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1.
Int J Mol Sci ; 23(7)2022 Apr 06.
Article in English | MEDLINE | ID: covidwho-1776253

ABSTRACT

The nasal epithelium is a key portal for infection by respiratory viruses such as SARS-CoV-2 and represents an important target for prophylactic and therapeutic interventions. In the present study, we test the safety and efficacy of a newly developed nasal spray (AM-301, marketed as Bentrio) against infection by SARS-CoV-2 and its Delta variant on an in vitro 3D-model of the primary human nasal airway epithelium. Safety was assessed in assays for tight junction integrity, cytotoxicity and cilia beating frequency. Efficacy against SARS-CoV-2 infection was evaluated in pre-viral load and post-viral load application on airway epithelium. No toxic effects of AM-301 on the nasal epithelium were found. Prophylactic treatment with AM-301 significantly reduced viral titer vs. controls over 4 days, reaching a maximum reduction of 99% in case of infection from the wild-type SARS-CoV-2 variant and more than 83% in case of the Delta variant. When AM-301 administration was started 24 h after infection, viral titer was reduced by about 12-folds and 3-folds on Day 4. The results suggest that AM-301 is safe and significantly decelerates SARS-CoV-2 replication in cell culture inhibition assays of prophylaxis (pre-viral load application) and mitigation (post-viral load application). Its physical (non-pharmaceutical) mechanism of action, safety and efficacy warrant additional investigations both in vitro and in vivo for safety and efficacy against a broad spectrum of airborne viruses and allergens.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/drug therapy , Epithelium , Humans , Nasal Mucosa , Nasal Sprays
2.
Epidemiol Health ; 43: e2021032, 2021.
Article in English | MEDLINE | ID: covidwho-1726410

ABSTRACT

OBJECTIVES: To evaluate the effectiveness of hydrogen peroxide (H2O2) in the form of mouthwash and nasal spray as an auxiliary treatment for coronavirus disease 2019 (COVID-19). METHODS: Forty hospitalized patients who tested positive for severe acute respiratory syndrome coronavirus 2 using a reverse-transcription polymerase chain reaction test were evaluated. They were randomly divided into an experimental group (n= 20; gargling with 1.0% H2O2 and nasal wash with 0.5% H2O2) or a control group (n= 20). The solutions were used for 7 days and the patients were monitored every 2 days, for a total of 8 days. At check-ups, patients were asked about their symptoms and possible adverse effects of the solutions. The presence and severity (mild, moderate, or severe) of symptoms were recorded. Data were compared using the Student test and the Fisher exact test (α= 0.05). RESULTS: There was no significant difference between the 2 groups in the length of hospital stay (p= 0.65). The most frequent symptom on day 0 was coughing (72.0% in the experimental group and 76.5% in the control group), which abated over time. There was no significant difference between the groups in the evaluated symptoms. Most (75.0%) of the patients in the experimental group presented a reduction in dyspnea between days 0 and 2. Few patients reported adverse effects from the use of the solutions. CONCLUSIONS: H2O2 as a mouthwash and nasal spray is safe to use. There is insufficient evidence to demonstrate that H2O2 is effective as an auxiliary treatment for hospitalized COVID-19 patients.


Subject(s)
Anti-Infective Agents, Local/administration & dosage , COVID-19/drug therapy , Hydrogen Peroxide/administration & dosage , SARS-CoV-2 , Adult , Brazil , COVID-19/virology , Double-Blind Method , Female , Hospitalization , Humans , Male , Middle Aged , Mouthwashes/administration & dosage , Nasal Sprays , Severity of Illness Index , Treatment Outcome
3.
Sci Immunol ; 7(67): eabl9929, 2022 Jan 28.
Article in English | MEDLINE | ID: covidwho-1673341

