A Pilot Study of 0.4% Povidone-Iodine Nasal Spray to Eradicate SARS-CoV-2 in the Nasopharynx

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Abstract

Purpose

This study aimed to evaluate the virucidal efficacy of 0.4% povidone-iodine (PVP-I) nasal spray against SARS-CoV-2 in the patients’ nasopharynx at 3 minutes and 4 hours after PVP-I exposure.

Patients and Methods

The study was an open-label, before and after design, single-arm pilot study of adult patients with RT-PCR-confirmed COVID-19 within 24 hours. All patients received three puffs of 0.4% PVP-I nasal spray in each nostril. Nasopharyngeal (NP) swabs were collected before the PVP-I spray (baseline, left NP samples), and at 3 minutes (left and right NP samples) and 4 hours post-PVP-I spray (right NP samples). All swabs were coded to blind assessors and transported to diagnostic laboratory and tested by RT-PCR and cultured to measure the viable SARS-CoV-2 within 24 hours after collection.

Results

Fourteen patients were enrolled but viable SARS-CoV-2 was cultured from 12 patients (85.7%). The median viral titer at baseline was 3.5 log TCID ₅₀/mL (IQR 2.8–4.0 log TCID ₅₀/mL). At 3 minutes post-PVP-I spray via the left nostril, viral titers were reduced in 8 patients (66.7%). At 3 minutes post-PVP-I, the median viral titer was 3.4 log TCID ₅₀/mL (IQR 1.8–4.4 log TCID ₅₀/mL) ( P=0.162). At 4 hours post-PVP-I spray via the right nostril, 6 of 11 patients (54.5%) had either the same or minimal change in viral titers. The median viral titer 3 minutes post-PVP-I spray was 2.7 log TCID ₅₀/mL (IQR 2.0–3.9 log TCID ₅₀/mL). Four hours post-PVP-I spray the median titer was 2.8 log TCID ₅₀/mL (IQR 2.2–3.9 log TCID ₅₀/mL) ( P=0.704). No adverse effects of 0.4% PVP-I nasal spray were detected.

Conclusion

The 0.4% PVP-I nasal spray demonstrated minimal virucidal efficacy at 3 minutes post-exposure. At 4 hours post-exposure, the viral titer was considerably unchanged from baseline in 10 cases. The 0.4% PVP-I nasal spray showed poor virucidal activity and is unlikely to reduce transmission of SARS-CoV-2 in prophylaxis use.

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Most cited references 21

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Estimating excess mortality due to the COVID-19 pandemic: a systematic analysis of COVID-19-related mortality, 2020–21

(2022)

Background Mortality statistics are fundamental to public health decision making. Mortality varies by time and location, and its measurement is affected by well known biases that have been exacerbated during the COVID-19 pandemic. This paper aims to estimate excess mortality from the COVID-19 pandemic in 191 countries and territories, and 252 subnational units for selected countries, from Jan 1, 2020, to Dec 31, 2021. Methods All-cause mortality reports were collected for 74 countries and territories and 266 subnational locations (including 31 locations in low-income and middle-income countries) that had reported either weekly or monthly deaths from all causes during the pandemic in 2020 and 2021, and for up to 11 year previously. In addition, we obtained excess mortality data for 12 states in India. Excess mortality over time was calculated as observed mortality, after excluding data from periods affected by late registration and anomalies such as heat waves, minus expected mortality. Six models were used to estimate expected mortality; final estimates of expected mortality were based on an ensemble of these models. Ensemble weights were based on root mean squared errors derived from an out-of-sample predictive validity test. As mortality records are incomplete worldwide, we built a statistical model that predicted the excess mortality rate for locations and periods where all-cause mortality data were not available. We used least absolute shrinkage and selection operator (LASSO) regression as a variable selection mechanism and selected 15 covariates, including both covariates pertaining to the COVID-19 pandemic, such as seroprevalence, and to background population health metrics, such as the Healthcare Access and Quality Index, with direction of effects on excess mortality concordant with a meta-analysis by the US Centers for Disease Control and Prevention. With the selected best model, we ran a prediction process using 100 draws for each covariate and 100 draws of estimated coefficients and residuals, estimated from the regressions run at the draw level using draw-level input data on both excess mortality and covariates. Mean values and 95% uncertainty intervals were then generated at national, regional, and global levels. Out-of-sample predictive validity testing was done on the basis of our final model specification. Findings Although reported COVID-19 deaths between Jan 1, 2020, and Dec 31, 2021, totalled 5·94 million worldwide, we estimate that 18·2 million (95% uncertainty interval 17·1–19·6) people died worldwide because of the COVID-19 pandemic (as measured by excess mortality) over that period. The global all-age rate of excess mortality due to the COVID-19 pandemic was 120·3 deaths (113·1–129·3) per 100 000 of the population, and excess mortality rate exceeded 300 deaths per 100 000 of the population in 21 countries. The number of excess deaths due to COVID-19 was largest in the regions of south Asia, north Africa and the Middle East, and eastern Europe. At the country level, the highest numbers of cumulative excess deaths due to COVID-19 were estimated in India (4·07 million [3·71–4·36]), the USA (1·13 million [1·08–1·18]), Russia (1·07 million [1·06–1·08]), Mexico (798 000 [741 000–867 000]), Brazil (792 000 [730 000–847 000]), Indonesia (736 000 [594 000–955 000]), and Pakistan (664 000 [498 000–847 000]). Among these countries, the excess mortality rate was highest in Russia (374·6 deaths [369·7–378·4] per 100 000) and Mexico (325·1 [301·6–353·3] per 100 000), and was similar in Brazil (186·9 [172·2–199·8] per 100 000) and the USA (179·3 [170·7–187·5] per 100 000). Interpretation The full impact of the pandemic has been much greater than what is indicated by reported deaths due to COVID-19 alone. Strengthening death registration systems around the world, long understood to be crucial to global public health strategy, is necessary for improved monitoring of this pandemic and future pandemics. In addition, further research is warranted to help distinguish the proportion of excess mortality that was directly caused by SARS-CoV-2 infection and the changes in causes of death as an indirect consequence of the pandemic. Funding Bill & Melinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom

