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BMJ 2020; 368 doi: https://doi.org/10.1136/bmj.m1252 (Published 26 March 2020) Cite this as: BMJ 2020;368:m1252

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A Case for Hydrogen Peroxide Mouthwash and Gargle to Limit SARS-CoV-2 Infection

Dear Editor,

Since the coronavirus disease (COVID-19) and its virus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) emerged in Wuhan in the Hubei Province of China, global attention has focused on its
control and containment. Its rapid spread and the absence of an effective treatment or vaccine has caused COVID-19 to overwhelm even the most robust health systems in the world. [1] From January 2020 to
date, the cumulative number of cases is over 8.5 million with more than 450,000 deaths globally. Conceivably, therefore COVID-19 has the potential to decimate large populations especially those of low and middle-income countries with limited health infrastructure, personnel and resources, and thus a reason for the unrelenting efforts to control and prevent its spread. Among those who have died from the condition are senior government officials, policy makers and key front line health workers who are critical in the fight against the disease. [2] [3]

The virus, as has been well established, spreads through contaminated surfaces, droplets from saliva, sneezes and coughs and through aerosols (micro droplets) in breath. [4 5]. Public health measures adopted so far to contain COVID-19 have thus focused mainly on preventing the virus from entering the nasal and oral cavities. These include the isolation and quarantining of confirmed and suspected individuals, physical distancing, staying at home, regular hand washing with soap under running water, rubbing hands withalcohol-based sanitizers and the use of face masks.[6 7]. The provision of personal protective equipment for frontline staff has been key, considering their increased risk of contracting the disease.

MOUTH AND THROAT EXPOSURE

With growing numbers of asymptomatic individuals increasing the spread of the virus in communities as well as increasing concerns among dentists about its potential spread especially during aerosol generating procedures [8 9], it is extremely difficult to restrict the virus from entering the oral and nasal cavities, even with the available protective measures for clinicians especially surgeons (Dental, Oropharyngeal, ENT) not to mention anesthetists, physicians, nurses and support staff in critical care. In that regard, attention should therefore focus also on interventions that prevent viruses that have gained access to these cavities from invading host cells to cause disease. Such a measure, which is our present focus, could protect especially contacts of infected persons and at the same time, reduce viable viral load shed in saliva by asymptomatic carriers and cases.

Notably, the virus attaches to the angiotensin-converting enzyme 2 (ACE2) receptors in the most superficial cells in the non-keratinized epithelium of the oral cavity and oropharynx. It then uses its signaling and trafficking pathways to gain further access to infect the body [10]. These ACE2 receptors are also found in several other areas including the epithelial cells of the respiratory tract down to the alveoli. [11 12].

The incubation period of COVID-19 is 14 days with an average of 6.4 days. [8] How long the virus takes on entering the oral cavity and oropharynx to invade host cells is uncertain. If it is assumed that the whole of the infective process in the upper respiratory and the oropharynx regions takes 2-5 days, there is very little time, albeit a day or two, to intervene to prevent the virus from infecting an individual who has been exposed to it through the oral cavity. This demonstrates how speedily action should be taken to prevent a contact of COVID-19 from being infected.

Therapeutic mouthwashes that inactivate microbes in the oral cavity, the palatine fossa and the oropharynx include hydrogen peroxide. [13] This communication is advocating its use to limit the infectivity and spread of SARS-CoV-2 especially in countries and communities with inadequate healthcare delivery systems.

HYDROGEN PEROXIDE

Hydrogen peroxide has been used in dental practice for nearly 100 years and has been considered safe when used in low concentrations. [13] In a review on its safety, it had been noted that 3% hydrogen peroxide daily use for up to six years, showed only occasional or transient irritations in a minimal number of subjects who also had pre-existing lesions. [13 14] Even though this solution has mutagenic potential through its reactive oxygen species that could induce DNA damage, there has been no substantive evidence in the literature to support assertions that it causes cancer in humans. [14] It has been stated that “there is strong evidence for the safety of low concentrations of hydrogen peroxide products when used on daily basis and over an extended period” [14] Earlier, the International Agency for Research on Cancer also concluded after reviewing animal and human studies that “hydrogen peroxide is not classifiable as to its carcinogenicity in humans”.[15] In a recent study assessing carcinogenicity associated with exposure to hydrogen peroxide neither tissue irritation nor tumor promotion was observed in animal models. [16]

The efficacy of hydrogen peroxide has not been in doubt, especially about its capacity to inactivate corona and influenza viruses.[17] A recent review of studies on human coronaviruses has suggested that 0.5% hydrogen peroxide will inactivate SARS-CoV-2 on surfaces.[18] Furthermore, a suggestion has been made quite recently to buttress the view that 1% hydrogen peroxide may serve to prevent entry of the virus
into susceptible cells and reduce the possibility of severe disease.[19] We are proposing, therefore, that use of 1% hydrogen peroxide mouthwash and gargle, at least twice a day be added to the established WHO preventive protocols for SARS-CoV-2. This could augment protection of frontline health personnel, contacts of COVID-19 cases, and the highly vulnerable individuals such as the aged, security personnel, media staff, persons with underlying health issues and individuals in communities where the burden of COVID-19 is high.

