According to the guidance of the collateral-disease theory, lianhua qingwen was initially developed due to the outbreak of SARS and has played an active role in China's fight against influenza A (H1N1) and the novel coronavirus pneumonia. However, in the context of the current global epidemic is still growing and the urgent need to develop new coronavirus treatment drugs, it should be considered whether these drugs have actual efficacy and good safety after rigorous clinical studies, and whether they can be quickly applied to a large number of people. 

Therefore, this study has important clinical value. First of all, the dosage form of lianhua qingwen capsule is the same as that of chemical drugs, which is convenient for clinical application. Secondly, lianhua qingwen has a fingerprint of the main medicinal ingredients, which ensures the stability of drug quality and is convenient for later clinical promotion and application (31,32). Third, previous studies have confirmed the clinical benefit and high safety of lianhua qingwen in the treatment of COVID-19 (8-10,33,34). However, these studies were all conducted in China, with small samples and certain limitations. Taking into account the differences between different regions and populations, the international multicenter randomized controlled trial study will collect a high level of evidence-based medical data. 

Combined with the current overall trend in the clinical characteristics of COVID-19 and the therapeutic advantages of lianhua qingwen, this trial will pay more attention to the evaluation of clinical symptoms than previous studies. First, we standardized the COVID-19 Symptom Assessment Scale (14) according to US FDA guidelines. Second, we will comprehensively and systematically assess the impact of lianhua qingwen on COVID-19 symptoms, including respiratory symptoms, gastrointestinal symptoms, systemic symptoms, smell and taste, rather than just assessing the three symptoms of fever, fatigue and cough. In addition, we will use the median time for sustained improvement or remission of the nine major symptoms as the primary efficacy endpoint, and pay more attention to the median time for the onset of fever reduction and the return of body temperature to normal. This will provide more detailed evidence of the efficacy of LHQW in the treatment of COVID-19. However, under China's "zero COVID-19" policy, we will evaluate measures of inflammation, but will not explore additional measures of hospitalization. We will also develop relevant economic endpoints, including utility, cost, and ICER, to assess the likely economic benefits of LHQW treatment and provide evidence for the accessibility and affordability of LHQW.

This is the first international multi-center RCT trial of traditional Chinese medicine for the treatment of early COVID-19 in accordance with the WHO guidelines for the management of COVID-19. We hope that this clinical study will provide a higher level of evidence on the efficacy, safety and economics of LHQW in the treatment of COVID-19. On the one hand, effective and affordable treatments and medicines can be made available to COVID-19 patients, especially in countries where traditional Chinese medicine is already established. On the other hand, the study may focus researchers' attention on treating COVID-19 in traditional Chinese medicine, which is becoming increasingly popular in Western countries.