Table 2.
Summary of data from clinical studies.
| Study | Country | Study design | Sample | Age | Mouthwash | Dosage | Treatment length | Detection method | Results | Study remarks | Risk of bias |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Gottsauner et al., 2020(Gottsauner et al., 2020) | Germany | Non-randomized clinical trial | 12 hospitalized patients positive to Sars-CoV-2 | 55 years (22–81 years) | H2O2 1% (gargling mouth and throat) |
20 mL for 30 sec | 1 time | RT-PCR | RT-PCR at baseline: 1.8 × 103 (3.1 × 102;4.7 × 104) copies/mL RT-PCR 30 min after procedure 1.5 × 103 (8.3 × 102;3.4 × 104) copies/mL No significant differences (p = 0.96) |
A H2O2 1% mouthrinse did not reduce the intraoral viral load of SARS-CoV-2. | Critical (high) risk |
| Avhad et al., 2020(Avhad et al., 2020) | India | Randomized clinical trial | 40 patients positive to SARS-CoV-2 | 19–49 years | Control group (n = 20): CHX 0.2% (rinse and gargle) Study group (n = 20): chlorine dioxide 0.1% (rinse and gargle) |
10 mL | 3 times a day for 7 days | RT-PCR | RT-PCR after one week: Control group: CHX 0.2% Positive cases: 12 Negative cases: 8 Study group: chlorine dioxide (0.1%) Positive cases: 8 Negative cases: 12 |
Chlorine dioxide mouthwash presented more cases with reduction of intensity of symptoms and negativity for COVID-19 in the patients. | Unclear risk |
| Choudhury et al., 2020(Choudhury et al., 2020) | Bangladesh | Randomized clinical trial | 606 patients positive to SARS-CoV-2 | 11–90 years | Group A (n = 303): PVP-I 1% (mouthwash/gargle, nasal drops and eye drops) Group B (n = 303): lukewarm water (mouthwash/gargle, nasal drops and eye drops) |
1 mL of PVP-I in 10 mL of sterile water/purified water 30 sec oral rinse, 30 sec gargle, 4–5 drop nasal, 2 eye drops |
4 hourly for 4 weeks | RT-PCR | RT-PCR positive: Group A: PVP-I 1% 3rd day: 11.55% 5th day: 7.92% 7th day: 2.64% Group B: lukewarm water 3rd day: 96.04% 5th day: 88.45% 7th day: 70.30% |
PVP-I 1% as mouthwash/gargle, nasal drop and eye drop, reduced mortality and morbidity by COVID-19, as well as reduce positivity cases at the 3rd, 5th and 7th day. |
High risk |
| Mohamed et al., 2020(Mohamed et al., 2020) | Malaysia | Randomized clinical trial | 20 patients positive to SARS-CoV-2 | 22–56 years | Group A (n = 5): PVP-I 1% – Betadine® (gargle) Group B (n = 5): essential oils, ethanol – Listerine Original (gargle) Group C (n = 5): tap water (gargle) Group D (n = 5): no intervention |
Group A: 10 mL for 30 sec Group B: 20 mL for 30 sec Group C: 100 mL for 30 sec |
3 times a day for 7 days | RT-PCR | RT-PCR results: Group A: PVP-I 1% 4th day: 100% negative 6th day: 100% negative 12th day: 100% negative Group B: essential oils 4th day: 80% negative, 20% positive 6th day: 80% negative, 20% positive 12th day: 80% negative, 20% positive Group C: tap water 4th day: 40% negative, 60% positive 6th day: 40% negative, 20% positive, 40% indeterminate 12th day: 40% negative, 40% positive, 20% indeterminate Group D: no intervention 4th day: 20% negative, 40% positive, 40% indeterminate 6th day: 60% positive, 40% indeterminate 12th day: 20% negative, 60% positive, 20% indeterminate |
