key: cord-0734661-cvp5qogk
authors: Jayaraman, B. G.; Rajan, G.; Kannian, P.; Lavanya, C.; Ravichandran, K.; Kumarasamy, N.; Ranganathan, K.; Ashwini, V.; Mahanathi, P.; Challacombe, S. J.; Webster-Cyriaque, J.; Johnson, N. W.
title: Povidone iodine, hydrogen peroxide and chlorhexidine mouthwashes reduce SARS-CoV2 burden in whole mouth fluid and respiratory droplets
date: 2021-03-01
journal: nan
DOI: 10.1101/2021.02.25.21252488
sha: 601c86ef5032b3158ccad0b4172379915d4c5819
doc_id: 734661
cord_uid: cvp5qogk

SARS-CoV2 is transmitted primarily through oral mouth secretions and respiratory droplets. Commercial mouthwashes, povidone iodine (PI), hydrogen peroxide (HP) and chlorhexidine (CHX) have been tested in cell culture and RT-PCR studies for their efficacy to reduce SARS-CoV2 burden. Here, we evaluated SARS-CoV2 burden in whole mouth fluid (WMF) and respiratory droplets (RD) samples before and after the use of PI, HP or CHX mouthwashes in hospitalized COVID-19 patients using RT-PCR and rapid antigen test (RAT). Thirty-six SARS-CoV2 RT-PCR-positive in-patients were randomly assigned to one of the four groups: 20 and 60 minutes after 1% w/v PI or 1.5% HP; 90 and 180 minutes after 1.5% HP or 0.2% w/v CHX. WMF and RD samples were collected concurrently at baseline and after the two different time points. RD (92%) showed a higher reduction in SARS-CoV2 burden than WMF samples (50%; p=0.008). SARS-CoV2 burden was statistically lower at both 20 minutes (p=0.02) and 60 minutes (p=0.03) with PI; at 20 minutes with HP (p=0.0001); and 90 minutes with CHX (p=0.04). The overall and individual mean logarithmic reductions in the WMF and RD samples were greater than 1.0 at 20, 60 and 90 minutes after PI, HP or CHX. RAT-positive patients at 90 minutes post-treatment (n=3) demonstrated a one log increase in virus copies. Among the three RAT-negative post-treatment patients, SARS-CoV2 burden declined by one log in two while the third patient had a slight increase in RNA copies. In conclusion, we have shown for the first time that the mouthwashes, PI, HP and CHX can reduce the SARS-CoV2 burden in the concurrently collected RD and WMF samples. RAT is more appropriate than RT-PCR to evaluate the efficacy of the mouthwashes.

Whole mouth fluid (WMF) and respiratory droplets (RD) primarily transmit SARS-CoV2. In vitro cell culture and RT-PCR studies in WMF have shown that commercial mouthwasheschlorhexidine (CHX), povidone iodine (PI) and hydrogen peroxide (HP) have significant virucidal activity against SARS-CoV2. 1, 2 However, RT-PCR of RNA viruses will detect both live and dead viruses, and should be interpreted cautiously. We have previously used rapid antigen testing (RAT) to detect SARS-CoV2 proteins in WMF thereby depicting its infectious state. 4 This study evaluates SARS-CoV2 burden in WMF and RD samples before and after the use of PI, HP or CHX mouthwashes in hospitalized COVID-19 patients using RT-PCR and RAT.

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The study was approved by VHS-Institutional Ethics Committee (VHS-IEC/60-2020). Thirtysix SARS-CoV2 RT-PCR-positive (nasopharyngeal swab [NPS] and WMF) in-patients were randomly assigned after written informed consent to one of the four groups -20 and 60 minutes after 1% w/v PI or 1.5% HP; 90 and 180 minutes after 1.5% HP or 0.2% w/v CHX. Early . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 1, 2021. ; https://doi.org/10.1101/2021.02.25.21252488 doi: medRxiv preprint

Among the 36 patients, 13 (36%) were RT-PCR positive in RD samples at baseline. A 50% or greater decrease in the SARS-CoV2 copies from the baseline was considered significant. The reduction was significantly higher in RD (92%; 12/13) than WMF samples (50%; 18/36; p=0.008), perhaps due to lower baseline burden in RD samples (Table 1 ). Compared to the baseline, the mean copy numbers were statistically lower at both 20 minutes (p=0.02) and 60 minutes (p=0.03) with PI; at 20 minutes with HP (p=0.0001); and 90 minutes with CHX (p=0.04). The overall and individual mean logarithmic reductions (MLR) in the WMF and RD samples were greater than 1.0 at 20, 60 and 90 minutes after PI, HP or CHX (Table 1) .

WMF samples from six patients were tested for SARS-CoV2 antigens by RAT at baseline and at either 20 minutes (n=3) or 90 minutes (n=3) after HP. Six baseline samples were RAT-positive.

Patients who remained RAT-positive at 90 minutes post-treatment (n=3) demonstrated a one log increase in virus copies (Table 2) . Among the three patients who became RAT-negative posttreatment, in two individuals the SARS-CoV2 burden declined by one log. However, in the third patient a slight increase in RNA copies was detected.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 1, 2021. ; https://doi.org/10.1101/2021.02.25.21252488 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted March 1, 2021. ; https://doi.org/10.1101/2021.02.25.21252488 doi: medRxiv preprint

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Is povidone iodine mouthwash effective against SARS-CoV-2? First in vivo tests

International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity