Abstract: www.nature.com/scientificreports OPEN Randomized controlled trial of favipiravir, hydroxychloroquine, and standard care in patients with mild/moderate COVID‑19 disease Manaf AlQahtani1,2,3*, Nitya Kumar3, Dhuha Aljawder4, Abdulkarim Abdulrahman1,5, Fatema Alnashaba4, Mohammed Abu Fayyad3, Faisal Alshaikh2, Fatima Alsahaf4, Sawsan Saeed3, Amal Almahroos4, Zainab Abdulrahim4, Sameer Otoom3 & Stephen L. Atkin3 Favipiravir has antiviral activity against influenza, West Nile virus, and yellow fever virus and against flaviviruses. The objective of this pilot study was to compare three arms: favipiravir; hydroxychloroquine; standard care (no specific SARS-CoV-2 treatment) only, in symptomatic patients infected by SARS-CoV-2 in an open-labelled randomized clinical trial. The trial was registered with Bahrain National Taskforce for Combatting COVID-19 on the 7th of May 2020 (registration code: NCT04387760). 150 symptomatic patients with COVID-19 disease were randomized into one of three arms: favipiravir, hydroxychloroquine, or standard care only. The primary outcome was the clinical scale at the end of study follow up (day 14 or on discharge/death) based on a points scale. The secondary outcomes were viral clearance, biochemical parameter changes and mortality at 30-days. Baseline characteristics did not differ between groups. The proportion of patients who achieved a clinical scale < 2 did not differ between groups. The favipiravir-treated and hydroxychloroquine-treated group showed increased viral clearance (OR, 95%CI 2.38, 0.83–6.78, OR, 95%CI 2.15, 0.78–5.92, respectively) compared to standard care, but this was not significant. The biochemical profile did not differ between groups, except for the platelet count (P < 0.03) and uric acid (P < 0.004) that were higher with favipiravir-treatment. Primary or secondary outcome measures did not differ between favipiravir, hydroxychloroquine, and standard therapy for mild to moderate COVID-19 disease; therefore, whilst favipiravir therapy appeared safe with a trend to increased viral clearance, there was no superior therapeutic utility. Clinical trials registration. NCT04387760. Registration date: 07/05/2020. Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) and has developed into a pandemic with serious global public health and economic sequelae. As of May 30th, 2021, more than 170,695,962 million cases have been confirmed worldwide, leading to over 3,550,234 ­deaths1. Several vaccines have been shown to prevent or ameliorate COVID-19 disease, and several are currently ­developing2. However, for those that establish COVID-19 disease, there is a need for effective therapeutic agents to prevent the progressive deterioration that may be seen. There have been several reports of medications, such as remdesivir, with antiviral properties that have shown efficacy with shorter time-to-recovery against SARSCoV-23. It has been suggested that corticosteroids should be used cautiously unless there is evidence of refractory septic shock, acute respiratory distress syndrome (ARDS), or another compelling indication for their ­Use4. Hydroxychloroquine was thought to show great promise at the time that this study was ­initiated5 but, in a large observational study, showed no differences in rates of intubation or d ­ eath6, and a randomized trial in 150 patients showed mild beneficial ­effects7. A subsequent report indicated that postexposure therapy..