Povidone Iodine Mouthwash, Gargle, and Nasal Spray to Reduce Nasopharyngeal Viral Load in Patients With COVID-19: A Randomized Clinical Trial | Pathology and Laboratory Medicine | JAMA Otolaryngology–Head & Neck Surgery | JAMA Network
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Figure.  Box Plots Indicating Median, Interquartile Range, and 5th and 95th Percentiles, by Treatment Group
Box Plots Indicating Median, Interquartile Range, and 5th and 95th Percentiles, by Treatment Group

RNA indicates ribonucleic acid; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TCID50, tissue culture infectious dose.

Table.  Patient Demographics and Baseline Clinical Characteristics
Patient Demographics and Baseline Clinical Characteristics
1.
Wiersinga  WJ, Rhodes  A, Cheng  AC, Peacock  SJ, Prescott  HC.  Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): A Review.   JAMA. 2020;324(8):782-793. doi:10.1001/jama.2020.12839PubMedGoogle ScholarCrossref
2.
Frank  S, Brown  SM, Capriotti  JA, Westover  JB, Pelletier  JS, Tessema  B.  In vitro efficacy of a povidone-iodine nasal antiseptic for rapid inactivation of SARS-CoV-2.   JAMA Otolaryngol Head Neck Surg. 2020;146(11):1-5. doi:10.1001/jamaoto.2020.3053PubMedGoogle ScholarCrossref
3.
Etievant  S, Bal  A, Escuret  V,  et al.  Performance assessment of SARS-CoV-2 PCR assays developed by WHO referral laboratories.   J Clin Med. 2020;9(6):1871. doi:10.3390/jcm9061871PubMedGoogle ScholarCrossref
4.
Kärber  G.,  Beitrag zur kollektiven Behandlung pharmakologischer Reihenversuche.   Archiv f experiment Pathol u Pharmakol. 1934;162:480-483.Google ScholarCrossref
5.
Farrell  NF, Klatt-Cromwell  C, Schneider  JS.  Benefits and safety of nasal saline irrigations in a pandemic—washing COVID-19 away.   JAMA Otolaryngol Head Neck Surg. 2020;146(9):787-788. doi:10.1001/jamaoto.2020.1622PubMedGoogle ScholarCrossref
6.
Pennington  JA.  A review of iodine toxicity reports.   J Am Diet Assoc. 1990;90(11):1571-1581.PubMedGoogle Scholar
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Research Letter
February 4, 2021

Povidone Iodine Mouthwash, Gargle, and Nasal Spray to Reduce Nasopharyngeal Viral Load in Patients With COVID-19: A Randomized Clinical Trial

Author Affiliations
  • 1Emergency Department, University Hospital of Poitiers, Poitiers, France
  • 2Virology laboratory, University Hospital of Poitiers, Poitiers, France
  • 3Department of Anesthesia, Intensive Care and Perioperative Medicine, University Hospital of Poitiers, Poitiers, France
JAMA Otolaryngol Head Neck Surg. 2021;147(4):400-401. doi:10.1001/jamaoto.2020.5490

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is primarily transmitted person-to-person through the aerosolization of droplets containing contaminated nasopharyngeal secretions.1 Povidone iodine (PI) solutions at concentrations as low as 0.5% rapidly inactivate SARS-CoV-2 in vitro with contact times as short as 15 seconds.2 We investigated whether nasopharyngeal application of PI could reduce the viral load of patients with nonsevere coronavirus disease 2019 (COVID-19) symptoms.

Methods

We included adult outpatients (≥18 years old) having tested highly positive (cycle threshold ≤20) for SARS-CoV-2 ribonucleic acid (RNA) by reverse transcription-polymerase chain reaction (RT-PCR) in nasopharyngeal swabs within the previous 48 hours. Patients with a history of thyroid disease were excluded. The study was approved by the South Mediterranean Institutional Review Board, and written informed consent was obtained from all participants. The trial protocol is included in Supplement 1.

Patients underwent an additional nasopharyngeal swab for viral quantification at baseline before being randomly assigned (1:1) to a control group (no intervention, n = 12) or an intervention group (n = 12). Intervention consisted of 4 successive mouthwashes and gargles with 25 mL of 1% aqueous PI solution each (Mylan, Merignac, France), followed by one 2.5-mL nasal pulverization of the same solution into each nostril using an intranasal mucosal atomization device (MAD Nasal, Teleflex, Morrisville, North Carolina) connected to a 5-mL syringe while sniffing and 1 application on each nasal mucosa of a dab of 10% PI ointment followed by a massage of the nostril to help spread the ointment. Patients were trained during the first decolonization session, and received the necessary materials and a guide to help them perform the following sessions 4 times a day for 5 days.

Follow-up was done on day 1 and then every 2 days until day 7 to assess the efficacy (viral quantification) and safety of the decolonization. Almost all (>95%) of the nasopharyngeal swabs were taken by the same skilled nurse at least 3 hours after the last PI application for quantification of viral RNA using RT-PCR,3 and viral titer using the dilution limit method on Vero cells and the Spearman-Karber approach with a limit of detection of 102.5 tissue culture infectious dose (TCID50) per mL.4 Changes in viral load over time were compared between study groups using a linear mixed model for repeated measures.

