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A Recommendation of PHTALOX ® Mouthwash for Preventing Infection and Progression of COVID-19

  • November 2020
DOI:10.31080/ASDS.2020.04.0991
Authors:
Paulo Santos at University of São Paulo
Paulo Santos
Bernardo da Fonseca Orcina at University of São Paulo
Bernardo da Fonseca Orcina
Lucas Marques da Costa Alves at São Paulo State University
Lucas Marques da Costa Alves
Rodrigo Cardoso Oliveira at University of São Paulo
Rodrigo Cardoso Oliveira
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Abstract

On a first trial, patients who tested positive for COVID-19 presented a rapid recovery after the use of PHTALOX® mouthwash protocol, with reduction of symptoms such as sore throats, mouth ulcers and cough. These patients became asymptomatic after a few days using the mouthwash. Other studies which are taking place in hospitals using the same protocol with patients diagnosed with COVID-19 also suggested the effectiveness of this mouthwash as an additional treatment. In this context, we urge scientists and governments to develop clinical trials to evaluate the effects of PHTALOX® mouthwash protocol in decreasing the SARS-COV-2 viral load, preventing the spread of the virus and the severity of COVID-19.
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Acta Scientific DENTAL SCIENCES (ISSN: 2581-4893)
Volume 4 Issue 12 December 2020
A Recommendation of PHTALOX® Mouthwash for Preventing Infection and
Progression of COVID-19
Paulo Sérgio da Silva Santos1*, Bernardo da Fonseca Orcina2, Lucas
Marques da Costa Alves3, Rodrigo Cardoso de Oliveira4, Mariana
Schutzer Ragghianti Zangrando5 and Fabiano Vieira Vilhena6
1Department of Surgery, Stomatology, Pathology and Radiology, Bauru School of
Dentistry of University of São Paulo, Brazil
2Postgraduate Student, Department of Surgery, Stomatology, Pathology and
Radiology, Bauru School of Dentistry of University of São Paulo, Brazil
3Physician of Hospital Infection Control Committee, Hospital Estadual de Bauru,
Brazil
4Department of Biological Sciences, Bauru School of Dentistry of University of São
Paulo, Brazil
5Department of Prosthesis and Periodontology, Bauru School of Dentistry of
University of São Paulo, Brazil
6Oral Health and Techonologies, Brazil
*Corresponding Author: Paulo Sérgio da Silva Santos, Department of Surgery,
Stomatology, Pathology and Radiology, Bauru School of Dentistry of University of
São Paulo, Brazil
Short Communcation
Received: November 13, 2020
Published: November 27, 2020
© All rights are reserved by Paulo Sérgio da
Silva Santos., et al.
           -
mission process of SARS - CoV-2. This happens due to the spread
of small droplets which makes the oral and oropharynx mucosa
easy targets for the virus [1]. Therefore, the oral cavity is directly
associated with the evolutionary process of SARS-CoV-2 in the in-
halation of environmental particles in the air and in the sputum,
because it can also be transmitted through saliva [2].
This relation takes place due to the presence of Angiotensin-2
Enzyme on the oral mucosa, especially on the tongue and salivary
glands [3]. From this interaction, it is clear the viral load is related
to the severity of COVID-19. This evidence showed that an early
intervention to decrease the viral load intensity is necessary. The
mouth, nose and throat wash can eradicate the viral particles, re-
ducing the viral load in patients exposed to the virus [4].
The use of mouthwashes for gargling can help prevent and treat
respiratory infections in the upper and lower tracts [5]. Techno-
logical rinses available on the market with antimicrobial action,
may have antiviral action [1]. In this sense, Meister., et al. [6] dem-
onstrated in the laboratory the capacity of some antiseptics in com-
bating SARS-CoV-2. Unfortunately, some of the technologies and
some types of mouthwash already tested have had no effect against
the new virus in clinical trials [7].
Functional dye is an archetypal of so-called photodynamic anti-
microbials, in which the combination of a sensitizing drug and vis-
ible light causes selective destruction of viruses, bacteria and other
pathogens when applied to consumers or medical products [8].
   ®, a bioactive functional
dye, promotes a self-activation and continuous production of re-
active oxygen in the presence of molecular oxygen. PHTALOX®
mouthwash has shown an antimicrobial activity associated with
the regeneration of soft tissues and reduction in gingival bleed-
ing [9]. This technology has already been approved by Brazilian
National Agency of Sanitary Monitoring due to its antiviral effect
against SARS-COV-2.