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SARS-CoV-2 variants with mutations at the S1/S2 cleavage site are generated in vitro during propagation in TMPRSS2-deficient cells

Michihito Sasaki, Kentaro Uemura, Akihiko Sato … (2021)

The spike (S) protein of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) binds to a host cell receptor which facilitates viral entry. A polybasic motif detected at the cleavage site of the S protein has been shown to broaden the cell tropism and transmissibility of the virus. Here we examine the properties of SARS-CoV-2 variants with mutations at the S protein cleavage site that undergo inefficient proteolytic cleavage. Virus variants with S gene mutations generated smaller plaques and exhibited a more limited range of cell tropism compared to the wild-type strain. These alterations were shown to result from their inability to utilize the entry pathway involving direct fusion mediated by the host type II transmembrane serine protease, TMPRSS2. Notably, viruses with S gene mutations emerged rapidly and became the dominant SARS-CoV-2 variants in TMPRSS2-deficient cells including Vero cells. Our study demonstrated that the S protein polybasic cleavage motif is a critical factor underlying SARS-CoV-2 entry and cell tropism. As such, researchers should be alert to the possibility of de novo S gene mutations emerging in tissue-culture propagated virus strains.

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Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore

Chaminda J. Seneviratne, Preethi Balan, Kwan Ki Karrie Ko … (2020)

Purpose One of the key approaches to minimize the risk of COVID-19 transmission would be to reduce the titres of SARS-CoV-2 in the saliva of infected COVID-19 patients. This is particularly important in high-risk procedures like dental treatment. The present randomized control trial evaluated the efficacy of three commercial mouth-rinse viz. povidone–iodine (PI), chlorhexidine gluconate (CHX) and cetylpyridinium chloride (CPC), in reducing the salivary SARS-CoV-2 viral load in COVID-19 patients compared with water. Methods A total of 36 SARS-CoV-2-positive patients were recruited, of which 16 patients were randomly assigned to four groups—PI group (n = 4), CHX group (n = 6), CPC group (n = 4) and water as control group (n = 2). Saliva samples were collected from all patients at baseline and at 5 min, 3 h and 6 h post-application of mouth-rinses/water. The samples were subjected to SARS-CoV-2 RT-PCR analysis. Results Comparison of salivary Ct values of patients within each group of PI, CHX, CPC and water at 5 min, 3 h and 6 h time points did not show any significant differences. However, when the Ct value fold change of each of the mouth-rinse group patients were compared with the fold change of water group patients at the respective time points, a significant increase was observed in the CPC group patients at 5 min and 6 h and in the PI group patients at 6 h. Conclusion The effect of decreasing salivary load with CPC and PI mouth-rinsing was observed to be sustained at 6 h time point. Within the limitation of the current study, as number of the samples analyzed, the use of CPC and PI formulated that commercial mouth-rinses may be useful as a pre-procedural rinse to help reduce the transmission of COVID-19. ISRCTN (ISRCTN95933274), 09/09/20, retrospectively registered

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Author and article information

Journal

Journal ID (nlm-ta): Infect Drug Resist

Journal ID (iso-abbrev): Infect Drug Resist

Journal ID (publisher-id): idr

Title: Infection and Drug Resistance

Publisher: Dove

ISSN (Electronic): 1178-6973

Publication date (Electronic): 21 December 2022

Publication date Collection: 2022

Volume: 15

Pages: 7529-7536

Affiliations

[1 ]Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok, Thailand

[2 ]Faculty of Medicine, Siam University , Bangkok, Thailand

[3 ]Samut Sakhon Hospital , Samut Sakhon, Thailand

[4 ]Department of Microbiology, Faculty of Science, Mahidol University , Bangkok, Thailand

Author notes

Correspondence: Amorn Leelarasamee, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University , 2 Thanon Wang Lang, Siriraj, Bangkoknoi, Bangkok, 10700, Thailand, Tel/Fax +66 2 419 7783, Email amorn.lee@mahidol.ac.th

Author information

Amorn Leelarasamee http://orcid.org/0000-0002-9865-4330

Arunee Thitithanyanont http://orcid.org/0000-0002-9756-4763

Article

Publisher ID: 391630

DOI: 10.2147/IDR.S391630

PMC ID: 9790155

PubMed ID: 36575672

SO-VID: bc0913b6-a95e-4586-878f-9e74bf4bb823

License:

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 04 October 2022

Date accepted : 09 December 2022

Page count

Figures: 1, Tables: 4, References: 23, Pages: 8

Funding

Funded by: Health Systems Research Institute, open-funder-registry 10.13039/501100010724;

Funded by: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript;

This work was supported by the Health Systems Research Institute (Thailand), Nonthaburi, Thailand; and, by the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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A Pilot Study of 0.4% Povidone-Iodine Nasal Spray to Eradicate SARS-CoV-2 in the Nasopharynx

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Abstract

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Most cited references 21

Estimating excess mortality due to the COVID-19 pandemic: a systematic analysis of COVID-19-related mortality, 2020–21

SARS-CoV-2 variants with mutations at the S1/S2 cleavage site are generated in vitro during propagation in TMPRSS2-deficient cells

Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore

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