University Of Connecticut Study Shows Intranasal Povidone-Iodine Limits COVID-19 Spread And Acts As Prophylaxis For Medical Staff

COVID-19- Povidone-Iodine: A study led by researchers from the University of Connecticut School of Medicine-Farmington along with experts from The Institute for Antiviral Research at Utah State University, Veloce BioPharma-Florida, ProHealth-Farmington and Ocean Ophthalmology-Florida has demonstrated that an antiseptic nasal spray containing povidone-iodine may help curb transmission of the SARS-CoV-2 coronavirus.


 
The research findings are published in the journal: JAMA Otolaryngology-Head and Neck Surgery. https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2770785?resultClick=1
 
High viral loads of SARS-CoV-2 have been detected in the nasopharynx and oropharynx of symptomatic patients and asymptomatic carriers. Nasal goblet and ciliated cells have the highest expression of angiotensin-converting enzyme 2 (ACE2), which is the main receptor for SARS-CoV-2. Many otolaryngologic procedures may produce aerosols that can last in the air for up to 3 hours without rapid filtration. 
 
Recently, study showed that ciliated cells with ACE2 expression were the cells most susceptible to infection, rather than submucosal glandular cells. https://www.cell.com/cell/fulltext/S0092-8674(20)30675-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867420306759%3Fshowall%3Dtrue
 
The infectivity of these cells was much higher than that of lower airway cells.
 
This study highlighted a virus transmission pathway that involves infection of ciliated cells of the upper airway within the nose as the dominant site of infection, followed by subsequent aspiration and seeding of the lungs. The nasal-oropharyngeal axis involves nasal secretions swept to the oropharynx by mucociliary clearance followed by aspiration of infected fluid into the lower airway. It is hypothesized that this upper–lower airway route may explain the observed differences between detection, persistence of viral load, and transmission dynamics seen between previous SARS-CoV outbreaks and the current COVID-19 pandemic. It is thought that this process may also play a role in the variable expression of clinical severity. Of note, a recent workon the transmission dynamics for influenza A also provides an example of this nasal-oropharyngeal axis with subsequent seeding of the lungs leading to respiratory disease. https://www.nature.com/articles/s41467-020-14626-0
 
To date transmission reduction has mainly focused on the use of physical barriers and personal protective equipment. However, multiple decontaminants have also been advocated.

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However, povidone-i odine has been a primary solution given its proven vitro efficacy against earlier SARS-CoV and the Middle East respiratory syndrome. Also, its oral antiseptic solution was recently demonstrated specifically against SARS-CoV-2 even at low concentrations.
 
Dr Samantha Frank, MD at the University of Connecticut School of Medicine, Farmington told Thailand Medical News, "The variable severity witnessed during the COVID-19 pandemic may be due to variable transmission of the virus from the nasal cavity to the lungs in positive patients. Therefore, trans-nasal viral inactivation may not only prevent person-to-person spread of the virus, but may also diminish the severity of disease in patients by limiting the spread and decreasing viral load delivered to the lungs.”
 
In laboratory test tube experiments, the researchers found that a povidone-iodine nasal spray inactivated the virus in as little as 15 seconds. The nasal spray they tested is typically used to disinfect the inside of the nose before surgery.
 
The researchers warned that formulations designed for use on the skin are not safe in the nose.
 
For this controlled in vitro laboratory study, the researchers used 3 different concentrations of study solution and ethanol, 70%, as a positive control on test media infected with SARS-CoV-2.
 
Also 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.
 
 The test solutions and virus were incubated at mean (SD) room temperature of 22 (2) °C for time periods of 15 and 30 seconds.
 
The study team came out with the following findings:
 
- Povidone-iodine nasal antiseptics at concentrations (0.5%, 1.25%, and 2.5%) completely inactivated SARS-CoV-2 within 15 seconds of contact.
 
-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.
 
With the above findings, the study team concluded that "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 povidone-iodine has demonstrated safety at concentrations of 1.25% and below and may play an adjunctive role in mitigating viral transmission beyond personal protective equipment."
 
While the study suggests that povidone-iodine solutions up to 1.25% would be well tolerated by the nasal epithelium for short-term use.
 
Clinical studies have demonstrated that lower concentrations can be administered acutely and over a period of months with no adverse effects. https://pubmed.ncbi.nlm.nih.gov/32520599/

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 Past studies have shown that repeated use of dilute 0.08% povidone-iodine every other day in patients with chronic rhinosinusitis for up to 7 weeks did not result in any adverse effects on mucociliary clearance or olfaction.
https://pubmed.ncbi.nlm.nih.gov/31560120/
https://www.eurjrhinol.org/Content/files/sayilar/95/45-50.pdf
 
When administered intranasally in humans, there is an effective dilution of the applied formulation as it is immediately combined with the existing nasal secretions. In addition to the 95% aqueous component of the nasal secretions, intranasally applied povidone-iodine also encounters mucin products released from goblet cells and submucosal glands including glycoproteins, proteoglycans, and lipids. There are also physiologic buffers, extracellular remnants of degenerating cells, and fragments of extracellular nucleic acids. All of this biological debris can act as an iodine sink and can lower the effective concentration of povidone-iodine delivered to the site of infection.
https://pubmed.ncbi.nlm.nih.gov/32262175/
https://pubmed.ncbi.nlm.nih.gov/31414403/
 
For these reasons, it is important to choose povidone-iodine concentrations below the threshold of in vitro CBF impairment but above the minimum effective biocidal level to account for iodine consumption and physiological buffering.
 
The study team has implemented the use of intranasal povidone-iodine in their practice and have updated all of their protocols to include use of 1.25% aqueous povidone-iodine formulations delivered to each nasal cavity in patients before any intranasal procedure.
 
The study team also advocates that nasal povidone-iodine irrigations should additionally be considered for use by health care professionals for prophylaxis.
 
It has been found that oral mucosa decontaminated with povidone-iodine remains sterilized for up to 4 hours. https://pubmed.ncbi.nlm.nih.gov/9462082/
 
Though this has not yet been proven in nasal mucosa, health care providers should consider use every 4 hours, or whenever donning or doffing a mask in high risk settings, up to 4 times daily.
 
At concentrations of 1.25%, iodine absorption is negligible. These simple, nonbuffered, slightly acidic, complexed povidone-iodine solutions would further limit any transmucosal absorption of molecular iodine, providing only a minimal theoretical risk of iodine absorption. Even if some noncomplexed iodine were absorbed transmucosally, it would still be orders of magnitude less than the average total daily iodine intake for a healthy adult of 150 μg.
 
Also use of 0.08% nasal povidone-iodine every other day for up to 7 weeks does not result in clinical thyroid disease. https://pubmed.ncbi.nlm.nih.gov/31560120/
https://www.eurjrhinol.org/Content/files/sayilar/95/45-50.pdf
 
Despite all this, as a precaution, thyroid function testing should be considered when povidone-iodine is regularly administered to patients for more than 3 months.
 
Use of intranasal PVP-I is contraindicated in patients with an allergy to iodine, patients who are pregnant, patients with active thyroid disease, and patients undergoing radioactive iodine therapy.
 
https://pubmed.ncbi.nlm.nih.gov/1345585/
https://pubmed.ncbi.nlm.nih.gov/9250480/
https://pubmed.ncbi.nlm.nih.gov/23724819/

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