Abstract: CLINICAL TRIAL published: 07 June 2022 doi: 10.3389/fphar.2022.898062 Oral Co-Supplementation of Curcumin, Quercetin, and Vitamin D3 as an Adjuvant Therapy for Mild to Moderate Symptoms of COVID-19 —Results From a Pilot Open-Label, Randomized Controlled Trial Amjad Khan 1,2*, Somia Iqtadar 3, Sami Ullah Mumtaz 3, Michael Heinrich 4, Domingo A. Pascual-Figal 5,6, Shona Livingstone 7 and Sajid Abaidullah 3 1 Edited by: Yusof Kamisah, Universiti Kebangaan Malaysia, Malaysia Reviewed by: Ruben Manuel Luciano Colunga Biancatelli, Old Dominion University, United States Syed Mohammed Basheeruddin Asdaq, University of Almaarefa, Saudi Arabia *Correspondence: Amjad Khan amjadkhan@lumhs.edu.pk Specialty section: This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology Received: 16 March 2022 Accepted: 27 April 2022 Published: 07 June 2022 Citation: Khan A, Iqtadar S, Mumtaz SU, Heinrich M, Pascual-Figal DA, Livingstone S and Abaidullah S (2022) Oral Co-Supplementation of Curcumin, Quercetin, and Vitamin D3 as an Adjuvant Therapy for Mild to Moderate Symptoms of COVID19—Results From a Pilot Open-Label, Randomized Controlled Trial. Front. Pharmacol. 13:898062. doi: 10.3389/fphar.2022.898062 INEOS Oxford Institute for AMR Research, University of Oxford, Oxford, United Kingdom, 2Department of Biochemistry, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan, 3Department of Medicine, King Edward Medical University, Lahore, Pakistan, 4UCL School of Pharmacy, University of London, London, United Kingdom, 5Department of Cardiology, University of Murcia Hospital Universitario Virgen de la Arrixaca Murcia, Murcia, Spain, 6Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain, 7School of medicine, University of Dundee, Dundee, United Kingdom Background: Curcumin, quercetin, and vitamin D3 (cholecalciferol) are common natural ingredients of human nutrition and reportedly exhibit promising anti-inflammatory, immunomodulatory, broad-spectrum antiviral, and antioxidant activities. Objective: The present study aimed to investigate the possible therapeutic benefits of a single oral formulation containing supplements curcumin, quercetin, and cholecalciferol (combinedly referred to here as CQC) as an adjuvant therapy for early-stage of symptomatic coronavirus disease 2019 (COVID-19) in a pilot open-label, randomized controlled trial conducted at Mayo Hospital, King Edward Medical University, Lahore, Pakistan. Methods: Reverse transcriptase polymerase chain reaction (RT-PCR) confirmed, mild to moderate symptomatic COVID-19 outpatients were randomized to receive either the standard of care (SOC) (n = 25) (control arm) or a daily oral co-supplementation of 168 mg curcumin, 260 mg quercetin, and 9 µg (360 IU) of cholecalciferol, as two oral soft capsules b.i.d. as an add-on to the SOC (n = 25) (CQC arm) for 14 days. The SOC includes paracetamol with or without antibiotic (azithromycin). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test, acute symptoms, and biochemistry including C-reactive protein (CRP), D-dimer, lactate dehydrogenase, ferritin, and complete blood count were evaluated at baseline and follow-up day seven. Results: Patients who received the CQC adjuvant therapy showed expedited negativization of the SARS-CoV-2 RT-PCR test, i.e., 15 (60.0%) vs. five (20.0%) of the control arm, p = 0.009. COVID-19- associated acute symptoms were rapidly resolved in the..