Summary of COVID-19 povidone-iodine studies

606 patient povidone-iodine early treatment RCT: 88% lower mortality (p=0.0006), 84% lower hospitalization (p<0.0001), and 96% improved viral clearance (p<0.0001).
RCT 606 patients in Bangladesh for povidone iodine mouthwash/gargle, nasal drops and eye drops showing significantly lower death, hospitalization, and PCR+ at day 7.
Dec 2020, Bioresearch Communications, https://www.banglajol.info/index.php/BRC/article/view/54245, https://c19p.org/choudhury

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

279 patient povidone-iodine early treatment RCT: 69% improved viral clearance (p=0.03).
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.
Nov 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-24683-8, https://c19p.org/matsuyama

3. Friedland et al., Phase II Trial of the Impact 0.5% Povidone‐Iodine Nasal Spray (Nasodine®) on Shedding of SARS‐CoV‐2

23 patient povidone-iodine early treatment RCT: 60% improved viral clearance (p=0.03) and 6% improved recovery.
RCT 23 early COVID-19 outpatients showing significantly improved reduction in viral load and significantly faster viral clearance with povidone-iodine nasal spray compared to placebo. The study was underpowered due to low recruitment, enrolling only 23 patients from a target of 144. Authors report generally mild symptoms and a 6% benefit over placebo on symptom scores (AUC symptom score days 2–5) without statistical significance, but do not provide details. Notably, no benefit was seen for rapid antigen test positivity, which is unable to distinguish viable and non-viable virus. The relatively poor diagnostic information from viral positivity using methods that cannot distinguish viable virus may present misleading results in many COVID-19 studies. Treatment 8 times daily for a total of 20 doses.
Mar 2024, The Laryngoscope, https://onlinelibrary.wiley.com/doi/10.1002/lary.31430, https://c19p.org/friedland2

4. Seet et al., Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial

1,354 patient povidone-iodine prophylaxis RCT: 45% fewer symptomatic cases (p=0.002) and 31% fewer cases (p=0.01).
Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C. Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters. There were no hospitalizations and no deaths.
Apr 2021, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(21)00345-3/fulltext, https://c19p.org/seetp

5. Karaaltin et al., Effect of the povidone iodine, hypertonic alkaline solution and saline nasal lavage on nasopharyngeal viral load in COVID-19

60 patient povidone-iodine early treatment RCT: 83% improved viral load (p=0.007).
RCT 120 outpatients in Turkey, showing improved reduction in viral load with PVP-I nasal irrigation. PVP-I prepared with hypertonic alkaline solution had better results. [Kreutzberger] show that SARS-CoV-2 requires acidic pH to infect cells, therefore alkalinization may add additional benefits. All patients received favipiravir. PVP-I 1% 4 times per day.
Oct 2022, Authorea, Inc., https://www.authorea.com/users/337860/articles/592062-effect-of-the-povidone-iodine-hypertonic-alkaline-solution-and-saline-nasal-lavage-on-nasopharyngeal-viral-load-in-covid-19?commit=bcb03d2ad8d86742ebd473271b70f5ab7211094d, https://c19p.org/karaaltin

6. Arefin et al., Virucidal effect of povidone iodine on COVID-19 in the nasopharynx: an open-label randomized clinical trial

189 patient povidone-iodine early treatment RCT: 79% improved viral clearance (p=0.02).
RCT with 189 patients showing significantly greater viral clearance with a single application of PVP-I. Authors recommend using PVP-I prophylactically in the nasopharynx and oropharynx. NCT04549376 [trialsjournal.biomedcentral.com].
May 2021, Indian J. Otolaryngology and Head & Neck Surgery, https://link.springer.com/article/10.1007/s12070-021-02616-7, https://c19p.org/arefin

7. Elsersy et al., Combined Nasal, Oropharyngeal Povidone Iodine Plus Glycyrrhizic Acid Sprays, Accelerate Clinical and Laboratory Recovery and Reduces Household Transmission of SARS-CoV-2: A Randomized Placebo-Controlled Clinical Trial

421 patient povidone-iodine early treatment RCT: 91% lower hospitalization (p=0.06), 15% faster recovery (p=0.008), 68% improved viral clearance (p<0.0001), and 92% lower transmission (p<0.0001).
RCT with 200 patients and 421 contacts in Egypt, with 100 patients and their contacts treated with nasal and oropharyngeal sprays containing povidone-iodine and glycyrrhizic acid, showing significantly faster viral clearance and recovery, and significantly lower transmission. SOC included vitamin C and zinc. The spray active ingredients included a compound of glycyrrhizic acid in the form of ammonium glycyrrhizate 2.5 mg/ml plus PVI 0.5% for oropharyngeal and dipotassium glycyrrhizinate 2.5 mg/ml plus PVI 0.5% for nasal spray. Patients were advised to concomitantly use oropharyngeal and nasal sprays 6 times per day. They were instructed to abstain from food, drink, and smoke for 20min, particularly after oropharyngeal spray. The oropharyngeal spray bottle contains an atomizer that ends with a long arm applicator to insert inside the mouth cavity and can be directed up, down, right, or left to cover the entire pharyngeal area.
Apr 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.863917/full, https://c19p.org/elsersy