Citation: Paulo Sérgio da Silva Santos., et al. “A Recommendation of PHTALOX® Mouthwash for Preventing Infection and Progression of COVID-19”. Acta
Scientific Dental Sciences 4.12 (2020): 111-112.
    -
sented a rapid recovery after the use of PHTALOX® mouthwash
protocol, with reduction of symptoms such as sore throats, mouth
ulcers and cough. These patients became asymptomatic after a few
days using the mouthwash. Other studies which are taking place
in hospitals using the same protocol with patients diagnosed with
COVID-19 also suggested the effectiveness of this mouthwash as an
additional treatment. In this context, we urge scientists and gov-
ernments to develop clinical trials to evaluate the effects of PHTAL-
OX® mouthwash protocol in decreasing the SARS-COV-2 viral load,
preventing the spread of the virus and the severity of COVID-19.
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Against Severe Acute Respiratory Syndrome Coronavirus 2”.
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 
Viruses, Basel. 11.10 (2019): 955.
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toxicity: in vitro Study”. Journal of Dental Research 99 (SpecIss
A): abstract number, 0839, 2020 IADR/AADR/CADR General
Session (Washington, D.C., USA) (2020).
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A Recommendation of PHTALOX® Mouthwash for Preventing Infection and Progression of COVID-19
Citation: Paulo Sérgio da Silva Santos., et al. “A Recommendation of PHTALOX® Mouthwash for Preventing Infection and Progression of COVID-19”. Acta
Scientific Dental Sciences 4.12 (2020): 111-112.
... It is clear that washing hands, wearing masks, and social distancing are effective measures to ght the pandemic [6,7]. In addition, considering that COVID-19 contagion, evolution and dissemination have strong associations with the mouth [8,9], gargling with antiseptic mouthwashes has been suggested as an extra preventive measure against COVID-19 [7,8,10,11,12,13,14,15,16,17]. However, in the cases of diseases, such as in uenza, which are caused by SARS-type viruses, virucidal activity is essential for such measures to be effective [8]. ...
... The virus enters the cell through the connection between the virus spike and the ACE2 receptor, which can be abundantly found in the salivary glands. Therefore, some recommendations have suggested the importance of controlling and reducing the viral load in the oral and oropharynx cavity by using an antiviral mouthwash [8, 9,10,11,13,14,33]. ...
... This hypothesis is con rmed by the effect of noncytotoxic, low concentrations (1.0 mg/mL up to 0.156 mg/mL) in reducing in the active viral load after proliferation in Vero CCL-81 cells as observed by RT-PCR and by the HTCI immuno uorescence-based assay, which showed the rapid cell nucleus localization based on DAPI staining (Fig. 1). Thus, the high effectiveness of APD can probably be explained by a dual mode of action, namely, by blocking the HR1 region and by promoting oxidative damage leading to inactivation of the virus, thus making APD a very promising molecule to reduce the SARS-CoV-2 viral load [13]. Thus, it can be suggested that a mouthwash containing APD can help improve the response of the organism to COVID-19 infection. ...
Beneficial effects of a mouthwash containing an antiviral phthalocyanine derivative on the length of hospital stay for COVID-19: Randomised trial
Preprint
Full-text available
  • Mar 2021
Background: The risk of contamination and dissemination by SARS-CoV-2 has a strong link with nasal, oral and pharyngeal cavities. Recently, our research group observed the promising performance of an anionic phthalocyanine derivative (APD) used in a mouthwash protocol without photoexcitation; this protocol improved the general clinical condition of patients infected with SARS-CoV-2. Methods: The present two-arm study evaluated in vitro the antiviral activity and cytotoxicity of APD. Additionally, a triple-blind randomized controlled trial was conducted with 41 hospitalized patients who tested positive for COVID-19. All the included patients received World Health Organization standard care hospital treatment (non-intensive care) plus active mouthwash (experimental group AM/n=20) or nonactive mouthwash (control group NAM/n=21). The adjunct mouthwash intervention protocol used in both groups consisted one-minute gargling/rinsing / 5 times/day until hospital discharge. Groups were compared considering age, number of comorbidities, duration of symptoms prior admission and length of hospital stay (LOS). The associations between group and sex, age range, presence of comorbidities, admission to Intensive care unit (ICU) and death were also evaluated. Results: The in vitro evaluation demonstrated that APD compound was highly effective for reduction of SARS-CoV-2 viral load in the 1.0 mg/mL (99.96%) to 0.125 mg/mL (92.65%) range without causing cytotoxicity. Regarding the clinical trial, the median LOS of the AM group was significantly shortened (4 days) compared with that of the NAM group (7 days) (p=0.0314). Additionally, gargling/rinsing with APD was very helpful in reducing the severity of symptoms (no ICU care was needed) compared to not gargling/rinsing with APD (28.6% of the patients in the NAM group needed ICU care, and 50% of this ICU subgroup passed way, p=0.0207). Conclusions: This study indicated that the mechanical action of the protocol involving mouthwash containing a compound with antiviral effects against SARS-CoV-2 may reduce the symptoms of the patients and the spread of infection. The use of APD in a mouthwash as an adjuvant the hospital COVID-19 treatment presented no contraindication and reduced the hospital stay period. Trial Registration: The clinical study was registered at REBEC - Brazilian Clinical Trial Register (RBR-58ftdj) in 10/28/2020.
