Oral Antiseptics against SARS-CoV-2: A Literature Review.

Dentists are health care workers with the highest risk of exposure to COVID-19, because the oral cavity is considered to be a reservoir for SARS-CoV-2 transmission. The identification of SARS-CoV-2 in saliva, the generation of aerosols, and the proximity to patients during dental procedures are conditions that have led to these health care workers implementing additional disinfection strategies for their protection. Oral antiseptics are widely used chemical substances due to their ability to reduce the number of microorganisms. Although there is still no evidence that they can prevent the transmission of SARS-CoV-2, some preoperative oral antiseptics have been recommended as control measures, by different health institutions worldwide, to reduce the number of microorganisms in aerosols and droplets during dental procedures. Therefore, this review presents the current recommendations for the use of oral antiseptics against SARS-CoV-2 and analyzes the different oral antiseptic options used in dentistry.

Effect of oral antiseptics in reducing SARS-CoV-2 infectivity: evidence from a randomized double-blind clinical trial.

ABSTRACTBackground: In vitro studies have shown that several oral antiseptics have virucidal activity against SARS-CoV-2. Thus, mouthwashes have been proposed as an easy to implement strategy to reduce viral transmission. However, there are no data measuring SARS-CoV-2 viability after mouthwashes in vivo. METHODS: In this randomized double-blind, five-parallel-group, placebo-controlled clinical trial, SARS-CoV-2 salivary viral load (by quantitative PCR) and its infectious capacity (incubating saliva in cell cultures) have been evaluated before and after four different antiseptic mouthwashes and placebo in 54 COVID-19 patients. RESULTS: Contrary to in vitro evidence, salivary viral load was not affected by any of the four tested mouthwashes. Viral culture indicated that cetylpyridinium chloride (CPC) significantly reduced viral infectivity, but only at 1-hour post-mouthwash. CONCLUSION: These results indicate that some of the mouthwashes currently used to reduce viral infectivity are not efficient in vivo and, furthermore, that this effect is not immediate, generating a false sense of security.Trial registration: ClinicalTrials.gov identifier: NCT04707742..

Application of normative documents for determination of biocidal activity of disinfectants and antiseptics dedicated to the medical area: a narrative review.

Disinfectants and antiseptics are important weapons to reduce the number of micro-organisms and thus limit the number of infections. Different methods of antimicrobial activity testing, often not standardized, without appropriate controls and not validated, are applied. To address these issues, several European Standards (EN) have been developed, describing the test methods to determine whether chemical disinfectants or antiseptic products have appropriate bactericidal, sporicidal, mycobactericidal or tuberculocidal activity; fungicidal or yeasticidal activity; or virucidal activity. In this narrative review, the 17 ENs concerning evaluation of the above-mentioned antimicrobial activity of preparations dedicated to the medical area are briefly reviewed, together with recent publications on this topic. Suspension and carrier tests have been performed in clean and dirty conditions simulating the medical area. In addition, a wide range of applications of these standards has been presented in the research of biocides for hand antisepsis, surfaces disinfection, including airborne disinfection as well as medical device and medical textile disinfection. The role of normative documents in the investigation of antimicrobial activity of disinfectants and antiseptics to limit infections has been underestimated. This narrative review aims to persuade researchers to conduct antimicrobial activity testing in line with validated ENs and highlights an existing gap in ongoing research. It also aims to raise awareness of the wide range of biocidal activity tests with standardized methods in the medical area. We also pay attention to the recently developed European Pharmacopoeia monography concerning the testing of bactericidal and fungicidal activity of antiseptics classified as medicinal products.

Mouthrinses against SARS-CoV-2 - High antiviral effectivity by membrane disruption in vitro translates to mild effects in a randomized placebo-controlled clinical trial.

