In Vitro Efficacy of a Povidone-Iodine Nasal Antiseptic for Rapid Inactivation of SARS-CoV-2
MD Samantha Frank, MD, MBA Seth M Brown, MD Joseph A Capriotti, PhD Jonna B Westover, MD Jesse S Pelletier, MD Belachew Tessema
JAMA Otolaryngology–Head & Neck Surgery, doi:10.1001/jamaoto.2020.3053
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 log 10 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.
ARTICLE INFORMATION Accepted for Publication: July 29, 2020. Published Online: September 17, 2020. doi:10.1001/jamaoto.2020.3053 Author Contributions: Drs Frank, Capriotti, and Tessema had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Funding/Support: The funding for the laboratory materials used in this study was supplied by Veloce BioPharma. Role of the Funder/Sponsor: Veloce BioPharma had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. However, the individual authors listed who are related to Veloce BioPharma did assist with design of the study and review of the manuscript.
References
Au-Duong, Vo, Lee, Bactericidal magnetic nanoparticles with iodine loaded on surface grafted poly(N-vinylpyrrolidone), J Mater Chem B,
doi:10.1039/C4TB01516A
Balakrishnan, Schechtman, Hogikyan, Teoh, Mcgrath et al., COVID-19 pandemic: what every otolaryngologist-head and neck surgeon needs to know for safe airway management, Otolaryngol Head Neck Surg,
doi:10.1177/0194599820919751
Bidra, Pelletier, Westover, Frank, Brown et al., Rapid in-vitro inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using povidone-iodine oral antiseptic rinse, Am J Epidemiol,
doi:10.1093/oxfordjournals.aje.a118408
Eggers, Farrales, Loya, Pura, Uy, The effect of 1% povidone iodine as a pre-procedural mouthrinse in 20 patients with varying degrees of oral hygiene, J Philipp Dent Assoc,
doi:10.1007/s40121-019-00260-x
Eggers, Koburger-Janssen, Eickmann, Zorn, In vitro bactericidal and virucidal efficacy of povidone-iodine gargle/mouthwash against respiratory and oral tract pathogens, Infect Dis Ther,
doi:10.1007/s40121-018-0200-7
Foley, The relationship between autoimmune thyroid disease and iodine intake: a review, Endokrynol Pol
Frank, Capriotti, Brown, Tessema, Povidone-iodine use in sinonasal and oral cavities: a review of safety in the COVID-19 era, Ear Nose Throat J. Published online
Furudate, Nishimaki, Muto, 125I uptake competing with iodine absorption by the thyroid gland following povidone-iodine skin application, Exp Anim,
doi:10.1538/expanim.46.197
Gray, Katelaris, Lipson, Recurrent anaphylaxis caused by topical povidone-iodine (betadine), J Paediatr Child Health,
doi:10.1111/jpc.12232
Hill, Casewell, The in-vitro activity of povidone-iodinecream against Staphylococcus aureus and its bioavailability in nasal secretions, J Hosp Infect,
doi:10.1053/jhin.2000.0733
Kariwa, Fujii, Takashima, Inactivation of SARS coronavirus by means of povidone-iodine, physical conditions and chemical reagents, Dermatology,
doi:10.1159/000089211
Kim, Rimmer, Mrad, Ahmadzada, Harvey, Betadine has a ciliotoxic effect on ciliated human respiratory cells, J Laryngol Otol,
doi:10.1017/S0022215114002746
Mady, Kubik, Baddour, Snyderman, Rowan, Consideration of povidone-iodine as a public health intervention for COVID-19: utilization as "personal protective equipment" for frontline providers exposed in high-risk head and neck and skull base oncology care, Oral Oncol,
doi:10.1016/j.oraloncology.2020.104724
Mullings, Panchmatia, Samoy, Habib, Thamboo et al., Topical povidone-iodine as an adjunctive treatment for recalcitrant chronic rhinosinusitis, Eur J Rhinol Allergy,
doi:10.5152/ejra.2019.166
Panchmatia, Payandeh, Al-Salman, The efficacy of diluted topical povidone-iodine rinses in the management of recalcitrant chronic rhinosinusitis: a prospective cohort study, Eur Arch Otorhinolaryngol,
doi:10.1007/s00405-019-05628-w
Parhar, Tasche, Brody, Topical preparations to reduce SARS-CoV-2 aerosolization in head and neck mucosal surgery, Head Neck,
doi:10.1002/hed.26200
Reimer, Wichelhaus, Schäfer, Antimicrobial effectiveness of povidone-iodine and consequences for new application areas, Dermatology,
doi:10.1159/000057738
Richard, Van Den Brand, Bestebroer, Influenza A viruses are transmitted via the air from the nasal respiratory epithelium of ferrets, Nat Commun,
doi:10.1038/s41467-020-14626-0
Sungnak, Huang, Bécavin, Biological Network. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes, Nat Med,
doi:10.1038/s41591-020-0868-6
Tessema, Frank, Bidra, SARS-CoV-2 viral inactivation using low dose povidone-iodine oral rinse-immediate application for the prosthodontic practice, J Prosthodont,
doi:10.1111/jopr.13207
Van Doremalen, Bushmaker, Morris, Aerosol and surface stability of SARS-CoV-2 compared with SARS-CoV-1, N Engl J Med,
doi:10.1056/NEJMc2004973
Workman, Cohen, The effect of drugs and other compounds on the ciliary beat frequency of human respiratory epithelium, Am J Rhinol Allergy,
doi:10.2500/ajra.2014.28.4092
Workman, Welling, Carter, Endonasal instrumentation and aerosolization risk in the era of COVID-19: simulation, literature review, and proposed mitigation strategies, Int Forum Allergy Rhinol,
doi:10.1002/alr.22577
Zou, Ruan, Huang, SARS-CoV-2 viral load in upper respiratory specimens of infected patients, N Engl J Med,
doi:10.1056/NEJMc2001737