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Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2

Ferrer et al., Scientific Reports, doi:10.1038/s41598-021-03461-y
Dec 2021  
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Viral load T4 vs. T1 32% Improvement Relative Risk Hydrogen Peroxide  Ferrer et al.  LATE TREATMENT  RCT Does late treatment with hydrogen peroxide reduce short-term viral load? RCT 28 patients in Spain No significant difference in viral load c19early.org Ferrer et al., Scientific Reports, Dec 2021 Favorshydrogen peroxide Favorscontrol 0 0.5 1 1.5 2+
20th treatment shown to reduce risk in May 2021
 
*, now with p = 0.029 from 7 studies.
Lower risk for viral clearance.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19early.org
Small very late (>50% 7+ days from symptom onset, 9 PVP-I patients) RCT testing mouthwashing with cetylpyridinium chloride, chlorhexidine, povidone-iodine, hydrogen peroxide, and distilled water, showing no significant differences. Over 30% of patients show >90% decrease in viral load @2 hrs with all 5. Authors note that a trend was observed for viral load decrease with PVP-I @2h for patients <6 days from onset (p=0.06, Wilcox test).
Analysis of short-term changes in viral load using PCR may not detect effective treatments because PCR is unable to differentiate between intact infectious virus and non-infectious or destroyed virus particles. For example Tarragó‐Gil, Alemany perform RCTs with cetylpyridinium chloride (CPC) mouthwash that show no difference in PCR viral load, however there was significantly increased detection of SARS-CoV-2 nucleocapsid protein, indicating viral lysis. CPC inactivates SARS-CoV-2 by degrading its membrane, exposing the nucleocapsid of the virus. To better estimate changes in viral load and infectivity, methods like viral culture that can differentiate intact vs. degraded virus are preferred.
This study is excluded in meta analysis: study only provides PCR-based short-term viral load results.
Study covers hydrogen peroxide and povidone-iodine.
relative viral load T4 vs. T1, 32.0% better, RR 0.68, p = 0.70, treatment 14, control 14, data from Table S1.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Ferrer et al., 22 Dec 2021, Randomized Controlled Trial, Spain, peer-reviewed, 19 authors.
This PaperHydrogen Per..All
Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2
Maria D Ferrer, Álvaro Sánchez Barrueco, Yolanda Martinez-Beneyto, María V Mateos-Moreno, Verónica Ausina-Márquez, Elisa García-Vázquez, Miguel Puche-Torres, Maria J Forner Giner, Alfonso Campos González, Jessica M Santillán Coello, Ignacio Alcalá Rueda, José M Villacampa Aubá, Carlos Cenjor Español, Ana López Velasco, Diego Santolaya Abad, Sandra García-Esteban, Alejandro Artacho, Xavier López-Labrador, Alex Mira
Scientific Reports, doi:10.1038/s41598-021-03461-y
Most public health measures to contain the COVID-19 pandemic are based on preventing the pathogen spread, and the use of oral antiseptics has been proposed as a strategy to reduce transmission risk. The aim of this manuscript is to test the efficacy of mouthwashes to reduce salivary viral load in vivo. This is a multi-centre, blinded, parallel-group, placebo-controlled randomised clinical trial that tests the effect of four mouthwashes (cetylpyridinium chloride, chlorhexidine, povidone-iodine and hydrogen peroxide) in SARS-CoV-2 salivary load measured by qPCR at baseline and 30, 60 and 120 min after the mouthrinse. A fifth group of patients used distilled water mouthrinse as a control. Eighty-four participants were recruited and divided into 12-15 per group. There were no statistically significant changes in salivary viral load after the use of the different mouthwashes. Although oral antiseptics have shown virucidal effects in vitro, our data show that salivary viral load in COVID-19 patients was not affected by the tested treatments. This could reflect that those mouthwashes are not effective in vivo, or