8. Guenezan et al., Povidone Iodine Mouthwash, Gargle, and Nasal Spray to Reduce Nasopharyngeal Viral Load in Patients With COVID-19: A Randomized Clinical Trial

24 patient povidone-iodine early treatment RCT: 63% improved viral load (p=0.25).
RCT of PCR+ patients with Ct<=20 with 12 treatment and 12 control patients, concluding that nasopharyngeal decolonization may reduce the carriage of infectious SARS-CoV-2 in adults with mild to moderate COVID-19. All patients but 1 had negative viral titer by day 3 (group not specified). There was no significant difference in viral RNA quantification over time. The mean relative difference in viral titers between baseline and day 1 was 75% [43%-95%] in the intervention group and 32% [10%-65%] in the control group. Thyroid dysfunction occurred in 42% of treated patients, with spontaneous resolution after the end of treatment. Patients in the treatment group were younger.
Feb 2021, JAMA Otolaryngol Head Neck Surg., https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2775984, https://c19p.org/guenezan

9. Jamir et al., Determinants of Outcome Among Critically Ill Police Personnel With COVID-19: A Retrospective Observational Study From Andhra Pradesh, India

266 patient povidone-iodine ICU study: 57% lower mortality (p=0.0004).
Retrospective 266 COVID-19 ICU patients in India, showing significantly lower mortality with PVP-I oral gargling and topical nasal use, and non-statistically significant higher mortality with ivermectin and lower mortality with remdesivir.
Dec 2021, Cureus, https://www.cureus.com/articles/73667-determinants-of-outcome-among-critically-ill-police-personnel-with-covid-19-a-retrospective-observational-study-from-andhra-pradesh-india, https://c19p.org/jamirp

10. Seneviratne et al., Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore

6 patient povidone-iodine late treatment RCT: 33% improved viral load (p=0.01).
Small mouthwash RCT with 4 PVP-I patients and 2 water patients concluding that PVP-I may have a sustained effect on reducing the salivary SARS-CoV-2 level in COVID-19 patients. ISRCTN95933274.
Dec 2020, Infection, https://link.springer.com/article/10.1007/s15010-020-01563-9, https://c19p.org/seneviratne

11. Mohamed et al., Early viral clearance among COVID-19 patients when gargling with povidone-iodine and essential oils: a pilot clinical trial

10 patient povidone-iodine early treatment RCT: 86% improved viral clearance (p=0.17).
Tiny RCT with 5 PVP-I patients, gargling 30 seconds, 3x per day, and 5 control patients (essential oils and tap water were also tested), showing improved viral clearance with PVP-I.
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.07.20180448v1, https://c19p.org/mohamed

12. Elzein et al., In vivo evaluation of the virucidal efficacy of chlorhexidine and povidone-iodine mouthwashes against salivary SARS-CoV-2. A randomized-controlled clinical trial

34 patient povidone-iodine early treatment RCT: 89% improved viral clearance (p=0.05).
Small RCT comparing mouthwashing with PVP-I, chlorhexidine, and water, showing significant efficacy for both PVP-I and chlorhexidine, with PVP-I increasing Ct by a mean of 4.45 (p < 0.0001) and chlorhexidine by a mean of 5.69 (p < 0.0001), compared to no significant difference for water.
Mar 2021, J. Evidence Based Dental Practice, https://www.sciencedirect.com/science/article/abs/pii/S1532338221000592, https://c19p.org/elzein

13. Ferrer et al., Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2

21 patient povidone-iodine late treatment RCT: 34% improved viral load (p=0.82).
Small very late (>50% 7+ days from symptom onset, 9 PVP-I patients) RCT testing mouthwashing with cetylpyridinium chloride, chlorhexidine, povidone-iodine, hydrogen peroxide, and distilled water, showing no significant differences. Over 30% of patients show >90% decrease in viral load @2 hrs with all 5. Authors note that a trend was observed for viral load decrease with PVP-I @2h for patients <6 days from onset (p=0.06, Wilcox test).
Dec 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-03461-y, https://c19p.org/ferrer2

14. Fantozzi et al., Efficacy of antiseptic mouthrinses against SARS-CoV-2: A prospective randomized placebo-controlled pilot study

38 patient povidone-iodine late treatment RCT: 57% improved viral load and 31% improved viral clearance (p=0.26).
Mouthrinse RCT in Italy comparing short-term viral load after a single 60 second treatment with povidone-iodine, hydrogen peroxide, chlorhexidine, and saline. The greatest efficacy was seen with povidone-iodine, especially for patients with low viral load at baseline.
Jul 2022, American J. Otolaryngology, https://www.sciencedirect.com/science/article/pii/S0196070922001764, https://c19p.org/fantozzi

15. Natto et al., 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

24 patient povidone-iodine early treatment RCT: 74% improved viral load (p=0.27).
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.
Jul 2022, Medicine, https://journals.lww.com/md-journal/Fulltext/2022/07290/The_short_term_effect_of_different_chlorhexidine.78.aspx, https://c19p.org/natto