The emergence of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) represents an unprecedented threat for the human population, necessitating rapid and effective intervention measures. Given the main infection route by airborne transmission, significant attention has been bestowed upon the use of antiseptic mouthrinses as a way to possibly reduce infectious viral titers. However, clinical evaluations are still sparse. Thus, we evaluated a wide variety of antiseptic agents that can be used as mouthrinses for their antiviral effects in vitro and their respective mode of action. One of the most promising antiseptic agents (benzalkoniumchloride, BAC) was used in a randomized placebo-controlled clinical trial with subsequent analysis of viral loads by RT-qPCR and virus rescue in cell culture. Mechanistic analysis revealed that treatment with BAC and other antiseptic agents efficiently inactivated SARS-CoV-2 in vitro by primarily disrupting the viral envelope, without affecting viral RNA integrity. However, the clinical application only resulted in a mild reduction of viral loads in the oral cavity. These results indicate that gargling with mouthrinses comprising single antiseptic agents may play a minor role towards a potential reduction of transmission rates and thus, these findings are of utmost importance when considering alternative COVID-19 prevention strategies.

Antiseptic Materials on the Base of Polymer Interpenetrating Networks Microgels and Benzalkonium Chloride.

Polymer microgels, including those based on interpenetrating networks (IPNs), are currently vastly studied, and their practical applications are a matter of thriving research. In this work, we show the perspective for the use of polyelectrolyte IPN microgels either as scavengers or carriers of antiseptic substances. Here, we report that poly-N-isopropylacrylamide/polyacrylic acid IPN microgels can efficiently absorb the common bactericidal and virucidal compound benzalkonium chloride. The particles can form a stable aqueous colloidal suspension or be used as building blocks for soft free-standing films. Both materials showed antiseptic efficacy on the examples of Bacillus subtilis and S. aureus, which was approximately equal to the commercial antibiotic. Such polymer biocides can be used as liquid disinfectants, stable surface coatings, or parts of biomedical devices and can enhance the versatility of the possible practical applications of polymer microgels.

Antimicrobial effects of microwave plasma-activated water with skin protective effect for novel disinfectants in pandemic era.

Skin antiseptics have important implications for public health and medicine. Although conventional antiseptics have considerable antimicrobial activity, skin toxicity and the development of resistance are common problems. Plasma-treated water has sterilization and tissue-regenerative effects. Therefore, the aim of this study was to identify whether plasma-activated water (PAW) manufactured by our microwave plasma system can be used as a novel antiseptic solution for skin protection. PAW was produced by dissolving reactive nitrogen oxide gas using microwave plasma in deionized water. The antibacterial effects of PAW against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus cereus, and Salmonella typhimurium and effective concentrations were investigated by a solid agar plate assay. The factors mediating the effects of PAW were evaluated by the addition of reactive species scavengers. Cytotoxicity and cell viability assays were performed to examine the protective effect of PAW on normal skin cells. PAW exhibited excellent sterilization and no toxicity in normal skin cells. Experiments also confirmed the potential of PAW as a sanitizer for SARS-CoV-2. Our findings support the use of PAW as an effective skin disinfectant with good safety in the current situation of a global pandemic.

[The role of local antiseptics in the prevention of coronavirus infection during endonasal interventions on the lacrimal ducts]. / Rol' mestnykh antiseptikov v profilaktike koronavirusnoi infektsii pri endonazal'nykh vmeshatel'stvakh na sleznykh putyakh.

