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      Assessment of Alcohol-Based Hand Sanitizers for Long-Term Use, Formulated with Addition of Natural Ingredients in Comparison to WHO Formulation 1

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          Abstract

          During the spread of COVID-19, many laboratories used the “ Formulation 1” proposed by the World Health Organization to prepare hand sanitizers. Taking into consideration its ingredients and the prolonged use of hand sanitizers, “ Formulation 1” (P1) was compared with two gel formulations (P2 and P3) prepared with the addition of natural emollients and two different viscosity enhancers to define their chemical–physical stability, biocidal efficacy, and in vivo acceptability and tolerability. P1 resulted in the most efficient biocide but was poorly tolerated by the skin and not acceptable in volunteer hedonic evaluation, especially in terms of irritation and drying effect, with an expectable reduction in the compliance. Moreover, its liquid formulation is unpractical and can cause ethanol evaporation. P2 and P3 proved to be both good products regarding pH and alcohol strength values. However, in terms of viscosity, texture, ease of use, and application, P3 seemed to be a better gel product than P2. Moreover, they were well tolerated by the skin, increasing the hydration of the stratum corneum, due to the addition of Calendula officinalis and Aloe vera. Despite a lower ethanol concentration than P1, P2 and P3 also showed a good biocide efficiency, with better results in P2. In conclusion, these gel formulations proved to be more convenient for long-term use with a good balance between efficacy, safety, and compatibility with the skin.

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          Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1

          To the Editor: A novel human coronavirus that is now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (formerly called HCoV-19) emerged in Wuhan, China, in late 2019 and is now causing a pandemic. 1 We analyzed the aerosol and surface stability of SARS-CoV-2 and compared it with SARS-CoV-1, the most closely related human coronavirus. 2 We evaluated the stability of SARS-CoV-2 and SARS-CoV-1 in aerosols and on various surfaces and estimated their decay rates using a Bayesian regression model (see the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org). SARS-CoV-2 nCoV-WA1-2020 (MN985325.1) and SARS-CoV-1 Tor2 (AY274119.3) were the strains used. Aerosols (<5 μm) containing SARS-CoV-2 (105.25 50% tissue-culture infectious dose [TCID50] per milliliter) or SARS-CoV-1 (106.75-7.00 TCID50 per milliliter) were generated with the use of a three-jet Collison nebulizer and fed into a Goldberg drum to create an aerosolized environment. The inoculum resulted in cycle-threshold values between 20 and 22, similar to those observed in samples obtained from the upper and lower respiratory tract in humans. Our data consisted of 10 experimental conditions involving two viruses (SARS-CoV-2 and SARS-CoV-1) in five environmental conditions (aerosols, plastic, stainless steel, copper, and cardboard). All experimental measurements are reported as means across three replicates. SARS-CoV-2 remained viable in aerosols throughout the duration of our experiment (3 hours), with a reduction in infectious titer from 103.5 to 102.7 TCID50 per liter of air. This reduction was similar to that observed with SARS-CoV-1, from 104.3 to 103.5 TCID50 per milliliter (Figure 1A). SARS-CoV-2 was more stable on plastic and stainless steel than on copper and cardboard, and viable virus was detected up to 72 hours after application to these surfaces (Figure 1A), although the virus titer was greatly reduced (from 103.7 to 100.6 TCID50 per milliliter of medium after 72 hours on plastic and from 103.7 to 100.6 TCID50 per milliliter after 48 hours on stainless steel). The stability kinetics of SARS-CoV-1 were similar (from 103.4 to 100.7 TCID50 per milliliter after 72 hours on plastic and from 103.6 to 100.6 TCID50 per milliliter after 48 hours on stainless steel). On copper, no viable SARS-CoV-2 was measured after 4 hours and no viable SARS-CoV-1 was measured after 8 hours. On cardboard, no viable SARS-CoV-2 was measured after 24 hours and no viable SARS-CoV-1 was measured after 8 hours (Figure 1A). Both viruses had an exponential decay in virus titer across all experimental conditions, as indicated by a linear decrease in the log10TCID50 per liter of air or milliliter of medium over time (Figure 1B). The half-lives of SARS-CoV-2 and SARS-CoV-1 were similar in aerosols, with median estimates of approximately 1.1 to 1.2 hours and 95% credible intervals of 0.64 to 2.64 for SARS-CoV-2 and 0.78 to 2.43 for SARS-CoV-1 (Figure 1C, and Table S1 in the Supplementary Appendix). The half-lives of the two viruses were also similar on copper. On cardboard, the half-life of SARS-CoV-2 was longer than that of SARS-CoV-1. The longest viability of both viruses was on stainless steel and plastic; the estimated median half-life of SARS-CoV-2 was approximately 5.6 hours on stainless steel and 6.8 hours on plastic (Figure 1C). Estimated differences in the half-lives of the two viruses were small except for those on cardboard (Figure 1C). Individual replicate data were noticeably “noisier” (i.e., there was more variation in the experiment, resulting in a larger standard error) for cardboard than for other surfaces (Fig. S1 through S5), so we advise caution in interpreting this result. We found that the stability of SARS-CoV-2 was similar to that of SARS-CoV-1 under the experimental circumstances tested. This indicates that differences in the epidemiologic characteristics of these viruses probably arise from other factors, including high viral loads in the upper respiratory tract and the potential for persons infected with SARS-CoV-2 to shed and transmit the virus while asymptomatic. 3,4 Our results indicate that aerosol and fomite transmission of SARS-CoV-2 is plausible, since the virus can remain viable and infectious in aerosols for hours and on surfaces up to days (depending on the inoculum shed). These findings echo those with SARS-CoV-1, in which these forms of transmission were associated with nosocomial spread and super-spreading events, 5 and they provide information for pandemic mitigation efforts.
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            Antimicrobial agents from plants: antibacterial activity of plant volatile oils.