ABSTRACT

The development of a tractable small animal model faithfully reproducing human coronavirus disease 2019 pathogenesis would arguably meet a pressing need in biomedical research. Thus far, most investigators have used transgenic mice expressing the human ACE2 in epithelial cells (K18-hACE2 transgenic mice) that are intranasally instilled with a liquid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suspension under deep anesthesia. Unfortunately, this experimental approach results in disproportionate high central nervous system infection leading to fatal encephalitis, which is rarely observed in humans and severely limits this model's usefulness. Here, we describe the use of an inhalation tower system that allows exposure of unanesthetized mice to aerosolized virus under controlled conditions. Aerosol exposure of K18-hACE2 transgenic mice to SARS-CoV-2 resulted in robust viral replication in the respiratory tract, anosmia, and airway obstruction but did not lead to fatal viral neuroinvasion. When compared with intranasal inoculation, aerosol infection resulted in a more pronounced lung pathology including increased immune infiltration, fibrin deposition, and a transcriptional signature comparable to that observed in SARS-CoV-2­infected patients. This model may prove useful for studies of viral transmission, disease pathogenesis (including long-term consequences of SARS-CoV-2 infection), and therapeutic interventions.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/physiopathology , Disease Models, Animal , Encephalitis, Viral/prevention & control , Keratin-18/genetics , Nasal Sprays , SARS-CoV-2/physiology , Administration, Inhalation , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/immunology , COVID-19/virology , Encephalitis, Viral/mortality , Epithelial Cells/metabolism , Female , Humans , Keratin-18/metabolism , Lung/immunology , Lung/pathology , Lung/physiopathology , Male , Mice , Mice, Transgenic , Promoter Regions, Genetic/genetics , Transcriptome , Virus Replication
4.
Viruses ; 13(12)2021 11 23.
Article in English | MEDLINE | ID: covidwho-1542792

ABSTRACT

The ongoing coronavirus disease (COVID-19) pandemic has required a variety of non-medical interventions to limit the transmission of the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One such option is over-the-counter nasal sprays that aim to block virus entry and transmission within the nasal cavity. In this study, we assessed the ability of three hydroxypropyl methylcellulose (HPMC)-based powder nasal sprays, produced by Nasaleze, to inhibit SARS-CoV-2 infection and release in vitro. Upon application, the HPMC powder forms a gel-like matrix within the nasal cavity-a process we recapitulated in cell culture. We found that virus release from cells previously infected with SARS-CoV-2 was inhibited by the gel matrix product in a dose-dependent manner, with virus levels reduced by >99.99% over a 72 h period at a dose of 6.4 mg/3.5 cm2. We also show that the pre-treatment of cells with product inhibited SARS-CoV-2 infection, independent of the virus variant. The primary mechanism of action appears to be via the formation of a physical, passive barrier. However, the addition of wild garlic provided additional direct antiviral properties in some formulations. We conclude that HPMC-based nasal sprays may offer an additional component to strategies to limit the spread of respiratory viruses, including SARS-CoV-2.


Subject(s)
COVID-19/prevention & control , Hypromellose Derivatives/pharmacology , SARS-CoV-2/drug effects , Animals , Chlorocebus aethiops , Dose-Response Relationship, Drug , Nasal Sprays , Vero Cells , Virus Internalization/drug effects , Virus Release/drug effects
6.
PLoS One ; 16(11): e0259943, 2021.
Article in English | MEDLINE | ID: covidwho-1526690

ABSTRACT

Last year observed a global pandemic caused by SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) infection affecting millions of individuals worldwide. There is an urgent unmet need to provide an easily producible and affordable medicine to prevent transmission and provide early treatment for this disease. Since the nasal cavity and the rhinopharynx are the sites of initial replication of SARS-CoV-2, a nasal spray may be an effective option to target SARS-CoV-2 infection. In this study, we tested the antiviral action of three candidate nasal spray formulations against SARS-CoV-2 in vitro. We determined that iota-carrageenan in concentrations as low as 6 µg/mL inhibits SARS-CoV-2 in vitro. The concentrations of iota-carrageenan with activity against SARS-CoV-2 in vitro may be easily achieved through the application of nasal sprays as commonly used in several countries. Recently a double-blind, placebo-controlled study showed that iota-carrageenan in isotonic sodium chloride reduces ca. five times the risk of infection by SARS-CoV-2 in health care personnel. Further, xylitol at a concentration of 50 mg/mL (ca. 329 mM) was found to exert some antiviral action, though this preliminary finding needs further confirmation.


