International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.04.045
Background: We examined whether existing licensed pharmacotherapies could reduce the spread of coronavirus disease 2019 . 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-CoV-2 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 C (4.7%), povidone-iodine (2.0%), and hydroxychloroquine (0.7%). Conclusions: Chemoprophylaxis with either oral hydroxychloroquine or povidone-iodine throat spray was superior to oral vitamin C in reducing SARS-CoV-2 infection in young and healthy men.
Authors contributions All authors have made substantial contributions to the publication. RSCS, QMLA, PAT, and MH contributed to the conception and design of the study and acquisition of data, drafted the article, revised it critically for important intellectual content, and approved the final version for submission. DSQO, SS, SRL, CYK, JBYS, BCG, KSL, DF, and HLT have contributed to the conception and design of the study and acquisition of data, revised it critically for important intellectual content, and approved the final version for submission. JS and ARC have contributed to statistical analysis, revised the manuscript for important intellectual content, and approved the final version for submission.
Conflicts of interest Dr. Seet reported receiving grants from the National Medical Research Council and Temasek Foundation, Singapore. Dr. Tambyah reported receiving grants from Johnson and Johnson, GlaxoSmithKline, and Roche.
Data availability statement The data underlying this article will be shared on reasonable request to the corresponding author. Data suppression rules apply to ensure the anonymity of the study participants.
NCT04446104 Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.ijid.2021.04.035.
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