In connection with the pandemic of coronavirus infection, it is urgent to develop measures to prevent the intraoperative spread of coronavirus particles and infection of the operating room staff. OBJECTIVE: Generalization and analysis of available data concerning local antiseptic therapy for the prevention of coronavirus infection during endonasal interventions on the lacrimal tract. MATERIAL AND METHODS: The search for literature sources was carried out using MEDLINE search engines and the Russian Science Citation Index for queries with the keywords "COVID-19", "coronavirus infection", "antiseptics", "protocol for otorhinolaryngological operations", "dacryosurgical operations" and similar in various combinations. RESULTS: It has been shown that during endonasal operations on the lacrimal tract, the number of risk factors for infection increases, since these procedures are aerosol-generating, and contact occurs not only with the nasal mucosa, but also with the lacrimal fluid, in which the coronavirus is also replicated. The data on the effectiveness of various antiseptics are summarized, the analysis of the possibility of their use in preoperative preparation for endonasal interventions on the lacrimal tract from the point of view of efficacy and safety is carried out. Information is provided on the proprietary protocol for the use of antiseptics to prevent the spread of coronavirus infection during endonasal dacryocystorhinostomy. It is shown that the preventive use of local disinfectants reduces the number of viral particles on the nasal mucosa, which leads to a decrease in contamination of the surrounding space. Among the available and studied antiseptics, the most suitable is povidone-iodine, which can be used in concentrations up to 1.25% to irrigate the nasal mucosa before surgery with an exposure of 30-60 sec. When performing operations on the lacrimal pathways, it is also advisable to carry out antiseptic treatment of the conjunctival cavity with a 5% solution of povidone-iodine and rinse the lacrimal pathways before the operation with povidone-iodine in a concentration of 0.4%. CONCLUSION: To date, information has been obtained that makes it advisable to use antiseptics before performing endonasal aerosol-generating interventions, in particular endonasal dacryocystorhinostomies and recanalization of the tear ducts.

Efficacy of Hexetidine, Thymol and Hydrogen Peroxide-Containing Oral Antiseptics in Reducing Sars-Cov-2 Virus in the Oral Cavity: A Pilot Study.

BACKGROUND: Studies have demonstrated the role of sputum as a site of severe acute respiratory syndrome-coronavirus-2 (SARSCoV-2) transmission. However, there is limited literature on the virucidal efficacy of oral antiseptics against SARS-CoV-2 virus. This study investigated the virucidal efficacy of three oral-antiseptics compared to a placebo-control in the sputum of SARS-CoV-2 infected individuals. METHODOLOGY: A pilot study of adults with SARS-CoV-2 positive results, as determined by reverse transcription-polymerase chain reaction (RT-PCR) of <7 days. The oral antiseptics investigated were: Hexetidine (0.1% w/v); Thymol (0.063% w/v) and H2O2(1.5%) compared to de-mineralized sterile water (Placebo-control). The primary outcome measure was the proportion of negative RT-PCR results at 15-mins, 30-mins, 1-hour, 2-hours and 4-hours After Oral antiseptics Interventions (AOI) compared to the placebo-control. Statistical analysis was done using STATA 15.0 software with p-values of <0.05 considered statistically significant. RESULTS: Data from a total of 66 participants that were RT-PCR SARS-CoV-2 positive at baseline (0-min) was analysed. At 15-mins AOI, the highest proportion of negativation from sputum samples was observed in the Hexedine group, with 69.2% of the baseline PCR positive cases converting to negative compared to 46.7% in the placebo-control group. In addition, H2O2 demonstrated efficacy at 2-hours AOI compared to placebo-control (62.5% vs 37.5% respectively) and other oral-antiseptics. Across all time-points, the oral-antiseptic groups compared to the placebo-control group, there was no statistically significant difference in the proportion of sputum samples which converted to a negative status (p>0.05). CONCLUSION: The findings in this study suggest there was no significant difference in the proportion of participants who converted to a negative sputum status across the treatment groups at various time points. Future studies could compare the cycle threshold (ct) viral titre values of sputum samples to determine quantitative differences.