View
... Populations pre-experienced in viral epidemics adopted now-proven preventive measures with risk reduction and benefits, such as social distancing, hand hygiene, wearing masks, and gargling/rinsing with antiseptic solutions [24], [25], [26], [27]. Since saliva has been an important source of virus transmission during the pandemic, protective measures such as the use of antiseptic gargles against SARS-CoV-2 were adopted and recommended by several countries and organizations [5], [10], [26], [27], [28]. Some studies have shown that the use of a mouthwash containing APD can reduce the viral load of SARS-CoV-2, acting as a therapeutic aid in reducing the severity and risk of COVID-19 transmission [8], [9], [28], [29], [30]. ...
... Since saliva has been an important source of virus transmission during the pandemic, protective measures such as the use of antiseptic gargles against SARS-CoV-2 were adopted and recommended by several countries and organizations [5], [10], [26], [27], [28]. Some studies have shown that the use of a mouthwash containing APD can reduce the viral load of SARS-CoV-2, acting as a therapeutic aid in reducing the severity and risk of COVID-19 transmission [8], [9], [28], [29], [30]. These data corroborate the findings of the present study. ...
Population-based virucidal phthalocyanine gargling/rinsing protocol to reduce the risk of coronavirus disease-2019: a community trial
Article
Full-text available
  • Dec 2022
Aim: In this community trial, the objective was to evaluate the incidence of coronavirus disease-2019 (COVID-19) cases in two similar communities in three distinct phases: 1 (before the intervention), 2 (during the intervention), and 3 (after the intervention). Methods: The test community received the oral antiseptic intervention (experimental), while the control community did not. The official information agency (“Statewise System for Data Analysis”) provided the number of confirmed COVID-19 cases. Data were analyzed according to the three phases per epidemiological week (epi) using the R Core Team (2021) program. The relative risk and 95% confidence intervals between the cumulative incidence values of the test and control communities were calculated for each period. In the test community, a total of 995 residents over 10 years of age received two bottles containing 600 ml of mouthwash containing antiviral phthalocyanine derivative (APD). The participants were asked to gargle/rinse with of 5 mL of the mouthwash containing ADP 3 to 5 times a day, for 1 min, until the bottles were empty. Results: In phases 1 and 3, the disease risk between the two communities did not differ significantly (p>0.05), while in phase 2, the disease risk was 54% lower in the test community than in the control community. Conclusion: The use of the APD mouthwash protocol seems to reduce the COVID-19 incidence at the population level, and further studies are and needed to confirm its protective effect under more precisely controlled conditions.
View
... The virus enters the cell through the connection between the virus spike and the ACE2 receptor, which can be abundantly found in the salivary glands. Therefore, some recommendations have suggested the importance of controlling and reducing the viral load in the oral and oropharynx cavity by using an antiviral mouthwash [8][9][10][11]13,14,35 . Several studies have demonstrated the antimicrobial (antiviral) and anti-inflammatory properties of phthalocyanines 20-23 after photoexcitation. ...
... This hypothesis is confirmed by the effect of noncytotoxic, low concentrations (1.0 mg/mL up to 0.0156 mg/mL) in reducing in the active viral load after proliferation in Vero CCL-81 cells as observed by RT-PCR and by the HTCI immunofluorescence-based assay, which showed the rapid cell nucleus localization based on DAPI staining (Fig. 1). Thus, the high effectiveness of APD can probably be explained by a dual mode of action, namely, by blocking the HR1 region and by promoting oxidative damage leading to inactivation of the virus, thus making APD a very promising molecule to reduce the SARS-CoV-2 viral load 13 . Thus, it can be suggested that a mouthwash containing APD can help improve the response of the organism to COVID-19 infection. ...
