Coronavirus and Cetylpyridinium Chloride (CPC) – Facts and Fiction
During the current health crisis, we have seen an exponential increase of information around COVID-19, the disease caused by the new coronavirus (SARS-CoV-2). Unfortunately, misinformation is spreading as well in the field of dentistry. In this article, we will show that there is no evidence to support circulating claims that mouthrinses containing Cetylpyridinium Chloride (CPC) can prevent infection with SARS-CoV-2.
The internet is full of tips, tricks, and products, sometimes even promoted by companies, that supposedly can help prevent infection from the virus. For example, by the end of February, Amazon had already banned more than 1 million products due to unsubstantiated claims that suggested protection against the coronavirus. However, while it is easy to understand the feebleness of some of these tips and claims, others might seem plausible or are even partly based on evidence. This makes it increasingly difficult to separate facts from fiction.
One of the current “hot topics” in dentistry is whether mouthrinses containing Cetylpyridinium Chloride (CPC) can help to fight COVID-19. More recently, mouthrinses containing the combination of alcohol and Chlorhexidine (CHX) were added to this discussion. To understand why this topic gained so much interest in the dental field, let us first have a deep dive into the transmission characteristics of SARS-CoV-2 that causes COVID-19.
SARS-CoV-2 in the dental office
The most common human-to-human transmission pathway is thought to be through respiratory droplets, spread when infected individuals cough or sneeze  . Proximity to patients and contact with body fluids such as saliva and blood already make dental professionals vulnerable for infection . However, there is an additional transmission route in the form of airborne spread through aerosols. These are microscopic droplets that can carry a variety of communicable respiratory pathogens, including coronaviruses . Besides coughing or sneezing, several dental procedures can also generate high numbers of aerosols . Often, this happens in a rather secluded space. Not only does this increase the risk for direct airborne transmission in the dental office , it also allows contamination of dental instruments and office surfaces  (Figure 1). This is worrying, since a study recently published in the renowned New England Journal of Medicine suggests that the virus can remain viable on several surfaces for up to 72 hours .
Adapted from Peng, Peng, Xian et al “Transmission routes of 2019-nCoV and controls in dental practice” International Journal of Oral Science (2020).
Now that it is clear why dental professionals are being considered as a highly vulnerable group, it is not surprising that there is a high demand for preventive measures. Following an early research paper from the epicenter of the virus outbreak , one of the first recommendations made by some authorities, such as the American Dental Association, was applying a preprocedural mouthrinse containing oxidative agents such as 1% hydrogen peroxide or 0.2% povidone. It is important to realize that this recommendation was meant to protect the dental professional, rather than the patient, by preventing release of infectious aerosols during treatment. And even so, several experts strongly question the protective effectiveness of any mouthrinse against SARS-CoV-2, and point out the absence of clinical studies that demonstrate this claim.
A while after this publication by Peng et al., the World Health Organization released a document where CPC was mentioned for the first time in the context of being a useful agent to disinfect toilets, for example. Nothing was written about CPC as active agent in mouthrinses. However, the conflation of these two publications resulted in the unsubstantiated claim of CPC mouthrinse as a protection against SARS-CoV-2 and companies then began promoting this message.
What does the evidence say?
So, what do we discover if we critically assess the current scientific literature that supposedly substantiates this claim? One of the studies brought forward indeed shows that CPC itself has anti-viral properties. In a laboratory experiment, CPC appears to disrupt the envelope of certain influenza viruses, thereby neutralizing the virus . However, from those results, it is impossible to claim that this is also true for SARS-CoV-2. Moreover, in order to translate these laboratory results into the prescription of a CPC mouthrinse in clinical practice, much more research would be needed. Also, whether the anti-viral properties are enough to decrease the viral load to such an extent that it prevents infection, we simply do not know. A secondary finding in this study was that mice treated with a CPC containing oral spray demonstrated significantly increased survival. Again, in order to generalize these results from an animal model to human subjects, several steps are required, and an oral spray is definitely not the same as a mouthrinse.
The second study that has been used as evidence investigated if using the same oral spray, containing CPC, could prevent viral upper respiratory tract infections . In the experimental group that applied the oral spray three times daily, two individuals (4%) developed an upper respiratory tract infection, compared to four in the control group (9%). This difference was far from statistically significant (p = 0.41), indicating that there is no proof for clinical efficacy in daily practice with human subjects. Moreover, CPC was not the only active agent in the oral spray, as it also contained agents (glycerin and xanthan gum) that coat the back of the throat, creating a protective barrier.
Looking deeper into literature, we can conclude that so far, there is no research available that investigated the effect of CPC mouthrinse in relation to COVID-19, or even to viral respiratory upper tract infections in general. Besides this unsubstantiated claim, the combination of alcohol and chlorhexidine (CHX) in mouthrinses recently became another discussion point. In several advertisements it was suggested that preprocedural rinsing with this combination helps preventing infection with coronavirus. However, the study that was supposed to substantiate this claim only showed reduced bacterial counts in aerosols , and did not investigate viral load in aerosols.
The mouth as porte d'entrée for SARS-CoV-2?
Then there is the question whether the oral cavity is even the main route of infection with SARS-CoV-2, a perquisite for a mouthrinse to be effective. To elucidate on this, let us consider the receptor angiotensin-converting enzyme 2 (ACE2). This receptor, present on several cell types throughout the human body, is involved in regulating critical processes, such as heart rate, blood pressure, and osmotic pressure . Besides that, recent evidence suggests that ACE2 also plays a crucial role in the internalization of SARS-CoV-2, a crucial step in the reproduction process of the virus  (Figure 2). There is some evidence that the oral mucosa, with the tongue in particular, presents a significant expression of the receptor ACE2, making it a candidate for initial infection with SARS-CoV-2 . However, a more recent high-quality publication suggests that other structures are more likely to be the main route of infection . This study found that the expression of so-called “viral entry-associated genes” was particularly high in nasal epithelial cells. This indicates that these cells probably are the site of initial infection and can act as source for transmission of the virus between people. This means that the most likely route to become infected with SARS-CoV-2 is through the nose, implying limited clinical relevance of a mouthrinse against spread of the virus, even if it would have enough anti-viral properties.
From the available literature, we can conclude that there is no evidence supporting the claim that mouthrinses containing Cetylpyridinium Chloride (CPC) can help protect against infection with SARS-CoV-2, nor can the combination of alcohol and CHX in mouthrinses..
As mentioned in the beginning of this article, false information is spreading on many different channels with the risk of conveying incorrect messages around mouthrinses containing CPC. These unsubstantiated claims could put dental professionals and patients at risk, giving them an untrustworthy sense of protection.
As an oral health company, we will continue to share science-based, up-to-date information and we strongly suggest that dental professionals continue following the recommendations and guidelines made by local and global authorities.
If you are interested in other content related to COVID-19, have a look at our blog post.