HCQ, povidone-iodine throat spray touted for COVID-19 prophylaxis

Short-term use of either oral hydroxychloroquine (HCQ) and povidone-iodine throat spray have shown a signal of reducing the incidence of SARS-CoV-2 infection among young men living in a closed and high-exposure setting, with either compound being superior to oral vitamin C, as shown in an open-label trial from Singapore.

“Our findings contrast with data from recent randomized trials, primate studies, and in vitro studies using human cell lines that suggested a lack of efficacy of HCQ for SARS-CoV-2 prevention,” according to a team of researchers from the National University of Singapore. [N Engl J Med 2020;383:517-525; JAMA Intern Med 2020;181:195-202; N Engl J Med 2020;384:417-427; Nature 2020;585:584-587; Nature 2020;585:588-590]

Compared with vitamin C, HCQ reduced the incidence of infection by 21 percent. The team pointed out that the drug was administered at a lower daily dose but for a longer period of 42 days, which ensured a higher cumulative level of exposure to HCQ. Also, in the previous studies, prophylaxis was initiated with a delay of up to 6 days following a self-reported exposure. [Int J Infect Dis 2021;doi:10.1016/j.ijid.2021.04.035]

Meanwhile, topical therapy with povidone-iodine lowered infection rate by 24 percent relative to vitamin C. This, said the researchers, supports in vitro data suggesting potent virucidal effects of the antiseptic against SARS-CoV-2, potentially capable of creating a relatively resistant environment within the oropharyngeal space  [Infect Dis Ther 2020;9:669-675; JAMA Otolaryngol Head Neck Surg 2020;146:1-5]

It means that povidone-iodine is “potentially capable of creating a relatively resistant environment within the oropharyngeal space,” they added. If viral load is lower, then so is the exposure of aerosolized virus particles to their close contacts during the incubation and asymptomatic phases of infection, the researchers explained. SARS-CoV-2 transmission is thereby interrupted.

Superior to vitamin C

The open-label trial was performed among healthy migrant workers quarantined in a large multi-storey dormitory in Singapore. Forty clusters, with each defined as individual floors of the dorm, were randomized to receive a 42-day prophylaxis regimen of either HCQ (400 mg once, followed by 200 mg/day), ivermectin (12 mg once), povidone-iodine throat spray (3 times/day, 270 µg/day), zinc (80 mg/day)/vitamin C (500 mg/day) combination, or vitamin C alone (500 mg/day).

A total of 3,037 asymptomatic men (mean age 33 years) who were seronegative to SARS-CoV-2 at baseline participated. They agreed to provide daily symptom feedback through a mobile application. Almost all of them completed the trial (99.6 percent).

More than half of the population (1,681, 55.4 percent) contracted the SARS-CoV-2 infection (confirmed by either serologic or PCR test). The number of infected individuals was significantly lower in the HCQ (212 out of 432, 49 percent) and povidone-iodine groups (338 out of 735, 46 percent) than in the vitamin C group (433 out of 619, 70 percent).

In fully adjusted logistic regression models, men given either HCQ or the throat spray were 60 percent less likely to catch the infection than those on vitamin C (adjusted odds ratio [aOR], 0.39, 98.75 percent confidence interval [CI], 0.15–0.99; p=0.0094 and aOR, 0.40, 98.75 percent CI, 0.15–0.88; p=0.012, respectively).

There were no statistically significant differences noted for zinc/vitamin C (300 out of 634, 47 percent; absolute risk reduction, 23 percent) and ivermectin (398 out of 617, 64 percent; absolute risk reduction, 5 percent) relative to vitamin C.

Adherence to the prophylactic regimen overall was moderately good. Interruptions due to side effects were highest for the zinc/vitamin C combination (6.9 percent), followed by vitamin C (4.7 percent), povidone-iodine (2.0 percent), and HCQ (0.7 percent).

“This is the first study to demonstrate the benefits of prophylactic therapy with either oral HCQ or povidone-iodine throat spray in reducing SARS-CoV-2 infection among quarantined [men] living in a closed and high-exposure setting. These pharmacotherapies could be used to complement existing nonpharmacological interventions in settings where transmission is high while awaiting roll out of a vaccine,” the researchers said.

The next step in the study, they added, is to analyse the prophylactic regimens’ effects in older people and women, and in those who are immunocompromised and have other significant comorbidities, over prolonged periods of time.