CONTEXTE: Des études ont démontré le rôle des expectorations comme un site de transmission du syndrome respiratoire aigu sévère-coronavirus- 2 (SRAS-CoV-2). Cependant, il existe peu de documentation sur l'efficacité virucide des antiseptiques oraux contre le virus du SRASCoV-2. Cette étude a examiné l'efficacité virucide de trois antiseptiques oraux par rapport à un contrôle placebo dans les expectorations de personnes infectées par le SRAS-CoV-2. MÉTHODOLOGIE: Une étude pilote menée auprès d'adultes dont les résultats sont positifs pour le SRAS-CoV-2, tels que déterminés par la réaction en chaîne de la polymérase par transcription inverse (RT-PCR) pendant 7 jours. Les antiseptiques oraux étudiés étaient : Hexetidine (0,1% p/v) ; Thymol (0,063% p/v) et H2O2 (1,5%) par rapport à l'eau stérile déminéralisée (Placebo-contrôle). Le principal critère d'évaluation était la proportion de résultats RT-PCR négatifs 15 minutes, 30 minutes, 1 heure, 2 heures et 4 heures après les interventions antiseptiques orales (AOI) par rapport au contrôle placebo. L'analyse statistique a été réalisée à l'aide du logiciel STATA 15.0, les valeurs p de <0,05 étant considérées comme statistiquement significatives. RÉSULTATS: Les données d'un total de 66 participants qui étaient positifs à la RT-PCR SARS-CoV-2 au départ (0 minute) ont été analysées. Au bout de 15 minutes, la plus forte proportion de négativation des échantillons d'expectoration a été observée dans le groupe Hexedine, 69,2 % des cas positifs au départ par PCR devenant négatifs, contre 46,7 % dans le groupe témoin placebo. En outre, l'H2O2 a démontré son efficacité à 2 heures après l'apparition de la maladie par rapport au groupe placebo (62,5 % contre 37,5 % respectivement) et aux autres antiseptiques oraux. Pour tous les points temporels, les groupes d'antiseptiques oraux comparés au groupe placebo n'ont pas présenté de différence statistiquement significative dans la proportion d'échantillons d'expectoration qui sont devenus négatifs (p>0,05). CONCLUSION: Les résultats de cette étude suggèrent qu'il n'y a pas de différence significative dans la proportion de participants qui sont passés à un statut négatif d'expectoration dans les groupes de traitement à différents moments. Les études futures pourraient comparer les valeurs du titre viral au seuil de cycle (ct) des échantillons d'expectoration afin de déterminer les différences quantitatives. MOTS CLÉS: SRAS-CoV-2, antiseptiques oraux, hexétidine, peroxyde d'hydrogène.

Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2.

Most public health measures to contain the COVID-19 pandemic are based on preventing the pathogen spread, and the use of oral antiseptics has been proposed as a strategy to reduce transmission risk. The aim of this manuscript is to test the efficacy of mouthwashes to reduce salivary viral load in vivo. This is a multi-centre, blinded, parallel-group, placebo-controlled randomised clinical trial that tests the effect of four mouthwashes (cetylpyridinium chloride, chlorhexidine, povidone-iodine and hydrogen peroxide) in SARS-CoV-2 salivary load measured by qPCR at baseline and 30, 60 and 120 min after the mouthrinse. A fifth group of patients used distilled water mouthrinse as a control. Eighty-four participants were recruited and divided into 12-15 per group. There were no statistically significant changes in salivary viral load after the use of the different mouthwashes. Although oral antiseptics have shown virucidal effects in vitro, our data show that salivary viral load in COVID-19 patients was not affected by the tested treatments. This could reflect that those mouthwashes are not effective in vivo, or that viral particles are not infective but viral RNA is still detected by PCR. Viral infectivity studies after the use of mouthwashes are therefore required. ( https://clinicaltrials.gov/ct2/show/NCT04707742 ; Identifier: NCT04707742).

Antiseptic 9-Meric Peptide with Potency against Carbapenem-Resistant Acinetobacter baumannii Infection.