Beneficial effects of a mouthwash containing an antiviral phthalocyanine derivative on the length of hospital stay for COVID-19: randomised trial
Article
Full-text available
  • Oct 2021
The risk of contamination and dissemination by SARS-CoV-2 has a strong link with nasal, oral and pharyngeal cavities. Recently, our research group observed the promising performance of an anionic phthalocyanine derivative (APD) used in a mouthwash protocol without photoexcitation; this protocol improved the general clinical condition of patients infected with SARS-CoV-2. The present two-arm study evaluated in vitro the antiviral activity and cytotoxicity of APD. Additionally, a triple-blind randomized controlled trial was conducted with 41 hospitalized patients who tested positive for COVID-19. All the included patients received World Health Organization standard care hospital treatment (non-intensive care) plus active mouthwash (experimental group AM/n = 20) or nonactive mouthwash (control group NAM/n = 21). The adjunct mouthwash intervention protocol used in both groups consisted one-minute gargling/rinsing / 5 times/day until hospital discharge. Groups were compared considering age, number of comorbidities, duration of symptoms prior admission and length of hospital stay (LOS). The associations between group and sex, age range, presence of comorbidities, admission to Intensive care unit (ICU) and death were also evaluated. The in vitro evaluation demonstrated that APD compound was highly effective for reduction of SARS-CoV-2 viral load in the 1.0 mg/mL (99.96%) to 0.125 mg/mL (92.65%) range without causing cytotoxicity. Regarding the clinical trial, the median LOS of the AM group was significantly shortened (4 days) compared with that of the NAM group (7 days) (p = 0.0314). Additionally, gargling/rinsing with APD was very helpful in reducing the severity of symptoms (no ICU care was needed) compared to not gargling/rinsing with APD (28.6% of the patients in the NAM group needed ICU care, and 50% of this ICU subgroup passed way, p = 0.0207). This study indicated that the mechanical action of the protocol involving mouthwash containing a compound with antiviral effects against SARS-CoV-2 may reduce the symptoms of the patients and the spread of infection. The use of APD in a mouthwash as an OPEN
View
... [10][11][12] Recent studies have demonstrated promising clinical and laboratory findings such as intraoral reduction of viral load of SARS-CoV-2, virucidal efficacy against salivary SARS-CoV-2, anti-inflammatory effectivity, and possible benefit for COVID-19 with evidence-based approach. [10][11][12][13][14][15][16] In contrast, the daily use of certain oral hygiene virucidal products could cause adverse in patients exposed to long-term povidone iodine (thyroid problems), and chlorhexidine (alteration in taste, staining of teeth, and calculus formation). [17][18] In the pandemic context, few oral antimicrobial products have been investigated for the maintenance of oral hygiene and as a measure to prevent COVID-19, especially those containing chlorhexidine, hydrogen peroxide, povidone-iodine, and, more recently, an antimicrobial phthalocyanine derivative (APD). ...
Use of mouthwash and dentifrice containing an antimicrobial phthalocyanine derivative for the reduction of clinical symptoms of COVID-19: A randomized triple-blind clinical trial
Article
Purpose: This clinical trial aimed to evaluate the use of mouthwash and dentifrice containing an antimicrobial phthalocyanine derivative (APD) to reduce the clinical symptoms in patients with COVID-19. Methods: This randomized, triple-blind clinical trial enrolled 134 patients aged 18 years or older who underwent COVID-19 testing through the use of nasopharyngeal swab RT-qPCR in a reference center for the diagnosis of COVID-19, had no clinical contraindications to mouthwash and gargle, and had access to cell phones with communication applications. According to the use of a mouthwash and dentifrice containing antimicrobial phthalocyanine derivatives (APD), patients were randomly assigned (1:1) to the APD or non-APD (control) group. All participants were instructed to floss twice a day, brush teeth for 2 min three times a day, and gargle/rinse (5 mL) for 1 min/three times a day for 7 days. An online questionnaire was sent to collect data on the clinical symptoms of COVID-19 three times: T0 (baseline before using the oral hygiene products), T3 (three days after), and T7 (7 days after). The investigators, patients, and outcome assessors were blinded to group assignment. The Mann-Whitney, Chi-Square, Fisher's exact, and Cochran's tests were used according to the nature of the variables studied, with the level of significance set at P < 0.05. Results: No statistically significant difference was found in the prevalence of symptoms between groups at baseline. A statistically significant reduction in clinical symptoms was found in the control group (fatigue, shortness of breath, hoarse voice, sore throat, nasal congestion, and chest pain) and APD group (cough, fatigue, shortness of breath, hyposmia/anosmia, dysgeusia, hoarse voice, sore throat, nasal congestion, chest pain, diarrhea, and irritability/confusion) during the follow-up period. There were statistically significant differences, with a higher prevalence of symptoms in the control group at T3 and T7. Dysgeusia, sore throat, and irritability/confusion were less prevalent in the APD group at T3, and shortness of breath, hyposmia/anosmia, dysgeusia, hoarse voice, sore throat, diarrhea, and irritability/confusion were more prevalent in the control group at T7. Conclusions: Based on this methodology, the results demonstrated that the regular use of mouthwash and dentifrice-containing APD had a positive impact on the clinical symptoms, as reported by patients with COVID-19.