that viral particles are not infective but viral RNA is still detected by PCR. Viral infectivity studies after the use of mouthwashes are therefore required. (https:// clini caltr ials. gov/ ct2/ show/ NCT04 707742; Identifier: NCT04707742) The coronavirus disease 2019 (COVID-19) outbreak was quickly declared by the World Health Organization (WHO) a public health emergency of international concern and has given rise to one of the most dramatic pandemics in recent human history 1 . The disease is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus, a single-stranded enveloped RNA virus which belongs to the betacoronavirus genus from the Coronaviridae family 2 . Because no effective treatment for COVID-19 is currently available, most public health measures to contain the pandemic are based on preventing the spread of the pathogen. The virus is transmitted by the respiratory route (respiratory droplets and aerosols) and by direct contact with contaminated surfaces and subsequent contact with nasal, oral or ocular mucosa 3 . Although patients with symptomatic COVID-19 have been the main source of transmission, asymptomatic and pre-symptomatic patients also have the ability to transmit SARS-CoV-2 4 . Higher viral loads are detected after the onset of COVID-19 symptoms, being significantly higher in the nose compared to the throat 5 . Angiotensin-converting Enzyme 2 (ACE2) is the main cellular receptor for SARS-CoV-2, which interacts with the spike protein to facilitate its entry. ACE2 receptors are highly expressed in the oral cavity and present at high levels in oral epithelial cells 6 . The mean expression of ACE2 was higher in the tongue compared to that in other oral tissues and it has been found to be higher in the minor salivary glands than in the lungs 6 . These
Author contributions Competing interests The authors declare no competing interests.
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The ' 'virucidal efficacy of oral rinse components against SARS-CoV-2. In Vitro ' 'https://doi.org/10.1101/2020.11.13.381079 (2020).', 'journal-title': 'In Vitro', 'DOI': '10.1101/2020.11.13.381079'}, { 'issue': 'Suppl 1', 'key': '3461_CR25', 'doi-asserted-by': 'publisher', 'first-page': '119', 'DOI': '10.1159/000089211', 'volume': '212', 'author': 'H Kariwa', 'year': '2006', 'unstructured': 'Kariwa, H., Fujii, N. & Takashima, I. Inactivation of SARS coronavirus ' 'by means of povidone-iodine, physical conditions and chemical reagents. ' 'Dermatology 212(Suppl 1), 119–123 (2006).', 'journal-title': 'Dermatology'}, { 'key': '3461_CR26', 'doi-asserted-by': 'publisher', 'first-page': '52', 'DOI': '10.1038/sj.bdj.4804743', 'volume': '152', 'author': 'S Duke', 'year': '1982', 'unstructured': 'Duke, S. & Forward, G. The conditions occurring in vivo when brushing ' 'with toothpastes. Br. Dent. J. 152, 52–54 (1982).', 'journal-title': 'Br. Dent. J.'}, { 'issue': '12', 'key': '3461_CR27', 'doi-asserted-by': 'publisher', 'first-page': '1690.e1', 'DOI': '10.1016/j.cmi.2020.08.043', 'volume': '26', 'author': 'J Sun', 'year': '2020', 'unstructured': 'Sun, J. et al. The kinetics of viral load and antibodies to SARS-CoV-2. ' 'Clin. Microbiol. Infect. 26(12), 1690.e1-1690.e4 (2020).', 'journal-title': 'Clin. Microbiol. Infect.'}, { 'issue': '20', 'key': '3461_CR28', 'doi-asserted-by': 'publisher', 'DOI': '10.3346/jkms.2020.35.e195', 'volume': '35', 'author': 'JG Yoon', 'year': '2020', 'unstructured': 'Yoon, J. G. et al. Clinical significance of a high SARS-CoV-2 viral load ' 'in the saliva. J. Korean Med. Sci. 35(20), e195 (2020).', 'journal-title': 'J. Korean Med. Sci.'}, { 'issue': '10', 'key': '3461_CR29', 'doi-asserted-by': 'publisher', 'first-page': '3707', 'DOI': '10.1007/s00784-020-03549-1', 'volume': '24', 'author': 'MJ Gottsauner', 'year': '2020', 'unstructured': 'Gottsauner, M. J. et al. 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Late treatment
is less effective
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