8, e70. Vincenzo Messina, Riccardo Nevola, Luigi Elio Adinolfi, Kara W. Chew, Carlee Moser, Davey M. Smith, Manaf AlQahtani, Nitya Kumar, Stephen L. Atkin, V. Spagnuolo, M. Guffanti, COVID-BioB study group, Manish C. Choudhary, Kara W. Chew, for the ACTIV-2/A5401 Study Team, Emma Pritchard, Philippa C. Matthews, Koen B. Pouwels, Vineet Agarwal, A. J. Venkatakrishnan, Venky Soundararajan, Pauline Maisonnasse, Jrmie Guedj, Roger Le Grand, Scientific Reports Lee, C. & Corren, J. Subgroups were analysed exploratorily (e.g., subgroups regarding gender, age, symptom severity, etc.). Pujadas, E. et al. PubMed Internet Explorer). The most common COVID-19 symptoms (loss of sense of smell, loss of taste, fever, cough, and coryza) improved over time in all 3 treatment groups; and no statistical differences were observed between groups. 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. Smell Retraining Therapy. Kim, M.-C. et al. was the deputy investigator. The physical and mental health summary scores of the SF-36 questionnaire improved during the course of the treatment without statistical differences between groups (data not shown). Postdoctoral Fellow Scholarship at Dept of Biochemistry of Vanderbilt University. The sample size calculation was based on the expected reduction of virus load during the treatment considering 3 treatment arms. Chem. reviewed, edited and finalised the manuscript. 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. Decreases of viral load were also reflected in increases of negative PCR results over time. and F.H. were investigators involved in the conduct of the study. N.W. Ct values reported as negative were replaced with the value 45, and respective cp/mL values with the value 1, and cp/mL values<2116 (ORF 1a/b gene) and cp/mL values<1950 (E gene) were replaced with the value 1. 83, 237279. One puff of the respective nasal spray was applied per nostril, 3 times a day (morning, midday, evening). Scientific Reports (Sci Rep) Chavda, V. P., Baviskar, K. P., Vaghela, D. A., Raut, S. S. & Bedse, A. P. (2023) Nasal sprays for treating COVID-19: A scientific note. A phase 1 study for IGM-6268 is still taking place, and it's expected to be finished by December 2022. From hydroxychloroquine and veterinarian doses of the antiparasitic drug ivermectin, questionableand potentially harmfultreatments for COVID-19 have circulated the internet. Instructions for storing, preparing, and administering the study treatment will be provided to participants. You can also search for this author in PubMed The reduction in virus load over the entire treatment period was clinically meaningful for all three groups (p<0.0001 for both genes). Of note, the decrease of viral load on day 4 was significantly greater in the 0.1% azelastine group (decrease by log10 1.901.03) compared to placebo (decrease by log10 1.050.70). Unlike a COVID vaccine that boosts a persons immune system as protection, the antiviral nasal spray works more directly by blocking the virus, acting as a "biological mask in the nasal cavity," according to, One of these smaller antibodies is being developed, to develop synthetic nanobodies; and in a third case, researchers isolated nanobodies. JPK and CL have received grants from the sponsor URSAPHARM Arzneimittel GmbH for performing this trial. Components are mixed from two chambers to create the final NO-producing formulation. The team will enrol 480 healthworkers, including nurses and doctors . Watts, A. M., Cripps, A. W., West, N. P. & Cox, A. J. Modulation of allergic inflammation in the nasal mucosa of allergic rhinitis sufferers with topical pharmaceutical agents. 00:00. Pharmacol. Identification of SARS-CoV-2 entry inhibitors among already approved drugs. The study, published March 28 in the journal Nature, employed experimental mice engineered with human . PubMed If delivery took place within 24h after sampling, samples were to be stored at<25C, if storage period was greater than 24h (e.g., on Sundays), samples had to be stored and shipped at 28C. Overall, none of the participating patients had clinically relevant increased values of body temperature (data not shown). 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. Outpatients visiting Corona test centres were informed about the possibility of participating in the trial. In a study funded by NIAID, researchers are using mice to look for genes that account for different COVID-19 symptoms. For clarity reason, only cp/mL values of the ORF 1a/b gene are shown in the main text of the manuscript. ISSN 1476-4687 (online) To infect a cell, the virus tricks several of that cells proteins, including one called TMPRSS2, to gain entry. The improvement of the symptom shortness of breath was significantly greater on days 3 (p=0.004) and 4 (p=0.011) in the 0.1% azelastine group compared to placebo (supplementary Figure S3). MG, PA, HM and HAS declare no conflict of interest. The median/mean viral load value (ORF 1a/b gene) of the ITT analysis set at enrolment was log10 7.23/6.851.31 cp/mL (approximately 7 million viral copies per mL, the highest values being~540 million cp/mL). D.G., C.S. Res. KaplanMeier analysis results regarding the ORF 1a/b gene from baseline (day 1) until day 11 of treatment (ITT analysis set). Z. Gesundheitswissenschaften J. Simon, M. W. The efficacy of azelastine in the prophylaxis of acute upper respiratory tract infections. COVID-19 vaccines teach the immune system to recognize a particular protein on SARS-CoV-2 that is known as the spike protein. Overall, no statistical differences between groups were determined. We are aware that this limited the capture of COVID-19 specific issues as questions were not specifically aimed for COVID-19 patients. Hamasaki, Y. et al. PubMed Identification of 14 known drugs as inhibitors of the main protease of SARS-CoV-2. 