View
... Letter to the editor Dear editor, The role of the oral cavity in the genesis, progression, and dissemination of COVID-19 has been revealed by breakthroughs in SARS-CoV-2 research [1]. As a result, in 2020, our research group presented a recommendation for PHTALOX ® mouthwash for reducing COVID-19 infection and progression [2]. On this occasion, we revealed the first clinical findings in patients with COVID-19 who utilized PHTALOX ® , an antiviral phthalocyanine derivative (APD), in a gargle/rinse mouthwash protocol [3]. ...
View
... Letter to the editor Dear editor, The role of the oral cavity in the genesis, progression, and dissemination of COVID-19 has been revealed by breakthroughs in SARS-CoV-2 research [1]. As a result, in 2020, our research group presented a recommendation for PHTALOX ® mouthwash for reducing COVID-19 infection and progression [2]. On this occasion, we revealed the first clinical findings in patients with COVID-19 who utilized PHTALOX ® , an antiviral phthalocyanine derivative (APD), in a gargle/rinse mouthwash protocol [3]. ...
A recommendation of PHTALOX® for preventing infection and progression of COVID-19: a 1-year summarized update of scientific approaches
Article
Full-text available
  • Jan 2022
As previously indicated, we emphasize how important it is for scientists and governments to evaluate the impact of APD policies in hospitals and the general community on SARS-COV-2 VL, hence reducing the virus's transmission and severity of COVID-19.
View
... Vaccines and other drugs have been developed and delivered to fight SARS-CoV-2. Successful measures to prevent infection with the virus, such as wearing masks, attention to hygiene and social distancing in conjunction with antiviral mouthwashes, have been recommended to the population for daily use during the COVID-19 pandemic [1], [2]. Scientific evidence has shown the presence of viruses in oral structures and indications for antiviral oral antiseptics have been investigated. ...
The use of antiviral Phthalocyanine mouthwash as a preventive measure against COVID-19
Article
Full-text available
  • Jul 2021
Vaccines and other drugs have been developed and de- livered to fight SARS-CoV-2. Successful measures to prevent infection with the virus, such as wearing masks, attention to hygiene and social distancing in conjunction with antiviral mouthwashes, have been recommended to the population for daily use during the COVID-19 pandemic.
View
Population-based virucidal phthalocyanine gargle/rinse protocol to reduce the risk of coronavirus disease-2019: a community trial
Preprint
Full-text available
  • Nov 2021
Purpose: In this community trial, the objective was to evaluate the incidence of coronavirus disease-2019 (COVID-19) cases in two similar communities in three distinct phases: phase 1 (before the intervention), 2 (during the intervention), and 3 (after the intervention). Methods: The test community received the oral antiseptic intervention (experimental), while the control community did not. The official information agency provided the number of confirmed COVID-19 cases. Data were analyzed according to the three phases per epidemiological week (epi) using the R Core Team (2021) program. The relative risk and 95% confidence intervals between the cumulative incidence values of the test and control communities were calculated for each period. In the test community, a total of 995 residents, over 10 years of age, received two bottles containing 600 ml of mouthwash with antiviral phthalocyanine derivative (APD). The participants were asked to gargle/rinse with of 5 mL of the mouthwash with ADP 3 to 5 times a day, for 1 min, until the end of the bottles. Results: In phases 1 and 3, disease risk between the two communities did not differ significantly (p> 0.05), while in phase 2, disease risk was 54% lower in the test community than in the control community. Conclusion: The use of the APD mouthwash protocol seems to reduce the COVID-19 incidence at the population level, and further studies are needed to confirm its protective effect in different contexts.
