Table III.

Oral antiseptics against the SARS-COV-2 virus: in-vivo and in-vitro studies

Study	Study type	Test product	Methods	Results
Martínez et al. [32]	In vivo	PVP-I 1%	15 mL 1% PVP-I, 1 min rinse. Four patients with positive initial detection for SARS-CoV-2 (nasopharyngeal virus detection by PCR). Serial saliva samples: baseline, 5 min, 1 h, 2 h, and 3 h after the rinse. Intra-oral viral load test by RT–PCR.	In two of the four participants the PVP-I resulted in a significant fall in viral load, which remained for at least 3 h.
Gottsauner et al. [33]	In vivo	H2O2 1%	20 mL 1% H2O2 30 s rinse gargling mouth and throat. 12 patients with positive initial detection for SARS-CoV-2 (nasopharyngeal virus detection by PCR). Saliva samples at baseline and 30 min after the rinse. Intra-oral viral load test performed by RT–PCR. Virus culture was performed for samples that had a viral load of ≥103 RNA copies/mL at baseline.	No significant differences between baseline viral load and viral load 30 min after the mouth rinse (P = 0.96). Replicating virus could only be detected in one baseline specimen.
Yoon et al. [34]	In vivo	Chlorhexidine 0.12%	15 mL chlorhexidine 0.12%, 30 s rinse. Two patients with positive initial detection for SARS-CoV-2 (nasopharyngeal virus detection by PCR). Saliva samples were taken: baseline, 1, 2, and 4 h after the rinse. Intra-oral viral load was determined by rRT–PCR.	Viral load in saliva decreased (a log10 reduction factor <×3) transiently for 2 h post mouthwash, but it increased again at 2–4 h post mouthwash.
Seneviratne et al. [35]	In vivo	PVP-I 0.5% (Betadine® Gargle and Mouthwash 10 mg) Chlorhexidine 0.2% (Pearly White Chlor-Rinse®) CPC 0.075% (Colgate Plax mouthwash®) Sterile water	16 patients positive for SARS-CoV-2 (nasopharyngeal virus detection by PCR), randomly assigned to four groups: PVP-I group (N = 4), CHX group (N = 6), CPC group (N = 4) and water as control group (N = 2). Saliva samples collected at baseline and at 5 min, 3 h, and 6 h post-application of mouth rinses/water. Samples subjected to SARS-CoV-2 RT–PCR analysis.	Salivary CT values of patients within each group at 5 min, 3 h, and 6 h time-points showed no significant differences. When the CT value fold change of each of the mouth rinse group patients was compared with the fold change of water group patients at the respective time-points, a significant increase was observed in the CPC group patients at 5 min and 6 h and in the PI group patients at 6 h.
Bidra et al. [36]	In vitro	PVP-I 0.5%, 0.75%, 1.5%	SARS-CoV-2 (USA-WA1/2020) in Vero 76 cells. Test solutions and virus incubated at RTa for 15 and 30 s.	Virucidal activity at 0.5%, 0.75%, and 1.5% concentrations and the shortest contact time (15 s). LRVb: 3.0. Virucidal activity at 0.5%, 0.75%, and 1.5% concentrations and the longest contact time (30 s). LRV: 3.33.
Anderson et al. [37]	In vitro	PVP-I 10% antiseptic solution PVP-I 7.5% skin cleanser PVP-I 1% gargle and mouthwash PVP-I 0.45% throat spray	SARS-CoV-2 (hCoV-19/Singapore/2/2020) in Vero-E6 cells. Exposure of the virus to PVP-I products was performed at RT for 30 s.	All four products achieved 99.99% virucidal activity at 30 s of contact. Reduction in viral titres (TCID50/mL) ≥4.00.
Pelletier et al. [38]	In vitro	PVP-I 0.5%, 0.75%, 1.5% oral rinse antiseptic solutions PVP-I 0.5%, 1.25%, 2.5% nasal antiseptic solutions	SARS-CoV-2 (USAWA1/2020) in Vero 76 cells. Test solutions and virus were incubated at RT for 60 s.	All products achieved 99.99% virucidal activity at 60 s of contact. LRV: 4.63.
Bidra et al. [39]	In vitro	PVP-I 0.5%, 1.25%, 1.5% H2O2 1.5%, 3%	SARS-CoV-2 (USAWA1/2020) in Vero 76 cells. The test solutions and virus were incubated at RT for 15 and 30 s.	Virucidal efficacy of PVP-I after 15 s: LRV >4.33 Viricudal efficacy of H2O2 after 15 s: LRV 1.00–1.33 Virucidal efficacy of PVP-I after 30 s: LRV >3.63 Virucidal efficacy of H2O2 after 30 s: LRV 1.0–1.8
Gudmundsdottir et al. [40]	In vitro	ColdZyme® (CZ-MD)	SARS-CoV-2 (USAWA1/2020) in Vero E6 cells (for SARS-CoV-2), and MRC-5 cells (for HCoV-229E).	CZ-MD inactivated SARS-CoV-2 by 98.3% (TCID50/mL reduction of 1.76) and HCoV-229E by 99.9% (TCID50/mL reduction of 2.88).
Steinhauer et al. [41]	In vitro	Formulation A (100 g contains: 0.1 g chlorhexidine bis-(d-gluconate) Formulation B (100 g contains: 0.2 g chlorhexidine bis-(d-gluconate) Formulation C (100 g contains: 0.1 g octenidine dihydrochloride, 2 g phenoxyethanol)	Isolated SARS-CoV-2 outbreak 100 strain, under conditions of low organic soiling (0.3 g/L bovine serum albumin; ‘clean 90 conditions’) as defined in EN 14476.	Formulation A reduced virus titre at a prolonged contact time of 10 min by a log10 reduction factor of <×1. Formulation B reduced virus titre within a contact time of 1 min and at a prolonged contact time of 5 min when tested at 80% (v/v) concentration by a log10 reduction factor of <×1. Formulation C reduced SARS-CoV-2 titres by a log10 reduction factor of x4.38 from 15 s, for both concentrations tested (80% (v/v) and 20% (v/v)).
Hassandarvish et al. [42]	In vitro	PVP-I 0.5% gargle and mouthwash PVP-I 1% gargle and mouthwash	SARS-CoV-2 (SARS-COV-2/MY/UM/6-3; TIDREC) in Vero E6 cells. The test solutions and virus were incubated at RT for 15, 30, and 60 s.	PVP-I 1% achieved a log10 reduction factor of ×5 in viral titres at 15, 30, and 60 s. PVP-I 0.5% demonstrated a log10 reduction factor in viral titres of >×4 at 15 s and >×5 at 30 and 60 s.

PVP-I, povidone-iodine; RT–PCR, reverse transcription–polymerase chain reaction; CHX, chlorhexidine digluconate; CPC, cetylpyridinium chloride.

^aRoom temperature: 22 ± 2°C.

^bLog₁₀ reduction value.