Carbapenem-resistant A. baumannii (CRAB) infection can cause acute host reactions that lead to high-fatality sepsis, making it important to develop new therapeutic options. Previously, we developed a short 9-meric peptide, Pro9-3D, with significant antibacterial and cytotoxic effects. In this study, we attempted to produce safer peptide antibiotics against CRAB by reversing the parent sequence to generate R-Pro9-3 and R-Pro9-3D. Among the tested peptides, R-Pro9-3D had the most rapid and effective antibacterial activity against Gram-negative bacteria, particularly clinical CRAB isolates. Analyses of antimicrobial mechanisms based on lipopolysaccharide (LPS)-neutralization, LPS binding, and membrane depolarization, as well as SEM ultrastructural investigations, revealed that R-Pro9-3D binds strongly to LPS and impairs the membrane integrity of CRAB by effectively permeabilizing its outer membrane. R-Pro9-3D was also less cytotoxic and had better proteolytic stability than Pro9-3D and killed biofilm forming CRAB. As an LPS-neutralizing peptide, R-Pro9-3D effectively reduced LPS-induced pro-inflammatory cytokine levels in RAW 264.7 cells. The antiseptic abilities of R-Pro9-3D were also investigated using a mouse model of CRAB-induced sepsis, which revealed that R-Pro9-3D reduced multiple organ damage and attenuated systemic infection by acting as an antibacterial and immunosuppressive agent. Thus, R-Pro9-3D displays potential as a novel antiseptic peptide for treating Gram-negative CRAB infections.

Real-Time Analysis of Antiproliferative Effects of Mouthwashes Containing Alcohol, Sodium Fluoride, Cetylpyridinium Chloride, and Chlorhexidine In Vitro.

OBJECTIVES: In this study, the cytotoxic responses of six different over-the-counter mouthwashes on L929 cells were analyzed by two different techniques: the traditional colorimetric tetrazolium-based reduction assay (MTT) and the modern impedance-based real-time cell analysis (RTCA) system to investigate their biocompatibility in vitro. Thus, the investigation of the antiproliferative effects of the specified materials via different techniques is vital to reach this goal. MATERIALS AND METHODS: First, L929 mouse fibroblasts were exposed to the dilutions of mouthwashes for 2 minutes. After incubation, the tetrazolium reduction method was used to assess the metabolic viability of cells measured by colorimetric MTT assay and morphological inspection of cells was performed via phase-contrast microscopy. Furthermore, the effect of each mouthwash on the proliferation, morphology, and adhesion of L929 cells was monitored continuously by a noninvasive and label-free RTCA system for 140 h. RESULTS: Our data showed that all of the mouthwashes had varying cytotoxic effects on fibroblasts compared to the control group in MTT assay. In addition to that, RTCA technology has provided the growth kinetic profiles that can be used to analyze if the treatment is causing antimitotic or DNA-damaging effect on cells. Thus, analysis via this system can tell us the mechanism of toxicity behind the cell growth inhibition in vitro. Here, we found that only mouthwash 1 moderately maintained the viability of the L929 cells, yet displaying antimitotic effects and the other mouthwashes (mouthwash 2-mouthwash 6) showed toxicity via DNA-damaging effects. CONCLUSIONS: Of the six types of mouthwash tested, the most biocompatible result was obtained from a mouthwash containing alcohol (i.e., mouthwash 1). On the other hand, sodium fluoride- (NaF-) and cetylpyridinium chloride- (CPC-) containing mouthwash (i.e., mouthwash 2) showed the most cytotoxic effect.

Safety alert for hospital environments and health professional: chlorhexidine is ineffective for coronavirus.

An alarming fact was revealed by recent publications concerning disinfectants: chlorhexidine digluconate is ineffective for disinfecting surfaces contaminated by the new coronavirus. This is a finding that requires immediate disclosure since this substance is widely used for the disinfection of hands and forearms of surgeons and auxiliaries and in the antisepsis of patients in minimally invasive procedures commonly performed in hospital environments. The objective of this study is to compare the different disinfectants used for disinfection on several surfaces, in a review of worldwide works. Scientific studies were researched in the BVS (Virtual Health Library), PubMed, Medline, and ANVISA (National Health Surveillance Agency) databases. The following agents were studied: alcohol 62-71%, hydrogen peroxide 0.5%, sodium hypochlorite 0.1%, benzalkonium chloride 0.05-0.2%, povidone-iodine 10%, and chlorhexidine digluconate 0.02%, on metal, aluminum, wood, paper, glass, plastic, PVC, silicone, latex (gloves), disposable gowns, ceramic, and Teflon surfaces. Studies have shown that chlorhexidine digluconate is ineffective for inactivating some coronavirus subtypes, suggesting that it is also ineffective to the new coronavirus.

