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

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 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.

The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2

“…The ratio for ACE2 was five-fold greater in the nose than in the distal respiratory tract [40]. Other repurposing treatments as a nasal antiseptic have been tested in vitro, such as Povidone-Iodine, which has shown activity against SARS-CoV-2 [48]. In the present study, we showed the in vitro therapeutic potential of BromAc against SARS-CoV-2 with a threshold efficient dose at 100 µg/20 mg/mL.…”

Nanodroplet-Benzalkonium Chloride Formulation DemonstratesIn VitroandEx-VivoBroad-Spectrum Antiviral Activity Against SARS-CoV-2 and other Enveloped Viruses

“…However, this approach has major limitations including patient experience of using povidone iodine in the nose, allergic potential, and thyroid disease concerns. Povidone Iodine can become ineffective when diluting from available commercial 5% or 10% solutions and can be effective only up to 4 hours post application 25 . NE-BZK has an added advantage that safety has been previously demonstrated in humans through two different phase 1 clinical trials using the same nanoemulsion technology with a similar cationic surfactant.…”

Prophylactic and therapeutic topical povidone‐iodine in coronavirus disease 2019 (COVID‐19): What is the evidence?

“…[20][21][22][23][24] Aqueous intranasal preparations of PVI-I at concentrations as low as 0.5% completely inactivated SARS-CoV-2 with contact times as short as 15 seconds, compared to 70% ethanol, which demonstrated only partial viral inactivation. 20,23 A 0.45% Betadine throat spray was similarly efficacious following a 30-second contact time. 21 A prior study using MERS-CoV and SARS-CoV showed viral inactivation with a PVP-I mouthwash concentration as low as 0.23% after 15 seconds.…”

“…Although in vivo efficacy of PVP‐I against SARS‐CoV‐2 remains unknown, several in vitro studies have demonstrated promising virucidal activity 20–24 . Aqueous intranasal preparations of PVI‐I at concentrations as low as 0.5% completely inactivated SARS‐CoV‐2 with contact times as short as 15 seconds, compared to 70% ethanol, which demonstrated only partial viral inactivation 20,23 . A 0.45% Betadine throat spray was similarly efficacious following a 30‐second contact time 21 .…”

“…Although an increase in the delivered concentration could potentially improve efficacy, higher doses have been associated with ciliotoxicity 26 . Furthermore, caution should be exercised when converting commercially available PVP‐I solutions into nasal applications as certain formulations may include additives that may be nasal toxic and are chemically unamenable to dilution 20 . The optimal in vivo concentration, dosing regimen, and delivery method of PVP‐I therefore all persist as open questions requiring further study.…”