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Sunstar research finds CPC-containing mouthwash reduces the SARS-CoV-2 viral load by more than 99.9 % in vitro. Mouthrinse containing CPC can inactivate the coronavirus within 30 seconds of being exposed to it.
New in vitro test results demonstrate that, within 30 seconds of exposure, mouthwash containing 0.05% CPC (Cetylpyridinium chloride) effectively reduces the SARS-CoV-2 viral load by more than 99.9%. This test was conducted at the request of Sunstar Inc. and Sunstar Suisse SA by an independent, internationally accredited testing facility, QTEC Services in Tokyo Japan.
In the Sunstar experiment, the tested CPC products were mixed with a solution containing SARS-CoV-2 and incubated for 30 seconds, after which the researchers measured the reduction in viral load. All mouthrinses containing 0.04% to 0.3% of CPC directly and significantly reduced the viral load by more than 99.9%. Dr Tsutomu Takatsuka, Senior Executive Officer, Global R&D at Sunstar commented: “The preliminary test results corroborate the work previously done which shows CPC reduces the SARS-CoV-2 viral load. This suggests the use of mouthwashes containing CPC could be an additional measure to reduce viral transmission of SARS-CoV-2. Of course, those preliminary in vitro data need further investigations, and we will explore its potential.
These preliminary test results show that using mouthwashes containing CPC technology could have an important role as a preventative measure in reducing viral transmission of COVID-19.
Reducing the risk of COVID-19 transmission during dental procedures
Even though the oral cavity is not likely to be the main route of infection for SARS-CoV-2, patients infected with SARS-CoV-2 often demonstrate particularly high levels of virus particles in the oral cavity. Reducing the so-called “viral load” could have important clinical consequences, particularly in dentistry.
Soon after the outbreak of the COVID-19 pandemic back in March 2020, it was suggested that rinsing with an antimicrobial mouthwash could be an effective way of reducing viral load in the mouth. Among others, Cetylpyridinium chloride (CPC) had been proposed as a candidate ingredient showing an effect against SARS-CoV-2. However, scientific evidence supporting the effectiveness of CPC or CPC-containing products against SARS-CoV-2 was missing until recently.
Preliminary results from Sunstar and others suggest that mouthwashes containing CPC technology can significantly reduce the viral load.1,, This is particularly important as significant amounts of aerosols are generated during dental procedures, posing risk to dental care personnel and patients. Thus, reducing the count of SARS-CoV-2 in the saliva of infected patients could be one of the key approaches in reducing the risk of COVID-19 transmission during dental procedures.
CPC technology can neutralise the virus up to 6 hours after use of mouthrinse in COVID-19 patients
Researchers at Singapore’s National Dental Research Institute (NDRIS) undertook the first ever randomised clinical study to examine the efficacy of commercial mouthrinses on SARS-CoV-2 in COVID-19 patients.
In the study, which has not yet been peer-reviewed or published in a medical journal but is available on a preprint server, COVID-19 positive patients were recruited from Singapore General Hospital (SGH) and randomly assigned to one of 4 groups – PI, CHX, CPC and water as control.
Saliva samples were collected at baseline and at 5 min, 3h and 6h post-application of mouthrinses/water, and then subjected to SARS-CoV-2 RT-PCR analysis. The study found that CPC-containing mouthrinse can5:
- Decrease the salivary SARS-CoV-2 levels within 5 minutes of use, compared to water rinsing, and that
- The effect persists 6 hours after rinsing, effectively demonstrating CPC’s ability to reduce the salivary SARS-CoV-2 viral load in COVID-19 patients
In their discussion, Drs Seneviratne and Sim Xiang Ying noted that “reducing the titres of SARS-CoV-2 in the saliva of infected patients could be one of the key approaches to reduce the risk of COVID-19 transmission during dental procedure”.
Indeed, health authorities such as the European Centre for Disease Prevention and Control (ECDC), the US Centre for Disease Control and Prevention (CDC)  and the Australian Dental Association (ADA)  have all recommended the use of pre-procedural mouthrinses without much robust clinical evidence on SARS-CoV-2 itself. Preliminary results such as from Singapore and others suggests this evidence is now on its way, and that, as it cumulates, it is very likely to change pre-procedural rinse practice in dental offices the world over.