The Effect of Recombinant Human Interferon Alpha Nasal Drops to Prevent COVID-19 Pneumonia for Medical Staff in an Epidemic Area.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known as Coronavirus disease-2019 (COVID-19), has caused the sixth world's public health emergency. Healthcare staff, as the frontline population fighting the pandemic, are exposed to a high risk of infection. Therefore, developing a protective intervention for medical staff is of significant importance. OBJECTIVE: The aim of the study was to explore the effectiveness and safety of recombinant human interferon alpha (rhIFN-α) nasal drops for the prevention of coronavirus disease 2019 (COVID-19) through administering it to medical staff. METHODS: This was a prospective open-label clinical trial with parallel intervention assignment conducted on 2944 medical staff including both doctors and nurses from Taihe Hospital, Shiyan City, Hubei Province, China from January 21, 2020 to July 30, 2020. The participants were bifurcated into two groups of low risk and high risk groups according to the level of direct exposure to COVID-19 patients. The individuals of the low-risk group received rhIFN-α nasal drops for one month in addition to first level protection, and the high-risk group received a combination of rhIFN-α nasal drops coupled with thymosin-α1 with either second or third-level protection protocol. Moreover, the new-outset of COVID-19 pneumonia diagnosed by chest computed tomography (CT), after thirty days, was the primary outcome. The adverse reactions were recorded in all participants. RESULTS: 2415 of 2944 individuals belonged to the low-risk group, while 529 to the high-risk group. There was no COVID-19 pneumonia in either of the group after thirty days. The pulmonary CT scans were negative for COVID-19 pneumonia in both the groups with no new clinical symptoms. No serious adverse event was observed during the course of the intervention. CONCLUSION: The rhIFN-α nasal drops along with augmented safeguards based on standard physical isolation could effectively protect medical staff against COVID-19 pneumonia.

In vitro studies evaluating the efficacy of mouth rinses on Sars-Cov-2: A systematic review.

This systematic review aims to evaluate the evidence on the efficacy of mouth rinses on SARS-CoV-2 from in vitro studies. Five electronic databases were searched up to February 2021; no language or time restrictions were used. Two independent reviewers conducted both selection and data extraction processes. The toxicological data reliability assessment tool was used to evaluate the risk of bias. Starting from 239 articles, retrieved by the electronic search, only eight studies were included in our systematic review. Povidone Iodine (PVP-I) was effective in killing SARS-CoV-2, demonstrated higher virucidal activity than other commonly used active ingredients. Conflicting results were found about the effectiveness of Chlorhexidine (CHX) while hydrogen peroxide (H2O2) proved less effective than PVP-I. Other active ingredients, such as quaternary ammonium compounds and Ethanol (particularly when combined with essential oils), have also shown promising results in reducing viral load, with results comparable to PVP-I.

In vivo evaluation of the virucidal efficacy of chlorhexidine and povidone-iodine mouthwashes against salivary SARS-CoV-2. A randomized-controlled clinical trial.

