Table 5 Characteristics and results of included studies

Gottsauner [23]

Clinical Pilot Study

10

Hydrogen peroxide 1%

Gargle for 30 s

Oropharyngeal specimens

30 min

5

Positive: 1 Negative: 4

(culture)

Positive: 0

Negative: 5

(culture)

Mohamed [24]

4-arms preliminary interventional study

20

1% PVP-I

gargle for 30 s, three times per day for 7 days

Nasopharyngeal and oropharyngeal swab

4d

5

___

Positive: 0

Negative: 5

6d

5

___

12d

5

___

Listerine (essential oil)

gargle for 30 s, three times per day for 7 days

Nasopharyngeal and oropharyngeal swab

4d

5

___

Positive: 1

Negative: 4

6d

5

___

Positive: 1

Negative: 4

12d

5

___

Positive: 0

Intermediate: 1

Negative: 4

Tap water

gargle for 30 s, three times per day for 7 days

Nasopharyngeal and oropharyngeal swab

4d

5

___

Positive: 3

Negative: 2

6d

5

___

Positive: 1

Intermediate: 2

Negative: 2

12d

5

___

Positive: 2

Intermediate: 1

Negative: 2

No intervention

___

Nasopharyngeal and oropharyngeal swab

4d

5

___

Positive: 2

Intermediate: 2

Negative: 1

6d

5

___

Positive: 3

Intermediate: 2

Negative: 0

12d

5

___

Positive: 3

Intermediate: 1

Negative: 1

Mukhtar

[25]

an investigator-initiated, randomized, phase IV clinical trial

92

10 ml of 0.2% Chlorhexidine gluconate and 5 ml of 6% Hydrogen peroxide ( a final concentration of 2%)

Gargling 15 ml three times daily

30 s for 2w

Initially, they were advised to use the mouthwash for one minute (not exceeding 2 min contact time with the oral cavity); however, due to the difficulty of prolonged use given the high oxygen requirements …

Nasopharyngeal and oropharyngeal swabs

5d

Baseline: 46

5d: 45

Positive: 46

Inconclusive: 0

Negative: 0

Mean: 22.6 [95% CI: 20.8–24.3]

Positive: 34

Inconclusive: 5

Negative: 6

15d

Baseline: 46

15d: 43

Positive: 46

Inconclusive: 0

Negative: 0

Mean: 22.6 [95% CI: 20.8–24.3]

Positive: 14

Inconclusive: 14

Negative: 15

Control

–-

Nasopharyngeal and oropharyngeal swabs

5d

Baseline: 46

5d: 44

Positive: 46

Inconclusive: 0

Negative: 0

Mean: 23.7 [95% CI: 21.9–25.5]

Positive: 38

Inconclusive: 6

Negative: 0

15d

Baseline: 46

15d: 44

Positive:46

Inconclusive: 0

Negative: 0

Mean: 23.7 [95% CI: 21.9–25.5]

Positive: 18

Inconclusive: 17

Negative: 9

Lamas [26]

Quasi-experimental

4

1% povidone iodine

15 ml for 1 min

Nasopharyngeal

–-

4

Positive:2

Negative: 2

Ct E 27.83 ± 11.33

Ct RdRp 29.94 ± 11.27

Ct N 30.12 ± 9.82

Saliva

5 min

4

Ct E 28.98 ± 7.59

Ct RdRp 32.39 ± 5.25

Ct N 32.70 ± 5.20

Ct E 29.35 ± 4.35

Ct RdRp 32.07 ± 2.64

Ct N 32.41 ± 3.85

Saliva

1 h

4

Ct E 28.98 ± 7.59

Ct RdRp 32.39 ± 5.25

Ct N 32.70 ± 5.20

Ct E 33.62 ± 2.30

Ct RdRp 37.08 ± 0.59

Ct N 36.06 ± 1.32

Saliva

2 h

4

Ct E 28.98 ± 7.59

Ct RdRp 32.39 ± 5.25

Ct N 32.70 ± 5.20

Ct E 35.88 ± 1.95

Ct RdRp 38.45 ± 0.60

Ct N 37.46 ± 2.43

Saliva

3 h

4

Ct E 28.98 ± 7.59

Ct RdRp 32.39 ± 5.25

Ct N 32.70 ± 5.20

Ct E 35.38 ± 3.59

Ct RdRp 35.32 ± 2.91

Ct N 36.62 ± 1.78

Yoon [27]

Quasi-experimental

2

CHX 0.12%

15 ml, 30 sex, Gargling

Nasopharynx

Day1

2

19.38 ± 2.56

Day3

2

24.21 ± 0.53

Day5

2

25.07 ± 4.33

Day7

2

23.17 ± 6.93

Day9

2

36.12 ± 2.41

Oropharynx

Day1

2

25.75 ± 1.82

Day3

2

35.29 ± 3.04

Day5

2

30.51 ± 1.25

Day7

2

0

Day9

2

0

Saliva

Day1

2

23.61 ± 1.27

Day3

2

27.52 ± 5.49

Day5

2

30.69 ± 0.59

Day6

2

32.13 ± 1.77

Day7

2

0

Day9

2

39.67 ± 0.21

Saliva-Day 3 of hospitalization (day 6 of disease)

