Reduction of SARS-CoV-2 salivary viral load with pre-procedural mouth rinses: a randomised, controlled, clinical trial

Abstract

Introduction The purpose of this study was to test the short-term efficacy of four commercial mouthwashes versus water in reducing SARS-CoV-2 viral load in the oral cavity over clinically relevant time points. Methods In total, 32 subjects that were proven SARS-CoV-2-positive via polymerase chain reaction (PCR)-based diagnostic test were recruited and randomised into five parallel arms. Cycle threshold (Ct) values were compared in saliva samples between the groups, as well as within the groups at baseline (pre-rinse), zero hours, one hour and two hours post-rinse, using SARS-CoV-2 reverse transcription-PCR analysis. Results We observed a significant increase in Ct values in saliva samples collected immediately after rinsing with all the four mouthwashes - 0.12% chlorhexidine gluconate, 1.5% hydrogen peroxide, 1% povidone iodine, or Listerine - compared to water. A sustained increase in Ct values for up to two hours was only observed in the Listerine and chlorohexidine gluconate groups. We were not able to sufficiently power this clinical trial, so the results remain notional but encouraging and supportive of findings in other emerging mouthwash studies on COVID-19, warranting additional investigations. Conclusions Our evidence suggests that in a clinical setting, prophylactic rinses with Listerine or chlorhexidine gluconate can potentially reduce SARS-CoV-2 viral load in the oral cavity for up to two hours. While limited in statistical power due to the difficulty in obtaining this data, we advocate for pre-procedural mouthwashing, like handwashing, as an economical and safe additional precaution to help mitigate the transmission of SARS-CoV-2 from a potentially infected patient to providers.

Efficacy of different mouthwashes against COVID-19: A systematic review and network meta-analysis

“…CHX 0.12% was found to be effective in reducing saliva viral load both after 5 and 60 min as compared to a placebo solution [27] . Similar results were observed in another study, at 60 and 120 min after rinsing [90] , while CHX at the same concentration did not significantly reduced viral load in other investigations [91] , [92] . In another RCT, in which multiple mouthwashes were tested, CHX 0.12% met minimum acceptance criteria of a ≥ 2-fold reduction compared to baseline, which was significant at 30 and 60 min, but not at the early time point [88] .…”

“…In all the selected studies a rinsing time of 30 or 60 s was adopted. A longer rinsing time was reported only for the combination of H 2 O 2 (60 s) and CHX (30 s) [88] and for all the mouthwashes investigated by Farmaha et al (120 s) [90] . The study design always involved a single rinse except for one study, in which the mouthwash was utilized 3 times daily for 7 days [98] .…”

“… Significant mean Ct difference between the paired samples before and after mouthwash with both PVP-I (p < 0.0001) and CHX (p < 0.0001). Farmaha et al, 2023 [90] 5 mL CHX 0.12% (N = 6; 120 s) 5 mL H 2 O 2 1.5% (N = 5; 120 s) 5 mL PVP-I 1% (N = 8; 120 s) 5 mL Listerine® (N = 7; 120 s) 5 mL water (N = 6; 120 s) Before mouthwash (T0) Immediately after (T1) 60 min (T2) 120 min (T3) Nasopharyngeal swab or saliva sample 410/32 Spitting (∼1 mL) Mean Ct values CHX: T0: ∼32; T1: ∼35; T2: ∼36; T3: ∼35 H 2 O 2 : T0: ∼27; T1: ∼32; T2: ∼32; T3: ∼31 PVP-I: T0: ∼30; T1: ∼32; T2: ∼30; T3: ∼29 Listerine®: T0: ∼35; T1: ∼38; T2: ∼37; T3: ∼36 Water: T0: ∼28; T1: ∼29; T2: ∼30; T3: ∼27 Compared to control, a significant increase in Ct values was observed immediately after rinsing with each of the mouthwashes testes (p < 0.05). The Ct values for the Listerine reached the statistical significance cut-off compared to H 2 O 2 and PVP-I; a statistically significant difference in Ct values was also observed between CHX group and Listerine group compared to the water group one and two hours after rinse.…”

“…All the included studies were RCTs comparing the use of at least one mouthwash with a non-active control solution. The most frequently investigated mouthwash was found to be chlorhexidine (CHX) at concentration of 0.12% [27] , [88] , [89] , [90] , [91] , [92] , [93] or 0.20% [28] , [29] , [93] . In one study the sequential use of hydrogen peroxide (H 2 O 2 ) 1.5% followed by CHX 0.12% was tested [88] .…”

“…In one study the sequential use of hydrogen peroxide (H 2 O 2 ) 1.5% followed by CHX 0.12% was tested [88] . Mouthwashes containing as active ingredients H 2 O 2 [88] , [89] , [90] , [91] , [92] , [94] , [95] , povidone-iodine (PVP-I) [28] , [29] , [89] , [90] , [91] , [92] , [94] , [95] , cetylpyridinium chloride (CPC) [29] , [90] , [91] , [92] , [95] , [96] , [97] , CPC in association with zinc lactate (Zn) [88] , β-cyclodextrin and Citrox® (CDCM) [98] , hypochlorous acid (HOCl) [95] , Listerine® [90] and cymenol (Cym) + Zinc chloride (ZnCl 2 ) [93] were also studied.…”