6). Xlear have developed and patented a xylitol containing nasal spray for the treatment of upper-respiratory tract infections. All authors contributed to the preparation of the manuscript, read and approved the manuscript. Allergy Asthma Immunol. Acta Pharmacol. By submitting a comment you agree to abide by our Terms and Community Guidelines. Multinomial regression analysis was done to 26 determine the association between nasal carriage of Bacillus and COVID-19 severity after 27 adjusting for age, sex, and co-morbidity status. During visits, nasopharyngeal swabs were taken for quantitative PCR measurements, and investigators assessed the patient status in accordance with the WHO clinical progression scale11. A complete list of inclusion and exclusion criteria is presented in Table 1. Cornell research team to develop COVID-19 nose spray treatment. R.M., S.M.S., S.A. and P.M. designed the study protocol. The researchers compared mice treated with TriSb92 before and after exposure to SARS-CoV-2. Expert. Shapira, T., Monreal, I. The azelastine 0.1% azelastine group displayed the greatest improvement of symptoms with 12.7410.74 mean score reduction. Cegolon, L. et al. analyzed 219,000 medical records in a retrospective data base survey study and demonstrated that azelastine showed the highest association between prior usage among these antihistamines and SARS-CoV-2 negative test results in patients above the age of 60 (OR: 2.43; 95% CI: 1.474.02). 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., . 538, 173179. To obtain EN, VS and GN are shareholders in CEBINA GmbH, RK and EN are inventors on related patent applications. All this made her work personal: for the past decade, Moscona, a molecular virologist, had been hunting for compounds that could stop viruses in their tracks, before the pathogens infect even a single cell in a persons body. Correspondence to The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. Preliminary results of the current study have been published as preprint15. Public Health 3, 21. https://doi.org/10.1007/BF02959944 (1995). 8, 701709. also provided experimental evidence for the inhibition of the enzyme in a kinetic activity assay7. The Ct<25 group consisted of 19 patients in the 0.1% azelastine group, 21 patients in the 0.02% azelastine group and of 17 patients in the placebo group (Fig. Med. 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. Detection of the alpha (B.1.1.7) variant was based on single nucleotide polymorphism analysis for SARS-CoV-2 spike gene mutation N501Y and deletion H69/V70. Front. Samples were processed on the day of receipt at the central processing laboratory (Institute of Virology, University Hospital Cologne, Cologne, Germany) by vortexing and aliquoting the viral transport medium and stored at80C until analysis. https://doi.org/10.1056/NEJMc2027040 (2021). In the meantime, to ensure continued support, we are displaying the site without styles Nature 602, 676681. & Ware, J. Investigators and trial participants were masked to the treatment as investigational medicinal products were identical in appearance. Lancet Respir. Following sampling, swabs were placed into 3mL Virus Transport Medium (VTM, Biocomma) and delivered to the laboratory as quickly as possible. De Vries, R. D. et al. All nasal sprays were composed of hypromellose, disodium edetate, citric acid, disodium phosphate dodecahydrate, sodium chloride and purified water. drafted the manuscript. CAS March 31, 2023 An antiviral therapy in early development has the potential to prevent COVID-19 infections when given as a nasal spray as little as 4 hours before exposure. It has been suggested that azelastine can inhibit the entry of the SARS-CoV-2 into the nasal mucosa by binding to the ACE2 receptor and also act via binding to the main protease of SARS-CoV-2 and to the host cells sigma-1 receptor, therewith facilitating both viral entry and replication-inhibiting effects6,9. Furthermore, three independent groups predicted interaction of azelastine hydrochloride with the main protease of SARS-CoV-2: main protease (Mpro) or 3C-like cysteine protease (3CLpro)7,8,9. Our study population was characterized by an initial mean viral load of log10 6.851.31cp/mL, which was higher than more recently reported SARS-CoV-2 viral load values26. N. Engl. 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. 48.9% (n=44) of the safety analysis set was male, and the average age was 35.6712.94years. SARS-CoV-2 RNA levels in nasopharyngeal swabs were determined by quantitative RT-PCR using the cobas SARS-CoV-2 Test on the cobas 6800 system (Roche Diagnostic, Mannheim, Germany). Although no significant differences between groups regarding the total symptom score was shown, it may be speculated that the 0.1% azelastine spray may have positive influences on single symptoms such as shortness of breath, which was improved significantly greater in this treatment group compared to placebo at early time points of infection. was responsible for data management activities. SARS-CoV-2 infection progression starts with viral entrance mediated by the spike glycoproteins interaction with the host ACE2 receptor molecule. It's a type of antibody that targets the coronavirus' spike protein. 