OBJECTIVES: The oral cavity is potentially high-risk transmitter of COVID-19. Antimicrobial mouthrinses are used in many clinical preprocedural situations for decreasing the risk of cross-contamination in the dental setting. It is important to investigate the efficacy of mouthwash solutions against salivary SARS-CoV-2 in order to reduce the exposure of the dental team during dental procedures. AIMS: The aim of this in vivo study was to evaluate the efficacy of 2 preprocedural mouthrinses in the reduction of salivary SARS-CoV-2 viral load and to compare the results of the mouthwashes to a control group. MATERIALS AND METHODS: In this randomized-controlled clinical trial, studied group comprised laboratory-confirmed COVID-19 positive patients through nasopharyngeal swabs. Participants were divided into 3 groups. For 30 s, the control group mouthrinsed with distilled water, the Chlorhexidine group mouthrinsed with 0.2% Chlorhexidine and the Povidone-iodine group gargled with 1% Povidone-iodine. Saliva samples were collected before and 5 min after mouthwash. SARS-CoV-2 rRT-PCR was then performed for each sample. Evaluation of the efficacy was based on difference in cycle threshold (Ct) value. The analysis of data was carried out using GraphPad Prism version 5 for Windows. Kristal wullis and Paired t-test were used. A probability value of less than 0.05 was regarded as statistically significant. RESULTS: Sixty-one compliant participants (36 female and 25 male) with a mean age 45.3 ± 16.7 years-old were enrolled. A significant difference was noted between the delta Ct of distilled water wash and each of the 2 solutions Chlorhexidine 0.2% (P = .0024) and 1% Povidone-iodine (P = .012). No significant difference was found between the delta Ct of patients using Chlorhexidine 0.2% and 1% Povidone-iodine solutions (P = .24). A significant mean Ct value difference (P < .0001) between the paired samples in Chlorhexidine group (n = 27) and also in Povidone-iodine group (n = 25) (P < .0001) was found. In contrast, no significant difference (P = .566) existed before and after the experiment in the control group (n = 9). CONCLUSION: Chlorhexidine 0.2% and 1% Povidone-iodine oral solutions are effective preprocedural mouthwashes against salivary SARS-CoV-2 in dental treatments. Their use as a preventive strategy to reduce the spread of COVID-19 during dental practice should be considered.

Disinfectant effectiveness against SARS-CoV-2 and influenza viruses present on human skin: model-based evaluation.

OBJECTIVES: Disinfection effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on human skin remains unclear because of the hazards of viral exposure. An evaluation model, which has been previously generated using human skin obtained from forensic autopsy samples, accurately mimics in vivo skin conditions for evaluating the effectiveness of disinfection against the virus. Using this model, we evaluated disinfection effectiveness against viruses on human skin. METHODS: Ethanol (EA), isopropanol (IPA), chlorhexidine gluconate (CHG) and benzalkonium chloride (BAC) were used as target disinfectants. First, disinfectant effectiveness against SARS-CoV-2 and influenza A virus (IAV) was evaluated in vitro. Disinfectant effectiveness against SARS-CoV-2 and IAV on human skin was then evaluated by titrating viruses present on the skin after applying each disinfectant on the skin for 5-60 seconds. RESULTS: Both, SARS-CoV-2 and IAV on human skin were completely inactivated within 5 seconds by 40%-80% EA and 70% IPA (log reduction values (LRVs) were >4). However, SARS-CoV-2 and IAV were barely inactivated by 20% EA (LRVs were <1). In vitro evaluation showed that, compared with EA and IPA, CHG and BAC were significantly inferior in terms of disinfection effectiveness. Conversely, the disinfection effectiveness of CHG and BAC against SARS-CoV-2 was higher on human skin than in vitro, and increased with increases in their concentration and reaction time (LRVs of 0.2% CHG/0.05% BAC were >2, and LRVs of 1.0% CHG/0.2% BAC were >2.5). CONCLUSIONS: Proper hand hygiene practices using alcohol-based disinfectants such as EA/IPA effectively inactivate SARS-CoV-2 and IAV on human skin.

Lowering the transmission and spread of human coronavirus.

