Abstract: medRxiv preprint doi: https://doi.org/10.1101/2022.05.16.22275074; this version posted May 20, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Jinhua Qinggan Granules for Nonhospitalized COVID-19 Patients: a Double-Blind, Placebo-Controlled, Randomized Controlled Trial Muhammad Raza Shah*1, Samreen Fatima1, Sehrosh Naz Khan1, Shafiullah1, Gulshan Himani2, Kelvin Wan3, Timothy Lin3, Johnson Y.N. Lau4, Qingquan Liu*5, Dennis S.C. Lam*3,4 1] Center for Bioequivalence Studies and Clinical Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, 2] The Indus Hospital Karachi, Plot C-76, Sector 31/5, Opposite Korangi Crossing, Darussalam Society Sector 39, Karachi, Sindh, Pakistan 3] Hong Kong Alliance of Integrated Medicine Against Covid, Hong Kong 4] School of Chinese Medicine of Hong Kong, Baptist University, Hong Kong 5] Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China *E-mail address for correspondence Muhammad Raza Shah: raza.shah@iccs.edu , Qingquan Liu: liuqingquan@bjzhongyi.com, Dennis S.C. Lam: dennislam@hkcmer.com NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2022.05.16.22275074; this version posted May 20, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Abstract Background: Key findings from the World Health Organization Expert Meeting on Evaluation of Traditional Chinese Medicine in treating COVID-19 reported that TCMs are beneficial, particularly for mild-to-moderate cases. The efficacy of Jinhua Qinggan Granules (JHQG) in COVID-19 patients with mild symptoms has yet to be clearly defined. Methods: We conducted a phase 2/3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with JHQG in mild, nonhospitalized, laboratoryconfirmed COVID-19 patients. Participants were randomly assigned to receive 5g/sacket of JHQG or placebo granules orally thrice daily for 10 days. The primary outcomes were the improvement in clinical symptoms and proportion tested negative on viral PCR after treatment. Secondary outcomes were the time to recovery from clinical symptoms and changes in white blood cells (WBC) and acute phase reactants (C-reactive protein (CRP) and ferritin) 10-15 days after treatment. Results: A total of 300 patients were randomly assigned to receive JHQG (150 patients) and placebo (150 patients). Baseline characteristics were similar in the two groups. In the modified intention-to-treat analysis, JHQG showed greater clinical efficacy (82.67%) after 10 days of treatment compared with the placebo group (10.74%) (rate difference: 71.93%; 95% CI 64.09 79.76). The proportion of patients with a negative PCR after treatment were comparable (rate difference: -4.67%; 95% CI -15.76 - 6.42). While all changes in WBC, ferritin, and CRP levels showed a statistically significant decline..