Abstract: www.nature.com/scientificreports OPEN Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS‑CoV‑2 Maria D. Ferrer 1,5, Álvaro Sánchez Barrueco 2,3, Yolanda Martinez‑Beneyto 4, María V. Mateos‑Moreno7, Verónica Ausina‑Márquez9, Elisa García‑Vázquez8, Miguel Puche‑Torres6, Maria J. Forner Giner6, Alfonso Campos González2, Jessica M. Santillán Coello2,3, Ignacio Alcalá Rueda2,3, José M. Villacampa Aubá2, Carlos Cenjor Español2,3, Ana López Velasco6, Diego Santolaya Abad6, Sandra García‑Esteban1, Alejandro Artacho1, Xavier López‑Labrador 1 & Alex Mira1,5* 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 ­history1. 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 ­family2. 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 ­mucosa3. Although patients with symptomatic COVID-19 have been the main source of transmission, asymptomatic and pre-symptomatic patients also have the ability to transmit SARSCoV-24. Higher viral loads are detected after the onset of COVID-19 symptoms, being significantly higher in the nose compared to the ­throat5. 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 c­ ells6. 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..