is available in the online version of this article at 10.1007/s11655-020-3192-6.
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              COVID-19: An Update on the Epidemiological, Clinical, Preventive and Therapeutic Evidence and Guidelines of Integrative Chinese–Western Medicine for the Management of 2019 Novel Coronavirus Disease

              As of 22 February 2020, more than 77662 cases of confirmed COVID-19 have been documented globally with over 2360 deaths. Common presentations of confirmed cases include fever, fatigue, dry cough, upper airway congestion, sputum production, shortness of breath, myalgia/arthralgia with lymphopenia, prolonged prothrombin time, elevated C-reactive protein, and elevated lactate dehydrogenase. The reported severe/critical case ratio is approximately 7–10% and median time to intensive care admission is 9.5–10.5 days with mortality of around 1–2% varied geographically. Similar to outbreaks of other newly identified virus, there is no proven regimen from conventional medicine and most reports managed the patients with lopinavir/ritonavir, ribavirin, beta-interferon, glucocorticoid and supportive treatment with remdesivir undergoing clinical trial. In China, Chinese medicine is proposed as a treatment option by national and provincial guidelines with substantial utilization. We reviewed the latest national and provincial clinical guidelines, retrospective cohort studies, and case series regarding the treatment of COVID-19 by add-on Chinese medicine. We have also reviewed the clinical evidence generated from SARS and H1N1 management with hypothesized mechanisms and latest in silico findings to identify candidate Chinese medicines for the consideration of possible trials and management. Given the paucity of strongly evidence-based regimens, the available data suggest that Chinese medicine could be considered as an adjunctive therapeutic option in the management of COVID-19.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                23 May 2020
                May 2020
                : 9
                : 5
                : 1583
                Affiliations
                [1 ]Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea; anglin2808@ 123456kiom.re.kr
                [2 ]Korean Convergence Medicine, University of Science and Technology, Daejeon 34113, Korea
                [3 ]Global Strategy Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea; esong@ 123456kiom.re.kr
                [4 ]Department of Preventive Medicine, College of Korean Medicine, Daejeon University, Daejeon 34520, Korea
                [5 ]Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea; hwlee@ 123456kiom.re.kr
                Author notes
                Author information
                https://orcid.org/0000-0001-6651-7641
                Article
                jcm-09-01583
                10.3390/jcm9051583
                7290825
                32456123
                93e88d5c-9b5d-4ec5-8e03-476e39757342
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 23 April 2020
                : 20 May 2020
                Categories
                Review

                systematic review,complementary and alternative medicine,herbal medicine,coronavirus disease,covid-19

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