Povidone iodine, hydrogen peroxide and chlorhexidine mouthwashes reduce SARS-CoV2 burden in whole mouth fluid and respiratory droplets

Jayaraman et al., medRxiv, doi:10.1101/2021.02.25.21252488 , Mar 2021
Viral clearance 50% improvement lower risk ← → higher risk Hydrogen Peroxide  Jayaraman et al.  EARLY TREATMENT Does hydrogen peroxide reduce short-term viral load for COVID-19? Prospective study of 12 patients in India Improved viral clearance with treatment (not stat. sig., p=0.18) c19early.org Jayaraman et al., medRxiv, March 2021 0 0.5 1 1.5 2+ RR
24th treatment shown to reduce risk in May 2021, now with p = 0.024 from 8 studies.
Lower risk for viral clearance.
No treatment is 100% effective. Protocols combine treatments.
6,200+ studies for 200+ treatments. c19early.org
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Study of SARS-CoV-2 burden in whole mouth fluid and respiratory droplets with povidone iodine, hydrogen peroxide, and chlorhexidine mouthwashes in 36 hospitalized COVID-19 patients using PCR and rapid antigen testing. There were significant reductions in SARS-CoV-2 burden with all treatments in both respiratory droplets and whole mouth fluid.
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 Tarragó-Gil, Alemany 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 that can differentiate intact vs. degraded virus are preferred. .
Authors perform antigen testing for 6 hydrogen peroxide patients, showing that 50% became negative after treatment.
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Study covers chlorhexidine, hydrogen peroxide, and povidone-iodine.
risk of no viral clearance, 50.0% lower, RR 0.50, p = 0.18, treatment 3 of 6 (50.0%), control 6 of 6 (100.0%), NNT 2.0, antigen results.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Jayaraman et al., 1 Mar 2021, prospective, India, preprint, 12 authors.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org November 2025 India United Kingdom Russia USA Sudan Angola Colombia Kenya Mozambique Pakistan Argentina Vietnam Peru Philippines Spain Brazil Italy France Japan China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Bosnia-Herzegovina Ukraine Côte d'Ivoire Bulgaria Greece Slovakia Singapore Iceland New Zealand Czechia Mongolia Israel Trinidad and Tobago Hong Kong North Macedonia Belarus Qatar Panama Serbia CAR Chad Syria India favored low-cost treatments.The average efficacy of treatments was moderate.Low-cost treatments improve early treatment, andprovide complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org November 2025 India United Kingdom Russia USA Sudan Angola Colombia Kenya Mozambique Pakistan Argentina Vietnam Peru Philippines Spain Brazil Italy France Japan China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Ukraine Côte d'Ivoire Eritrea Bulgaria Greece Slovakia Singapore New Zealand Czechia Mongolia Israel Trinidad and Tobago North Macedonia Belarus Qatar Panama Benin Serbia CAR Syria India favored low-cost treatments.The average efficacy was moderate.Low-cost protocols improve early treatment,and add complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
Abstract: medRxiv preprint doi: https://doi.org/10.1101/2021.02.25.21252488; this version posted March 1, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Povidone iodine, hydrogen peroxide and chlorhexidine mouthwashes reduce SARS-CoV2 burden in whole mouth fluid and respiratory droplets Bagavad Gita Jayaraman1*, Gunaseelan Rajan1, Priya Kannian2*, Chandra Lavanya4, Krittika Ravichandran1, Nagalingeswaran Kumarasamy3, Kannan Ranganathan4, Veeraraghavan Aswini2, Pasuvaraj Mahanathi2, Stephen Challacombe5, Jennifer Webster-Cyriaque6, Newell W Johnson1,3,5,7 1 2 Chennai Dental Research Foundation, Chennai, India VHS Laboratory Services, Department of Clinical Research, VHS Hospital, Chennai, India 3 VHS-Infectious Diseases Medical Centre, VHS Hospital, Chennai, India 4 Department of Oral Pathology, Ragas Dental College and Hospital, Chennai, India 5 Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, UK 6 University of North Carolina, Chapel Hill, USA 7 Menzies Health Institute Queensland, Griffith University, Queensland, Australia Address for Correspondence: * Dr. Bagavad Gita Jayaraman Research Scientist Chennai Dental Research Foundation No. 56, Dr. R. K. Salai 6th Floor, Mylapore Chennai – 600004 Tamil Nadu, India Ph: 91-44-42103440 Email: gita70.geetha@gmail.com * Dr. Priya Kannian Scientist & Head Department of Clinical Research VHS Hospital Rajiv Gandhi Salai Taramani, Chennai – 600113 Tamil Nadu, India Ph: 91-44-22541972 Email: priyakannian@gmail.com Word count: 599 words 1 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2021.02.25.21252488; this version posted March 1, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license .