1 h

2

27.52 ± 5.49

0 (not detected)

2 h

2

27.52 ± 5.49

0 (not detected)

4 h

2

27.52 ± 5.49

30.16 ± 6.57

Saliva-Day 6 of hospitalization (day 9 of disease)

1 h

2

32.13 ± 1.77

33.55 ± 2.13

2 h

2

32.13 ± 1.77

37.17 ± 2.52

4 h

2

32.13 ± 1.77

32.85 ± 9.75

Seneviratne

[28]

Randomized clinical trial

16

–-

Saliva

Baseline

16

Positive: 17

Negative: 19

27.7 ± 4.8

(n = 16)

Povidone iodine (PI)

5 ml, 0.5% w/v

Saliva

5 min

4

22.53 ± 5.42

24.20 ± 8.08

3 h

4

22.53 ± 5.42

24.21 ± 5.63

6 h

4

22.53 ± 5.42

23.03 ± 5.17

CHX

15 ml, 0.2% w/v

Saliva

5 min

6

29.90 ± 2.41

27.89 ± 2.57

3 h

6

29.90 ± 2.41

30.01 ± 1.82

6 h

6

29.90 ± 2.41

27.90 ± 2.34

CPC

20 ml, 0.075%

Saliva

5 min

4

32.08 ± 2.27

32.91 ± 2.48

3 h

4

32.08 ± 2.27

30.65 ± 3.20

6 h

4

32.08 ± 2.27

31.86 ± 2.76

Water (control)

15 ml

Saliva

5 min

2

26.33 ± 1.83

25.30 ± 2.17

3 h

2

26.33 ± 1.83

23.16 ± 1.13

6 h

2

26.33 ± 1.83

22.00 ± 2.80

Carrouel [29]

double-blind randomized

controlled trial with two parallel arms

176

b-cyclodextrin (0.1%) and citrox (0.01%) (CDCM)

Participants were instructed to use three mouthwashes per day (at 09.00, 14.00 and 19.00), with either 30 mL of CDCM or placebo for 1 min

Saliva

Baseline (T1: day 1, 9:00am)

88

log10 copies/mL

Median (IQR)

4.05 (2.94–4.96)

mean: 3.87

SD: 1.25

Ct value: 30.09

SD:4,135

4 h (T2: day 1, 13:00)

88

log10 copies/mL

Median (IQR)

4.05 (2.94–4.96)

mean: 3.87

SD: 1.25

Ct value: 30.09

SD:4,135

log10 copies/mL

Median (IQR)

3.33 (2.29–4.23)

mean: 3.19

SD:1.18

Ct value: 32.34

SD:3.90

Median difference T1-T2 (IQR)

-0.38 (-1.39 to 0.00)

% decrease T1-T2

median (IQR)

-12.58% (-29.55% to -0.16%)

9 h (T3: day 1, 18:00)

88

log10 copies/mL

Median (IQR)

4.05 (2.94–4.96)

mean: 3.87

SD: 1.25

Ct value: 30.09

SD:4,135

log10 copies/mL

Median (IQR)

3.08 (0–4.19)

Mean: 2.88

SD: 0.91

Ct value: 33.37

SD:3.01

Median difference T1-T3 (IQR)

-0.24 (-1.55 to 0.06)

% decrease T1-T3

median (IQR)

-10.67% (-37.30% to 3.25%)

Day 7

88

log10 copies/mL

Median (IQR)

4.05 (2.94–4.96)

mean: 3.87

SD: 1.25

Ct value: 30.09

SD:4,135

log10 copies/mL

Median (IQR)

0 (0–1.34)

Meadn: 0.78

SD:0.6

Ct: 40.31

SD: 1.98

Median difference T1-day 7 (IQR)

-2.07 (-4.03 to -0.50)

% decrease T1-day 7

median (IQR)

-58.62% (-100% to -34.36%)

Placebo

Placebo

Saliva

Baseline (T1: day 1, 9:00am)

88

log10 copies/mL

Median (IQR)

3.85 (2.97–5.08)

Mean: 4.01

SD: 0.87

4 h (T2: day 1, 13:00)

88

log10 copies/mL

Median (IQR)

3.85 (2.97–5.08)

Mean: 4.01

SD: 0.87

Ct value: 29.63

SD:2.87

log10 copies/mL

Median (IQR)

3.60 (2.07–4.83)

mean: 3.46

SD: 1.34

Ct value: 30.09

SD:4.43

Median difference T1-T2 (IQR)

-0.15 (-0.97 to 0.33)

