Effects of Licorice on clinical symptoms and laboratory signs in moderately ill patients with pneumonia from COVID-19: A structured summary of a study protocol for a randomized controlled trial

Abstract

Objectives We investigate the effects of Licorice (Glycyrrhiza glabra L.) root extract, an anti-inflammatory natural medicine, compared to the usual therapeutic regimen on clinical symptoms and laboratory signs in patients with confirmed COVID-19 that are moderately ill. Trial design This is a single-center, open-label, randomized, clinical trial with parallel-group design. This study is being conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. Participants Both male and female patients with ≥18 years of age (≥ 35 kg of weight), admitted at the Shahid Mohammadi Hospital, Hormozgan University of Medical Sciences, Bandar Abbas for treatment, screened for the following criteria. Inclusion criteria: 1. Confirmed diagnosis of SARS-CoV-2 infection (via polymerase chain reaction [PCR] and/or antibody test). 2. Presenting as moderate COVID-19 pneumonia (via chest computed tomography (CT) and/or X-ray) requiring hospitalization. 3. Hospitalized ≤48 hours. 4. Signing informed consent and willingness of study participant to accept randomization to any assigned treatment arm. Exclusion criteria: 1. Underlying diseases, including chronic heart disease, chronic hypertension, severe renal failure, severe liver failure, and thyroid disorders. 2. Severe and critical COVID-19 pneumonia. 3. Use of warfarin, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), diuretics, corticosteroids, and antiarrhythmic drugs. 4. Treatment with Investigational and antiviral therapy in a clinical study within one month before randomization. 5. History of allergy to Licorice. 6. Pregnancy and breastfeeding. Intervention and comparator Intervention group: The standard treatment regimen for COVID-19 along with a Licorice-based herbal preparation (D-Reglis ®, Irandarouk Pharmaceutical Company, Iran) at a dose of 760 mg three times a day for a period of seven days. Control group: The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education's protocol for a period of seven days. Main outcomes The recovery rate of clinical symptoms, including fever, dry cough, and tiredness, as well as paraclinical features, including thrombocytopenia, lymphocytopenia, and C-reactive protein, are evaluated as primary outcomes within seven days of randomization. Time to improvement of clinical and paraclinical features and length of stay in a hospital, along with the incidence of adverse reactions are also evaluated as the secondary outcomes within seven days of randomization. Randomization An electronic table of random numbers will be used to allocate the included participants into either control or intervention groups (in a 1:1 ratio) using the simple randomization method. Blinding (masking) This is an open-label trial without blinding and placebo control. Numbers to be randomized (sample size) A total of 60 participants randomizes (30 patients allocated to the intervention group and 30 patients allocated to the control group). Trial Status The protocol is Version 1.0, May 31, 2020. Recruitment began July 30, 2020, and is anticipated to be completed by October 30, 2020. Trial registration This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is “IRCT20200506047323N2”, https://www.irct.ir/trial/47990. The registration date is 31 May 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Can Antiviral Activity of Licorice Help Fight COVID-19 Infection?

“…In addition to conventional therapy, patients receive one capsule twice daily containing 250 mg of standardized licorice extract, corresponding to 62.5 mg GR, for 10 days, and 2 g four times daily for 15 days of Boswellia gum resin. The other is a single-center, open-label, randomized clinical trial with parallel-group design, registered in the Iranian Registry of Clinical trials (IRCT20200506047323N2) which will look at the effects of licorice root extracts in moderately ill patients with pneumonia from COVID-19 [87]. In addition to the standard treatment, D-REGLIS tablets containing 380 mg of standardized dry extract of licorice with less than 3% GR at a dose of 760 mg were given three times a day for 14 days.…”

Natural products and phytochemicals as potential anti‐SARS‐CoV‐2 drugs

“…The authors have also determined that the glycyrrhizin mechanism of action was likely the induction of nitric oxide synthase (Cinatl et al, 2003 ). Finally, a new clinical study led by Safa et al to investigate Licorice root extract effect on clinical symptoms of SARS‐CoV‐2 is ongoing (Safa et al, 2020 ).…”

“…Finally, a new clinical study led bySafa et al to investigate Licorice root extract effect on clinical symptoms of SARS-CoV-2 is ongoing(Safa et al, 2020).6.3.2 | Jinhua Qinggan granulesEighty cases of SARS-CoV-2 positive patients in Beijing YouAn Hospital, China, were analyzed. All the subjects have been treated with symptomatic along with supportive therapy.…”

Safety Review of Herbs and Supplements in Heart Disease, Diabetes, and COVID-19

“…Clinical trials of licorice use during COVID-19 are ongoing. Daily doses range from 250 mg 25% extract (62.5 mg glycyrrhizin) for 10 days to 2.28 g 3% extract (70 mg glycyrrhizin) for 7 days [47,48].…”