key: cord-0874410-1xk4dd7y authors: Styles, C. T.; Vanden Oever, M.; Brown, J.; Rai, S.; Walsh, S.; Ryan, F. M.; Barclay, W. S.; Edgar, R. S. title: Treatment of irritant contact dermatitis in healthcare settings during the COVID19 pandemic: The emollient Dermol 500 exhibits virucidal activity against influenza A virus and SARS-CoV-2. date: 2021-02-16 journal: nan DOI: 10.1101/2021.02.12.21251419 sha: 432739eaba632368ab27377d2a1c1a389c2a2b33 doc_id: 874410 cord_uid: 1xk4dd7y ABSTRACT Objectives: To investigate whether the antimicrobial emollient Dermol 500 and its active components, benzalkonium chloride (BAK) and chlorohexidine dihydrochloride (CD), exhibit virucidal activity thus informing whether Dermol 500 is a suitable soap substitute for use during the COVID19 pandemic, to combat the increased incidence of work-related contact dermatitis in clinical settings that we report here. Methods: Inactivation of influenza A virus and SARS-CoV-2 by Dermol 500 and the independent and combined virucidal activity of the Dermol 500 components BAK and CD was assessed by influenza A virus and SARS-CoV-2 infectivity assays. Viruses were treated with concentrations of BAK and CD comparable to Dermol 500, and lower, and infectivity of the viruses assessed by titration. Results: Dermol 500 exhibits comparable virucidal activity to alcohol-based sanitisers against influenza A virus and SARS-CoV-2. In addition, the Dermol 500 components BAK and CD exhibit independent and synergistic virucidal activity against influenza A virus and SARS-CoV-2, the causative agent of COVID19. Conclusions: The synergistic virucidal activity of the Dermol 500 components BAK and CD makes Dermol 500 suitable as a soap substitute to treat and prevent work-related contact dermatitis in healthcare settings. Hand hygiene is imperative in healthcare settings and hand washing with soap or use of alcohol-based hand Notably, Dermol 500 lotion is usually prescribed as an antimicrobial emollient and soap substitute to aid skin 105 conditions such as dermatitis 10 . However, due to a lack of evidence regarding whether Dermol 500 can 106 inactivate virus particles, its use in clinical settings was discouraged during the COVID19 pandemic 11 . . CC-BY-ND 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint Synergistic or cumulative virucidal activity of BAK and CD within the context and concentration found in 121 Dermol 500 lotion has not previously been reported. The purpose of this study was to assess the virucidal 122 activity of Dermol 500 and its antimicrobial components BAK and CD against influenza A virus (IAV) and SARS- is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint Influenza infectivity assay The influenza A virus used in this study was strain A/PR8/8/34 (H1N1), henceforth referred to as IAV. The Due to their viscosity, Dermol 500 lotion and commercially available alcohol-based sanitisers were diluted Virus was incubated with the treatment for the stated times at either room temperature (RT) or 32°C 153 (average skin temperature). Following incubation, SFM was added to the virus/treatment samples to a 10 -1 154 dilution then subject to 10-fold serial dilutions. The limit of detection was therefore 10 1 virus particles/mL. Due to adverse effects of BAK and CD on cultured in vitro cell lines the limit of detection for BAK and CD 156 treatments between 0.05 -0.1% was 10 2 virus particles/mL without filtration. Where noted, IAV was filtered 157 to remove BAK/CD post-incubation using 15 mLlAmicon Ultra-15 centrifugal filter with a 50,000 molecular 158 weight cut off (UFC905008, Merck) and centrifugation (4000 x g, 10 min). Filtered virus was resuspended in 159 SFM and serially diluted as above. Infectious virus was titred via standard plaque assay. Briefly, confluent MDCK cells were incubated with 1ml is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint Dermol 500 exhibits virucidal activity against IAV and SARS-CoV-2 comparable to alcohol-based hand 187 sanitisers. To assess whether Dermol 500 emollient exhibits virucidal activity, we examined the capacity of IAV and 190 SARS-CoV-2 to infect cells following incubation with Dermol 500 (Figure 2 ). Dermol 500 lotion was diluted in 191 cell culture medium to allow for accurate pipetting, therefore could only be assessed at maximum 25% of its 192 original concentration. Even at this dilution, we observed a significant reduction in the amount of infectious 193 IAV after 30min incubation at skin temperature 32 o C (~100-fold reduction in virus particles; Figure 2A is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 16, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 16, 2021. to minimise exposure to harmful substances and avoid health problems including skin conditions. The 241 provision of emollients and soap substitutes, such as Dermol 500 lotion, are advised for treatment and 242 prevention of dermatitis 3 , but not recommended currently due to a lack of evidence regarding their virucidal 243 efficacy 11 . This study clearly demonstrates Dermol 500, and its antimicrobial components BAK and CD, exhibit 244 robust virucidal activity against IAV and SARS-CoV-2, enabling its use against work-related contact dermatitis 245 during the COVID19 pandemic. Synonymous with the cumulative activity of BAK and CD against bacteria 15 , these compounds act 248 synergistically to inactivate two different enveloped viruses, IAV and SARS-CoV-2. Extrapolating these results, 249 we predict that Dermol 500 will be effective against other enveloped viruses, especially as both BAK and CD The mechanisms underpinning BAK and CD viral inactivation are poorly understood, and beyond the scope is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint longer incubation times to achieve viral inactivation 14 . BAK and CD virucidal activity could also encompass 263 denaturation of viral glycoproteins required for attachment and entry. Indeed, chlorohexidine antimicrobial 264 activity has been associated with inhibition of membrane bound proteins as well as coagulation and 265 denaturation of cytoplasmic components, and may therefore access and denature viral proteins, especially 266 in the presence of BAK 12 29 . The virucidal activity of these compounds and Dermol 500 lotion against non-267 enveloped viruses requires further study, but we predict they will be at least as efficacious as alcohol-based 268 sanitisers, which inefficiently inactivate the majority of non-enveloped viruses 1 30 . To conclude, this study confirms Dermol 500 lotion and its constituents inactivate SARS-CoV-2 and the is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted February 16, 2021. ; https://doi.org/10.1101/2021.02.12.21251419 doi: medRxiv preprint WHO Guidelines on Hand Hygiene in Health Care: First Global Patient Safety Challenge Clean 316 Care Is Safer Care Management of occupational dermatitis in healthcare 318 workers: a systematic review Concise guidance: diagnosis, management and prevention of 321 occupational contact dermatitis Adverse skin reactions among healthcare workers during the 324 coronavirus disease 2019 outbreak: a survey in Wuhan and its surrounding regions Introduction of a hand dermatitis clinic to reduce occupational dermatoses during 327 the covid-19 pandemic A guide to the Health and Safety at Work Act. 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