Virucidal effects of mouthwashes or mouth rinses: a world of caution for molecular detection of SARS-CoV-2 in saliva

To the Editor,

Several lines of evidence, summarized in recent meta-analyses [1, 2], support the concept that viral RNA detection by means of molecular testing in saliva should be considered a reliable alternative to traditional nasopharyngeal swabbing for diagnosing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Additional evidence has also been recently provided that saliva testing may be even more sensitive than using upper respiratory specimens (e.g., nose-throat or nasopharyngeal swabs) for detecting SARS-CoV-2 RNA in asymptomatic individuals [3]. These findings have recently persuaded the US Centers for Disease Control and Prevention (CDC) to endorse the use of saliva (self-collected with or without supervision) as reliable specimen for SARS-CoV-2 detection [4], whilst the European Centre for Disease Control and Prevention (ECDC) also encourages the use of saliva samples for molecular testing when nasopharyngeal swabs cannot be collected in symptomatic patients or during repeated screening of asymptomatic people [5]. The advantages of detecting SARS-CoV-2 RNA in saliva are many and mostly obvious compared to conventional analysis of nasopharyngeal specimens, encompassing higher patient compliance, lower risk of side effects, self-collection, as well as better suitability for mass (population) decentralized screening, especially in public places (e.g., school, airports, concerts, sport events, other mass gatherings, etc.).

On this premise, and with the awareness that preanalytical issues play a critical role in influencing the quality of all laboratory examinations [6], thus including SARS-CoV-2 testing [7], we highlight here recent evidence that SARS-CoV-2 detection in saliva may be seriously jeopardized in patients who have made recent use of mouthwashes or mouth rinses. Although the terms “mouthwash” and “mouth rinse” are often used interchangeably, they are not actually the same, since a mouth rinse is typically used before brushing the teeth with purpose of preventing plaques formation and freshening the breath, while a mouthwash is conventionally used after brushing and flossing the teeth, with bactericidal intentions [8]. Regardless of this almost pedantic distinction, there is a large variety of such products available on the market, and their use is now widespread (a recent survey carried out in Scotland underpinned that nearly 50% of the population make regular use of mouthwashes, daily in 25% of cases) [9], and also widely recommended by many dentists and dental care professionals organizations [10]. Notably, the website Statista also reports that the majority of the US population (i.e., over 60%) regularly uses mouthwashes and/or dental rinses [11].

Nonetheless, what has clearly emerged now, is that many of such products posses an important virucidal activity on a short and medium term (i.e., within 2–3 h), which may hence lower SARS-CoV-2 viral load in oral cavity. Besides the potentially favorable clinical effects (some studies reported that the use of some of these products may be associated with lower transmissibility and reduced odds of developing severe/critical COVID-19 illness) [12, 13], along with the attenuated biological risk for the healthcare personnel performing oral care or procedures with potential risk of generating aerosols or droplets emission [14], it is important to remember here that the considerable reduction of oral viral load may dramatically impair the sensitivity of SARS-CoV-2 molecular detection in saliva. A list of some of the most active substances in waning (or potentially annulling) SARS-CoV-2 oral viral load are summarized in Table 1 (references available in Supplementary File 1). These compounds may exert a wide spectrum of antiviral functions, such as disruption of viral envelope and RNA, impairment of surface glycoprotein structure, inhibition of SARS-CoV-2 interaction with host cells receptors [15].

Taken together, the current evidence would hence suggest major caution before collecting saliva samples for SARS-CoV-2 molecular testing from patients who have recently used mouthwashes or mouth rinses, since these products may have substantially decreased the viral load in the oral cavity, thus triggering a considerable risk of obtaining false negative test results. Obtaining patient history on recent usage of these compounds is hence almost mandatory before collecting saliva specimens. In such cases when mouthwashes or mouth rinses have been recently used by the patient, obtaining nasal samples (but not nasopharyngeal swabs, since the presence of antiviral compounds in the oropharynx may still impair viral RNA detection) may be advisable. Further studies are then needed to assess whether repeated gargles or rinses with water or other inert solutions before taking saliva samples may be effective to annul the antiviral activity of mouthwashes or mouth rinses, as well as for establishing if SARS-CoV-2 antigen tests in saliva [16] may be less vulnerable to this important preanalytical variable.