Effectiveness and Safety of Chinese Herbal Acupoint Application in Adult Patients with Fever and Mild-to-Moderate COVID-19: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

Yicheng Liu¹Jiaheng Shi^1*Xinting Liu¹Zongchen Jiang¹Benliang Zou²Rui Zhang²Qiuyan Li²Peili Wang²Chenhao Zhang³Jia Wang³Zhixi Zhang⁴Jiao Huang⁴Baojin Hua¹Luqi Huang⁵Wensheng Qi^1*

• ¹Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
• ²Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
• ³Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, Beijing Municipality, China
• ⁴Eye Hospital, China Academy of Chinese Medical Sciences, Beijing, China, Beijing, China
• ⁵China Academy of Chinese Medical Sciences, Beijing, Beijing Municipality, China

Background: Chinese herbal acupoint application is recommended by certain guidelines for treating mild-to-moderate COVID-19; however, evidence supporting its effectiveness remains limited. This study aimed to evaluate the effectiveness and safety of Chinese herbal acupoint application in adult patients with fever and mild-to-moderate COVID-19. Methods: This multicenter, randomized, double-blind, placebo-controlled trial was conducted at six hospitals in China. Overall, 364 participants were randomly assigned in a 1:1 ratio to receive either the herbal or placebo acupoint application. All participants received applications at the Dazhui (GV14) and Feishu (BL13) acupoints three times daily for 2 h per application over five days and Fuzheng Jiebiao Decoction orally three times daily, three bags per dose. The primary outcome was complete fever relief time. Secondary outcomes included the onset time of fever reduction, changes in symptom scores, routine blood tests, and acetaminophen usage rates and dosages.Results: Regarding the primary outcome, herbal acupoint application significantly reduced complete fever relief time compared to placebo (31.75 h vs. 52.00 h; P < 0.0001). Regarding secondary outcomes, the herbal group also demonstrated a shorter onset time of fever reduction than the placebo group (24.35 h vs. 34.42 h; P < 0.0001). Herbal acupoint application significantly reduced total symptom scores, particularly fever, headache, and cough symptoms. Moreover, 52 patients (29.05%) in the herbal group used acetaminophen, with a median dosage of 0.3 g (0.3, 0.6), which was significantly lower than that in the placebo group, with 94 patients using 0.6 g (0.3, 0.9) (P < 0.05). No significant differences were observed in routine blood test results between the groups (P > 0.05), and no serious adverse events were reported in either group. Conclusion: Chinese herbal acupoint application effectively and safely shortened the complete fever relief time and onset time of fever reduction; alleviated clinical symptoms, particularly fever, headache, and cough; and reduced the need for antipyretic analgesics in adult patients with fever and mild-to-moderate COVID-19.