Qingjin Yiqi granules for post-COVID-19 condition: A randomized clinical trial.

OBJECTIVE: To evaluate the effectiveness and safety of Qingjin Yiqi granules (QJYQ) on post-COVID-19 condition (PCC). METHOD: Patients who met the inclusion criteria were randomly assigned to two groups, the QJYQ group received QJYQ combined with standard rehabilitation treatments (SRTs) and the control group only received SRTs. The treatment course was 14 days. The primary outcomes were modified Medical Research Council (mMRC) scale and Borg scale, while the secondary outcomes included symptoms score and 6-minute walking distance (6MWD). The safety outcome was the incidence of adverse events. RESULTS: A total of 388 patients with PCC were enrolled and randomly assigned to the QJYQ group (n = 194) and the control group (n = 194). Compared to the controls, the mMRC scale was improved in the QJYQ group, which was better than that of the control group [ß (95%CI): -0.626 (-1.101, -0.151), p = 0.010]. A significant improvement in Borg scale was also observed in the QJYQ group compared to the control group [ß (95%CI): -0.395(-0.744, -0.046), p = 0.026]. There was no statistically significant difference in symptoms score and 6MWD between the two groups (p = 0.293, p = 0.724). No treatment-related adverse events were observed in either group. CONCLUSIONS: QJYQ can bring benefits to patients with PCC, mainly in the improvement of breathlessness and fatigue.

PROSPERO's systematic review protocols of traditional Chinese medicine for COVID-19: An overview.

BACKGROUND: A large number of protocols for Systematic Reviews (SR) of Traditional Chinese Medicine (TCM) for coronavirus disease 2019 (COVID-19) have been registered in the International Prospective Register of Systematic Reviews (PROSPERO). This study aimed to analyze the innovativeness and rigorousness of the SR protocols and make recommendations for the design and implementation of future SRs on TCM for COVID-19. This effort is likely to enhance the value of the produced information and prevent the futility of the research. METHODS: PROSPERO was searched comprehensively for identifying SRs of TCM for COVID-19 from the inception of the database to August 2020. Two researchers independently screened the literature, extracted the data, and cross-checked the retrieved information for consistency. The following details were recorded: database, registration time, organizations, types of research included, participants, interventions, and outcome measures. All extracted data were analyzed by an overview. The "P - participants, I - interventions, C - controls, and O - outcomes (PICO)" included in the protocols were compared for similarity. The outcomes of the included SR protocols were compared with the newly published Core Outcome Sets (COSs). RESULTS: A total of 80 protocols of SR related to TCM for COVID-19 were obtained after a primary search, and finally 71 protocols were included. The majority of the protocols were from China. Thirty-two organizations participated in the protocol registrations, including 11 hospitals and 21 universities/colleges. However, some protocols were not innovative or rigorous enough, as the PICO of some protocols were similar and non-specific, and the searched literature was incomprehensive. In addition, COS is not commonly adopted. CONCLUSIONS: Registering a protocol of SR is an effective way to ensure the usefulness of the produced information, and to avoid the duplication of research and the wastage of resources. In future SR protocols, it is important to focus on and solve the methodological problems such as non-specific PICO, incomprehensive literature retrieval, and improper outcome measures.

Evidence for the medicinal value of Squama Manitis (pangolin scale): A systematic review.

BACKGROUND: Squama Manitis (pangolin scale) has been used in traditional Chinese medicine for thousands of years. However, its efficacy has not been systematically reviewed. This review aims to fill the gap. METHODS: We searched six electronic databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure Database (CNKI), WanFang Database and SinoMed from inception to May 1, 2020. Search terms included "pangolin", "Squama Manitis", "Manis crassicaudata", "Manis javanica", "Malayan pangolins", "Manis pentadactyla", "Ling Li", "Chuan Shan Jia", "Shan Jia", "Pao Jia Zhu", "Jia Pian" and "Pao Shan Jia". The Cochrane Risk of Bias (RoB) assessment tool and Newcastle-Ottawa Scale (NOS) were used to evaluate the risk of bias of the included randomized controlled trials (RCTs) and case control studies (CCSs). RESULTS: After screening, 15 articles that met the inclusion criteria were finally included. There were 4 randomized controlled trials, 1 case control study, 3 case series and 7 case reports. A total of 15 different diseases were reported in these studies, thus the data could not be merged to generate powerful results. Two RCTs suggested that Squama Manitis combined with herbal decoction or antibiotics could bring additional benifit for treating postpartum hypogalactia and mesenteric lymphadenitis. However, this result was not reliable due to low methodological quality and irrational outcomes. The other two RCTs generated negative results. All the non-RCTs did not add any valuable evidence to the efficacy of Squama Manitis beacause of small samples, incomplete records, non-standardized outcome detection. In general, currently available evidence cannot support the clinical use of Squama Manitis. CONCLUSION: There is no reliable evidence that Squama Manitis has special medicinal value. The removal of Squama Manitis from Pharmacopoeia is rational.

