[Skip to Content]
[Skip to Content Landing]

In Vitro Efficacy of a Povidone-Iodine Nasal Antiseptic for Rapid Inactivation of SARS-CoV-2

Educational Objective
To understand the in vitro efficacy of a povidone-iodine nasal antiseptic for rapid inactivation of SARS-CoV-2
1 Credit CME
Key Points

Question  What is the minimum contact time of povidone-iodine (PVP-I) nasal antiseptic required for inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro?

Findings  In this controlled in vitro laboratory research study, test media infected with SARS-CoV-2 demonstrated complete inactivation of SARS-CoV-2 by concentrations of PVP-I nasal antiseptic as low as 0.5% after 15 seconds of contact, as measured by a log reduction value of greater than 3 log10 of the 50% cell culture infectious dose of the virus.

Meaning  Intranasal PVP-I rapidly inactivates SARS-CoV-2 and may play an adjunctive role in mitigating viral transmission beyond personal protective equipment.

Abstract

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.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: July 29, 2020.

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 06030 (sfrank@uchc.edu).

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.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: Frank, Capriotti, Westover, Tessema.

Drafting of the manuscript: Frank, Capriotti, Pelletier, Tessema.

Critical revision of the manuscript for important intellectual content: Frank, Brown, Capriotti, Westover, Tessema.

Statistical analysis: Capriotti, Westover.

Obtained funding: Capriotti.

Administrative, technical, or material support: Brown, Capriotti, Westover, Tessema.

Supervision: Brown, Capriotti, Westover, Pelletier, Tessema.

Conflict of Interest Disclosures: Dr Brown reported personal financial investment in Halodine outside the submitted work. Dr Capriotti is the executive director of Veloce BioPharma and reported a patent to multiple related drugs issued and licensed by Veloce BioPharma. Dr Pelletier is a consultant for Veloce BioPharma and reported equity in both Veloce BioPharma and Halodine. Dr Tessema reported personal financial investment in Halodine outside the submitted work, and has a patent to multiple drug products pending. No other disclosures were reported.