Subject(s)
Carrageenan/pharmacology , SARS-CoV-2/drug effects , Xylitol/pharmacology , Animals , Antiviral Agents/pharmacology , Chlorocebus aethiops , Nasal Sprays , Vero Cells
7.
Ital J Pediatr ; 47(1): 225, 2021 Nov 13.
Article in English | MEDLINE | ID: covidwho-1515449

ABSTRACT

BACKGROUND: In Italy only recently, for the 2020-21 season, has the flu vaccination been extended to all children. A quadrivalent live attenuated influenza vaccine (qLAIV) was administered to children aged 2-17 years for the first time. We registered the number and severity of adverse reactions to (Fluenz Tetra™) and the factors influencing them, evaluated uniformity of access to care and assessed the degree of satisfaction with the vaccination of both parents and health care providers, in order to improve the 2021-22 vaccination program. METHODS: On vaccination day, a questionnaire was given out to collect information about the children and their parents. Between 1 and 3 months later, the parents were contacted to record any adverse reactions following (Fluenz Tetra™) and rate the degree of satisfaction. RESULTS: We received data of 3226 children from 2152 families. Adverse events were reported in 24.8% of children: 80.6% mild, 18.1% moderate and 1.3% significant. The most common were rhinitis (52.5%) and fever (24.4%). Statistical analysis performed with a multiple regression model, showed that children aged 2-5 years have an increased risk of adverse events compared to both 6-10 years old (aRR 1.7, 95% CI 1.5-1.9, p < 0. 001) and 11-17 years old (aRR 1.5, 95% CI 1-2.2, p = 0.051). Most families chose to vaccinate their children to protect them and because they were concerned about Covid19. The main channel through which parents became aware of a new flu vaccination was word-of-mouth (39.8%), which occurred mostly among parents of the same school group, followed by information from the child's doctor (30.6%), the Internet (26.9%), personal research (15%), newspapers (4%), telecommunications (7.5%) and other (2.6%). Most parents (83.3%) were very satisfied and intend to vaccinate their children with qLAIV again (83.8%). The majority of operators (93%) considered the experience as excellent and are willing to repeat it (94.6%). CONCLUSION: (Fluenz Tetra™) proved to be easy to administer and the degree of satisfaction was high among both health workers and parents. Considering its substantial safety profile especially in school-age children and adolescents, all these aspects make the nasal qLAIV optimal for widespread immunization. Schools offer the best setting to reach more families and physicians should be actively involved.


Subject(s)
Influenza Vaccines/administration & dosage , Nasal Sprays , Adolescent , Child , Child, Preschool , Female , Humans , Italy , Vaccines, Attenuated/administration & dosage
8.
J Hosp Infect ; 120: 9-13, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1500052

ABSTRACT

The highest viral loads of severe acute respiratory syndrome coronavirus-2 are detectable in the oral cavity, so a potential reduction of infectious virus by nasal and oral sprays could reduce transmission. Therefore, the inactivation capacity of nine nasal and oral sprays was evaluated according to EN 14476. One nasal spray based on sodium hypochlorite and one oral spray containing essential oils reduced viral titres by two to three orders of magnitude. Although clinical data are still sparse, nasal and oral sprays display a more convenient application for elderly people or those who are unable to rinse/gargle.


Subject(s)
COVID-19 , Nasal Sprays , Aged , Humans , Mouth , Mouthwashes , SARS-CoV-2
9.
Eur Phys J E Soft Matter ; 44(11): 132, 2021 Oct 30.
Article in English | MEDLINE | ID: covidwho-1495656

ABSTRACT

Understanding the physical and chemical properties of viral infections at molecular scales is a major challenge for the scientific community more so with the outbreak of global pandemics. There is currently a lot of effort being placed in identifying molecules that could act as putative drugs or blockers of viral molecules. In this work, we computationally explore the importance in antiviral activity of a less studied class of molecules, namely surfactants. We employ all-atoms molecular dynamics simulations to study the interaction between the receptor-binding domain of the SARS-CoV-2 spike protein and the phospholipid lecithin (POPC), in water. Our microsecond simulations show a preferential binding of lecithin to the receptor-binding motif of SARS-CoV-2 with binding free energies significantly larger than [Formula: see text]. Furthermore, hydrophobic interactions involving lecithin non-polar tails dominate these binding events, which are also accompanied by dewetting of the receptor binding motif. Through an analysis of fluctuations in the radius of gyration of the receptor-binding domain, its contact maps with lecithin molecules, and distributions of water molecules near the binding region, we elucidate molecular interactions that may play an important role in interactions involving surfactant-type molecules and viruses. We discuss our minimal computational model in the context of lecithin-based liposomal nasal sprays as putative mitigating therapies for COVID-19.


