It's a type of antibody that targets the coronavirus' spike protein. 48.9% (n=44) of the safety analysis set was male, and the average age was 35.6712.94years. Expert. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Inhibition of leukotriene synthesis by azelastine. We are aware that this limited the capture of COVID-19 specific issues as questions were not specifically aimed for COVID-19 patients. The number of possibly and probably related adverse events was comparable between treatment groups (supplementary Table S6), and no safety concerns regarding the treatment regime were raised. When given in advance, none of the treated mice had SARS-CoV-2 RNA in their lungs, while untreated mice in the comparison group had abundant levels. But the spike protein may mutate to evade immune response. When treated with N-0385, 70% of the mice survived and had little to no lung damage. At the end of the treatment, 48.2% of the patients of the 0.1% azelastine group showed no detection of the ORF 1a/b gene, whereas only 23.1% of patients of the placebo group showed negative PCR results (supplementary Table S4). The aim of our study was to support the preclinical evidence for azelastines antiviral activity in patients tested positive for SARS-CoV-2. The sample size calculation was based on the expected reduction of virus load during the treatment considering 3 treatment arms. These agents essentially trick the virus by changing the structure of the outside of cells, so they look like a virus has already fused to them. SARS-CoV-2 infection progression starts with viral entrance mediated by the spike glycoproteins interaction with the host ACE2 receptor molecule. First report on a double-blind placebo-controlled phase II clinical trial. By application of a novel computational approach based on Shannon entropy homology, Konrat et al. For quantification of SARS-CoV-2-RNA in copies/mL, a standard curve derived from a dilution series of a SARS-CoV-2 cell culture isolate in VTM and adjusted to Ct values obtained from two samples with defined SARS-CoV-2-RNA copy numbers (106 and 105 copies/mL; INSTAND e.V., Duesseldorf, Germany) was used. Overall, data of the primary outcome did not show a normal distribution (ShapiroWilk test, p<0.05). Inhibition of SARS-CoV-2 by bentonite-based nasal spray. Following sampling, swabs were placed into 3mL Virus Transport Medium (VTM, Biocomma) and delivered to the laboratory as quickly as possible. 76, 469475. Zapor, M. Persistent detection and infectious potential of SARS-CoV-2 virus in clinical specimens from COVID-19 patients. Of note, the known bitter taste of azelastine was only negatively reported by a single patient, and compliance between treatment groups was comparable (meanSD: 97 0.129.7% compliance), thus indicating that the taste did not negatively influence treatment adherence. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Biochem. The overall AUC of the Azelastine 0.1% group (red area) was significantly greater than that of placebo (green area), p=0.007. Asthma Allergy Immunol. Article Chem. All rights reserved. https://doi.org/10.1007/s10787-021-00847-2 (2021). Recent publications indicating that in vitro infectivity correlates with high virus concentrations (Ct25) in nasal swabs28,29,30 underline the importance of analysis of this subset population. 2 and supplementary Table S2). Treatment kits were manufactured by URSAPHARM Arzneimittel GmbH, Saarbruecken, Germany, according to the randomization list (as sequentially numbered containers). Bullinger, M., Kirchberger, I. Cornell Daily Sun. Early intervention with azelastine nasal sprays reduces viral load in SARS-CoV-2 infected patients. Pharmacol. Yang, L. et al. In a study examining the effect of azelastine nasal spray on upper respiratory infections in children, it was found that the placebo group, receiving hypertonic saline solution (twice daily) also produced a favourable response compared to those receiving no treatment31. Rep. 117 https://doi.org/10.1007/s43440-023-00463-7. It's being studied as a potential way to prevent mild to moderate cases of COVID-19. Front. A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic. In addition, intervals between swab sampling were short and the overall number of performed PCR tests was high to allow a very close determination of the viral clearance. https://doi.org/10.1016/j.jinf.2021.05.009 (2021). Early intervention with azelastine nasal spray may reduce viral load in SARS-CoV-2 infected patients, https://doi.org/10.1038/s41598-023-32546-z. Because N-0385 was suitable for use as a nasal spray, researchers used a mouse model that develops severe COVID-19 and gave the mice either N-0385 or control doses of saline in their noses. EudraCT number: 2020-005544-34. was responsible for data management activities. JPK and CL have received grants from the sponsor URSAPHARM Arzneimittel GmbH for performing this trial. However, examples of prolonged nasal positivity have also been reported, and many factors are known to have an influence on the individual viral load and clearance27. Following translocation from nucleus to the endoplasmic reticulum (ER), the sigma-1 receptor (among other factors) plays a role in viral replication. Lee, C. & Corren, J. The azelastine 0.1% azelastine group displayed the greatest improvement of symptoms with 12.7410.74 mean score reduction. Comirnaty is FDA-approved as a 2-dose series for the prevention of COVID-19 in individuals 12 years of age and older. Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. In a study funded by NIAID, researchers are using mice to look for genes that account for different COVID-19 symptoms. A nasal and mouth spray called "IGM-6268" is in the early stages of clinical trials. Because we get infected with SARS-CoV-2 primarily by breathing it in, a nasal spray might be an easy and efficient way to offer protection against the virus, especially in crowded places. Shmuel, K., Dalia, M., Tair, L. & Yaakov, N. Low pH Hypromellose (Taffix) nasal powder spray could reduce SARS-CoV-2 infection rate post mass-gathering event at a highly endemic community: An observational prospective open label user survey. Importantly, newly emerging virus variants have the potential to evade the immune response, thereby affecting the efficacy of specific therapies and underlining the importance of new treatment strategies. For calibration purposes of quantitative assessments, reference samples were included with each PCR run. 31(6), 113. Med. volume13, Articlenumber:6839 (2023) The product targets a stable site on the spike protein of the virus that is not known to mutate. Killingley, B. et al. Amdal, C. D. et al. Associate Professor Peter Friedland, from UWA's Medical School, was lead author of the study In vivo . Components are mixed from two chambers to create the final NO-producing formulation. On day 16, an on-site visit (V8) for female patients was conducted to perform a urine pregnancy test and to assess the safety of the therapy. Jean, F. (2022). Marshall, J. C. A minimal common outcome measure set for COVID-19 clinical research. Slider with three articles shown per slide. Ninety SARS-CoV-2 positive patients were randomized into 3 groups receiving placebo, 0.02% or 0.1% azelastine nasal spray for 11days, during which viral loads were assessed by quantitative PCR. https://doi.org/10.1038/s41586-020-2196-x (2020). P.A.de.A., H.M. and H.A.S. Dings, C. et al. E.N., V.S., G.N., R.K., A.B., M.F. With the changing epidemiology of COVID-19 and its impact on our daily lives, there is still an unmet need of COVID-19 therapies treating early infections to prevent progression. 62, 50937, Cologne, Germany, Henning Gruell,Maike Schlotz&Florian Klein, Ursatec GmbH, Marpinger Weg 4, 66636, Tholey, Germany, ClinCompetence Cologne GmbH, Theodor-Heuss-Ring 14, 50668, Cologne, Germany, Belisa Russo,Susanne Mller-Scholtz,Cengizhan Acikel,Hacer Sahin,Nina Werkhuser,Silke Allekotte&Ralph Msges, Institute of Medical Statistics and Computational Biology (IMSB), Faculty of Medicine, University of Cologne, Kerpener Str. This was a prospective, randomized, double-blind, placebo-controlled dose-finding proof-of-concept study, in which azelastine nasal spray was used in 2 doses: the commercially available concentration of 0.1% and a fivefold lower concentration of 0.02%. These nanobodies and TriSb92 target a specific part of the coronavirus spike protein called the receptor-binding domain (RBD). Topol is also editor-in-chief of Medscape, WebMD's sister site for medical professionals. JAMA Otolaryngol. 16, 275282. Absolute changes of total symptom scores from baseline (day 1) until day 11 of treatment (ITT analysis set). We would like to thank Prof. G.A. https://doi.org/10.6026/97320630016236 (2020). A., Dion, S. P., Buchholz, D. W., Imbiakha, B., Olmstead, A. D., Jager, M., Dsilets, A., Gao, G., Martins, M., Vandal, T., Thompson, C. A. H., Chin, A., Rees, W. D., Steiner, T., Nabi, I. R., Marsault, E., Sahler, J., Diel, D. G., . A newly discovered small molecule could be sprayed into people's noses to prevent COVID-19 illness prior to exposure and provide early treatment if administered soon after infection, according to a study in mice led by Cornell researchers. were investigators involved in the conduct of the study. TMPRSS2 is a protein in mouse and human cells that SARS-CoV-2 uses as a gateway to infect humans. Therefore, during the treatment phase, patients were required to document the severity of their COVID-19 related symptoms in an electronic diary on a daily basis. performed the statistical analysis. https://cornellsun.com/2022/04/27/cornell-research-team-to-develop-covid-19-nose-spray-treatment/, Shapira, T., Monreal, I. https://cornellsun.com/2022/04/27/cornell-research-team-to-develop-covid-19-nose-spray-treatment/, https://doi.org/10.1038/s41586-022-04661-w, Antiviral Nasal Spray Shows Promise Fighting COVID-19. TriSb92 isone of multiple nasal spray approaches but unlikely to be as durable as effective nasal vaccines, saidEricTopol, MD, a professor of molecular medicine and executive vice president of Scripps Research in La Jolla, CA. Correspondence to On days 1, 5, 8 and 11, patients completed the standardized SF-36 questionnaire of quality of life. Quality of life was assessed with the SF-36 questionnaire as no COVID-19 specific patient-reported outcome measures were available at the time of study. Investigators assessed patients status throughout the trial including safety follow-ups (days 16 and 60). Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. The efficacy of the treatment was judged as good or very good by 75.0% (0.1% azelastine treatment), 74.1% (0.02% azelastine treatment) and 50.0% (placebo treatment) of patients. J. Med. https://doi.org/10.1038/s41591-021-01316-7 (2021). Anticipating a drop-out rate of 20%, the aim was to randomize 90 patients in total (30 patients per treatment group) to result in 23 patients per treatment group completing the study and being eligible for analysis. Allergy Asthma Immunol. In the meantime, to ensure continued support, we are displaying the site without styles Symptoms were evaluated on a 5-point scale from 1=symptom absent or present very weakly to 5=symptom present very strongly: anosmia, ageusia, cough, sore throat, shortness of breath, coryza, general weakness, headache, aching limb, loss of appetite, pneumonia, nausea, abdominal pain, vomiting, diarrhea, conjunctivitis, rash, lymph node swelling, apathy, somnolence. 62, 50937, Cologne, Germany, Medical Faculty, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Kerpener Str. Outpatients visiting Corona test centres were informed about the possibility of participating in the trial. 1). After treatment, virus load was reduced in all groups (p<0.0001) but was greater in the 0.1% group compared to placebo (p=0.007). Head Neck Surg. Recently, Shmuel et al. A., Dion, S. P., Buchholz, D. W., Imbiakha, B., Olmstead, A. D., Jager, M., Dsilets, A., Gao, G., Martins, M., Vandal, T., Thompson, C. A. H., Chin, A., Rees, W. D., Steiner, T., Nabi, I. R., Marsault, E., Sahler, J., Diel, D. G., . This could happen by limiting how much virus could replicate early in the skin inside the nose and nasopharynx (the upper part of the throat), saidMkel, who is also CEO of Pandemblock Oy, the company set up to develop the product. Suitable for Within this context it is important to point out that in vitro data indicate efficacy of azelastine against various SARS-CoV-2 variants tested10. CAS Google Scholar. MG, PA, HM and HAS declare no conflict of interest. Nasal steroid sprays may reduce the severity of COVID-19, according to a new study. https://doi.org/10.1016/j.bbrc.2020.11.095 (2021). Identification of SARS-CoV-2 entry inhibitors among already approved drugs. 42, 17. Both have the allure of being variant-proof, Topol added., Many laboratories are shifting from treatments using monoclonal antibodies to treatments using smaller antibody fragments called "nanobodies" because they are more cost-effective and are able to last longer in storage, Mkel and colleagues noted., Several of these nanobodies have shown promise against viruses in cell culture or animal models, including as an intranasal preventive treatment for SARS-CoV-2.. These devices release a low-velocity aerosol mist that can be slowly inhaled over a longer period of time than metered dose and dry powder inhalers. One study of about 400 health-care workers suggests a nasal spray may reduce the incidence of COVID-19 by up to 80 per cent. J. 3). . The sprays generally require multiple doses per day, whereas a single dose of a nasal vaccine may protect for months, he said. Information on individual variants was obtained through the original laboratory reports, when available. 538, 173179. The active substance (azelastine hydrochloride) is a histamine-1 receptor antagonist, which shows anti-inflammatory effects via mast cell stabilization and inhibition of leukotriene and pro-inflammatory cytokine production2,3,4. C.A. One puff of the respective nasal spray was applied per nostril, 3 times a day (morning, midday, evening). Article Health-related quality of life in patients with COVID-19; international development of a patient-reported outcome measure. The antiviral also could offer an alternative to people who cannot or do not respond to a vaccine. AB is employed at Ursatec GmbH, supplier of primary packing materials to Ursapharm. Pujadas, E. et al. Google Scholar. However, the overall small number of participants limits conclusions, and results should be interpreted with care. In addition, investigators measured body temperature during V1V7 and oxygen saturation of the blood (using a finger pulse oximeter) on V1, V3, and V5, V6 and V7. Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, Kerpener Str.
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