16. Sevinç Gül et al., Effect of oral antiseptics on the viral load of SARS-CoV-2: A randomized controlled trial

41 patient povidone-iodine early treatment RCT: 99% improved viral load (p=0.37).
RCT with 21 PVP-I and 20 saline patients gargling for 30 seconds and testing PCR Ct after 30 minutes, showing greater improvement with PVP-I, without statistical significance. Ct values differ across testing platforms, however the reported Ct value difference can represent a large difference in viral load. For example, using the calibration included with the ct2vl converter, the reported difference in mean Ct values corresponds to a reduction in viral load of over 3x for PVP-I.
Jul 2022, Dental and Medical Problems, https://dmp.umw.edu.pl/en/ahead-of-print/150831/, https://c19p.org/sevincgul

17. Sulistyani et al., The effects of mouth rinsing and gargling with mouthwash containing povidone-iodine and hydrogen peroxide on the cycle threshold value of Severe Acute Respiratory Syndrome Coronavirus 2: A randomized controlled trial of asymptomatic and mildly symptomatic patients

30 patient povidone-iodine early treatment RCT: 6% improved viral clearance (p=0.74).
Small mouth rinsing and gargling RCT with 15 1% PVP-I, 12 0.5% PVP-I, 15 3% hydrogen peroxide, 12 1.5% hydrogen peroxide, and 15 water patients, showing rapid improvement in Ct value in all groups, and no significant differences between groups.
Mar 2022, F1000Research, https://f1000research.com/articles/11-1238/v1, https://c19p.org/sulistyani

18. Pablo-Marcos et al., Utility of mouth rinses with povidone-iodine and hydrogen peroxide in patients with COVID-19

71 patient povidone-iodine early treatment study: 29% improved viral clearance (p=0.4).
Small prospective study with 31 patients gargling povidone-iodine, 17 hydrogen peroxide, and 40 control patients, showing lower viral load mid-recovery with povidone-iodine, without reaching statistical significance. Oropharyngeal only, and only every 8 hours for two days. Results may be better with the addition of nasopharyngeal use, more frequent use, and without the two day limit. Authors report only one of the 7 previous trials for PVP-I and COVID-19. Non-randomized study with no adjustments or group details. Some results in Figure 1 appear to be switched compared to the text and the labels in the figure. The viral clearance figures do not match the group sizes - for example authors report 62% PCR- for PVP-I at the 3rd test, however there is no number of 31 patients that rounds to 62%.
Oct 2021, Enfermedades Infecciosas y Microbiología Clínica, https://www.sciencedirect.com/science/article/pii/S0213005X21002950, https://c19p.org/pablomarcos

19. Sirijatuphat et al., A pilot study of 0.4% povidone-iodine nasal spray to eradicate SARS-CoV-2 in the nasopharynx

12 patient povidone-iodine early treatment study: 33% improved viral load (p=0.58).
Small single-arm trial testing short-term viral load change after a single administration of three puffs of 0.4% PVP-I, showing lower viral titer at 3 minutes and 4 hours, not reaching statistical significance. Authors note that one reason for the lower change compared to in vitro results is that the spray administration may be less effective.
Aug 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.08.18.22278340, https://c19p.org/sirijatuphat3

20. Baxter et al., Rapid initiation of nasal saline irrigation to reduce severity in high-risk COVID+ outpatients

79 patient povidone-iodine early treatment RCT: 57% improved recovery (p=0.03) and 14% lower transmission (p=1).
Small RCT 79 PCR+ patients 55+ comparing pressure-based nasal irrigation with povidone-iodine and sodium bicarbonate, showing improved recovery with povidone-iodine. Not all results comparing povidone-iodine and sodium bicarbonate are in the journal version, as authors focus on the comparison with CDC data. Earlier versions can be found at [medrxiv.org]. The reported hospitalization switched groups between the preprint and the journal version.
Aug 2022, Ear, Nose & Throat J., http://journals.sagepub.com/doi/10.1177/01455613221123737, https://c19p.org/baxter

21. Zarabanda et al., The Effect of Povidone-Iodine Nasal Spray on COVID-19 Nasopharyngeal Viral Load in Patients: A Randomized Control Trial

24 patient povidone-iodine late treatment RCT: 27% worse recovery (p=1) and no change in viral clearance (p=1).
Very late treatment (7 days from onset) RCT comparing 11 & 13 PVP-I (0.5% and 2%), and 11 saline spray patients in the USA, showing no significant differences. There was no control group (saline is likely not a placebo, showing efficacy in other trials). There are large unadjusted differences between groups, e.g. 7.1 days from onset for PVP-I versus 4.8 for saline. Baseline Ct was higher for PVP-I, providing less room for improvement. Authors note that they cannot determine if earlier use is more beneficial.
Oct 2021, Laryngoscope, https://onlinelibrary.wiley.com/doi/abs/10.1002/lary.29935, https://c19p.org/zarabanda

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