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. Nasal steroid sprays may reduce the severity of COVID-19, according to a new study. Studies into Xlear's antiviral effects on SARS . Objectives: The Hungarian vaccination campaign was conducted with five different vaccines during the third wave of the coronavirus disease 2019 (COVID-19) pandemic in 2021. A summary of study activities is displayed in Table 2. Mitze, T. & Rode, J. Early-stage spatial disease surveillance of novel SARS-CoV-2 variants of concern in Germany with crowdsourced data. Additionally, safety follow-ups were performed at 2 time-points. 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. 1). 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. ACS Med. By blocking that access, compounds that target TMPRSS2 have the potential to be effective against both current and future variants. 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. Eric Topol, MD, director and founder, Scripps Research Translational Institute, La Jolla, CA; editor-in-chief, Medscape. One of these smaller antibodies is being developedfrom llamas for example; another comes fromexperiments with yeast to develop synthetic nanobodies; and in a third case, researchers isolated nanobodiesfrom llamas and from mice and showed they could neutralize the SARS-CoV-2 virus. It was assumed that all treatment groups present identical baseline virus load at enrolment with a mean value of 5.5 log10 copies/mL3 SD13,14. JAMA Otolaryngol. H.S. New research has answers, COVID's future: mini-waves rather than seasonal surges, Are repeat COVID infections dangerous? Of those, 27 patients belonged to the 0.1% azelastine group, 28 patients to the 0.02% azelastine group and 26 patients to the placebo group (Fig. The nasal sprays for COVID have been shown to surpass existing antibody treatments in engineered mice and have been effective in treating and preventing not only standard COVID-19 infections. In addition, presence or absence of fever (38.0C) was documented daily (0=no fever, 3=fever). Symptoms were analyzed as single symptom scores, and as the total symptom score (TSS) reflecting the sum of all 20 single symptoms and presence/absence of fever (reaching a minimum value of 20 and maximum value of 103). It would be desirable to use a validated, COVID-19 specific questionnaire in future studies, and first attempts for its development are promising32. Viruses 12, 1384. https://doi.org/10.3390/v12121384 (2020). The anti-histamine azelastine, identified by computational drug repurposing, inhibits infection by major variants of SARS-CoV-2 in cell cultures and reconstituted human nasal tissue. Initial viral loads were log10 6.851.31 (meanSD) copies/mL (ORF 1a/b gene). Sci Rep 13, 6839 (2023). Infect. https://doi.org/10.1016/s1473-3099(20)30483-7 (2020). and JavaScript. For male patients, the assessment was done via phone call. Smell retraining therapy (SRT) is a treatment for loss of smell, also referred to as hyposmia or anosmia. Expert Opin. The dual-target RT-PCR independently targets the ORF1a/b and the sarbecovirus E genes, and assays were considered positive if at least one target returned a positive result (Ct values reflecting an inverse relationship with viral load). Molecular docking and dynamics simulation of FDA approved drugs with the main protease from 2019 novel coronavirus. Article Rep. 117 https://doi.org/10.1007/s43440-023-00463-7. Nature 605, 340348 (2022). Sci. Loading Twitter content. https://doi.org/10.1038/s41586-021-04388-0 (2022). To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Liu, L. et al. The spritz developed by Moscona's team is one of a raft of proposed nasal sprays to prevent SARS-CoV-2 infection. Topol is also editor-in-chief of Medscape, WebMD's sister site for medical professionals. TriSb92 could effectively tip the balance in favor of the [the person] and thereby help to reducethe risk of severe COVID-19 disease, she said.. Those compounds were tested in human lung and colon cells that were then exposed to SARS-CoV-2. Jean, F. (2022). The study was termed CARVIN (referring to COVID-19: Azelastine nasal spray Reduces Virus-load In Nasal swabs). ISSN 2045-2322 (online). Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2. Infect. Those parameters were based on the COVID-19 symptoms published by the Robert Koch Institute (https://www.rki.de) at the time of the study. Health-related quality of life in patients with COVID-19; international development of a patient-reported outcome measure. https://doi.org/10.1021/acsmedchemlett.0c00521 (2020). Rev. Killingley, B. et al. It also appears to work as a treatment if used within 4 hours after infection inside the nose, new research reveals., Known as TriSb92(brand name Covidin, from drugmaker Pandemblock Oy in Finland), the viral inhibitoralso appears effective against all coronavirus variants of concern, neutralizing even the Omicron variants BA.5, XBB, and BQ.1.1 in laboratory and mice studies., Unlike a COVID vaccine that boosts a persons immune system as protection, the antiviral nasal spray works more directly by blocking the virus, acting as a "biological mask in the nasal cavity," according to the biotechnology company set up to develop the treatment.. Cornell Daily Sun. 