Furthermore, since there is evidence that even 0.5% hydrogen peroxide could inactivate the SARS-CoV-2 on surfaces [18], this lower concentration could be used by individuals who may be more susceptible to tissue irritation, considering that its prophylactic use might be required over a long period. To further limit the risk of infecting others, asymptomatic individuals and mild to moderate cases could use hydrogen peroxide mouthwash and gargle to inactivate SARS-CoV-2 shed.

In conclusion, Hydrogen Peroxide that has been in use in dental practice with proven safety and efficacy could be employed in limiting the infectivity and spread of SARS-CoV-2 whilst awaiting the emergence of fail-proof prophylactic and therapeutic measures. We have planned a clinical trial of mouthwash and gargle with hydrogen peroxide compared with mouthwash or gargle with water only, in asymptomatic cases of
COVID-19.

*Andrews S. Ayettey. MB. ChB. PhD. Retired Professor, University of Ghana Medical School, College of Health Sciences. University of Ghana, Legon. Ghana. Email: seth.ayettey@gmail.com Twitter@ayettey_seth

Emerita Professor, Isabella A. Quakyi. PhD. FGA. School of Public Health, College of Health Sciences, University of Ghana, Legon. Ghana.

Hannah N.G. Ayettey-Anie. BSc (Med Sc) MB ChB FGCP, Senior Specialist, National Radiotherapy Oncology and Nuclear Medicine Centre, Korle Bu Teaching Hospital, Accra, Ghana.

Kwamena W. Sagoe. MSc PhD. Associate Professor, Department of Medical Microbiology, University of Ghana Medical School, College of Health Sciences. University of Ghana, Legon. Ghana.

Mary N. B. Ayettey-Adamafio. BSc (Med Sc) BDS FGCS FWACS. Senior Specialist, Department of Dentistry, Korle Bu Teaching Hospital, Korle Bu, Accra. Ghana.

Merley Newman-Nartey BDS MClD FGCS. Senior Lecturer, University of Ghana Dental School, College of Health Sciences, University of Ghana.

Ruth N. A. Ayettey Brew BSc (Med Sc), MB.ChB. Resident, Department of Obstetrics and Gynecology, Korle Bu Teaching Hospital, Accra. Ghana.

Nii Otu Nartey BDS MSc FAAOP MRCD FWACS FGCS Retired Associate Professor, University of Ghana Dental School, College of Health Sciences, University of Ghana.

Albert G.B. Amoah MB ChB, PhD, FWACP, FGCP, FGA. Retired Professor, University of Ghana Medical School, College of Health Sciences, University of Ghana.

Felix I D Konotey-Ahulu MD(Lond) FRCP(Lond & Glasg) DTMH(L'pool) Distinguished Professor of Human Genetics University of CapeCoast, Honorary Consultant Physician Specialist to Ghana Ministry of Health through Commissioner of Health Brigadier Odartey-Wellington 1976, and Former Consultant Physician, Korle Bu Teaching Hospital, Accra, and Phoenix Hospital Group 9 Harley St, London W1G 9AL.

*Corresponding Author Professor Seth Ayettey: Twitter@ayettey_seth

Acknowledgement: The authors acknowledge Mr. Benjamin Yankah of Accra, Ghana, for encouragement.

References
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2. Thompson Adrian. OBITUARY of Amged El-Hawrani. Consultant ear, nose, and throat surgeon. (Born 1964; Qualified 1993), died from COVID-19 on 28 March 2020. BMJ 2020;369:m1658. Print Edition May 30
page 335.

3. Ali Jawad. A PERSONAL REFLECTION: Professor Jacob Plange-Rhule, BSc PhD MB. ChB. FWACP, FGCP, FRCP, Rector, Ghana College of Physicians and Surgeons (GCPS), Accra. Ghana. Born, 27th July 1957. Passed away on 10th April 2020 from COVID-19 https://www.rcplondon.ac.uk/news/professor-jacob-plange-rhule-personal-r.... (And Ali Jawad BMJ 2020; 369:m1982 (Print Edition 20 June page 461)

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16. DeSesso JM, Lavin AL, Hsia SM, Mavis RD. Assessment of the carcinogenicity associated with oral exposures to hydrogen peroxide. Food Chem Toxicol 2000; 38(11): 1021-41.

17. Mentel R, Shirrmakher R, Kevich A, Dreĭzin RS, Shmidt I. [Virus inactivation by hydrogen peroxide]. Vopr Virusol 1977; (6): 731-3.

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19. Caruso AA, Del Prete A, Lazzarino AI, Capaldi R, Grumetto L. May hydrogen peroxide reduce the hospitalization rate and complications of SARS-CoV-2 infection? Infect Control Hosp Epidemiol 2020: 1-5.

Competing interests: No competing interests

02 July 2020
Andrews S Ayettey
Retired Professor, University of Ghana Medical School, College of Health Sciences, University of Ghana, Legon, Ghana
Isabella A Quakyi, Hannah NG Ayettey-Annie, Kwamena W Sagoe, Mary MB Ayettey-Adamafio, Merley Newman-Nartey, Ruth NA Ayettey Brew, Nii Otu Nartey, Albert GB Amoah, Felix ID Konotey-Ahulu
.