Abstract: Research JAMA Otolaryngology–Head & Neck Surgery | Original Investigation In Vitro Efficacy of a Povidone-Iodine Nasal Antiseptic for Rapid Inactivation of SARS-CoV-2 Samantha Frank, MD; Seth M. Brown, MD, MBA; Joseph A. Capriotti, MD; Jonna B. Westover, PhD; Jesse S. Pelletier, MD; Belachew Tessema, MD IMPORTANCE Research is needed to demonstrate the efficacy of nasal povidone-iodine (PVP-I) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OBJECTIVE To evaluate the in vitro efficacy of PVP-I nasal antiseptic for the inactivation of SARS-CoV-2 at clinically significant contact times of 15 and 30 seconds. INTERVENTIONS The SARS-CoV-2, USA-WA1/2020 strain, virus stock was tested against nasal antiseptic solutions consisting of aqueous PVP-I as the sole active ingredient. Povidone-iodine was tested at diluted concentrations of 0.5%, 1.25%, and 2.5% and compared with controls. The test solutions and virus were incubated at mean (SD) room temperature of 22 (2) °C for time periods of 15 and 30 seconds. DESIGN AND SETTING This controlled in vitro laboratory research study used 3 different concentrations of study solution and ethanol, 70%, as a positive control on test media infected with SARS-CoV-2. Test media without virus were added to 2 tubes of the compounds to serve as toxicity and neutralization controls. Ethanol, 70%, was tested in parallel as a positive control and water only as a negative control. MAIN OUTCOMES AND MEASURES The primary study outcome measurement was the log reduction value after 15 seconds and 30 seconds of given treatment. Surviving virus from each sample was quantified by standard end point dilution assay, and the log reduction value of each compound was compared with the negative (water) control. RESULTS Povidone-iodine nasal antiseptics at concentrations (0.5%, 1.25%, and 2.5%) completely inactivated SARS-CoV-2 within 15 seconds of contact as measured by log reduction value of greater than 3 log10 of the 50% cell culture infectious dose of the virus. The ethanol, 70%, positive control did not completely inactivate SARS-CoV-2 after 15 seconds of contact. The nasal antiseptics tested performed better than the standard positive control routinely used for in vitro assessment of anti–SARS-CoV-2 agents at a contact time of 15 seconds. No cytotoxic effects on cells were observed after contact with each of the nasal antiseptics tested. CONCLUSIONS AND RELEVANCE Povidone-iodine nasal antiseptic solutions at concentrations as low as 0.5% rapidly inactivate SARS-CoV-2 at contact times as short as 15 seconds. Intranasal use of PVP-I has demonstrated safety at concentrations of 1.25% and below and may play an adjunctive role in mitigating viral transmission beyond personal protective equipment. Author Affiliations: University of Connecticut School of Medicine, Farmington (Frank, Brown, Tessema); ProHealth, Ear, Nose and Throat, Farmington, Connecticut (Brown, Tessema); Veloce BioPharma, Fort Lauderdale, Florida (Capriotti); The Institute for Antiviral Research at Utah State University, Logan (Westover); Ocean Ophthalmology, Miami, Florida (Pelletier). JAMA Otolaryngol Head Neck Surg. 2020;146(11):1054-1058. doi:10.1001/jamaoto.2020.3053 Published online September 17, 2020. 1054 Corresponding Author: Samantha Frank, MD, Division of Otolaryngology−Head and Neck Surgery, Department of Surgery, University of Connecticut School of Medicine, 263 Farmington Ave, Farmington, CT..