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      Add-on effect of Chinese herbal medicine in the treatment of mild to moderate COVID-19: A systematic review and meta-analysis

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          Abstract

          Introduction

          Coronavirus disease 2019 (COVID-19) has emerged as a global pandemic since its outbreak in Wuhan, China. It is an urgent task to prevent and treat COVID-19 effectively early. In China’s experience combating the COVID-19 pandemic, Chinese herbal medicine (CHM) has played an indispensable role. A large number of epidemiological investigations have shown that mild to moderate COVID-19 accounts for the largest proportion of cases. It is of great importance to treat such COVID-19 cases, which can help control epidemic progression. Many trials have shown that CHM combined with conventional therapy in the treatment of mild to moderate COVID-19 was superior to conventional therapy alone. This review was designed to evaluate the add-on effect of CHM in the treatment of mild to moderate COVID-19.

          Methods

          Eight electronic databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, the Clinical Trials.gov website, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database and China Biology Medicine (CBM) were searched from December 2019 to March 2021 without language restrictions. Two reviewers searched and selected studies, and extracted data according to inclusion and exclusion criteria independently. Cochrane Risk of Bias (ROB) tool was used to assess the methodological quality of the included RCTs. Review Manager 5.3.0 software was used for statistical analysis.

          Results

          Twelve eligible RCTs including 1393 participants were included in this meta-analysis. Our meta-analyses found that lung CT parameters [RR = 1.26, 95% CI (1.15, 1.38), P<0.00001] and the clinical cure rate [RR = 1.26, 95%CI (1.16, 1.38), P<0.00001] of CHM combined with conventional therapy in the treatment of mild to moderate COVID-19 were better than those of conventional therapy. The rate of conversion to severe cases [RR = 0.48, 95%CI (0.32, 0.73), P = 0.0005], TCM symptom score of fever [MD = -0.62, 95%CI (-0.79, -0.45), P<0.00001], cough cases [RR = 1.43, 95%CI (1.16, 1.75), P = 0.0006], TCM symptom score of cough[MD = -1.07, 95%CI (-1.29, -0.85), P<0.00001], TCM symptom score of fatigue[MD = -0.66, 95%CI (-1.05, -0.28), P = 0.0007], and CRP[MD = -5.46, 95%CI (-8.19, -2.72), P<0.0001] of combination therapy was significantly lower than that of conventional therapy. The WBC count was significantly higher than that of conventional therapy[MD = 0.38, 95%CI (0.31, 0.44), P<0.00001]. Our meta-analysis results were robust through sensitivity analysis.

          Conclusion

          Chinese herbal medicine combined with conventional therapy may be effective and safe in the treatment of mild to moderate COVID-19. More high-quality RCTs are needed in the future.

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          Most cited references49

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          Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

          In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
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            Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

            Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.
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              Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: SoftwareRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Supervision
                Role: ValidationRole: Writing – review & editing
                Role: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                20 August 2021
                2021
                20 August 2021
                : 16
                : 8
                : e0256429
                Affiliations
                [1 ] College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, People’s Republic of China
                [2 ] Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing, People’s Republic of China
                [3 ] Department of Chinese Traditional Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
                [4 ] Department of Cardiovascular U nit, Traditional Chinese medicine hospital Dianjiang Chongqing, Chongqing, People’s Republic of China
                Zagazig University, EGYPT
                Author notes

                Competing Interests: The authors declare that they have no competing interests.

                Author information
                https://orcid.org/0000-0002-4478-0622
                Article
                PONE-D-20-38124
                10.1371/journal.pone.0256429
                8378756
                34415962
                85442045-2fbb-4326-b6d5-ae7d91f3ed28
                © 2021 Du et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 3 December 2020
                : 6 August 2021
                Page count
                Figures: 7, Tables: 2, Pages: 19
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81573860
                Award Recipient :
                Funded by: chongqing medical university postdoctoral foundation
                Award ID: R11004
                Award Recipient :
                Funded by: chongqing postdoctoral special foundation
                Award ID: Yuren Social Office [2020] No. 379
                Award Recipient :
                This work was supported by the National Natural Science Foundation of China (No.81573860), Chongqing Medical University Postdoctoral Foundation (No. R11004), and Chongqing Postdoctoral Special Foundation (Yuren Social Office [2020] No. 379). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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                Medicine and Health Sciences
                Medical Conditions
                Infectious Diseases
                Viral Diseases
                Covid 19
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                Physical Sciences
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