Traditional Chinese Medicine for COVID-19: A Network Meta-Analysis and Systematic Review.

To compare the efficacy of different traditional Chinese medicine (TCM) therapies for the treatment of coronavirus disease 2019 (COVID-19) and provide a higher level of evidence in the form of network meta-analysis (NMA) and systematic review. We searched the studies from the following databases: CNKI, VIP, WanFang, SinoMed, PubMed, Embase, and Web of Science from the establishment of the respective database until December 2021. Relevant studies were screened according to the pre-established inclusion criteria. The quality of the included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) were assessed using the risk of bias (ROB) tool and the Methodological Index for Non-Randomized Studies (MINORS), respectively. R software 4.1.1 and Stata 13.1 were used for data analysis and mapping. A total of 34 studies were included in this network meta-analysis that tested 24 TCM interventions and included 3443 patients. Using cluster analysis of time to negative SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR), the length of hospital stay and composite events, we found that Jinyinhua oral liquid (JYH, 120 mL) + conventional Western medicine (CWM) has the highest SUCRA value at 88.64%, 85.61% and 84.24%. The traditional meta-analysis results revealed that Qingfei Paidu decoction + CWM were significantly different compared with CWM alone for the score of clinical symptoms (MD =-0.75, 95% CI [-1.04, -0.47]). Nine studies reported 57 adverse reactions (ADRs) and 3 adverse events (ADEs) in TCM + CWM groups, and eight studies reported 33 ADRs and 8 ADEs in CWM groups. In conclusion, the combination of TCM and CWM approaches may enhance the efficacy of CWM in COVID-19 patients. Based on the NMA result, JYH (120 mL) + CWM may be a more effective treatment and deserves further investigation. However, the differences in many comparisons between TCM interventions did not reach statistical significance; therefore, further high-quality studies are required to validate these findings.

Comorbidities and complications of COVID-19 associated with disease severity, progression, and mortality in China with centralized isolation and hospitalization: A systematic review and meta-analysis.

Background: Coronavirus disease 2019 (COVID-19) causes life-threatening with the high-fatality rates and spreads with high-infectious disease worldwide. We aimed to systematically review the comorbidities and complications of COVID-19 that are associated with various disease severity, progression, and mortality in China, to provide contemporary and reliable estimates in settings with centralized isolation and hospitalization. Methods: In this systematic review and meta-analysis, we searched four main English language databases, and four main Chinese language databases for observational studies published from inception to January 2022, to identify all the related comorbidities and complications of COVID-19, in the China region with centralized isolation and hospitalization, with disease severity, progression, and mortality. Literature search, data extraction, and quality assessment were independently conducted by two reviewers. We used the generalized linear mixed model to estimate pooled effect sizes for any comorbidities and complications, and subgroup in gender ratio was done to further address the potential heterogeneity. Results: Overall, 187 studies describing 77,013 patients, namely, 54 different comorbidities and 46 various complications of COVID-19, were identified who met our inclusion criteria. The most prevalent comorbidities were hypertension [20.37% 95% CI (15.28-26.63), 19.29% (16.17-22.85), 34.72% (31.48-38.10), and 43.94% (38.94-49.06)] and diabetes [7.84% (5.78-10.54), 8.59% (7.25-10.16), 17.99% (16.29-19.84), and 22.68% (19.93-25.69)] in mild, moderate, severe, and critical cases. The most prevalent complications were liver injury [10.00% (1.39-46.72), 23.04% (14.20-35.13), and 43.48% (39.88-47.15)] in mild, moderate, and severe cases, and acute respiratory distress syndrome [ARDS; 94.17% (20.78-99.90)] and respiratory failure [90.69% (28.08-99.59)] in critical cases. Renal insufficiency [odds ratio (OR) 17.43 (6.69-45.43)] in comorbidities and respiratory failure [OR 105.12 (49.48-223.33)] in complications were strongly associated in severe/critical than in mild/moderate cases. The highest estimated risk in intensive care unit (ICU) admission, progression, and mortality was an autoimmune disease, nervous system disease, and stroke in comorbidities, shock, and ARDS in complications. Conclusion: Comorbidities and complications in inpatients with COVID-19 were positively associated with increased risk in severe and critical cases, ICU admission, exacerbation, and death during centralized isolation and hospitalization. Prompt identification of comorbidities and complications in inpatients with COVID-19 can enhance the prevention of disease progression and death and improve the precision of risk predictions.

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.

Efficacy and safety of Reduning injection in the treatment of COVID-19: a randomized, multicenter clinical study.

