Efficacy and adverse effects of Phyllanthus emblica combined with Andrographis paniculata syrup versus brown mixture for symptomatic cough relief in Long-COVID patients: A single-blind randomized controlled trial

Abstract

Objective: To compare the efficacy and side effects of herbal cough syrup containing Phyllanthus emblica and Andrographis paniculata with a brown mixture in relieving cough symptoms in patients with post-COVID-19 condition (long COVID). Methods: This study was a phase 2a clinical trial designed as a single-blind randomized controlled trial conducted between April and September 2025 at the Center of Thai Traditional and Alternative Medicine. The participants were 58 volunteers with a persistent cough associated with a post-COVID-19 condition for more than two months. They were randomly assigned to either the treatment group or the control group, with 29 participants in each group. All participants received the assigned treatment for 3 consecutive days and were followed up over 7 days. Outcome measures included the Leicester Cough Questionnaire (LCQ), used to assess cough-related quality of life, and the Cough Severity Diary (CSD), used to evaluate the daily severity of cough symptoms. Results: The treatment group, of which 82.76% were female, had a mean age of 42.34 ± 11.16 years, while the control group consisted of 68.96% female participants with a mean age of 40.72 ± 11.68 years. Following treatment, the treatment group demonstrated a significant improvement in total LCQ scores, increasing from 13.15 ± 3.55 to 16.83 ± 3.09 (p < 0.001), and a significant reduction in total CSD scores from 3.95 ± 1.87 to 1.42 ± 1.78 (p < 0.001). Similarly, the control group showed an increase in LCQ scores from 12.51 ± 2.79 to 15.90 ± 3.33 (p < 0.001) and a decrease in total CSD scores from 4.46 ± 1.86 to 1.44 ± 1.46 (p < 0.001). However, between-group comparisons revealed no statistically significant difference in post-treatment LCQ scores (p = 0.276) or CSD scores (p = 0.794). Regarding side effects, one adverse event (3.45%) was reported in the experimental group, presenting as facial edema and assessed as "possible" according to the Naranjo algorithm; the symptom resolved following dose reduction. No adverse events were observed in the control group. Conclusion: The herbal cough syrup containing Phyllanthus emblica and Andrographis paniculata demonstrates comparable efficacy to Brown mixture in alleviating cough symptoms and improving the quality of life in patients with post-COVID-19 conditions. It may represent an appropriate alternative treatment for post-COVID-19 cough. Further studies with larger sample sizes and long-term follow-up are recommended to confirm its efficacy and safety.