Subject(s)
Lecithins/chemistry , Molecular Docking Simulation , Phosphatidylcholines/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Surface-Active Agents/chemistry , Binding Sites , Hydrophobic and Hydrophilic Interactions , Nasal Sprays , Protein Binding , Spike Glycoprotein, Coronavirus/metabolism
11.
Sci Rep ; 11(1): 20012, 2021 10 08.
Article in English | MEDLINE | ID: covidwho-1462029

ABSTRACT

There are currently no cures for coronavirus infections, making the prevention of infections the only course open at the present time. The COVID-19 pandemic has been difficult to prevent, as the infection is spread by respiratory droplets and thus effective, scalable and safe preventive interventions are urgently needed. We hypothesise that preventing viral entry into mammalian nasal epithelial cells may be one way to limit the spread of COVID-19. Here we show that N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ), a positively charged polymer that has been through an extensive Good Laboratory Practice toxicology screen, is able to reduce the infectivity of SARS-COV-2 in A549ACE2+ and Vero E6 cells with a log removal value of - 3 to - 4 at a concentration of 10-100 µg/ mL (p < 0.05 compared to untreated controls) and to limit infectivity in human airway epithelial cells at a concentration of 500 µg/ mL (p < 0.05 compared to untreated controls). In vivo studies using transgenic mice expressing the ACE-2 receptor, dosed nasally with SARS-COV-2 (426,000 TCID50/mL) showed a trend for nasal GCPQ (20 mg/kg) to inhibit viral load in the respiratory tract and brain, although the study was not powered to detect statistical significance. GCPQ's electrostatic binding to the virus, preventing viral entry into the host cells, is the most likely mechanism of viral inhibition. Radiolabelled GCPQ studies in mice show that at a dose of 10 mg/kg, GCPQ has a long residence time in mouse nares, with 13.1% of the injected dose identified from SPECT/CT in the nares, 24 h after nasal dosing. With a no observed adverse effect level of 18 mg/kg in rats, following a 28-day repeat dose study, clinical testing of this polymer, as a COVID-19 prophylactic is warranted.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Nasal Sprays , SARS-CoV-2/drug effects , A549 Cells , Animals , Antiviral Agents/administration & dosage , Chlorocebus aethiops , Humans , Male , Methylation , Mice, Inbred BALB C , Mice, Transgenic , SARS-CoV-2/physiology , Surface-Active Agents/administration & dosage , Surface-Active Agents/therapeutic use , Vero Cells , Viral Load/drug effects
12.
Future Microbiol ; 16: 119-130, 2021 01.
Article in English | MEDLINE | ID: covidwho-1389070

ABSTRACT

A review of nasal sprays and gargles with antiviral properties suggests that a number of commonly used antiseptics including povidone-iodine, Listerine®, iota-carrageenan and chlorhexidine should be studied in clinical trials to mitigate both the progression and transmission of SARS-CoV-2. Several of these antiseptics have demonstrated the ability to cut the viral load of SARS-CoV-2 by 3-4 log10 in 15-30 s in vitro. In addition, hypertonic saline targets viral replication by increasing hypochlorous acid inside the cell. A number of clinical trials are in process to study these interventions both for prevention of transmission, prophylaxis after exposure, and to diminish progression by reduction of viral load in the early stages of infection.


Subject(s)
Anti-Infective Agents, Local/administration & dosage , Anti-Infective Agents, Local/therapeutic use , COVID-19/prevention & control , SARS-CoV-2/drug effects , COVID-19/transmission , Carrageenan/therapeutic use , Chlorhexidine/therapeutic use , Drug Combinations , Hydrogen Peroxide/therapeutic use , Nasal Sprays , Oils, Volatile/therapeutic use , Povidone-Iodine/therapeutic use , Salicylates/therapeutic use , Terpenes/therapeutic use , Viral Load/drug effects
14.
Viruses ; 13(8)2021 08 20.
Article in English | MEDLINE | ID: covidwho-1367923