% decrease T1-T2

median (IQR)

-6.74% (-21.16% to 10.44%)

9 h (T3: day 1, 18:00)

88

log10 copies/mL

Median (IQR)

3.85 (2.97–5.08)

Mean: 4.01

SD: 0.87

Ct value: 29.63

SD:2.87

log10 copies/mL

Median (IQR)

3.31 (1.18–4.75)

mean: 3.17

SD: 1.20

CT value: 32.41

SD: 3.96

Median difference T1-T3 (IQR)

-0.30 (-1.23 to 0.22)

% decrease T1-T3

median (IQR)

-9.79% (e28.53% to 9.21%)

Day 7

88

log10 copies/mL

Median (IQR)

3.85 (2.97–5.08)

Mean: 4.01

SD: 0.87

Ct value: 29.63

SD:2.87

log10 copies/mL

Median (IQR)

1.62 (0–1.70)

Mean: 1.38

SD:0.32

Ct value: 38.33

SD:1.05

Median difference T1-day 7 (IQR)

-2.11 (-3.35 to -0.86)

% decrease T1-day 7

median (IQR)

-50.62% (-100% to -27.66%)

Eduardo [30]

randomized, double-blinded, placebo-controlled,

single-center pilot clinical trial

60

Placebo

rinse with 20 mL for 1 min

Saliva

Immediately after rinsing

9

Positive: 100%

Negative: 0%

30.07 ± 1.92

Positive: 100%

Negative: 0%

29.46 ± 3.16

30 min

9

Positive: 100%

Negative: 0%

30.07 ± 1.92

Positive: 100%

Negative: 0%

28.85 ± 2.90

60 min

9

Positive: 100%

Negative: 0%

30.07 ± 1.92

Positive: 100%

Negative: 0%

29.03 ± 2.92

CPC + Zn

(0.075% cetylpyridinium chloride plus 0.28% zinc lactate (CPC ‏ Zn)

rinse with 20 mL for 30 s

Saliva

Immediately after rinsing

7

Positive: 100%

Negative: 0%

28.16 ± 3.53

Positive: 100%

Negative: 0%

31.89 ± 4.46

30 min

7

Positive: 100%

Negative: 0%

28.16 ± 3.53

Positive: 100%

Negative: 0%

29.07 ± 5.54

60 min

7

Positive: 100%

Negative: 0%

28.16 ± 3.53

Positive: 100%

Negative: 0%

28.66 ± 6.52

HP

(1.5% hydrogen peroxide)

rinse with 10 mL for 1 min

Saliva

Immediately after rinsing

7

Positive: 100%

Negative: 0%

28.73 ± 3.40

Positive: 100%

Negative: 0%

32.03 ± 5.19

30 min

7

Positive: 100%

Negative: 0%

28.73 ± 3.40

Positive: 100%

Negative: 0%

30.15 ± 3.93

60 min

7

Positive: 100%

Negative: 0%

28.73 ± 3.40

Positive: 100%

Negative: 0%

24.54 ± 6.06

CHX

(0.12% chlorhexidine gluconate)

rinse with 15 mL for 30 s

Saliva

Immediately after rinsing

8

Positive: 100%

Negative: 0%

26.35 ± 6.20

Positive: 100%

Negative: 0%

26.78 ± 5.76

30 min

8

Positive: 100%

Negative: 0%

26.35 ± 6.20

Positive: 100%

Negative: 0%

27.77 ± 5.95

60 min

8

Positive: 100%

Negative: 0%

26.35 ± 6.20

Positive: 100%

Negative: 0%

27.46 ± 5.59

HP + CHX

rinse with 10 mL of HP mouthwash for 1 min,

followed by rinsing with 15 mL of CHX mouthwash for 30 s

Saliva

Immediately after rinsing

12

Positive: 100%

Negative: 0%

30.74 ± 5.50

Positive: 100%

Negative: 0%

31.20 ± 6.74

30 min

12

Positive: 100%

Negative: 0%

30.74 ± 5.50

Positive: 100%

Negative: 0%

30.24 ± 7.24

60 min

12

Positive: 100%

Negative: 0%

30.74 ± 5.50

Positive: 100%

Negative: 0%

28.35 ± 8.68

Chaudhary [31]

Randomized,

triple-blinded study

40 out of 200

1% hydrogen peroxide, 0.12% chlorhexidine gluconate or 0.5% povidone-iodine

7.5 ml of the mouth rinse for 30 s

Saliva

15 and 45 min post-rinsing

40 subjects in each group

–-

All four mouth rinses reduced salivary carriage of SARS-CoV-2. A median reduction of 61–89% (mean of 25–74%) was observed at 15 min, while the median reduction ranged from 70–97% at 45 min (mean of 30–43%). Neither the 15-miniute reduction in viral load, nor the persistence of reduction at 45 min differed between the mouthrinses (p > 0.05, Dunn’s test)