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0 0.5 1 1.5 2+ Viral infectivity, culture 69% Improvement Relative Risk Viral clearance, PCR 38% primary Povidone-Iodine  Matsuyama et al.  EARLY TREATMENT  RCT Is early treatment with povidone-iodine beneficial for COVID-19? RCT 279 patients in Japan (November 2020 - March 2021) Improved viral clearance with povidone-iodine (p=0.025) Matsuyama et al., Scientific Reports, Nov 2022 Favors povidone-iodine Favors control

A prospective, randomized, open-label trial of early versus late povidone-iodine gargling in patients with COVID-19

Matsuyama et al., Scientific Reports, doi:10.1038/s41598-022-24683-8, jRCT1051200078
Nov 2022  
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RCT 430 COVID+ patients in Japan, showing significantly lower viral infectivity from culture, and significantly faster PCR viral clearance with PVP-I.
For days 2-4 the study compares treatment with PVP-I vs. water (on day 5 both groups received PVP-I). Most patients were asymptomatic. 4 times per day mouthwashing and gargling with 20mL of 15-fold diluted PVP–I 7% or water.
Targeted administration to the respiratory tract provides treatment directly to the typical source of initial SARS-CoV-2 infection and replication, and allows for rapid onset of action, higher local drug concentration, and reduced systemic side effects.
viral infectivity, 69.0% lower, RR 0.31, p = 0.03, treatment 4 of 139 (2.9%), control 13 of 140 (9.3%), NNT 16, viral infectivity from culture, day 5.
risk of no viral clearance, 38.0% lower, HR 0.62, p = 0.01, treatment 139, control 140, inverted to make HR<1 favor treatment, day 5, primary outcome.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Matsuyama et al., 28 Nov 2022, Randomized Controlled Trial, Japan, peer-reviewed, mean age 45.1, 4 authors, study period 30 November, 2020 - 17 March, 2021, trial jRCT1051200078.
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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.
Anderson, Povidone-iodine demonstrates rapid in vitro virucidal activity against SARS-CoV-2, the virus causing COVID-19 disease, Infect. Dis. Ther
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Nobukuni, The influence of long-term treatment with povidone-iodine on thyroid function, Dermatology
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