Abstract: International Journal of Infectious Diseases 106 (2021) 314–322 Contents lists available at ScienceDirect International Journal of Infectious Diseases journal homepage: www.elsevier.com/locate/ijid Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: An open-label randomized trial Raymond Chee Seong Seeta,b,* , Amy May Lin Queka,b , Delicia Shu Qin Ooic,d, Sharmila Senguptae , Satish Ramapatna Lakshminarasappaf , Chieh Yang Koog , Jimmy Bok Yan Soh , Boon Cher Gohi , Kwok Seng Lohj, Dale Fishera,e, Hock Luen Teoha,b , Jie Sunk , Alex R. Cookk , Paul Anantharajah Tambyaha,e, Mikael Hartmanh,k a Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Division of Neurology, Department of Medicine, National University Hospital, Singapore Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore d Division of Pediatric Endocrinology, Khoo Teck Puat-National University Children’s Medical Institute, National University Hospital, Singapore e Division of Infectious Diseases, Department of Medicine, National University Hospital, Singapore f Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore g Department of Cardiology, National University Heart Centre, Singapore h Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore i Department of Hematology-Oncology, National University Cancer Institute, Singapore j Department of Otolaryngology-Head and Neck Surgery, National University Hospital, Singapore k Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore b c A R T I C L E I N F O A B S T R A C T Article history: Received 30 March 2021 Received in revised form 8 April 2021 Accepted 9 April 2021 Background: We examined whether existing licensed pharmacotherapies could reduce the spread of coronavirus disease 2019 (COVID-19). Methods: An open-label parallel randomized controlled trial was performed among healthy migrant workers quarantined in a large multi-storey dormitory in Singapore. Forty clusters (each defined as individual floors of the dormitory) were randomly assigned to receive a 42-day prophylaxis regimen of either oral hydroxychloroquine (400 mg once, followed by 200 mg/day), oral ivermectin (12 mg once), povidone-iodine throat spray (3 times/day, 270 mg/day), oral zinc (80 mg/day)/vitamin C (500 mg/day) combination, or oral vitamin C, 500 mg/day. The primary outcome was laboratory evidence of SARS-CoV2 infection as shown by either: (1) a positive serologic test for SARS-CoV-2 antibody on day 42, or (2) a positive PCR test for SARS-CoV-2 at any time between baseline and day 42. Results: A total of 3037 asymptomatic participants (mean age, 33.0 years; all men) who were seronegative to SARS-CoV-2 at baseline were included in the primary analysis. Follow-up was nearly complete (99.6%). Compared with vitamin C, significant absolute risk reductions (%, 98.75% confidence interval) were observed for oral hydroxychloroquine (21%, 2–42%) and povidone-iodine throat spray (24%, 7–39%). No statistically significant differences were observed with oral zinc/vitamin C combination (23%, –5 to +41%) and ivermectin (5%, –10 to +22%). Interruptions due to side effects were highest among participants who received zinc/vitamin C combination (6.9%), followed by vitamin..