The emergence of the severe acute respiratory syndrome coronavirus 2 pandemic has created an unprecedented healthcare, social, and economic disaster. Wearing of masks and social distancing can significantly decrease transmission and spread, however, due to circumstances such as medical or dental intervention and personal choice these practices have not been universally adopted. Additional strategies are required to lessen transmission. Nasal rinses and mouthwashes, which directly impact the major sites of reception and transmission of human coronaviruses (HCoV), may provide an additional level of protection against the virus. Common over-the-counter nasal rinses and mouthwashes/gargles were tested for their ability to inactivate high concentrations of HCoV using contact times of 30 s, 1 min, and 2 min. Reductions in titers were measured by using the tissue culture infectious dose 50 (TCID50 ) assay. A 1% baby shampoo nasal rinse solution inactivated HCoV greater than 99.9% with a 2-min contact time. Several over-the-counter mouthwash/gargle products including Listerine and Listerine-like products were highly effective at inactivating infectious virus with greater than 99.9% even with a 30-s contact time. In the current manuscript we have demonstrated that several commonly available healthcare products have significant virucidal properties with respect to HCoV.

Oral antiseptics against coronavirus: in-vitro and clinical evidence.

Angiotensin converting enzyme 2 (ACE2) is the cellular receptor for SARS-CoV-2, so ACE2-expressing cells can act as target cells and are susceptible to infection. ACE2 receptors are highly expressed in the oral cavity, so this may be a potential high-risk route for SARS-CoV-2 infection. Furthermore, the virus can be detected in saliva, even before COVID-19 symptoms appear, with the consequent high risk of virus transmission in asymptomatic/presymptomatic patients. Reducing oral viral load could lead to a lower risk of transmission via salivary droplets or aerosols and therefore contribute to the control of the pandemic. Our aim was to evaluate the available evidence testing the in-vitro and in-vivo effects of oral antiseptics to inactivate or eradicate coronaviruses. The criteria used were those described in the PRISMA declaration for performing systematic reviews. An electronic search was conducted in Medline (via PubMed) and in Web of Sciences, using the MeSH terms: 'mouthwash' OR 'oral rinse' OR 'mouth rinse' OR 'povidone iodine' OR 'hydrogen peroxide' OR 'cetylpyridinium chloride' AND 'COVID-19' OR 'SARS-CoV-2' OR 'coronavirus' OR 'SARS' OR 'MERS'. The initial search strategy identified 619 articles on two electronic databases. Seventeen articles were included assessing the virucidal efficacy of oral antiseptics against coronaviruses. In conclusion, there is sufficient in-vitro evidence to support the use of antiseptics to potentially reduce the viral load of SARS-CoV-2 and other coronaviruses. However, in-vivo evidence for most oral antiseptics is limited. Randomized clinical trials with a control group are needed to demonstrate its clinical efficacy.

The European tiered approach for virucidal efficacy testing - rationale for rapidly selecting disinfectants against emerging and re-emerging viral diseases.

When facing an emerging virus outbreak such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a quick reaction time is key to control the spread. It takes time to develop antivirals and vaccines, and implement vaccination campaigns. Therefore, preventive measures such as rapid isolation of cases and identification and early quarantine of cases' close contacts-as well as masks, physical distancing, hand hygiene, surface disinfection and air control-are crucial to reduce the risk of transmission. In this context, disinfectants and antiseptics with proven efficacy against the outbreak virus should be used. However, biocidal formulations are quite complex and may include auxiliary substances such as surfactants or emollients in addition to active substances. In order to evaluate disinfectants' efficacy objectively, meaningful efficacy data are needed. Therefore, the European Committee for Standardisation technical committee 216 'Chemical disinfectants and antiseptics' Working Group 1 (medical area) has developed standards for efficacy testing. The European tiered approach grades the virucidal efficacy in three levels, with corresponding marker test viruses. In the case of SARS-CoV-2, disinfectants with proven activity against vaccinia virus, the marker virus for the European claim 'active against enveloped viruses', should be used to ensure effective hygiene procedures to control the pandemic.