Results

All patients completed the study, and none required hospital admission. Compared with the control group, patients in the intervention group were younger (Table). Median (IQR) age of patients in the control group was 57 (45-68) years and in the intervention group was 33 (23-46) years. A total of 4 patients (33%) in each group were male. All patients but 1 had negative viral titer by day 3. Use of PI had no influence on changes of viral RNA quantification over time (Figure). Mean relative difference in viral titers between baseline and day 1 was 75% (95% CI, 43%-95%) in the intervention group and 32% (95% CI, 10%-65%) in the control group (Figure). All patients exposed to PI experienced unpleasant nasal tingling but completed the study. Thyroid stimulating hormone elevation (median [IQR], 3.4 [2.6-4.3] mIU/L vs 2.1 [1.4-3.1] mIU/L at baseline) was observed in all patients after 5 days of PI exposure, exceeding the upper normal value in 5 patients, with a return to baseline values 7 to 12 days later. No modification in thyroid hormone (T3, T4) or creatinine levels was observed.

Discussion

Nasopharyngeal decolonization may reduce the carriage of infectious SARS-CoV-2 in adults with mild to moderate COVID-19.5 Thyroid dysfunction occurred in 42% of the patients exposed to PI, with spontaneous resolution upon treatment discontinuation, as previously reported.6 Strengths of this study include assessment of viral titer to determine whether the virus was viable and thus potentially transmissible. Limitations include the small number of patients and the single-center design. These data call for a larger clinical trial to confirm the benefit of PI in limiting the excretion and resulting human-to-human transmission of SARS-CoV-2, using lower PI concentrations to minimize adverse effects.

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Article Information

Accepted for Publication: December 2, 2020.

Published Online: February 4, 2021. doi:10.1001/jamaoto.2020.5490

Corresponding Author: Olivier Mimoz, MD, PhD, Emergency Department, University Hospital of Poitiers, 2 Rue de la Miletrie, Poitiers, France 86021 (olivier.mimoz@chu-poitiers.fr).

Author Contributions: Dr Guenezan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Guenezan, Garcia, Lévêque, Frasca, Mimoz.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Guenezan, Garcia, Mimoz.

Critical revision of the manuscript for important intellectual content: Guenezan, Garcia, Strasters, Jousselin, Lévêque, Frasca.

Statistical analysis: Frasca.

Obtained funding: Mimoz.

Administrative, technical, or material support: Guenezan, Garcia, Jousselin.

Supervision: Guenezan, Strasters, Lévêque, Frasca, Mimoz.

Conflict of Interest Disclosures: Dr Mimoz reported receiving grants from Becton Dickinson and Cooper, and personal fees from Becton Dickinson, Cooper, and 3M, all outside the submitted work. No other disclosures were reported.

Funding/Support: This project was supported by the University Hospital of Poitiers, France. This study did not benefit from financial support.

Role of the Funder/Sponsor: University Hospital of Poitiers, France, 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.

Data Sharing Statement: See Supplement 2.

Additional Contributions: We acknowledge Cynthia Bordage, RN, Bertrand Drugeon, MD, Amélie Mabille, MD, Nicolas Marjanovic, MD, Severine Mousse, MSc, Alexandre Rahoui, MD and Camille Raynaud, MD, who assisted in data collection and patient follow-up, Pierre Dupuis, PharmD, who performed the biochemical tests, and Jeffrey Arsham for editing assistance, all from the University hospital of Poitiers, France. There was no financial compensation for these contributions.

Trial Registration: ClinicalTrials.gov Identifier: NCT04371965

References
1.
Wiersinga  WJ, Rhodes  A, Cheng  AC, Peacock  SJ, Prescott  HC.  Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): A Review.   JAMA. 2020;324(8):782-793. doi:10.1001/jama.2020.12839PubMedGoogle ScholarCrossref
2.
Frank  S, Brown  SM, Capriotti  JA, Westover  JB, Pelletier  JS, Tessema  B.  In vitro efficacy of a povidone-iodine nasal antiseptic for rapid inactivation of SARS-CoV-2.   JAMA Otolaryngol Head Neck Surg. 2020;146(11):1-5. doi:10.1001/jamaoto.2020.3053PubMedGoogle ScholarCrossref
3.
Etievant  S, Bal  A, Escuret  V,  et al.  Performance assessment of SARS-CoV-2 PCR assays developed by WHO referral laboratories.   J Clin Med. 2020;9(6):1871. doi:10.3390/jcm9061871PubMedGoogle ScholarCrossref
4.
Kärber  G.,  Beitrag zur kollektiven Behandlung pharmakologischer Reihenversuche.   Archiv f experiment Pathol u Pharmakol. 1934;162:480-483.Google ScholarCrossref
5.
Farrell  NF, Klatt-Cromwell  C, Schneider  JS.  Benefits and safety of nasal saline irrigations in a pandemic—washing COVID-19 away.   JAMA Otolaryngol Head Neck Surg. 2020;146(9):787-788. doi:10.1001/jamaoto.2020.1622PubMedGoogle ScholarCrossref
6.
Pennington  JA.  A review of iodine toxicity reports.   J Am Diet Assoc. 1990;90(11):1571-1581.PubMedGoogle Scholar
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