View
Erratum to: Virucidal Efficacy of Different Oral Rinses Against Severe Acute Respiratory Syndrome Coronavirus 2
Article
Full-text available
The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic creates a significant threat to global health. Recent studies suggested the significance of throat and salivary glands as major sites of virus replication and transmission during early coronavirus disease 2019, thus advocating application of oral antiseptics. However, the antiviral efficacy of oral rinsing solutions against SARS-CoV-2 has not been examined. Here, we evaluated the virucidal activity of different available oral rinses against SARS-CoV-2 under conditions mimicking nasopharyngeal secretions. Several formulations with significant SARS-CoV-2 inactivating properties in vitro support the idea that oral rinsing might reduce the viral load of saliva and could thus lower the transmission of SARS-CoV-2. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
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A prospective clinical pilot study on the effects of a hydrogen peroxide mouthrinse on the intraoral viral load of SARS-CoV-2
Article
Full-text available
  • Sep 2020
Objectives: SARS-CoV-2 is mainly transmitted by inhalation of droplets and aerosols. This puts healthcare professionals from specialties with close patient contact at high risk of nosocomial infections with SARS-CoV-2. In this context, preprocedural mouthrinses with hydrogen peroxide have been recommended before conducting intraoral procedures. Therefore, the aim of this study was to investigate the effects of a 1% hydrogen peroxide mouthrinse on reducing the intraoral SARS-CoV-2 load. Methods: Twelve out of 98 initially screened hospitalized SARS-CoV-2-positive patients were included in this study. Intraoral viral load was determined by RT-PCR at baseline, whereupon patients had to gargle mouth and throat with 20 mL of 1% hydrogen peroxide for 30 s. After 30 min, a second examination of intraoral viral load was performed by RT-PCR. Furthermore, virus culture was performed for specimens exhibiting viral load of at least 103 RNA copies/mL at baseline. Results: Ten out of the 12 initially included SARS-CoV-2-positive patients completed the study. The hydrogen peroxide mouthrinse led to no significant reduction of intraoral viral load. Replicating virus could only be determined from one baseline specimen. Conclusion: A 1% hydrogen peroxide mouthrinse does not reduce the intraoral viral load in SARS-CoV-2-positive subjects. However, virus culture did not yield any indication on the effects of the mouthrinse on the infectivity of the detected RNA copies. Clinical relevance: The recommendation of a preprocedural mouthrinse with hydrogen peroxide before intraoral procedures is questionable and thus should not be supported any longer, but strict infection prevention regimens are of paramount importance. Trial registration: German Clinical Trials Register (ref. DRKS00022484).
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High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa
Article
Full-text available
  • Dec 2020
It has been reported that ACE2 is the main host cell receptor of 2019-nCoV and plays a crucial role in the entry of virus into the cell to cause the final infection. To investigate the potential route of 2019-nCov infection on the mucosa of oral cavity, bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas (TCGA) and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression (FANTOM5 CAGE) dataset were collected. RNA-seq profiling data of 13 organ types with para-carcinoma normal tissues from TCGA and 14 organ types with normal tissues from FANTOM5 CAGE were analyzed in order to explore and validate the expression of ACE2 on the mucosa of oral cavity. Further, single-cell transcriptomes from an independent data generated in-house were used to identify and confirm the ACE2-expressing cell composition and proportion in oral cavity. The results demonstrated that the ACE2 expressed on the mucosa of oral cavity. Interestingly, this receptor was highly enriched in epithelial cells of tongue. Preliminarily, those findings have explained the basic mechanism that the oral cavity is a potentially high risk for 2019-nCoV infectious susceptibility and provided a piece of evidence for the future prevention strategy in dental clinical practice as well as daily life.
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Nanoparticles as Anti-Microbial, Anti-Inflammatory, and Remineralizing Agents in Oral Care Cosmetics: A Review of the Current Situation
Article
Full-text available
  • Jan 2020
Many investigations have pointed out widespread use of medical nanosystems in various domains of dentistry such as prevention, prognosis, care, tissue regeneration, and restoration. The progress of oral medicine nanosystems for individual prophylaxis is significant for ensuring bacterial symbiosis and high-quality oral health. Nanomaterials in oral cosmetics are used in toothpaste and other mouthwash to improve oral healthcare performance. These processes cover nanoparticles and nanoparticle-based materials, especially domains of application related to biofilm management in cariology and periodontology. Likewise, nanoparticles have been integrated in diverse cosmetic produces for the care of enamel remineralization and dental hypersensitivity. This review summarizes the indications and applications of several widely employed nanoparticles in oral cosmetics, and describes the potential clinical implementation of nanoparticles as anti-microbial, anti-inflammatory, and remineralizing agents in the prevention of dental caries, hypersensitivity, and periodontitis.
