Recent evidence sustains the use of chlorhexidine-based mouthwash for dental patients during the coronavirus disease 2019 epidemic.

It 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. , 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, 8, 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. PVP-1’s better benefits reported by Lamas are based on data from unusual clinical trials, including salivary tests in 2 patients, without statistical evaluation. Recently, a similar trial has shown CHX analogous benefit.

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. 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.

Unlike hydrogen peroxide and PVP-1, CHX shows the highest affinity with SARS-CoV2 proteins from computational drug modeling. 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 −10.4, −4.5, and −3.2 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.