ABSTRACT

Strategies to combat COVID-19 require multiple ways to protect vulnerable people from infection. SARS-CoV-2 is an airborne pathogen and the nasal cavity is a primary target of infection. The K18-hACE2 mouse model was used to investigate the anti-SARS-CoV-2 efficacy of astodrimer sodium formulated in a mucoadhesive nasal spray. Animals received astodrimer sodium 1% nasal spray or PBS intranasally, or intranasally and intratracheally, for 7 days, and they were infected intranasally with SARS-CoV-2 after the first product administration on Day 0. Another group was infected intranasally with SARS-CoV-2 that had been pre-incubated with astodrimer sodium 1% nasal spray or PBS for 60 min before the neutralisation of test product activity. Astodrimer sodium 1% significantly reduced the viral genome copies (>99.9%) and the infectious virus (~95%) in the lung and trachea vs. PBS. The pre-incubation of SARS-CoV-2 with astodrimer sodium 1% resulted in a significant reduction in the viral genome copies (>99.9%) and the infectious virus (>99%) in the lung and trachea, and the infectious virus was not detected in the brain or liver. Astodrimer sodium 1% resulted in a significant reduction of viral genome copies in nasal secretions vs. PBS on Day 7 post-infection. A reduction in the viral shedding from the nasal cavity may result in lower virus transmission rates. Viraemia was low or undetectable in animals treated with astodrimer sodium 1% or infected with treated virus, correlating with the lack of detectable viral replication in the liver. Similarly, low virus replication in the nasal cavity after treatment with astodrimer sodium 1% potentially protected the brain from infection. Astodrimer sodium 1% significantly reduced the pro-inflammatory cytokines IL-6, IL-1α, IL-1ß, TNFα and TGFß and the chemokine MCP-1 in the serum, lung and trachea vs. PBS. Astodrimer sodium 1% nasal spray blocked or reduced SARS-CoV-2 replication and its sequelae in K18-hACE2 mice. These data indicate a potential role for the product in preventing SARS-CoV-2 infection or for reducing the severity of COVID-19.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/drug therapy , Dendrimers/administration & dosage , Nasal Cavity/virology , Nasal Sprays , Polylysine/administration & dosage , SARS-CoV-2/drug effects , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antiviral Agents/therapeutic use , Brain/virology , COVID-19/prevention & control , COVID-19/virology , Dendrimers/therapeutic use , Disease Models, Animal , Female , Liver/virology , Male , Mice , Mice, Transgenic , Polylysine/therapeutic use , Respiratory System/virology , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Viral Load/drug effects , Viremia , Virus Replication/drug effects
15.
Int J Nanomedicine ; 16: 4063-4072, 2021.
Article in English | MEDLINE | ID: covidwho-1278261

ABSTRACT

BACKGROUND: Ivermectin is an FDA-approved broad-spectrum anti-parasitic agent that has been shown to inhibit SARS-CoV-2 replication in vitro. OBJECTIVE: We aimed to assess the therapeutic efficacy of ivermectin mucoadhesive nanosuspension intranasal spray in treatment of patients with mild COVID-19. METHODS: This clinical trial included 114 patients diagnosed as mild COVID-19. Patients were divided randomly into two age and sex-matched groups; group A comprising 57 patients received ivermectin nanosuspension nasal spray twice daily plus the Egyptian protocol of treatment for mild COVID-19 and group B comprising 57 patients received the Egyptian protocol for mild COVID-19 only. Evaluation of the patients was performed depending on improvement of presenting manifestations, negativity of two consecutive pharyngeal swabs for the COVID-19 nucleic acid via rRT-PCR and assessments of hematological and biochemical parameters in the form of complete blood counts, C-reactive protein, serum ferritin and d-dimer which were performed at presentation and 7 days later. RESULTS: Of the included patients confirmed with mild COVID-19, 82 were males (71.9%) and 32 females (28.1%) with mean age 45.1 ± 18.9. In group A, 54 patients (94.7%) achieved 2 consecutive negative PCR nasopharyngeal swabs in comparison to 43 patients (75.4%) in group B with P = 0.004. The durations of fever, cough, dyspnea and anosmia were significantly shorter in group A than group B, without significant difference regarding the duration of gastrointestinal symptoms. Duration taken for nasopharyngeal swab to be negative was significantly shorter in group A than in group B (8.3± 2.8 days versus 12.9 ± 4.3 days; P = 0.0001). CONCLUSION: Local use of ivermectin mucoadhesive nanosuspension nasal spray is safe and effective in treatment of patients with mild COVID-19 with rapid viral clearance and shortening the anosmia duration. CLINICALTRIALSGOV IDENTIFIER: NCT04716569; https://clinicaltrials.gov/ct2/show/NCT04716569.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Ivermectin/therapeutic use , Respiratory Tract Diseases/drug therapy , Adult , Antiviral Agents/administration & dosage , COVID-19/etiology , COVID-19 Nucleic Acid Testing , Cough/drug therapy , Cough/virology , Egypt , Female , Fever/drug therapy , Fever/virology , Humans , Ivermectin/administration & dosage , Ivermectin/adverse effects , Male , Middle Aged , Nanostructures/administration & dosage , Nanostructures/chemistry , Nasal Sprays , Nasopharynx/virology , Prospective Studies , Respiratory Tract Diseases/etiology , Respiratory Tract Diseases/virology , Treatment Outcome
16.
Pharmacol Res Perspect ; 9(4): e00810, 2021 08.
Article in English | MEDLINE | ID: covidwho-1269137

