Discussion
DISEASE, CRITICAL ILLNESS
The FLOSAN study is the first international multicenter randomized controlled trial that evaluates the safety and efficacy of LHQW capsules among patients with mild-to-moderate COVID-19 in the western Pacific region. Treatment with LHQW for 14 days significantly shortened the time to sustained improvement or resolution of most cardinal symptoms and all symptoms combined. LHQW did not markedly accelerate the negative conversion of NAAT findings. No patient progressed into severe or critical illness or died. LHQW was well tolerated (Additional files With greater scientific rigor in the study design, findings of the FLOSAN study echoed the principal results of our previously published multicenter randomized study [Our findings were consistent with other published studies pertinent to Chinese herbs for treatment of COVID-19. Several meta-analyses, each with different sample sizes and studies with different design, have concluded the therapeutic benefits of LHQW capsules for mild-to-moderate COVID-19 [LHQW capsules were safe among patients with COVID-19, evidenced by the similar safety profile as compared with placebo group, which echoed with our [The main strengths included the international multicenter trial which has recruited a large sample size of patients from four countries of the western Pacific region, with no major differences in the therapeutic responses and safety profiles across the countries. Therefore, the findings were likely generalizable to patients from Asia. The double-blind study design with matching placebo has provided more solid evidence pertaining to the efficacy of LHQW capsules. Few clinical trials of the existing marketed drugs have been conducted during the Omicron outbreak, when the current trial was initiated.Our findings have further validated the efficacy of LHQW capsules for Omicron, the prevailing variant of SARS-CoV-2 circulating globally. This is important because of the scarcity of marketed medications and the large number of vulnerable population within mainland China, where some of the repurposed herbs with notable therapeutic potentials have already been marketed. LHQW capsules might help reduce healthcare burden during the surge of Omicron wave among community-dwelling patients with mild-to-moderate COVID-19.Some limitations should also be considered. First, there existed an imbalance in the sample size within individual countries, although we have not identified the signals indicating differential therapeutic responses across the nations. However, our findings were not materially altered in the main study outcomes when stratified by the countries (China vs. The rest combined). Second, the relatively short duration of observation cannot provide further evidence of the longer-term efficacy of LHQW (e.g. at day 28 or beyond). Third, caution should be exercised when extrapolating our conclusions to other populations, such as those with multiple comorbidities or immunosuppression. Furthermore, our study cannot directly address the molecular mechanisms underlying the efficacy of LHQW for the treatment of COVID-19. Finally,we did not employ the stratified randomization scheme. However, randomization was well balanced across the different metrics that could have affected the study outcomes (e.g. sex, age, duration of symptoms, disease severity). In light of the difference in the study regions and study sites, we have adopted the central block randomization scheme, and the results demonstrated balanced distribution of the demographic and other baseline disease severity metrics.