The therapeutic efficacy of Xuanfei Baidu Formula combined with conventional drug in the treatment of coronavirus disease 2019

Abstract Background: Coronavirus disease 2019 (COVID-19) is a new acute espiratory infectious disease that has been in a public health emergency of international concern. In China, the combination of Xuanfei Baidu Formula (XBF) and conventional drug is used in the clinical treatment of patients with new coronary pneumonia, However, there is no comprehensive and systematic evidence on the effectiveness and safety of XBF. Materials and Methods: We search for research in PubMed, China National Knowledge Infrastructure, Wan-fang Database, China Biomedical Database, and Chinese Science Citation Database. For “Xuanfei Baidu Formula” and “COVID-19,” we screened suitable articles without language restrictions on keywords, Review Manager 5.3 and STATA 14.2 software was used for the data analysis. Results: The systematic review and meta-analysis will evaluate the efficacy and safety of XBF combined with conventional drug in the treatment of COVID-19. Conclusion: We will provide evidence of XBF for the treatment on COVID-19 patients. INPLASY Registration number: INPLASY2020120011


Introduction
Corona Virus Disease 2019 (COVID-19) is an RNA virus caused respiratory disease, which has posed an enormous threat to public health. [1] its long incubation period, strong contagiousness, the main transmission route is Respiratory droplet, also, it could be transmitted through person-to-person contacts by asymptomatic carriers. [2] According to statistics from the World Health Organization, as of Dec 3, 2020, This brings the cumulative numbers to over 61.8 million reported cases and 1.4 million deaths globally since the start of the pandemic. [3] There is no effective way to control the COVID-19 and no vaccine is currently available. [4] The treatment is only symptomatic, Therefore, the effective prevention and treatment of COVID-19 are a very urgent task.
Traditional Chinese medicine (TCM) has been proven effective for COVID-19 treatment. [5] Xuanfei Baidu Formula was recommended as the treatment agent in the 8th edition of the "Diagnosis and Treatment Scheme for New Coronavirus Infected Pneumonia. [6] Xiong Wuzhong et al recent study showed that Xuanfei Baidu Formula (XBF) is safe and effective for COVID-19 and can significantly improve COVID-19 patient's clinical symptoms, increase the number of white blood cells and lymphocytes to improve immunity, and also significantly reduce C-reactive protein and erythrocyte sedimentation rate to play an anti-inflammatory effect. [7] Because of comprehensive and systematic evidence, we will collect all randomized controlled trials on XBF in the treatment of COVID-19, and present a metaanalysis protocol and systematic reviews.

Methods and program
The protocol has been registered on the International prospective register of systematic review (INPLASY), the registration number is INPLASY2020120011 (DOI: 10.37766/inplasy2020.12.0011). Because of no issues about participant privacy, the review will not require ethical approval.
The authors have no conflicts of interest to disclose.
All data generated or analyzed during this study are included in this published article [and its supplementary information files. The protocol followed Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) guidelines. [  The full screening process is shown in PRISMA flow chart (Fig. 1).

Data extraction and quality assessment
Summarize the searched literatures, including basic characteristics, basic information, intervention measures, Outcome indicators. For example, author, publication time, number of samples in each group, age, ratio of male to female, drugs, time used in treatment, and so on. Then extracted data were assessed for Cochrane bias risk by 2 investigators independently. [9] as follows: random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias) and other bias. Each term was judged with 3 levels-Low risk, High risk, Unclear risk" bias, If there are disagreements during the evaluation process, it will be resolved through discussion with a third investigator.

Data analysis
Data analysis was performed using Review Manager 5.3 (Cochrane Collaboration) and STATA 16.0 software. Outcome measures such as the total effective rate, the disappearance rate of main clinical features and the disappearance rate of minor symptoms were regarded as dichotomous variables and presented as the odds ratio (OR) with 95% confidence intervals (95% CI), and the risk ratio (OR) with 95% confidence intervals (95% CI). Contents of inflammatory cytokines were continuous variables that presented as the mean difference (MD) with 95% CI, Q statistic and I 2 tests were applied to assess the heterogeneity among studies.
When I 2 25%, the data is considered homogeneous. A fixedeffects model was used to analyze data with low heterogeneity (25% I 2 50%) and data with high heterogeneity (P < .1 or I 2 > 50%) was estimated using random-effects model. Potential publication bias was revealed by funnel plots. [10,11]

Discussion
We study to evaluate the clinical effect and safety of XBF on patients infected with COVID-19. With the advent of winter, many experts predict that the epidemic caused by COVID-19 will once again erupt globally. [12,13] Traditional Chinese medicine has a history of more than 2000 years in the prevention and treatment of epidemics and plagues, [14] In light of its experience treating SARS and H1N1 influenza, in the fight against COVID-19, China achieved effect. Network pharmacology and molecular docking studies of XBF show that it has effect in the treatment of COVID-19 patients, by regulating key targets such as IL6, MAPK3, MAPK1, IL1b, CCL2, EGFR. [15] This study aims to evaluate the effectiveness and safety of XBF in the treatment of COVID-19, and to provide ways for the treatment of COVID-19.