ABSTRACT

In this individual patient data meta-analysis we examined datasets of two randomized placebo-controlled trials which investigated the effect of nasal carrageenan separately on children and adults. In both trials, iota-carrageenan was administered nasally three times per day for 7 days for patients with the common cold and follow-up lasted for 21 days. We used Cox regression to estimate the effect of carrageenan on recovery rate. We also used quantile regression to calculate the effect of carrageenan on colds of differing lengths. Nasal carrageenan increased the recovery rate from all colds by 54% (95% CI 15%-105%; p = .003). The increase in recovery rate was 139% for coronavirus infections, 119% for influenza A infections, and 70% for rhinovirus infections. The mean duration of all colds in the placebo groups of the first four quintiles were 4.0, 6.8, 8.8, and 13.7 days, respectively. The fifth quintile contained patients with censored data. The 13.7-day colds were shortened by 3.8 days (28% reduction), and 8.8-day colds by 1.3 days (15% reduction). Carrageenan had no meaningful effect on shorter colds. In the placebo group, 21 patients had colds lasting over 20 days, compared with six patients in the carrageenan group, which corresponds to a 71% (p = .003) reduction in the risk of longer colds. Given that carrageenan has an effect on diverse virus groups, and effects at the clinical level on two old coronaviruses, it seems plausible that carrageenan may have an effect on COVID-19. Further research on nasal iota-carrageenan is warranted.


Subject(s)
Antiviral Agents/administration & dosage , Carrageenan/administration & dosage , Common Cold/virology , Coronavirus Infections/drug therapy , Influenza, Human/drug therapy , Picornaviridae Infections/drug therapy , Administration, Intranasal , Adult , Antiviral Agents/therapeutic use , Carrageenan/pharmacology , Child, Preschool , Common Cold/drug therapy , Female , Humans , Male , Nasal Sprays , Randomized Controlled Trials as Topic , Regression Analysis , Survival Analysis , Time Factors , Treatment Outcome
17.
Int Immunopharmacol ; 98: 107871, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1267705

ABSTRACT

The aim of this study was to evaluate the usage of mometasone furoate nasal spray in the recovery of patients with severe microsmia or anosmia induced by COVID-19. This was a prospective clinical trial on non-hospitalized adult patients with COVID-19 (>18 years) who had severe microsmia or anosmia within two weeks. The subjects were randomly assigned to the mometasone furoate group (100 mcg twice daily) or sodium chloride group (0.9%); both groups also received olfactory training for 4 weeks. The primary outcome was the improvement of the olfactory score at the end of the study. Visual analog scale (VAS) and the University of Pennsylvania Smell Identification Test (UPSIT) were used to assess primary outcome. A total of 80 patients were recruited, 77 of them completed the study and were analyzed. There was no statistically significant difference in terms of demographics and baseline clinical characteristics. The olfactory scores (based on VAS) at weekly intervals showed a significant difference between the two groups (P:0.318, <0.001, <0.001, <0.001, respectively). The analyses also showed significant within-group differences from baseline. Nevertheless, the changes were not significant between the two groups (P: 0.444, 0.402, 0.267, 0.329). There was no significant difference between the two groups in terms of the UPSIT results (p > 0.239). However, a significant between-group difference was noted in the severity of loss of smell (P < 0.001). Compared to olfactory training, mometasone furoate nasal spray combination with olfactory training showed a higher improvement in severe chronic anosmia by COVID-19.


