Oral HCQ and Throat Spray Proves Effective in Reducing Spread of COVID-19

A team of clinician-scientists has found that oral hydroxychloroquine and povidone-iodine throat spray were effective in reducing the spread of COVID-19 infection in high transmission settings.

The findings were reported by clinician-scientists from the National University Health System (NUHS; Singapore) who conducted a randomized clinical trial among 3,037 healthy migrant workers quarantined in a large multi-storey dormitory in Singapore.


Beginning April 2020, Singapore witnessed a surge in COVID-19 cases following widespread outbreaks in residential dormitories of migrant workers. Efforts to isolate and quarantine infected workers were challenging given the high population density in the dormitories. As part of efforts to contain transmission among residents, a randomized controlled trial was conducted among healthy migrant workers quarantined in at Tuas South Dormitory, 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 (preventive) regimen of either oral hydroxychloroquine (400mg once, followed by 200mg/day), oral ivermectin (12mg once), povidone-iodine throat spray (3times/day, 270 μg/day), oral zinc (80mg/day)/vitamin C (500mg/day) combination, or oral vitamin C, 500mg/day. Vitamin C is used as a comparator medication as it was a widely-used remedy during the pandemic, despite a lack of preclinical evidence of efficacy against coronaviruses. The primary outcome was laboratory evidence of SARS-CoV-2 infection as shown by either a positive serologic test for SARS-CoV-2 antibody on Day 42, or a positive PCR test for SARS-CoV-2 at any time between baseline and Day 42.

Primary outcomes reported laboratory confirmed COVID-19 infection was diagnosed in 1,681 of 3,037 (55.4%) men. The frequency of COVID-19 infection was significantly lower in participants receiving hydroxychloroquine (212 out of 432 participants, 49%) and povidone-iodine throat spray (338 out of 735 participants, 46%) as compared with vitamin C (433 out of 619 participants, 70%). There were no statistically differences observed between zinc/vitamin C (300 out of 634 participants, 47%) and ivermectin (398 out of 617 participants, 64%), compared with vitamin C. Compared with vitamin C, significant absolute risk reductions were observed for oral hydroxychloroquine (21%) and povidone-iodine throat spray (24%). Reduction in the incidence of SARS-CoV-2 infection in the hydroxychloroquine and povidone-iodine throat spray groups remained statistically significant after adjustments were made for potential confounders (previous room exposure, age categories, nationalities, compliance to medications and baseline seropositivity within the same cluster).

In terms of secondary outcomes, a total of 201 (6.6%) men reported acute respiratory symptoms during the trial. Despite no evidence of their having lower infection rates, men who received ivermectin had fewer symptomatic infections compared with vitamin C. No pneumonia requiring hospitalization or death occurred. A total of 309 men had COVID-19 diagnosed by COVID-19 RNA detection from nasopharyngeal swabs. Consistently, men with greater medication adherence were significantly less likely to be infected. The study is novel in that it includes topical therapy in the form of povidone-iodineadministration by throat spray which lowered SARS-CoV-2 infection by 24% (in terms of absolute risk reduction) compared with vitamin C.

These findings support in vitro data that suggest potent virucidal effects of povidone-iodine against SARS-CoV-2 potentially capable of creating a relatively resistant environment within the oropharyngeal space. A reduction in viral load could also possibly reduce the exposure of aerosolized virus particles to their close contacts during the incubation and asymptomatic phases of infection, thereby interrupting transmission of SARS-CoV-2. Compared with other interventions, participants who received povidone-iodine throat spray reported highest medication adherence with fewer reporting side effects and medication discontinuation as compared with vitamin C arm, thereby supporting their tolerability and future applications.

“This is the first study to demonstrate the benefits of prophylactic, or preventive, therapy with either oral hydroxychloroquine or povidone-iodine throat spray in reducing SARS-CoV-2 infection among quarantined individuals living in a closed and high exposure setting,” said lead author of the interventional clinical study, Associate Professor Raymond Seet, Senior Consultant, Division of Neurology, Department of Medicine, NUH and Department of Medicine, NUS Medicine. “These are existing drugs that are easily available and have known safety profiles. This can represent a viable preventive strategy for individuals living in a closed and high-exposure setting, especially in areas and countries where COVID-19 vaccination is not available or widespread.”

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