A prospective, randomized, open-label trial of early versus late povidone-iodine gargling in patients with COVID-19
Akifumi Matsuyama, Hanayuki Okura, Shyoji Hashimoto, Toshio Tanaka
Scientific Reports, doi:10.1038/s41598-022-24683-8
Povidone-iodine (PVP-I) is a broad-spectrum antiseptic reagent that has been used for over 50 years. The purpose of this study is to look into the effect of gargling with PVP-I gargling on virus clearance and saliva infectivity in COVID-19. A prospective, randomized, open-label trial of intervention with PVP-I was conducted at three quarantine facilities in Osaka, Japan, enrolling adolescents and adults with asymptomatic-to-mild COVID-19. Patients were randomly allocated to the early and late intervention group at a 1:1 ratio. The early group gargled with PVP-I from days 2 to day 6; the late group gargled with water first, then with PVP-I from day 5 after sampling till day 6. The primary and secondary endpoints were viral clearance for SARS-CoV-2 using RT-qPCR at days 5 and 6, respectively, and the investigational endpoint was saliva infectivity clearance on day5. We enrolled 430 participants, with 215 assigned to each group, and 139 in the early group and 140 in the late had a positive saliva RT-qPCR test on day 2. On day 5, the early group had a significantly higher RT-qPCR negative rate than that of the late group (p = 0.015), and the early had a significantly higher clearance rate of infectivity (p = 0.025). During the PVP-I intervention, one participant reported oropharyngeal discomfort. Gargling with PVP-I may hasten virus clearance and reduce viral transmission via salivary droplets and aerosols in patients with asymptomatic-to-mild COVID-19. (Clinical trial registration numbers: jRCT1051200078 and dateof registration: 24/11/2020). The salivary SARS-CoV-2 viral load is thought to play a significant role in the accelerated transmission of coronavirus disease 2019 (COVID-19) 1 . A reduction in salivary viral load is thought to suppress transmission 2 , and some studies have suggested that mouthwash and/or gargling with povidone-iodine (PVP-I) may have an antiseptic effect for SARS-CoV-2, reducing its viral load 3 . However, it is unknown whether gargling with PVP-I would eliminate salivary viral load and infectivity in COVID-19 patients in vivo. PVP-I is a polyvinylpyrrolidone (PVP) and iodine complex that has an antiseptic effect by releasing iodine. Its mechanism of action involves the use of iodine to oxidize microbial components. PVP-I has previously been shown to have an antiseptic effect on SARS-CoV and MERS in vitro 4, 5 , and it was also effective against SARS-CoV-2 6 . A single in vitro gargle with PVP-I reduced the salivary viral load in two of four patients with a high salivary viral load 7 . Although recent studies have confirmed the short-term effects of reducing salivary viral load in a small number of patients with COVID-19 8 , there have been no prospective randomized intervention studies involving PVP-I gargling. The purpose of this study was to see if gargling with PVP-I will reduce viral load and SARS-CoV-2 infectivity in patients with COVID-19.
Materials and methods Study design. This was a prospective, randomized,..
Author contributions A.M. had full access to all data in the study. A.M., S.H., and T.T. were responsible for the trial design. A.M. was responsible for the acquisition and analysis of data. H.O. acquired the laboratory data. A.M. drafted the paper. SH. and T.T. revised one. A.M. was responsible for the integrity of the data, the accuracy of the data analysis and decided to publish the manuscript. All authors contributed to conducting the trial.
Competing interests The authors declare no competing interests.
References
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Ather, Patel, Ruparel, Diogenes, Hargreaves, Coronavirus Disease 19 (COVID-19): Implications for clinical dental care, J. Endod
Bidra, Rapid in-vitro inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using povidoneiodine oral antiseptic rinse, J. Prosthodont
Burton, Antimicrobial mouthwashes (gargling) and nasal sprays administered to patients with suspected or confirmed COVID-19 infection to improve patient outcomes and to protect healthcare workers treating them, Cochrane Database Syst. Rev
Burton, Use of antimicrobial mouthwashes (gargling) and nasal sprays by healthcare workers to protect them when treating patients with suspected or confirmed COVID-19 infection, Cochrane Database Syst. Rev
Eggers, Eickmann, Zorn, Rapid and effective virucidal activity of povidone-iodine products against Middle East respiratory syndrome coronavirus (MERS-CoV) and modified vaccinia virus Ankara (MVA), Infect. Dis. Ther
Eggers, Koburger-Janssen, Eickmann, Zorn, In vitro bactericidal and virucidal efficacy of povidone-iodine gargle/ mouthwash against respiratory and oral tract pathogens, Infect. Dis. Ther
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Kariwa, Fujii, Takashima, Inactivation of SARS coronavirus by means of povidone-iodine, physical conditions, and chemical reagents, Jpn. J. Vet. Res
Khan, Parab, Tolerability and usability of 0.5% PVP-I gargles and nasal drops in 6692 patients: Observational study, Am. J. Otolaryngol
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