Subject(s)
Anosmia/drug therapy , COVID-19/complications , Mometasone Furoate/administration & dosage , Smell/drug effects , Administration, Intranasal , Adult , Anosmia/diagnosis , Anosmia/etiology , Anosmia/physiopathology , COVID-19/diagnosis , Double-Blind Method , Female , Humans , Iran , Male , Mometasone Furoate/adverse effects , Nasal Sprays , Prospective Studies , Recovery of Function , Time Factors , Treatment Outcome , Young Adult
19.
Adv Mater ; 33(26): e2008304, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1248674

ABSTRACT

Airborne pathogens pose high risks in terms of both contraction and transmission within the respiratory pathways, particularly the nasal region. However, there is little in the way of adequate intervention that can protect an individual or prevent further spread. This study reports on a nasal formulation with the capacity to combat such challenges, focusing on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Formulation of a polysaccharide-based spray, known for its mucoadhesive properties, is undertaken and it is characterized for its mechanical, spray distribution, and antiviral properties. The ability to engineer key mechanical characteristics such as dynamic yield stresses and high coverage is shown, through systematic understanding of the composite mixture containing both gellan and λ-carrageenan. Furthermore, the spray systems demonstrate highly potent capacities to prevent SARS-CoV-2 infection in Vero cells, resulting in complete inhibition when either treating, the cells, or the virus, prior to challenging for infection. From this data, a mechanism for both prophylaxis and prevention is proposed; where entrapment within a polymeric coating sterically blocks virus uptake into the cells, inactivating the virus, and allowing clearance within the viscous medium. As such, a fully preventative spray is formulated, targeted at protecting the lining of the upper respiratory pathways against SARS-CoV-2.


Subject(s)
Drug Compounding , Nasal Sprays , Polymers/chemistry , SARS-CoV-2/physiology , Animals , COVID-19/pathology , COVID-19/virology , Carrageenan/chemistry , Chlorocebus aethiops , Humans , Polymers/pharmacology , Polysaccharides, Bacterial/chemistry , SARS-CoV-2/isolation & purification , Vero Cells , Virus Internalization/drug effects
20.
Sci Rep ; 11(1): 371, 2021 01 11.
Article in English | MEDLINE | ID: covidwho-1242035

ABSTRACT

Vaccines and therapeutics using in vitro transcribed mRNA hold enormous potential for human and veterinary medicine. Transfection agents are widely considered to be necessary to protect mRNA and enhance transfection, but they add expense and raise concerns regarding quality control and safety. We found that such complex mRNA delivery systems can be avoided when transfecting epithelial cells by aerosolizing the mRNA into micron-sized droplets. In an equine in vivo model, we demonstrated that the translation of mRNA into a functional protein did not depend on the addition of a polyethylenimine (PEI)-derived transfection agent. We were able to safely and effectively transfect the bronchial epithelium of foals using naked mRNA (i.e., mRNA formulated in a sodium citrate buffer without a delivery vehicle). Endoscopic examination of the bronchial tree and histology of mucosal biopsies indicated no gross or microscopic adverse effects of the transfection. Our data suggest that mRNA administered by an atomization device eliminates the need for chemical transfection agents, which can reduce the cost and the safety risks of delivering mRNA to the respiratory tract of animals and humans.


Subject(s)
Horses , Nasal Sprays , RNA, Messenger/administration & dosage , Respiratory Mucosa , Animals , Animals, Newborn , Cells, Cultured , Drug Carriers/administration & dosage , Drug Carriers/adverse effects , Drug Carriers/pharmacokinetics , Drug Delivery Systems/adverse effects , Drug Delivery Systems/methods , Drug Delivery Systems/veterinary , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Female , Lung/drug effects , Lung/metabolism , Nebulizers and Vaporizers/veterinary , Polyethyleneimine/administration & dosage , Polyethyleneimine/chemistry , RNA, Messenger/adverse effects , RNA, Messenger/pharmacokinetics , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , Transcription, Genetic , Transfection/methods , Transfection/veterinary , Vaccines, DNA/administration & dosage , Vaccines, DNA/adverse effects , Vaccines, DNA/pharmacokinetics
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