Abstract: CLINICAL TRIAL published: 28 May 2021 doi: 10.3389/fphar.2021.669362 Oral Curcumin With Piperine as Adjuvant Therapy for the Treatment of COVID-19: A Randomized Clinical Trial Kirti S Pawar 1*, Rahul N Mastud 1, Satheesh K Pawar 2, Samragni S Pawar 3, Rahul R Bhoite 4, Ramesh R Bhoite 1, Meenal V Kulkarni 5 and Aditi R Deshpande 6 1 Giriraj Hospital and Intensive Care unit, Baramati, India, 2Siddhivinayak Ultrasound Research Center, Baramati, India, 3HBT Medical College and Dr R N Cooper Municipal General Hospital, Mumbai, India, 4Medstar Good Samaritan Hospital, Baltimore, MD, United States, 5Department of Preventive and Social Medicine, N K P Salve Medical College Nagpur, Nagpur, India, 6 Freelance Statistician, Nagpur, India Edited by: Dâmaris Silveira, University of Brasilia, Brazil Reviewed by: Omar Estrada, Instituto Venezolano de Investigaciones Científicas (IVIC), Venezuela Bharat B Aggarwal, University of Texas MD Anderson Cancer Center, United States *Correspondence: Kirti S. Pawar kirti.skpawar@gmail.com Specialty section: This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology Received: 18 February 2021 Accepted: 20 April 2021 Published: 28 May 2021 Citation: Pawar KS, Mastud RN, Pawar SK, Pawar SS, Bhoite RR, Bhoite RR, Kulkarni MV and Deshpande AR (2021) Oral Curcumin With Piperine as Adjuvant Therapy for the Treatment of COVID-19: A Randomized Clinical Trial. Front. Pharmacol. 12:669362. doi: 10.3389/fphar.2021.669362 Background: Coronavirus disease-2019 (COVID-19) has a wide range of pathophysiological effects. Curcumin, an active constituent of Curcuma longa (turmeric), has several properties, including anti-inflammatory, antioxidant, antiviral, antithrombotic, and anti-proliferative effects, which make it a promising candidate for the symptomatic treatment of COVID-19. Objective: We aimed to determine the effects of curcumin administered with piperine (to optimize absorption) on symptoms in patients with COVID-19 in a double-blind, randomized, controlled trial at a 30-bed dedicated COVID Health Center (DCHC) in Maharashtra, India. Methods: In addition to conventional COVID-19 treatment, patients in the control group received a dose of probiotics twice a day, and patients in the study group received curcumin (525 mg) with piperine (2.5 mg) in tablet form twice a day. The effects of curcumin/piperine treatment on primary and secondary outcomes were assessed for the duration of hospitalization. Results: Patients with mild, moderate, and severe symptoms who received curcumin/ piperine treatment showed early symptomatic recovery (fever, cough, sore throat, and breathlessness), less deterioration, fewer red flag signs, better ability to maintain oxygen saturation above 94% on room air, and better clinical outcomes compared to patients of the control group. Furthermore, curcumin/piperine treatment appeared to reduce the duration of hospitalization in patients with moderate to severe symptoms, and fewer deaths were observed in the curcumin/piperine treatment group. Conclusions: Administration of oral curcumin with piperine as an adjuvant symptomatic therapy in COVID-19 treatment could substantially reduce morbidity and mortality, and ease the logistical and supply-related burdens on the healthcare system. Curcumin could be a safe and natural therapeutic option to prevent Post-Covid thromboembolic events. Clinicaltrials.gov identifier: CTRI/2020/05/025482 Keywords: curcumin,..