Abstract: Integrative Medicine Research 11 (2022) 100869 Contents lists available at ScienceDirect Integrative Medicine Research journal homepage: www.elsevier.com/locate/imr Original Article Efficacy of a Persian herbal medicine compound on coronavirus disease 2019 (COVID-19): A randomized clinical trial Mohammad Setayesh a, Mehrdad Karimi b, Arman Zargaran c, Hamid Abousaidi d, Armita Shahesmaeili e, Fatemeh Amiri f, Fatemeh Sadat Hasheminasab g,∗ a Department of Traditional Medicine, School of Persian medicine, Kerman University of Medical Sciences, Kerman, Iran Department of Traditional Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran Department of Traditional Pharmacy, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran d Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran e HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health Kerman University of Medical Sciences, Kerman, Iran f Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran g Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran b c a r t i c l e i n f o Article history: Received 31 December 2021 Revised 27 May 2022 Accepted 30 May 2022 Available online 3 June 2022 Keywords: Glycyrrhiza glabra Nigella sativa Rheum palmatum COVID-19 Persian medicine herbal medicine a b s t r a c t Background: The global attention to the capacities of traditional medicine for alleviating the clinical manifestations of COVID-19 has been growing. The present trial aimed to evaluate the efficacy and safety of a Persian herbal medicine formula among patients with COVID-19. Methods: The present trial was conducted in Afzalipour hospital, Kerman, Iran, from June to September 2020. Hospitalized COVID-19 patients were randomly divided into intervention (Persian herbal medicine formula + routine treatment) or control (only routine treatment) groups. The intervention group received both capsule number 1 and 2 every 8 hours for 7 days. Capsule number 1 contained extract of the Glycyrrhiza glabra, Punica granatum, and Rheum palmatum, and the second capsule was filled by Nigella sativa powder. Participants were followed up to 7 days. The primary outcome was the number of hospitalization days, while cough, fever, and respiratory rate, days on oxygen (O2 ) therapy, and mortality rate were considered as the secondary outcomes. Results: Eighty-two patients were enrolled to the study, while 79 cases completed the trial and their data were analyzed (mean age: 59.1 ± 17.1 years). Based on the results, the Persian medicine formula decreased the mean hospitalization days, so that the mean difference of length of hospitalization as primary outcome was 2.95 ± 0.43 days. A significant clinical improvement was observed regarding dyspnea, need for O2 ) therapy, and respiratory rate in the intervention group. No adverse effects were reported. Conclusion: The present study supported the use of the Persian medicine formula as an adjuvant therapy for hospitalized COVID-19 patients. Study registration: Iranian Registry of Clinical Trials (www.irct.ir): IRCT2020 0330 046899N1. Study registration: Iranian Registry of Clinical Trials (www.irct.ir): IRCT2020 0330 046899N1. © 2022 Korea Institute of Oriental Medicine. Published by Elsevier B.V. This is an open access article under the CC..