BACKGROUND: Reduning injection is a traditional Chinese medicine (TCM) with known efficacy against a variety of viral infections, but there is no data about its efficacy against coronavirus disease 2019 (COVID-19). METHODS: To explore the efficacy and safety of Reduning injection in the treatment of COVID-19, a randomized, open-labeled, multicenter, controlled trial was conducted from 12 general hospitals between 2020.02.06 and 2020.03.23. Patients with COVID-19 who met the diagnostic criteria of the "Diagnosis and Treatment Program for Novel Coronavirus Infection Pneumonia (Trial Fifth Edition)". Patients were randomized to routine treatment with or without Reduning injection (20 mL/day for 14 days) (ChiCTR2000029589). The primary endpoint was the rate of achieving clinical symptom recovery on day 14 of treatment. RESULTS: There were 77 and 80 participants in the Reduning and control groups. The symptom resolution rate at 14 days was higher in the Reduning injection than in controls [full-analysis set (FAS): 84.4% vs. 60.0%, P=0.0004]. Compared with controls, the Reduning group showed shorter median time to resolution of the clinical symptoms (143 vs. 313.5 h, P<0.001), shorter to nucleic acid test turning negative (146.5 vs. 255.5 h, P<0.001), shorter hospital stay (14.1 vs. 18.1 days, P<0.001), and shorter time to defervescence (29 vs. 71 h, P<0.001). There was no difference in AEs (3.9% vs. 8.8%, P=0.383). CONCLUSIONS: This preliminary trial suggests that Reduning injection might be effective and safe in patients with symptomatic COVID-19.

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.

[Whole-process prevention and treatment model of traditional Chinese medicine for coronavirus disease 2019 epidemics].

Traditional Chinese medicine (TCM) has a long history in treating infectious diseases, and the form of intervention varies with different medical conditions and disease types. "The battle field of Chinese doctor for anti-epidemic" was formed in fighting against severe acute respiratory syndrome (SARS) epidemics in China, and from the battle, valuable experiences of using TCM for prevention and treatment had been obtained. During responding to coronavirus disease 2019 (COVID-19) epidemics, we followed the principle of keeping summary and perfection while treament. And a whole process of TCM pattern or a model was organized, including early prevention in communities, cluster intervention in isolated places, comprehensive intervention in mobile cabin hospitals, centralized treatment in designated hospitals and rehabilitation support in rehabilitation posts. Thus, the innovation of whole process of TCM intervention was involved in the "trench warfare" strategy and platform system for prevention and treatment of new infectious COVID-19 epidemics. At different stages or conditions, different TCMs were used to play advantageous roles to solve various problems and elevate the effects of prevention and treatment of the disease. The construction of TCM mobile cabin hospitals was an innovation of organization form that might offset the constraints in technology and scale of simple community isolation or simple hospital treatment, exploring a new way for TCM to cope with public health emergencies.

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.

Core Outcome Set for Clinical Trials on Coronavirus Disease 2019 (COS-COVID).

Since its outbreak in December 2019, a series of clinical trials on coronavirus disease 2019 (COVID-19) have been registered or carried out. However, the significant heterogeneity and less critical outcomes of such trials may be leading to a waste of research resources. This study aimed to develop a core outcome set (COS) for clinical trials on COVID-19 in order to tackle the outcome issues. The study was conducted according to the Core Outcome Measures in Effectiveness Trials (COMET) Handbook: Version 1.0, a guideline for COS development. A research group was set up that included experts in respiratory and critical medicine, traditional Chinese medicine (TCM), evidence-based medicine, clinical pharmacology, and statistics, in addition to medical journal editors. Clinical trial registry websites (www.chictr.org.cn and clinicaltrials.gov) were searched to retrieve clinical trial protocols and outcomes in order to form an outcome pool. A total of 78 clinical trial protocols on COVID-19 were included and 259 outcomes were collected. After standardization, 132 outcomes were identified within seven different categories, of which 58 were selected to develop a preliminary outcome list for further consensus. After two rounds of Delphi survey and one consensus meeting, the most important outcomes for the different clinical classifications of COVID-19 were identified and determined to constitute the COS for clinical trials on COVID-19 (COS-COVID). The COS-COVID includes one outcome for the mild type (time to 2019 novel coronavirus (2019-nCoV) reverse transcription-polymerase chain reaction (RT-PCR) negativity), four outcomes for the ordinary type (length of hospital stay, composite events, score of clinical symptoms, and time to 2019-nCoV RT-PCR negativity), five outcomes for the severe type (composite events, length of hospital stay, arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2), duration of mechanical ventilation, and time to 2019-nCoV RT-PCR negativity), one outcome for critical type (all-cause mortality), and one outcome for rehabilitation period (pulmonary function). The COS-COVID is currently the most valuable and practical clinical outcome set for the evaluation of intervention effect, and is useful for evidence assessment and decision-making. With a deepening understanding of COVID-19 and application feedback, the COS-COVID should be continuously updated.