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
1.
Zou  L , Ruan  F , Huang  M ,  et al.  SARS-CoV-2 viral load in upper respiratory specimens of infected patients.   N Engl J Med. 2020;382(12):1177-1179. doi:10.1056/NEJMc2001737PubMedGoogle ScholarCrossref
2.
Sungnak  W , Huang  N , Bécavin  C ,  et al; HCA Lung Biological Network.  SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes.   Nat Med. 2020;26(5):681-687. doi:10.1038/s41591-020-0868-6PubMedGoogle ScholarCrossref
3.
van Doremalen  N , Bushmaker  T , Morris  DH ,  et al.  Aerosol and surface stability of SARS-CoV-2 compared with SARS-CoV-1.   N Engl J Med. 2020;382(16):1564-1567. doi:10.1056/NEJMc2004973PubMedGoogle ScholarCrossref
4.
Balakrishnan  K , Schechtman  S , Hogikyan  ND , Teoh  AYB , McGrath  B , Brenner  MJ .  COVID-19 pandemic: what every otolaryngologist–head and neck surgeon needs to know for safe airway management.   Otolaryngol Head Neck Surg. 2020;162(6):804-808. doi:10.1177/0194599820919751PubMedGoogle ScholarCrossref
5.
Workman  AD , Welling  DB , Carter  BS ,  et al.  Endonasal instrumentation and aerosolization risk in the era of COVID-19: simulation, literature review, and proposed mitigation strategies.   Int Forum Allergy Rhinol. 2020;10(7):798-805. doi:10.1002/alr.22577PubMedGoogle ScholarCrossref
6.
Hou  YJ , Okuda  K , Edwards  CE ,  et al.  SARS-CoV-2 reverse genetics reveals a variable infection gradient in the respiratory tract.   Cell. 2020;182(2):429-446.e14. doi:10.1016/j.cell.2020.05.042PubMedGoogle ScholarCrossref
7.
Wölfel  R , Corman  VM , Guggemos  W ,  et al.  Virological assessment of hospitalized patients with COVID-2019.   Nature. 2020;581(7809):465-469. doi:10.1038/s41586-020-2196-xPubMedGoogle ScholarCrossref
8.
Richard  M , van den Brand  JMA , Bestebroer  TM ,  et al.  Influenza A viruses are transmitted via the air from the nasal respiratory epithelium of ferrets.   Nat Commun. 2020;11(1):766. doi:10.1038/s41467-020-14626-0PubMedGoogle ScholarCrossref
9.
Tessema  B , Frank  S , Bidra  A .  SARS-CoV-2 viral inactivation using low dose povidone-iodine oral rinse—immediate application for the prosthodontic practice.   J Prosthodont. 2020. doi:10.1111/jopr.13207PubMedGoogle Scholar
10.
Mady  LJ , Kubik  MW , Baddour  K , Snyderman  CH , Rowan  NR .  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. 2020;105:104724. doi:10.1016/j.oraloncology.2020.104724PubMedGoogle Scholar
11.
Parhar  HS , Tasche  K , Brody  RM ,  et al.  Topical preparations to reduce SARS-CoV-2 aerosolization in head and neck mucosal surgery.   Head Neck. 2020;42(6):1268-1272. doi:10.1002/hed.26200PubMedGoogle ScholarCrossref
12.
Challacombe  SJ , Kirk-Bayley  J , Sunkaraneni  VS , Combes  J .  Povidone iodine.   Br Dent J. 2020;228(9):656-657. doi:10.1038/s41415-020-1589-4PubMedGoogle ScholarCrossref
13.
Eggers  M , Koburger-Janssen  T , Eickmann  M , Zorn  J .  In vitro bactericidal and virucidal efficacy of povidone-iodine gargle/mouthwash against respiratory and oral tract pathogens.   Infect Dis Ther. 2018;7(2):249-259. doi:10.1007/s40121-018-0200-7PubMedGoogle ScholarCrossref
14.
Kariwa  H , Fujii  N , Takashima  I .  Inactivation of SARS coronavirus by means of povidone-iodine, physical conditions and chemical reagents.   Dermatology. 2006;212(suppl 1):119-123. doi:10.1159/000089211PubMedGoogle ScholarCrossref
15.
Bidra  AS , Pelletier  JS , Westover  JB , Frank  S , Brown  SM , Tessema  B .  Rapid in-vitro inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using povidone-iodine oral antiseptic rinse.   J Prosthodont. 2020;29(6):529-533. doi:10.1111/jopr.13209PubMedGoogle Scholar
16.
Reed  LJ , Muench  H .  A simple method of estimating fifty percent endpoints.   Am J Epidemiol 1938;27(3):493-497. doi:10.1093/oxfordjournals.aje.a118408Google ScholarCrossref
17.
Reimer  K , Wichelhaus  TA , Schäfer  V ,  et al.  Antimicrobial effectiveness of povidone-iodine and consequences for new application areas.   Dermatology. 2002;204(suppl 1):114-120. doi:10.1159/000057738PubMedGoogle ScholarCrossref
18.
Kim  JH , Rimmer  J , Mrad  N , Ahmadzada  S , Harvey  RJ .  Betadine has a ciliotoxic effect on ciliated human respiratory cells.   J Laryngol Otol. 2015;129(suppl 1):S45-S50. doi:10.1017/S0022215114002746PubMedGoogle ScholarCrossref
19.
Frank  S , Capriotti  J , Brown  SM , Tessema  B .  Povidone-iodine use in sinonasal and oral cavities: a review of safety in the COVID-19 era.   Ear Nose Throat J. Published online June 10, 2020.PubMedGoogle Scholar
20.
Panchmatia  R , Payandeh  J , Al-Salman  R ,  et al.  The efficacy of diluted topical povidone-iodine rinses in the management of recalcitrant chronic rhinosinusitis: a prospective cohort study.   Eur Arch Otorhinolaryngol. 2019;276(12):3373-3381. doi:10.1007/s00405-019-05628-wPubMedGoogle ScholarCrossref
21.
Mullings  W , Panchmatia  R , Samoy  K , Habib  A , Thamboo  A , Al-Salman  R ,  et al  Topical povidone-iodine as an adjunctive treatment for recalcitrant chronic rhinosinusitis.   Eur J Rhinol Allergy 2019;2(2):45-50. doi:10.5152/ejra.2019.166Google ScholarCrossref
22.
Hill  RL , Casewell  MW .  The in-vitro activity of povidone-iodinecream against Staphylococcus aureus and its bioavailability in nasal secretions.   J Hosp Infect. 2000;45(3):198-205. doi:10.1053/jhin.2000.0733PubMedGoogle ScholarCrossref
23.
Au-Duong  AN , Vo  DT , Lee  CK .  Bactericidal magnetic nanoparticles with iodine loaded on surface grafted poly(N-vinylpyrrolidone).   J Mater Chem B. 2015;3(5):840-848. doi:10.1039/C4TB01516APubMedGoogle ScholarCrossref
24.
Eggers  M .  Infectious disease management and control with povidone iodine.   Infect Dis Ther. 2019;8(4):581-593. doi:10.1007/s40121-019-00260-xPubMedGoogle ScholarCrossref
25.
Domingo  MA , Farrales  MS , Loya  RM , Pura  MA , Uy  H .  The effect of 1% povidone iodine as a pre-procedural mouthrinse in 20 patients with varying degrees of oral hygiene.   J Philipp Dent Assoc. 1996;48(2):31-38.PubMedGoogle Scholar
26.
Foley  TP  Jr .  The relationship between autoimmune thyroid disease and iodine intake: a review.   Endokrynol Pol. 1992;43(suppl 1):53-69.PubMedGoogle Scholar
27.
Furudate  S , Nishimaki  T , Muto  T .  125I uptake competing with iodine absorption by the thyroid gland following povidone-iodine skin application.   Exp Anim. 1997;46(3):197-202. doi:10.1538/expanim.46.197PubMedGoogle ScholarCrossref
28.
Gray  PEA , Katelaris  CH , Lipson  D .  Recurrent anaphylaxis caused by topical povidone-iodine (betadine).   J Paediatr Child Health. 2013;49(6):506-507. doi:10.1111/jpc.12232PubMedGoogle ScholarCrossref
29.
Quadir  M , Zia  H , Needham  TE .  Toxicological implications of nasal formulations.   Drug Deliv 1999;6(4):227-242. doi:10.1080/107175499266823Google ScholarCrossref
30.
Workman  AD , Cohen  NA .  The effect of drugs and other compounds on the ciliary beat frequency of human respiratory epithelium.   Am J Rhinol Allergy. 2014;28(6):454-464. doi:10.2500/ajra.2014.28.4092PubMedGoogle ScholarCrossref
31.
Povidone. United States Pharmacopeia and National Formulary. United States Pharmacopeia. May 1, 2019. Accessed August 18, 2020. https://www.usp.org/sites/default/files/usp/document/harmonization/excipients/m68070.pdf
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Close
Close

Lookup An Activity

or

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close