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. Receive 51 print issues and online access, Get just this article for as long as you need it, Prices may be subject to local taxes which are calculated during checkout, doi: https://doi.org/10.1038/d41586-022-03341-z. Comirnaty is also authorized . Cite this article. 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. contributed to the study conceptualisation. Continuous data were described by statistical estimates (mean, standard deviation, median, minimum, and maximum values). Symptoms were documented in patient diaries. Of note, 30 (non-related) adverse events in 13 patients (7 patients with 16 events in the 0.1% azelastine, 2 patients with 4 events in the 0.02% azelastine, and 4 patients with 10 events in the placebo group) were still ongoing at the final safety follow up on day 60. Thus, it should be kept in mind that treatment started at a time point where the peak of viral load had probably passed. Only one of the 20 mice given saline survived. If all goes well, the hope is that we'll have a safe and effective nasal spray to serve as an extra line of defense in the fight against COVID-19. Klussmann, J. P. et al. 17(2), 19. You are using a browser version with limited support for CSS. Wiesmller (health authorities Cologne, Germany) for his support regarding regulatory issues, PD Dr. E. Raskopf for editorial assistance, and H. Papp for her assistance in PCR control experiments. B.R. Similarly, no clinically relevant differences regarding blood oxygen saturation values were detected between groups (data not shown). https://doi.org/10.1038/s41598-023-32546-z, DOI: https://doi.org/10.1038/s41598-023-32546-z. June 10, 2022 at 2:00 pm. Lee, K. (2022, April 27). Assuming a pooled standard deviation of =3 units, a two-sided =0.05 and a power of 90%, a sample size of 23 patients per treatment group was calculated. Of note, the mean viral load value showed small variability, thereby supporting the power of the current study. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Guenezan, J. et al. Patients were visited and tested at home on regular basis by the investigators, physicians specialised in otorhinolaryngology, medical hygiene, or general medicine. Treatment kits were manufactured by URSAPHARM Arzneimittel GmbH, Saarbruecken, Germany, according to the randomization list (as sequentially numbered containers). The higher viral load value may be explained with the dominance of the alpha (B.1.1.7) SARS-CoV-2 variant during the enrolment phase (Spring 2021, Germany16), which is known to infect the human nasal mucosa more efficiently than the wild-type and has been associated with higher viral load13,14. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. The investigators judged the efficacy as good or very good in 74.1% (0.1% azelastine treatment), 82.1% (0.02% azelastine treatment) and 73.1% (placebo treatment) of treated patients. The sprays would be fast-acting and would be applied frequently, perhaps once or. Absolute changes of total symptom scores from baseline (day 1) until day 11 of treatment (ITT analysis set). Sirijatuphat, R., Leelarasamee, A., Puangpet, T. & Thitithanyanont, A. Der deutsche SF-36 health survey bersetzung und psychometrische testung eines krankheitsbergreifenden instruments zur erfassung der gesundheitsbezogenen lebensqualitt. Of those, 81 patients belonged to the Intention-To-Treat (ITT) population, comprising randomised patients meeting the key eligibility criteria and having evaluable viral load data on day 1 (baseline) and on day 11 (end of treatment). We acknowledge support for the Article Processing Charge from the DFG (German Research Foundation, 491454339). Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. As a sensitivity analysis based on the SARS-CoV-2 E gene PCR tended to show overall the same effects, PCR results of the E gene are shown in the supplementary material (supplementary Table S3 and S4). ISSN 0028-0836 (print). contracts here. Google Scholar. 16, 275282. Researchers plan to continue testing the timing of when N-0385 should be administered and to expand testing into human clinical trials. Within the subgroup of patients with baseline Ct values below 25, a similar progression of viral load data was observed (Fig. Bearing in mind the low number of participants in the current proof-of-concept study, the results still build a promising foundation for a currently running phase III study, during which effects of azelastine nasal spray on symptom severity and progression to severe COVID-19 disease are investigated in a greater patient population. Overall, data of the primary outcome did not show a normal distribution (ShapiroWilk test, p<0.05). Comirnaty is FDA-approved as a 2-dose series for the prevention of COVID-19 in individuals 12 years of age and older. https://doi.org/10.1016/j.jinf.2021.05.009 (2021). the epithelium, to recreate the first line of defense against respiratory viruses. 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.
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