Chinese medical drugs for coronavirus disease 2019: A systematic review and meta-analysis.

BACKGROUND: Integration of Chinese medical drugs (CMD) and western medicine (WM) has been widely used in the treatment of Coronavirus Disease 2019 (COVID-19). This systematic review aimed to evaluate the efficacy and safety of CMD for COVID-19. METHOD: A literature search was performed in six databases from injection to June 2020. Both randomized controlled trials (RCTs) and quasi-RCTs were considered as eligible. The quality of included RCTs were assessed by Cochrane Risk of Bias Tool, and Review Manager 5.3 software was used to do meta-analysis. RESULT: Eleven studies with 1259 patients were included in this study. CMD included herbal decoction and Chinese patent medicine. The methodological quality was evaluated as generally unclear. The results of meta-analysis showed that the integration of CMD and WM had better efficacy than WM in number of patients turned to severe and critical type (RR = 0.47, 95% CI=[0.32, 0.69], P < 0.0001), length of hospital stay (MD= -7.95, 95% CI=[-14.66, -1.24], P = 0.02), defervescence time (MD= -1.20, 95% CI=[-2.03, -0.38], P = 0.004), cough resolution rate (RR = 1.37, 95% CI=[1.15, 1.64], P = 0.0004), fatigue resolution rate (RR = 1.37, 95% CI=[1.02, 1.83], P = 0.04), and tachypnea resolution rate (RR = 2.20, 95% CI=[1.11, 4.39], P = 0.02). As for safety, there was no significant difference between two groups. CONCLUSION: CMD may bring potential benefit to patients suffered from COVID-19. However, the quality of included trials is not good enough. High quality study with core outcome set are still required.

Tongue features of patients with coronavirus disease 2019: a retrospective cross-sectional study.

BACKGROUND: Traditional Chinese medicine (TCM) has been widely used in the treatment of coronavirus disease 2019 (COVID-19). Tongue features should be referred for diagnosis and treatment of diseases in TCM. Therefore, it is necessary to analyze the tongue features of the patients suffered from COVID-19. METHODS: COVID-19 Symptom Database (established by Evidence-based Medicine Center of Tianjin University of TCM) was searched for eligible tongue pictures. The tongue pictures were assessed by TCM experts to extract the data of tongue color, coating color, tongue body shape and coating proper feature. The relationship between tongue features and patient's condition was analyzed. RESULTS: Patients diagnosed as mild and moderate COVID-19 commonly had light red tongue and white coating. Severe patients had purple tongue and yellow coating. The proportion of critical patients with tender tongue increased to 75%. Greasy coating was a significant characteristic of patients with COVID-19. The proportions of greasy coating were 53.33%, 73.30%, 83.67 and 87.5% in disease category of mild, moderate, severe and critical. In addition, the thick coating proportion increased from mild (24.89%) to critical (50.00%). CONCLUSIONS: Tongue features have certain relationship with the category of COVID-19. Tongue features can serve as potential indicators for the evaluation of patient's condition and prognosis. Further studies are needed to enhance the quantification of tongue features and develop standards.

[Analysis on pattern of prescriptions and syndromes of traditional Chinese medicine for prevention and treatment of COVID-19].