PVP-I 1% PCR results were significantly reduced (p < 0.05) after the 4th, 6th and 12th day, when compared to the control. High rate of viral reduction after 4 days of PVP-I 1% and essential oil mouthwashes was achieved. |
High risk |
| Seneviratne et al., 2021(Seneviratne et al., 2021) | Singapore | Randomized clinical trial | 16 patients positive to SARS-CoV-2 | Group 1: 40.7 ± 11.5 Group 2: 43.6 ± 8.6 Group 3: 35.7 ± 8.5 Group 4: 36 ± 14.1 |
Group 1 (n = 4): PVP-I 0.5% – Betadine® (mouthwash) Group 2 (n = 6): CHX 0.2% (mouthwash) Group 3(n = 4): CPC 0.075% (mouthwash) Group 4 (n = 2): sterile water |
PVP-I: 5 mL for 30 sec CHX: 15 mL for 30 sec CPC: 20 mL for 30 sec Water: 15 mL for 30 sec |
1 time | RT-PCR | Relative fold change of cycle threshold: Group 1: PVP-I 5 min: fold change: 1.1 3 h: fold change: 1.2 6 h: fold change: 1 (p < 0.01) Group 2: CHX 0.2% 5 min: 0.9 (varied effect) 3 h: fold change: 1 6 h: fold change: 0.9 Group 3: CPC 5 min: fold change: 1 (p < 0.05) 3 h: fold change: 0.9 6 h: fold change: 0.9 (p < 0.05) |
There were not significant differences within all 3 mouthwashes. When comparing the mouthwashes with the water group, there was a significant increase in fold change for CPC after 5 min at 6 h, and for PVP-I at 6 h. The decrease of salivary load was maintained after 6 h for CPC and PVP-I mouthwashes. |
Unclear risk |
| Guenezan et al., 2021(Guenezan et al., 2021) | France | Randomized clinical trial | 24 ambulatory patients positive to SARS-CoV-2 | Control: 57 (45–68 years) Intervention: 33 (23–46 years) |
Control group (n = 12): no intervention Intervention group (n = 12): PVP-I 1% (mouthwash, gargles, nasal pulverization) + PVP-I10% (nasal ointment) |
25 mL for mouthwash and gargles, 0.5 mL for nasal pulverization |
4 times a day for 5 days | RT-PCR, TCID50 |
Mean relative difference in viral titers: Baseline – Day 1: Control: 32% (95% CI, 10%-65%) Intervention: 75% (95% CI, 43%-95%) No statistical differences between groups over time. |
The use of PVP-I had no influence on the changes of viral RNA quantification over time. | Unclear risk |
| Elzein et al., 2021(Elzein et al., 2021) | Lebanon | Randomized clinical trial | 61 patients positive to SARS-CoV-2 | 45.3 ± 16.7 years-old | Group A(n = 11): distilled water (mouth rinse) Group B (n = 33): CHX 0.2% (mouth rinse) Group C(n = 33): PVP 1% (mouth rinse) |
15 mL for 30 sec |
1 time | RT-PCR | A significant difference of Ct values between water group and CHX: (p = 0.0024) PVP-I: (p = 0.012) No significant difference between: CHX and PVP-I: p = 0.24 Differences before and after mouthwash: CHX Ct difference: 5.69 increase (p < 0.0001) PVP-I: Ct difference: 4.45 increase (p < 0.0001) No difference for water group (p = 0.566) |
Both CHX 0.2% and PVP-I 1% are effective against salivary SARS-CoV-2. | Unclear risk |
| Carrouel et al., 2021(Florence Carrouel et al., 2021a) |
France | Randomized clinical trial | 176 ambulatory patients positive to SARS-Cov-2 | Control: 44.08 ± 16.16 years Intervention: 42.06 ± 14.97 |
Control group (n = 88): Placebo(mouthwash) Intervention group (n = 88): CDCM (β-cyclodextrin-citrox) (mouthwash) |