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Ultrastructural Aspects of Photodynamic Inactivation of Highly Pathogenic Avian H5N8 Influenza Virus
Article
Full-text available
  • Oct 2019
Ultrastructural studies revealing morphological differences between intact and photodynamically inactivated virions can point to inactivation mechanisms and molecular targets. Using influenza as a model system, we show that photodynamic virus inactivation is possible without total virion destruction. Indeed, irradiation with a relatively low concentration of the photosensitizer (octacationic octakis(cholinyl) zinc phthalocyanine) inactivated viral particles (the virus titer was determined in Madin Darby Canine Kidney (MDCK) cells) but did not destroy them. Transmission electron microscopy (TEM) revealed that virion membranes kept structural integrity but lost their surface glycoproteins. Such structures are known as “bald” virions, which were first described as a result of protease treatment. At a higher photosensitizer concentration, the lipid membranes were also destroyed. Therefore, photodynamic inactivation of influenza virus initially results from surface protein removal, followed by complete virion destruction. This study suggests that photodynamic treatment can be used to manufacture “bald” virions for experimental purposes. Photodynamic inactivation is based on the production of reactive oxygen species which attack and destroy biomolecules. Thus, the results of this study can potentially apply to other enveloped viruses and sources of singlet oxygen. Keywords: influenza; H5N8; photodynamic inactivation; photosensitizer; transmission electron microscopy
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Use of antimicrobial mouthwashes (gargling) and nasal sprays by healthcare workers to protect them when treating patients with suspected or confirmed COVID-19 infection
Article
  • Sep 2020
Background: COVID-19 infection poses a serious risk to patients and - due to its contagious nature - to those healthcare workers (HCWs) treating them. If the mouth and nose of HCWs are irrigated with antimicrobial solutions, this may help reduce the risk of active infection being passed from infected patients to HCWs through droplet transmission or direct contact. However, the use of such antimicrobial solutions may be associated with harms related to the toxicity of the solutions themselves, or alterations in the natural microbial flora of the mouth or nose. Understanding these possible side effects is particularly important when the HCWs are otherwise fit and well. Objectives: To assess the benefits and harms of antimicrobial mouthwashes and nasal sprays used by healthcare workers (HCWs) to protect themselves when treating patients with suspected or confirmed COVID-19 infection. Search methods: Information Specialists from Cochrane ENT and Cochrane Oral Health searched the Central Register of Controlled Trials (CENTRAL 2020, Issue 6); Ovid MEDLINE; Ovid Embase and additional sources for published and unpublished trials. The date of the search was 1 June 2020. SELECTION CRITERIA: This is a question that urgently requires evidence, however at the present time we did not anticipate finding many completed randomised controlled trials (RCTs). We therefore planned to include the following types of studies: RCTs; quasi-RCTs; non-randomised controlled trials; prospective cohort studies; retrospective cohort studies; cross-sectional studies; controlled before-and-after studies. We set no minimum duration for the studies. We sought studies comparing any antimicrobial mouthwash and/or nasal spray (alone or in combination) at any concentration, delivered to HCWs, with or without the same intervention being given to the patients with COVID-19. Data collection and analysis: We used standard Cochrane methodological procedures. Our primary outcomes were: 1) incidence of symptomatic or test-positive COVID-19 infection in HCWs; 2) significant adverse event: anosmia (or disturbance in sense of smell). Our secondary outcomes were: 3) viral content of aerosol, when present (if intervention administered to patients); 4) other adverse events: changes in microbiome in oral cavity, nasal cavity, oro- or nasopharynx; 5) other adverse events: allergy, irritation/burning of nasal, oral or oropharyngeal mucosa (e.g. erosions, ulcers, bleeding), long-term staining of mucous membranes or teeth, accidental ingestion. We planned to use GRADE to assess the certainty of the evidence for each outcome. Main results: We found no completed studies to include in this review. We identified three ongoing studies (including two RCTs), which aim to enrol nearly 700 participants. The interventions included in these trials are povidone iodine, nitric oxide and GLS-1200 oral spray (the constituent of this spray is unclear and may not be antimicrobial in nature). AUTHORS' CONCLUSIONS: We identified no studies for inclusion in this review. This is not surprising given the relatively recent emergence of COVID-19 infection. It is promising that the question posed in this review is being addressed by two RCTs and a non-randomised study. We are concerned that only one of the ongoing studies specifically states that it will evaluate adverse events and it is not clear if this will include changes in the sense of smell or to the oral and nasal microbiota, and any consequences thereof. Very few interventions have large and dramatic effect sizes. If a positive treatment effect is demonstrated when studies are available for inclusion in this review, it may not be large. In these circumstances in particular, where those receiving the intervention are otherwise fit and well, it may be a challenge to weigh up the benefits against the harms if the latter are of uncertain frequency and severity.