To investigate the regularity of prescription and clinical syndromes by analyzing the diagnosis and treatment protocols of traditional Chinese medicine(TCM) for coronavirus disease 2019(COVID-19), so as to provide references for syndrome differentiation and relevant researches. The diagnosis and treatment protocols of COVID-19 published by national and regional health authorities were searched, and information was extracted in regard to disease stages, type of syndromes, and prescriptions, etc. Frequency statistics and relative analysis were used to analyze the rule of syndrome differentiation and prescription with TCM, and further discussion on the pathogenesis and progress of the disease. A total of 26 diagnosis and treatment protocols of TCM for COVID-19 were retrieved after screening(including 1 national scheme and 25 regional ones), among which 16 contained aspects of both prevention and treatment, 7 only involved treatment contents and 3 were prevention schemes. The courses of COVID-19 can be divided into early stage, middle stage, severe stage and recovery stage. The pathogeny of COVID-19 in TCM is damp-toxin, with the core pathogenesis of damp-toxin retention in lung and Qi repression. Its pathological features can be summarized as "damp, toxin, obstruction, deficiency". The location of the disease is lung, always involving spleen and stomach, and may further affect heart and kidney in severe cases. The major treatments for each course are Fanghua Shizuo, Xuanfei Touxie(early stage); Qingre Jiedu, Xuanxie Feire(middle stage); Kaibi Gutuo, Huiyang Jiuni(severe stage); Qingjie Yure, Yiqi Yangyin(recovery stage). There were many diagnosis and treatment protocols for COVID-19 have been published, which generally followed the national edition, through with certain personalities in different regional protocols. There were common features with respect to the disease stage, syndrome differentiation, therapeutic principles and methods, as well as prescriptions; the treatment were generally carried out against the core pathogenesis and progress of the disease. Along with the deepening recognition of COVID-19, the diagnosis and treatment protocols are still need further concretization and standardization. We hope researchers and decision-makers can pay more attention to the treatment of Huayu Tongluo in severe and recovery period.

[Analysis on clinical study protocols of traditional Chinese medicine for coronavirus disease 2019].

To analyze the registered clinical trial protocols of traditional Chinese medicine(TCM) for the prevention and treatment of coronavirus disease 2019(COVID-19), in order to provide information for improving the quality of research design. The website of the Chinese Clinical Trial Registry(www.chictr.org.cn) and the American Clinical Trial Registry(clinicaltrials.gov) were searched to collect protocols of TCM for COVID-19. Documents were screened following the inclusion criteria, and data were extracted in regard to registration date, study objective, type of design, sponsor, patient, sample size, intervention, and evaluation index. Descriptive analysis was conducted. A total of 49 clinical trial protocols of TCM for COVID-19 were included. Primary sponsors were mainly hospitals or universities in places like Hubei, Beijing, Zhejiang and other regions. The implementation units are mainly in Hubei, Guangdong, Zhejiang, Henan and other regional hospitals. The types of study design were mainly experimental studies(40), including 30 randomized parallel controlled trials, 7 non-randomized controlled trials, 2 single arm trials and 1 consecutively recruited trial; besides, there were also 6 observational studies, 2 health service studies and 1 preventive study. The sample size reached a total of 30 562 cases, with a maximum of 20 000 for a single study and a minimum of 30. The 49 trials subjects included healthy people(3), isolation and observation cases(1), suspected cases(10),confirmed COVID-19 patients(31) and COVID-19 recovery patients(4). Of the 31 trials planned to include confirmed COVID-19 patients, 16 protocols no definite disease classification, 3 with a clear exclusion of severe subjects, 4 with common subjects, 2 with light, common or severe subjects, 1 with light and common subjects, 1 with common or severe subjects, 3 with severe subjects, and 1 with severe or critical subjects. The experimental interventions included Chinese patent medicine(Lianhua Qingwen Capsules/Granules, Huoxiang Zhengqi Dropping Pills/Oral Liquid, Babao Dan, Gubiao Jiedu Ling, Jinhao Jiere Granules, Compound Yu-xingcao Mixture, Jinye Baidu Granules, Shufeng Jiedu Capsuless, Shuanghuanglian Oral Liquid, Tanreqing Injection, Xuebijing Injection, Reduning Injection, Xiyanping Injection), Chinese medicinal decoction and taichi. The primary evaluation outcomes mainly included antipyretic time, clinical symptom relief, novel coronavirus nucleic acid turning to negative, conversion rate of severe cases and chest CT. There was a quick response of clinical research on the prevention and treatment of COVID-19 with TCM, with the current registered protocols covers the whole process of disease prevention, treatment and rehabilitation. However, issues need to be concerned, including unclear definition of patient's condition, unclear research objectives, unclear intervention process and inappropriate outcomes, etc. In addition, researchers should consider the actual difficulties and workload of doctors in epidemic response environment, and make effort to optimize the process and improve the operability of research protocols under the principle of medical ethics.