key: cord-1052425-4h1vuor0
authors: Barenghi, Livia; Barenghi, Alberto; Garagiola, Umberto; Giannì, Aldo Bruno; Spadari, Francesco
title: Recent evidence sustains the use of chlorhexidine-based mouthwash for dental patients during the coronavirus disease 2019 epidemic
date: 2022-02-17
journal: Am J Orthod Dentofacial Orthop
DOI: 10.1016/j.ajodo.2021.08.017
sha: db124e64fef7d28c4e7b88f4475c4113c41bb274
doc_id: 1052425
cord_uid: 4h1vuor0

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I t was with great interest that we read the Letter to the Editor by Singh and colleagues (Singh H, Sharma P, Kapoor P, Maurya RK. Virucidal mouth rinses for patients during the coronavirus disease 2019 outbreak. Am J Orthod Dentofacial Orthop 2021;159:707-9) on the use of prophylactic preprocedural mouth rinses (PPMR) to limit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and recommendation to use povidone iodine (PVP-1)-based PPMR. The letter did not consider recent data concerning the virucidal effects of chlorhexidine (CHX) and PVP-1 and could lead to some rash conclusions, raising unfounded choices. 1, 2 Therefore, we would like to highlight a few points.

The use of a specific compound in PPMR was not recommended in the last Guidance for Dental Settings by either the Centers for Disease Control and Prevention or the European Centre for Disease Prevention and Control, and the use is not sustained by clear evidence. [3] [4] [5] [6] The virucidal effect of CHX against SARS-CoV-2 is plain when the experiments are planned to avoid cell toxicity. 7-9 Toxicity is present at 1:100 dilution and is known to be also caused by other components of commercial PPMR. Unfortunately, avoiding toxicity is tricky and expensive to achieve according to in vitro testing on the basis of European Standard EN 14476 and laboratories rated BioContainment level 3 or higher. 10 PVP-1's better benefits reported by Lamas are based on data from unusual clinical trials, 11 including salivary tests in 2 patients, without statistical evaluation. Recently, a similar trial has shown CHX analogous benefit. 9 PVP-1, hydrogen peroxide, and CHX mouthwashes significantly reduce SARS-CoV-2 burden in mouth fluid and respiratory droplets by reverse transcriptase polymerase chain reaction of RNA viruses and rapid antigen testing of virus protein. 12 Nevertheless, the reduction is time-dependent, and CHX seems more suitable before orthodontic care, which usually takes \60 minutes.

Evidence on CHX (0.2%, mouth rinsed for 30 seconds) and PVP-1 (1%, gargled for 30 seconds) was similar to a randomized-controlled clinical trial and cycle threshold values, the indicator of viral load in the salivary sample. 13 Unlike hydrogen peroxide and PVP-1, CHX shows the highest affinity with SARS-CoV2 proteins from computational drug modeling. 14 CHX shows strong binding sites in SARS-CoV-2's spike protein and on the ACE2-Spike (receptor-binding domain) interface of SARS-CoV-2, similar to those exerted by antiviral drugs. CHX affinity to spike proteins is remarkable: the binding energy for CHX, PVP, and hydrogen peroxide is respectively À10.4, À4.5, and À3.2 kcal/mol. In addition, only CHX binds to papain-like protease, known to be essential for viral RNA replication and controlling host cells.

Because of different optimal pH, CHX (pH 5.5-7.0), both PVP-1 (pH 2.0-7.0) and hydrogen peroxide (pH 2.5-3.6) are expected to differently influence dental demineralization, frequent in orthodontic patients.

In our opinion, we need sound data to sustain the preferential use of PVP-1 in favor of CHX. Dental teams deserve clarity and need updated guidelines on PPMR use in orthodontic patients.

Livia , and thus were somewhat inconclusive. We respectfully maintain that when we wrote our Letter to the Editor, emerging robust scientific data concerning the virucidal effects of CHX and PVP-1 were taken into consideration. In reference to the other queries put forth by Berenghi et al, we wish to supplement evidence-based literature regarding the use and composition of preprocedural mouthrinses as has been recently updated in scientific literature.

We acknowledge that in the early stages of a pandemic, health authorities such as the Centers for Disease Control and Prevention 3 recommended preprocedural mouthrinses for dental treatment even without robust clinical evidence. However, we would like to highlight the fact that despite relatively fewer in vitro studies being published during the first wave of the pandemic, the Guidance for Dental Settings by the Centers for Disease Control (last updated on December 9, 2020) did not reflect the emerging evidence supporting virucidal effectiveness of PVP-1 against SARS-CoV-2.

Regarding the European Centre for Disease Prevention and Control 4 guidance, there is no mention regarding the use of prophylactic preprocedural mouth rinse (PPMR). In addition, the Cochrane review by Burton et al 5 could identify only ongoing studies, including 14 randomized controlled trials (RCTs) but found no completed studies worth including. Given the unprecedented dynamic nature of COVID-19 infection and being a translational research field, it is not surprising that Cochrane reviews are likely to conclude as low certainty or unclear evidence because of a lack of RCTs. However, we firmly believe that the absence of evidence may not necessarily reflect evidence of absence. 6 On further exploration, we found that at the time of publishing of the review commentary by Kelly et al, 7 only insufficient direct in vitro evidence of the efficacy of specific compounds in PPMR against SARS-CoV-2 was available. The majority of the evidence was extrapolated from other viruses, including influenza, HIV, and herpes simplex.

A critical analysis of the studies by Jain et al 8 and Yoon et al 9 revealed that cell toxicity effects were not considered while assessing virucidal effects of CHX against SARS-CoV-2. In contrast, after the use of a suspension assay on the basis of EN14476 methodology, no cytotoxic effects have been reported with the use of 1% PVP-1 mouthwash at a concentration of 0.63 mg/mL or a 1:16 or lower dilution of the product. 10 Moreover, in early periods of the outbreak, a first report on the in vitro efficacy of PVP-1 (1.0%, 1.5%, and 3% concentration) also demonstrated complete inactivation of SARS-CoV-2 without any cytotoxic effects. 11 In accordance with EN 14476 standards, a recent in vitro study 12

Summary of European guidelines on infection control and prevention during COVID-19 pandemic

A study on using mouthwash before providing dental treatment to patients in dental clinics during the COVID-19 pandemic

Centers for Disease Control and Prevention