But is the oral cavity relevant in the SARS-CoV-2 pandemic?
It is well established that SARS-CoV-2’s entry into host cells is mediated by its spike glycoprotein (S-glycoprotein), and that the angiotensin-converting enzyme 2 (ACE2) is the key cellular receptor, with the S-glycoprotein binding to the ACE2 receptor to enter cells.
Writing in the International Journal of Oral Science, a Nature Journal, Hao Xu at the Chinese Academy of Medical Sciences in Sichuan, China found that ACE2 is expressed on epithelial cells of the oral mucosa, and that it is highly enriched in epithelial cells of tongue. Xu and co-authors conclude that their findings suggest « that the oral cavity is a potentially high risk for SARS-CoV-2 infectious susceptibility and provide a piece of evidence for the future prevention strategy in dental clinical practice as well as daily life ».
In a literature review on SARS-CoV-2, COVID-19, oral cavity, and antimicrobial agents, David Herrera at the University of Madrid found that the oral viral load of SARS-CoV-2 is associated with the severity of COVID-19, and thus, that a reduction in the oral viral load could be associated with a decrease in the severity of the condition. The authors therefore suggest that « a decrease in the oral viral load would diminish the amount of virus expelled and reduce the risk of transmission ». This is a very significant consideration, requiring more research to complete our understating of the possible link between oral viral load, severity and transmission of COVID-19.
How does CPC technology inactivate SARS-CoV-2?
CPC technology works by breaking down the SARS-CoV-2 protective shield. Coronaviruses including SARS-CoV-2 are surrounded by a lipid membrane or “envelope” which contains the spike glycoprotein responsible for the infection.9 CPC’s anti-viral effect involves the rapid disruption of the viral lipid envelope.5,11
Rethinking pre-procedural rinses
Oral care professionals have been identified as one of the highest-risk groups for contracting SARS-CoV-2. Dental practices are exposed to SARS-CoV-2 infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and due to the handling of sharp instruments, warn two recent publications in the International Journal of Oral Science and in the Journal of Dental Research. 
This concern is warranted. Work undertaken at Hong Kong’s Laboratory for Emerging Infectious Disease at the University of Hong Kong, detected the presence of SARS-CoV-2 in the saliva of 91.7% COVID-19 patients, with a median viral load of 3.3 × 106 copies/mL.
Confirming this finding in the New England Journal of Medicine, Anne L. Wyllie in Yale reported the detection rate of SARS-CoV-2 to be higher in saliva than nasopharyngeal swabs.
Thus, it seems certain that saliva can carry a risk of transmission of COVID-19, either via direct contact or indirect contact with contaminated objects, and that appropriate infection control measures are critical in the dental office.
Accordingly, reducing the salivary viral load in COVID-19 or potential COVID-19 patients could be one of the key approaches to preventing transmission of COVID-19 in the dental settings.
“I think that the use of CPC should be implemented in daily practice because of its properties against SARS-CoV-2. We need more studies to confirm the effectiveness in terms of contagion prevention in case of treatment of asymptomatic patients, but for sure this is the best pre-procedural mouthrinse method of we have to date”.
Professor Magda Mensi, of the Periodontology Department of the University of Brescia in Italy
Mouthrinse research: what is next?
Dr Richard Stanton and colleagues at Cardiff University who recently completed an in vitro study of different mouthwashes containing CPC3, will continue their work and are planning a clinical trial at the University Hospital of Wales that will examine how effective different mouthwashes are in reducing the amount of coronavirus found in the saliva of COVID-19 patients.
Similarly, Stuart Gansky of the University of California San Francisco’s (UCSF) School of Dentistry is planning a study entitled « Effect of Antiseptic Mouthwash/Gargling Solutions and Pre-procedural Rinse on SARS-CoV-2 Load (COVID-19) ».
This will be a blinded randomized controlled parallel group design trial involving 150 COVID-19 patients. The objective is to further evaluate the effect of different over-the-counter antiseptic mouthwashes, compared to distilled water as control, in reducing SARS-CoV-2 load.
