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0 0.5 1 1.5 2+ Viral load, combined 74% Improvement Relative Risk Viral load, E 96% Viral load, S 44% Povidone-Iodine  Natto et al.  EARLY TREATMENT  RCT Does povidone-iodine reduce short-term viral load for COVID-19? RCT 24 patients in Saudi Arabia (June - July 2021) Trial compares with saline, results vs. placebo may differ Improved viral load with povidone-iodine (not stat. sig., p=0.27) Natto et al., Medicine, July 2022 Favors povidone-iodine Favors saline

The short-term effect of different chlorhexidine forms versus povidone iodine mouth rinse in minimizing the oral SARS-CoV-2 viral load: An open label randomized controlled clinical trial study

Jul 2022  
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60 patient RCT comparing chlorhexidine, PVP-I, and saline in Saudi Arabia with a single mouth rinse treatment and PCR testing 5 minutes later, showing statistically significant improvement in Ct value for PVP-I. PVP-I showed greater improvement than saline, without statistical significance.
Analysis of short-term changes in viral load using PCR may not detect effective treatments because PCR is unable to differentiate between intact infectious virus and non-infectious or destroyed virus particles. For example Alemany, Tarragó‐Gil perform RCTs with cetylpyridinium chloride (CPC) mouthwash that show no difference in PCR viral load, however there was significantly increased detection of SARS-CoV-2 nucleocapsid protein, indicating viral lysis. CPC inactivates SARS-CoV-2 by degrading its membrane, exposing the nucleocapsid of the virus. To better estimate changes in viral load and infectivity, methods like viral culture or antigen detection that can differentiate intact vs. degraded virus are preferred.
This study is excluded in the after exclusion results of meta analysis: study only provides short-term viral load results.
This study includes chlorhexidine and povidone-iodine.
risk of viral load, 74.0% lower, RR 0.26, p = 0.27, treatment 12, control 12, relative improvement in Ct value, both genes combined.
risk of viral load, 96.2% lower, RR 0.04, p = 0.12, treatment mean 4.43 (±4.78) n=12, control mean 0.17 (±7.67) n=12, relative improvement in Ct value, E gene.
risk of viral load, 44.4% lower, RR 0.56, p = 0.60, treatment mean 3.33 (±5.6) n=12, control mean 1.85 (±7.68) n=12, relative improvement in Ct value, S gene.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Natto et al., 29 Jul 2022, Randomized Controlled Trial, Saudi Arabia, peer-reviewed, 7 authors, study period June 2021 - July 2021, this trial compares with another treatment - results may be better when compared to placebo, trial NCT04941131 (history).
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This PaperPovidone-Iod..All
The short-term effect of different chlorhexidine forms versus povidone iodine mouth rinse in minimizing the oral SARS-CoV-2 viral load: An open label randomized controlled clinical trial study
DrPH Zuhair S Natto, PhD Muhammed A Bakhrebah, MSc Marwah Afeef, BA Samiah Al-Harbi, PhD Majed S Nassar, PhD Abdulkarim F Alhetheel, PhD Heba Ashi
Medicine, doi:10.1097/md.0000000000028925
Several investigations evaluated the possibility of different types of mouth wash rinse in minimizing the SARS-CoV-2 load. However, results still controversial. The study aim is to assess the short-term efficiency of several over-the-counter mouth rinses and lozenges in minimizing the salivary viral load for SARS-CoV-2 in patients with confirmed COVID-19 in comparison to saline. This is a randomized controlled clinical trial with 4 arms. The recruited cases were randomized using a simple randomization technique and were assigned to chlorhexidine digluconate mouth rinse (CHX mouth rinse), 2 mg of chlorhexidine digluconate lozenges (CHX lozenges), povidone iodine mouth rinse (PVP-I mouth rinse) or saline as a control group. Saliva were collected from all study subjects by passive drool technique at two time points. First, prior to intervention with mouth rinse or the lozenges, the baseline saliva sample was collected. Second saliva samples were collected immediately after the mouth rinse. Real time PCR was conducted and the value threshold cycle (Ct) for each sample was recorded. Majority of the participants had an education level of high school or less (60%), were married (68.3), males (58.3%), and nonsmokers (58.5%). No statistically significant differences between groups at the two times test (P > .05). However, a significant decrease of salivary viral load in all four groups combined (P-value for E genes = .027, and for S genes = .006), and in PVP-I mouth rinse specifically (P = .003 and P = .045, respectively). Povidone iodine mouth rinse showed a potential influence on the reduction of the viral load on a short-term basis. However, longer-term studies of the effect of these products should be conducted. Abbreviations: CHX mouth rinse = digluconate mouth rinse, CHX lozenges = chlorhexidine digluconate lozenges, PVP-I mouth rinse = povidone iodine mouth rinse, Ct = threshold cycle, SARS-CoV-2 = Severe Acute Respiratory Syndrome Coronavirus 2, KFGH = King Fahad General Hospital, RT-PCR = Real-time polymerase chain reaction.
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