Salivary SARS-CoV-2 load reduction with mouthwash use: A randomized pilot clinical trial

Abstract

The saliva of patients with COVID-19 has a high SARS-CoV-2 viral load. The risk of spreading the virus is high, and procedures for viral load reduction in the oral cavity are important. Little research to date has been performed on the effect of mouthwashes on the salivary SARS-CoV-2 viral load. This pilot randomized single-center clinical trial investigated whether three types of mouthwash with solutions containing either 0.075% cetylpyridinium chloride plus 0.28% zinc lactate (CPC þ Zn), 1.5% hydrogen peroxide (HP), or 0.12% chlorhexidine gluconate (CHX) reduce the SARS-CoV-2 viral load in saliva at different time points. Sixty SARS-CoV-2-positive patients were recruited and randomly partitioned into a placebo (oral rinsing with distilled water) group and other groups according to the type of mouthwash. Saliva samples were collected from the participants before rinsing (T0), immediately after rinsing (T1), 30 min after rinsing (T2), and 60 min after rinsing (T3). The salivary SARS-CoV-2 viral load was measured by qRT-PCR assays. Rinsing with HP and CPC þ Zn resulted in better reductions in viral load, with 15.8 AE 0.08-and 20.4 AE 3.7-fold reductions at T1, respectively. Although the CPC þ Zn group maintained a 2.6 AE 0.1-fold reduction at T3, this trend was not observed for HP. HP mouthwash resulted in a significant reduction in the SARS-CoV-2 viral load up to 30 min after rinsing (6.5 AE 3.4). The CHX mouthwash significantly reduced the viral load at T1, T2, and T3 (2.1 AE 1.5-, 6.2 AE 3.8-, and 4.2 AE 2.4-fold reductions, respectively). In conclusion, mouthwash with CPC þ Zinc and CHX resulted in significant reductions of the SARS-CoV-2 viral load in saliva up to 60 mins after rinsing, while HP mouthwash resulted in a significant reduction up to 30 mins after rinsing. Despite this transitory effect, these results encourage further studies and suggest that these products could be considered as risk-mitigation strategies for patients infected with SARS-CoV-2.

Virucidal activity of CPC-containing oral rinses against SARS-CoV-2 variants and are active in the presence of human saliva

“…whereas CHX containing mouthwashes are reported to have modest ability to inactive SARS -CoV-2 [6,19,21]. The virucidal action of CPC mouthwash was maintained in the presence of whole human saliva, consistent with human clinical trials which report that rinsing with CPC mouthwash can lower SARS-CoV-2 salivary count for several hours after use [7,28].…”

Virucidal efficacy of chlorhexidine: a systematic review

“…2 ) [ 23 – 38 , 40 , 44 – 47 ]. Based on RoB 2 assessment, overall low risk of bias was detected in two studies [ 41 , 42 ]. The other RCTs presented some concerns [ 43 ] and high [ 39 ] risk of bias.…”

“…The substance was in direct contact with contaminated cells Influenza A Virus titers in plaque-forming units, PFU/ml. Values are presented, respectively, for CHX and control groups: Strain/Bethesda 1/85 CHX in direct contact with contaminated cells CHX demonstrated an effective virucidal effect against Influenza A after 30' of contact 30’: 93% and 0% 5’: > 98% and 1% 15’: > 98% and 1% 30″, 5’, and 15’ 30″, 5’, and 15’ Davies et al 2021 [ 40 ] United Kingdom Product 1—CHX 0.2%—formulation contains ethanol; Product 1—CHX 0.2%—alcohol-free formulation HP (1.5%) PVP-I (0.58%) Essential oils mouthrinse (Listerine total care) SARS-CoV-2 Log 10 reduction of virus titer calculated as log 10 TCID 50 of control—log 10 TCID 50 of CHX England 2 strain CHX in direct contact with contaminated cells Antiseptic agents in direct contact with contaminated cells TCF unconcentrated—mean (95% CI) 1’ 1’ Product 1—CHX (0.2%) formulation ethanol: 0.5 (0.1–0.9) Product 2—CHX (0.2%) alcohol-free formulation: 0.2 (-0.2–0.7) HP (1.5%): 0.2 (-0.1–0.5) PVP-I (0.58%): ≥ 4.1 (3.8–4.4) Essential oils mouthrinse (Listerine total care): ≥ 4.1 (3.8–4.4) Eduardo et al 2021 [ 41 ] Brazil 0.12% Placebo—distilled water; CPC (0.075%) + zinc (Zn) lactate (0.28%) HP (1.5%) SARS-CoV-2 RRT‐PCR cycle threshold (Ct). RRT‐PCR assessed before rising, immediately after, 30'' and 60'' after.…”

“…Still, in this context, three recent RCTs evaluated the efficacy of CHX in reducing the salivary SARS-CoV-2 viral load in patients diagnosed with coronavirus disease 2019 (COVID-19) [ 39 , 41 , 42 ]. One study assessed the reduction of the viral load of SARS-CoV-2 in the oropharynx [ 43 ].…”

“…This study also showed no significant difference when CHX and povidone-iodine were compared [ 42 ]. Another study also showed that a single rinse with CHX significantly reduced the viral load of SARS-CoV-2 after 30 min and 60 min [ 41 ]. However, this study showed that higher reductions in viral load were detected in individuals that rinsed with hydrogen peroxide or with cetylpyridinium chloride + zinc mouthwashes [ 41 ].…”