In addition, study participants will be assessed for the severity of their clinical symptoms during the 4-week study period, to see whether there is a relationship between viral load in the oral cavity and the severity of COVID-19 symptoms. This study will help improve our understanding of the relationship between the oral cavity’s infectious susceptibility to SARS-CoV-2 and the stage and progression of COVID-19.
From the professional perspective, the identification of SARS-CoV-2 in saliva, the proximity to the patient during dental care and the high generation of aerosols, make the oral cavity a potential reservoir for COVID-19 transmission. It is important for dentists and hygienists to protect themselves with pre-procedural mouthrinses such as those containing CPC, shown in vitro to reduce the SARS-CoV-2 viral load by more than 99.9%.
From the wider perspective of a world facing a once-in-a-generation pandemic, findings suggest CPC-containing mouthwashes have the potential to become an additional measure to reduce the transmission of SARS-CoV-2 particularly, but not only, in the dental office setting. By limiting the viral load in the oral cavity, mouthwash has the potential to become an important addition in our fight to protect against coronavirus along with hand sanitising, social distancing and consistent mask use, as recommended by health authorities.
 QTEC Services in Tokyo Japan. Test according to EU “Standard Practice to Assess the Activity of Microbicides against Viruses in Suspension” (E1052-20), and American Society for Testing and Materials (ASTM) standards. Commissioned by Sunstar Inc. and Sunstar Suisse SA, Dec 2020
 Xu Hao, Zhong Liang et al « High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa” [i]International Journal of Oral Science, 24 Feb 2020. https://www.nature.com/articles/s41368-020-0074-x
 Evelina Statkute, Richard Stanton et al ”Brief Report: The Virucidal Efficacy of Oral Rinse Components Against SARS-CoV-2 In Vitro” bioRxiv preprint, November 13, 2020 https://www.biorxiv.org/content/10.1101/2020.11.13.381079v1.full.pdf
 Green, A. et al “In vitro assessment of the virucidal activity of four mouthwashes containing Cetylpyridinium Chloride, ethanol, zinc and a mix of enzyme and proteins against a human coronavirus, bioRxiv preprint, 2020https://www.biorxiv.org/content/10.1101/2020.10.28.359257v1
 Seneviratne Chaminda J., Sim Xiang Ying J. et al “Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: Randomized Control Trial in Singapore” medRxiv preprint; September 18, 2020 https://www.medrxiv.org/content/10.1101/2020.09.14.20186494v1
 European Centre for Disease Prevention and Control (ECDC) Infection prevention and control in dentistry in EU/EEA Countries https://www.ecdc.europa.eu/en/publications-data/directory-guidance-prevention-and-control/core-requirements-healthcare-settings-1
 US Centre for Disease Control and Prevention (CDC) “Guidance for Dental Settings » Updated Aug 28, 2020 https://www.cdc.gov/coronavirus/2019-ncov/hcp/dental-settings.html
 Australian Dental Association (ADA) « ADA COVID-19 Risk Management Guidance » Last updated 4 Aug 2020 https://www.ada.org.au/Covid-19-Portal/Files/pdf/COVID-19-Risk-Management-Guidance.aspx
 Jinsung Yang, David Alsteens et al “Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor” Nature Communications, volume 11, Article number: 4541, 2020 https://www.nature.com/articles/s41467-020-18319-6
 Op. Cit. 2
 Herrera D, Serrano J, RoldánS, Sanz M. Is the oral cavity relevant in SARS-CoV-2 pandemic?. Clinical oral investigations. 2020 Aug;24(8):2925-30, 2020.
 Meng L, Bian Z et al “Coronavirus Disease 2019 (COVID-19): Emerging and Future Challenges for Dental and Oral Medicine”, Journal of Dental Research, March 12 2020 https://doi.org/10.1177/0022034520914246
 To KK-W, et al. “Consistent detection of 2019 novel coronavirus in saliva”; Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, July 28, 2020 https://pubmed.ncbi.nlm.nih.gov/32047895/
 Wyllie AL, Moore AJ et al.”Saliva or Nasopharyngeal Swab Specimens for Detection of SARS-CoV-2. N Engl J Med.2020. Page 2” https://www.nejm.org/doi/full/10.1056/NEJMc2016359
 Op. Cit. 3