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.
A prospective, randomized,
open‑label trial of early versus late
in patients with COVID‑19
Akifumi Matsuyama 1*, Hanayuki Okura 1, Shyoji Hashimoto 2 & Toshio Tanaka 3,4
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 transmission2,
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 l oad3. 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 vitro4,5, and it was also effective against SARSCoV-26. A single in vitro gargle with PVP–I reduced the salivary viral load in two of four patients with a high
salivary viral load7. 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, and open-label trial that looked at the efficacy and
safety of gargling with PVP–I in asymptomatic-to-mild COVID-19 patients (aged ≥ 16 years) quarantined in
three different locations. The protocol was approved by the Medical Center Clinical Research Review Board
Please send us corrections, updates, or comments. Vaccines and
treatments are complementary. All practical, effective, and safe means should
be used based on risk/benefit analysis. No treatment, vaccine, or intervention
is 100% available and effective for all current and future variants. We do not
provide medical advice. Before taking any medication, consult a qualified
physician who can provide personalized advice and details of risks and
benefits based on your medical history and situation. FLCCC and WCH
provide treatment protocols.