            The volatile oils of black pepper [Piper nigrum L. (Piperaceae)], clove [Syzygium aromaticum (L.) Merr. & Perry (Myrtaceae)], geranium [Pelargonium graveolens L'Herit (Geraniaceae)], nutmeg [Myristica fragrans Houtt. (Myristicaceae), oregano [Origanum vulgare ssp. hirtum (Link) Letsw. (Lamiaceae)] and thyme [Thymus vulgaris L. (Lamiaceae)] were assessed for antibacterial activity against 25 different genera of bacteria. These included animal and plant pathogens, food poisoning and spoilage bacteria. The volatile oils exhibited considerable inhibitory effects against all the organisms under test while their major components demonstrated various degrees of growth inhibition.
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              Inactivation of Severe Acute Respiratory Syndrome Coronavirus 2 by WHO-Recommended Hand Rub Formulations and Alcohols

              Infection control instructions call for use of alcohol-based hand rub solutions to inactivate severe acute respiratory syndrome coronavirus 2. We determined the virucidal activity of World Health Organization–recommended hand rub formulations, at full strength and multiple dilutions, and of the active ingredients. All disinfectants demonstrated efficient virus inactivation.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                17 April 2021
                April 2021
                : 13
                : 4
                : 571
                Affiliations
                [1 ]Department of Drug and Health Science, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy; francescafallica19@ 123456gmail.com (F.F.); debora.santonocito@ 123456unict.it (D.S.)
                [2 ]Department of Biological, Geological and Environmental Sciences, University of Catania, Via Androne 81, 95124 Catania, Italy; chiara.leonardi@ 123456unict.it
                [3 ]Research & Develepment Department, PLB Cosmetici, Via Collodi 1, 95024 Acireale, Italy; paola.leonardi@ 123456biocosme.it
                [4 ]National Research Council, Institute for Agricultural and Forest Systems in the Mediterranean, Via Empedocle 58, 95128 Catania, Italy; valeria.toscano@ 123456cnr.it
                Author notes
                [* ]Correspondence: capuglia@ 123456unict.it
                Author information
                https://orcid.org/0000-0002-8595-9338
                https://orcid.org/0000-0003-2641-7456
                https://orcid.org/0000-0001-9024-6909
                https://orcid.org/0000-0002-7694-3641
                Article
                pharmaceutics-13-00571
                10.3390/pharmaceutics13040571
                8073725
                13817ade-032b-4fc0-8405-05a506607495
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 13 March 2021
                : 14 April 2021
                Categories
                Article

                covid-19,gel formulation,viscosity enhancer,skin hydration,biocide efficiency,hedonic values

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