DOI record: { "DOI": "10.1101/2021.02.25.21252488", "URL": "http://dx.doi.org/10.1101/2021.02.25.21252488", "abstract": "<jats:p>SARS-CoV2 is transmitted primarily through oral mouth secretions and respiratory droplets. Commercial mouthwashes, povidone iodine (PI), hydrogen peroxide (HP) and chlorhexidine (CHX) have been tested in cell culture and RT-PCR studies for their efficacy to reduce SARS-CoV2 burden. Here, we evaluated SARS-CoV2 burden in whole mouth fluid (WMF) and respiratory droplets (RD) samples before and after the use of PI, HP or CHX mouthwashes in hospitalized COVID-19 patients using RT-PCR and rapid antigen test (RAT). Thirty-six SARS-CoV2 RT-PCR-positive in-patients were randomly assigned to one of the four groups: 20 and 60 minutes after 1% w/v PI or 1.5% HP; 90 and 180 minutes after 1.5% HP or 0.2% w/v CHX. WMF and RD samples were collected concurrently at baseline and after the two different time points. RD (92%) showed a higher reduction in SARS-CoV2 burden than WMF samples (50%; p=0.008). SARS-CoV2 burden was statistically lower at both 20 minutes (p=0.02) and 60 minutes (p=0.03) with PI; at 20 minutes with HP (p=0.0001); and 90 minutes with CHX (p=0.04). The overall and individual mean logarithmic reductions in the WMF and RD samples were greater than 1.0 at 20, 60 and 90 minutes after PI, HP or CHX. RAT-positive patients at 90 minutes post-treatment (n=3) demonstrated a one log increase in virus copies. Among the three RAT-negative post-treatment patients, SARS-CoV2 burden declined by one log in two while the third patient had a slight increase in RNA copies. In conclusion, we have shown for the first time that the mouthwashes, PI, HP and CHX can reduce the SARS-CoV2 burden in the concurrently collected RD and WMF samples. RAT is more appropriate than RT-PCR to evaluate the efficacy of the mouthwashes.</jats:p>", "accepted": { "date-parts": [ [ 2021, 3, 1 ] ] }, "author": [ { "affiliation": [], "family": "Jayaraman", "given": "Bagavad Gita", "sequence": "first" }, { "affiliation": [], "family": "Rajan", "given": "Gunaseelan", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-2790-6676", "affiliation": [], "authenticated-orcid": false, "family": "Kannian", "given": "Priya", "sequence": "additional" }, { "affiliation": [], "family": "Lavanya", "given": "Chandra", "sequence": "additional" }, { "affiliation": [], "family": "Ravichandran", "given": "Krittika", "sequence": "additional" }, { "affiliation": [], "family": "Kumarasamy", "given": "Nagalingeswaran", "sequence": "additional" }, { "affiliation": [], "family": "Ranganathan", "given": "Kannan", "sequence": "additional" }, { "affiliation": [], "family": "Aswini", "given": "Veeraraghavan", "sequence": "additional" }, { "affiliation": [], "family": "Mahanathi", "given": "Pasuvaraj", "sequence": "additional" }, { "affiliation": [], "family": "Challacombe", "given": "Stephen", "sequence": "additional" }, { "affiliation": [], "family": "Webster-Cyriaque", "given": "Jennifer", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-5866-262X", "affiliation": [], "authenticated-orcid": false, "family": "Johnson", "given": "Newell W", "sequence": "additional" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2021, 3, 1 ] ], "date-time": "2021-03-01T17:25:17Z", "timestamp": 1614619517000 }, "deposited": { "date-parts": [ [ 2021, 3, 3 ] ], "date-time": "2021-03-03T16:05:25Z", "timestamp": 1614787525000 }, "group-title": "Infectious Diseases (except HIV/AIDS)", "indexed": { "date-parts": [ [ 2023, 8, 22 ] ], "date-time": "2023-08-22T17:16:08Z", "timestamp": 1692724568451 }, "institution": [ { "name": "medRxiv" } ], "is-referenced-by-count": 4, "issued": { "date-parts": [ [ 2021, 3, 1 ] ] }, "link": [ { "URL": "https://syndication.highwire.org/content/doi/10.1101/2021.02.25.21252488", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "246", "original-title": [], "posted": { "date-parts": [ [ 2021, 3, 1 ] ] }, "prefix": "10.1101", "published": { "date-parts": [ [ 2021, 3, 1 ] ] }, "publisher": "Cold Spring Harbor Laboratory", "reference": [ { "DOI": "10.1177/0022034520967933", "doi-asserted-by": "crossref", "key": "2021030308050679000_2021.02.25.21252488v1.1", "unstructured": "Carrouel F , Goncalves LS , Conte MP , et al. Antiviral Activity of Reagents in Mouth Rinses against SARS-CoV-2. J Dent Res. 2020 Oct 22 : 0022034520967933." }, { "DOI": "10.1001/jamaoto.2020.5490", "doi-asserted-by": "publisher", "key": "2021030308050679000_2021.02.25.21252488v1.2" }, { "DOI": "10.1111/odi.13793", "doi-asserted-by": "publisher", "key": "2021030308050679000_2021.02.25.21252488v1.3" }, { "DOI": "10.1111/odi.13526", "doi-asserted-by": "publisher", "key": "2021030308050679000_2021.02.25.21252488v1.4" }, { "DOI": "10.1101/2020.09.14.20186494", "doi-asserted-by": "publisher", "key": "2021030308050679000_2021.02.25.21252488v1.5" } ], "reference-count": 5, "references-count": 5, "relation": {}, "resource": { "primary": { "URL": "http://medrxiv.org/lookup/doi/10.1101/2021.02.25.21252488" } }, "score": 1, "short-title": [], "source": "Crossref", "subtitle": [], "subtype": "preprint", "title": "Povidone iodine, hydrogen peroxide and chlorhexidine mouthwashes reduce SARS-CoV2 burden in whole mouth fluid and respiratory droplets", "type": "posted-content" }
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