30 mL for 1 min | 3 times a day (at 09.00, 14.00 and 19.00), for 7 days |
RT-PCR | % decrease T1-T2 (log10 copies/mL): Control group: −6.74% (-21.16% to 10.44%) Intervention group: −12.58% (-29.55% to −0.16%) % decrease T1-T3 (log10 copies/mL): Control group: −9.79% (-28.53% to 9.21%) Intervention group: −10.67% (-37.30% to 3.25%) % decrease T1-day 7 (log10 copies/mL): Control group: −50.62% (-100% to −27.66%) Intervention group: −58.62% (-100% to −34.36%) Only statistical difference at T1-T2 difference |
CDCM had a significant beneficial effect on reducing SARS-CoV-2 salivary viral load in adults with asymptomatic or mild COVID-19, 4 h after the initial dose. |
Low risk |
| Eduardo et al., 2021(Eduardo et al., 2021) |
Brazil | Randomized clinical trial | 60 patients positive to SARS-Cov-2 | 18–90 years-old | Group A (n = 9): Placebo (distilled water rinse) Group B (n = 7): CPC 0.075% + Zinc lactate 0.28% (Colgate Total 12® rinse) Group C (n = 7): H2O2 1.5% (Peroxyl® rinse) Group D (n = 8): CHX 0.12% (PerioGard® rinse) Group E (n = 12): H2O21.5% + CHX 0.12% (Peroxyl® + PerioGard® rinse) |
Group A: 20 mL for 1 min Group B: 20 mL for 30 s Group C: 10 mL for 1 min Group D: 15 mL for 30 sec Group E: 10 mL of H2O2 for 1 min, followed by 15 mL of CHX for 30 sec |
1 time | RT-PCR | Group A (placebo): minor changes Group B (CPC + Zinc): 20.4 ± 3.7-fold reduction Group C (H2O2): 15.8 ± 0.08-fold reduction Group D (CHX): ≥ 2-fold reduction Group E (H2O2 + CHX): ≥ 2-fold reduction |
CPC + Zinc and CHX mouthwashes reduced significantly SARS-CoV-2 viral load in saliva up to 60 min after rinsing·H2O2 reduced significantly the viral load up to 30 min after rinsing. H2O2 + CHX presented minimal reduction in the salivary viral load. |
Unclear risk |
|
Chaudhary et al., 2021(Chaudhary et al., 2021) |
US | Randomized clinical trial | 40 patients positive to SARS-Cov-2 | 21–80 years-old | Group 1 (n = 10): normal saline (mouth rinse) Group 2 (n = 10): H2O2 1% (mouth rinse) Group 3 (n = 10): CHX 0.12% (mouth rinse) Group 4 (n = 10): PVP-I 0.5% (mouth rinse) |
15 mL (total): rinse with 7.5 mL for 30 sec and expectorate, and then, rinse with the remaining 7.5 mL for 30 sec |
1 time | RT-PCR | Median reduction after 15 min: 61% − 89% for all groups (CHX, H2O2, normal saline, PVP-I) Median reduction at 45 min: 70% − 97% for all groups (CHX, H2O2, normal saline, PVP-I) No statistical difference between groups at neither 15-minute nor 45-minute (P > 0.05). |
Mouthrinses are a simple and highly efficacious for the reduction of the virus on the oral environment for up to 45 min. |
High risk |
| Schürmann et al., 2021(Schürmann et al., 2021) | Germany | Non-randomized clinical trial | 34 SARS-CoV-2 positive hospitalized patients | Not mentioned | Sorbitol and xylitol (Linolasept ® mouthwash) |
1 min | 1 time | RT-qPCR | Mean Ct values after rinsing: Increase of 3.1 (standard deviation 3.6). Reduction of viral load of 90%. |
Mouthwashing can reduce the viral load by 90%. |
Critical (high) risk |
1 H2O2: Hydrogen peroxide; CHX: Chlorhexidine digluconate; PVP-I: Povidone-iodine; CPC: Cetylpyridinium chloride.