Clinical trials for Traditional Chinese Medicine against coronavirus disease 2019 (COVID-19): Interpretation based on bibliometric analysis

The coronavirus disease 2019 (COVID-19) has been spreading worldwide, posing a significant threat to human health. Currently, vaccines are available, but there is still no reliable cure for this disease. Traditional Chinese Medicine (TCM) has played an important role in addressing this epidemic, and several clinical studies have emerged regarding treatments for COVID-19 by TCM; status of those treatments, and patterns regarding these are worth summarizing and interpreting systematically. A comprehensive search of clinical trials was performed in various platforms, including PubMed, Embase, Web of Science, medRxiv, China National Knowledge Infrastructure, WanFang Data, and SinoMed, from January 1, 2020 to March 1, 2021. Analyzed information included language, received date, quantity, citations, affiliation, number of authors, research type (randomized controlled trial or non-randomized controlled trial), trial registry information, disease severity, sample size, specific interventions, outcomes, and adverse reactions, among others. Based on the aforementioned information, a quantitative and qualitative literature analysis was done. A total of 47 articles were retrieved, most of which were published in Chinese (42 articles, 89.36%). Based on the results of the number of trial registrations (12 articles), the number of citations (the maximum for a single article was 62), and the modified Chalmers scale (total: 100 points, average: 61.40 points), the overall study quality still needs improvement. Most patients presented with the mild and common type of COVID-19 and were recruited in Hubei Province, while researchers from these studies were from all over the country (135 institutions). TCM interventions included 66 different formulas and 134 herbs, of which Armeniacae semen amarum (Kuxingren), Agastache rugosa (Huoxiang), Ephedra sinica stapf (Mahuang), Gypsum fibrosum (Shigao), Glycyrrhizae radix et rhizome (Gancao), and Gtractylodes rhizoma (Cangzhu) appeared at high frequencies. Highlighted outcomes from these studies included the following: Clinical symptoms (fever, cough, fatigue, etc.), progression rate from normal stage to heavy stage, laboratory indices including leukocyte and lymphocyte counts, and c-reactive protein levels, imaging diversity of lung computed tomography (CT), and recorded adverse reactions. With a certain number of published clinical trials, the landscape of TCM clinical trials for COVID-19 was established. Most studies have a relatively low quality and impact, and standardized implementation of evidence-based research in TCM was lacking. The mainstay TCM treatment for COVID-19 involved clearing heat, releasing the exterior, and resolving its dampness. Additionally, the Maxing Shigan Decoction was one of the most common classical prescriptions for COVID-19, and the "three drugs and three perceptions" were also widely used. Some symptoms, laboratory indicators, and imaging diversity of lung CT were found to have significantly improved after taking these decoctions. Overall, TCM is safe, and no serious adverse reactions have been reported. Through multiple mechanisms, TCM has shown great clinical effects, but its underlying mechanisms and patterns should be further explored. It is of great practical significance to enhance the level of clinical and evidence-based research for TCM application in the prevention and treatment of acute and emergent infectious diseases. Furthermore, such research will help strengthen clinical expertise in this field and further standardize the implementation of evidence-based TCM medical research.