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Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study
Article
Background Coronavirus disease 2019 (COVID-19) causes severe community and nosocomial outbreaks. Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses. Methods We did a cohort study at two hospitals in Hong Kong. We included patients with laboratory-confirmed COVID-19. We obtained samples of blood, urine, posterior oropharyngeal saliva, and rectal swabs. Serial viral load was ascertained by reverse transcriptase quantitative PCR (RT-qPCR). Antibody levels against the SARS-CoV-2 internal nucleoprotein (NP) and surface spike protein receptor binding domain (RBD) were measured using EIA. Whole-genome sequencing was done to identify possible mutations arising during infection. Findings Between Jan 22, 2020, and Feb 12, 2020, 30 patients were screened for inclusion, of whom 23 were included (median age 62 years [range 37–75]). The median viral load in posterior oropharyngeal saliva or other respiratory specimens at presentation was 5·2 log10 copies per mL (IQR 4·1–7·0). Salivary viral load was highest during the first week after symptom onset and subsequently declined with time (slope −0·15, 95% CI −0·19 to −0·11; R²=0·71). In one patient, viral RNA was detected 25 days after symptom onset. Older age was correlated with higher viral load (Spearman's ρ=0·48, 95% CI 0·074–0·75; p=0·020). For 16 patients with serum samples available 14 days or longer after symptom onset, rates of seropositivity were 94% for anti-NP IgG (n=15), 88% for anti-NP IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15). Anti-SARS-CoV-2-NP or anti-SARS-CoV-2-RBD IgG levels correlated with virus neutralisation titre (R²>0·9). No genome mutations were detected on serial samples. Interpretation Posterior oropharyngeal saliva samples are a non-invasive specimen more acceptable to patients and health-care workers. Unlike severe acute respiratory syndrome, patients with COVID-19 had the highest viral load near presentation, which could account for the fast-spreading nature of this epidemic. This finding emphasises the importance of stringent infection control and early use of potent antiviral agents, alone or in combination, for high-risk individuals. Serological assay can complement RT-qPCR for diagnosis. Funding Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service, and Sanming Project of Medicine.
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Prevention of Respiratory Infections by Povidone-Iodine Gargle
Article
  • Feb 2002
Bacterial attachment to host cells is the initial step in the pathogenesis of infection. Our studies and those of others also showed that there is a significant correlation between the attachment of bacteria to human pharyngeal epithelial cells and the occurrence of respiratory tract infections. We identified the receptor on human pharyngeal epithelial cells which mediate binding of Moraxella catarrhalis and Haemophilus influenzae. In an attempt to prevent occurrence of infections, the effects of povidone-iodine gargling on the incidence of respiratory infections were investigated. The subjects included a total of 23 adult patients, both males and females, with chronic respiratory diseases showing repeated infections. Patients were asked to gargle more than 4 times/day with povidone-iodine gargle over extended periods of time, i.e. from several months up to over 2 years. The incidence of episodes of acute exacerbation of chronic respiratory infections decreased significantly when compared with that before use of povidone-iodine gargle. Episodes of infections with Pseudomonas aeruginosa, Staphylococcus aureus (including MRSA) and H. influenzae were reduced by about 50%. Results of this study suggest that povidone-iodine gargle is effective in providing a significant reduction in the incidence of acute exacerbations of chronic respiratory disease. We assume that the colonized bacteria were destroyed and thus infection could not occur. Therefore, povidone-iodine gargle may be used in these patients as a preventive therapy. Further studies are needed to find out the mechanism of action of this drug for the prevention of respiratory tract infections.
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PHTALOX® Antimicrobial Action and Cytotoxicity: in vitro Study
  • Jan 2020
  • J DENT RES
Teodoro G., et al. "PHTALOX® Antimicrobial Action and Cytotoxicity: in vitro Study". Journal of Dental Research 99 (SpecIss A): abstract number, 0839, 2020 IADR/AADR/CADR General Session (Washington, D.C., USA) (2020).