Eric Topol, MD, director and founder, Scripps Research Translational Institute, La Jolla, CA; editor-in-chief, Medscape. Smell retraining therapy (SRT) is a treatment for loss of smell, also referred to as hyposmia or anosmia. We would like to thank Prof. G.A. The nasal spray, which contains carragelose, a patented version of iota-carrageenan (a form of seaweed), has already been proven to help shorten the duration and severity of cold and flu-like. 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). 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. Biochem. It would be desirable to extend the investigation of azelastine nasal spray as potential antiviral treatment with in vitro culture experiments. To evaluate the total load during the study, AUC was calculated using a linear equation. Importantly, the AUC analysis depicting the viral load decrease based on the detection of the ORF 1a/b gene over the 11-day treatment period showed a significantly greater reduction of virus load in the 0.1% azelastine group compared to placebo. Lancet Respir. J.P.K. Early negativization of SARS-CoV-2 infection by nasal spray of seawater plus additives: The RENAISSANCE open-label controlled clinical trial. The sprays would be fast-acting and would be applied frequently, perhaps once or. Pharmaceutics 14, 2502. https://doi.org/10.3390/pharmaceutics14112502 (2022). Dual Defence Nasal Spray is an easy to use nasal spray containing clinically proven Carragelose to help shorten the duration and severity of cold and flu-like symptoms. The primary endpoint of the CARVIN study was the assessment of virus load kinetics of SARS-CoV-2 by determining the presence and amount of viral carriage via PCR. Levine-Tiefenbrun, M. et al. 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. Assignment of the treatment with the investigational medicinal product in the different doses vs. placebo to each treatment number was performed in a centrally conducted, computer-generated 1:1:1 randomization procedure. Konrat, R. et al. Pawar, R. D. et al. Anna R. Mkel, PhD, senior scientist, Department of Virology, University of Helsinki, Finland. These latch onto ACE2 receptors on human cells, allowing the virus to enter and infect the cells. Get the most important science stories of the day, free in your inbox. https://doi.org/10.1007/s10787-021-00847-2 (2021). 1). ISSN 1476-4687 (online) Will there be a COVID winter wave? . Inhibition of leukotriene synthesis by azelastine. Prevention is the best medicine, and COVID-19 vaccines block most SARS-CoV-2 infections. Symptoms were documented in patient diaries. These nanobodies and TriSb92 target a specific part of the coronavirus spike protein called the receptor-binding domain (RBD). Slider with three articles shown per slide. By blocking that access, compounds that target TMPRSS2 have the potential to be effective against both current and future variants. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. On Day 8, 5 of the 27 (18.5%) and 6 of the 28 (21.4%) patients in the 0.1% azelastine and 0.02% azelastine groups, respectively were negative for the ORF1a/b gene, compared to the 0 of 26 patients in the placebo group. Applied treatment regimens aimed to explore differences regarding viral carriage upon treatment with azelastine compared to placebo. 15, 75297536. Nature 581, 465469. Comirnaty may help your body develop immunity to SARS-CoV-2, the virus that causes COVID-19. and B.S. Whether the current data can be extrapolated to other SARS-CoV-2 variants needs to be investigated. Following sampling, swabs were placed into 3mL Virus Transport Medium (VTM, Biocomma) and delivered to the laboratory as quickly as possible. Indeed, the majority of the study subjects carried this variant. Infect. Secondary endpoints included the assessment of symptoms, patient status (using a 11-category ordinal score as proposed by the WHO11), body temperature and blood oxygen saturation, quality of life (reported in the SF-36 generic quality of life questionnaires) and safety (adverse events, including worsening of patient status/symptoms) over time. https://doi.org/10.2147/idr.S391630 (2022). 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. Monoclonal antibodies can block SARS-CoV-2 from . Bullinger, M., Kirchberger, I. Ethics approval was granted by the Ethics Committee of the Faculty of Medicine of Cologne University on the 10th of February 2021. https://doi.org/10.1080/14787210.2021.1908127 (2021). Article 1). KaplanMeier survival analyses with log-rank test were performed to display the occurrence of negative PCR test results upon treatment. When the treatment course was shortened to four days, starting one day before infection, all 10 of the mice treated with N-0385 survived. 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). *p=0.005 comparing the decrease of viral load on day 4 in the 0.1% azelastine group (log10 1.901.03) compared to placebo (log10 1.050.70; p=0.005). Emerg. reviewed, edited and finalised the manuscript. Chem. De Vries, R. D. et al. The shown effects of azelastine nasal spray may thus be suggestive of azelastines potential as an antiviral treatment. Nineteen of those were common COVID-19 symptoms (shortness of breath [n=4], loss of smell [n=4], loss of taste [n=3], [muscle] weakness [n=2], tiredness/exhaustion [n=2], muscle ache, concentration impaired, headache, and cough). Early intervention with azelastine nasal sprays reduces viral load in SARS-CoV-2 infected patients. Researchers began to work on compounds that stifle TMPRSS2s ability to interact with the viral protein. In a highly relevant and translational in vitro model using reconstituted human nasal tissue, a fivefold diluted commercially available azelastine nasal spray solution inhibited viral replication almost completely within 72h after SARS-CoV-2 infection10. PubMed Central Virol. 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. PubMed ACS Med. Pujadas, E. et al. 20, e192e197. Killingley, B. et al. What scientists say. 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. It would be desirable to use a validated, COVID-19 specific questionnaire in future studies, and first attempts for its development are promising32. Patients had to daily document their COVID-19 specific symptoms in an electronic patient diary. Nature 605, 340348 (2022). Thus, a nitric oxide nasal spray was shown to reduce the viral load in adult patients with mild COVID-19 infection, and an accelerated SARS-CoV-2 clearance compared to placebo was demonstrated18. The study was funded by URSAPHARM Arzneimittel GmbH, Saarbruecken, Germany and CEBINA GmbH Vienna, Austria. 18, 110. https://doi.org/10.1186/s12985-021-01559-3 (2021). 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. (2021) COVID-19: Azelastine nasal spray reduces virus-load in nasal swabs (CARVIN). 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. 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. How nasal-spray vaccines could change the pandemic, How much virus does a person with COVID exhale? 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. Nat. The data that support the findings of this study are available from URSAPHARM Arzneimittel GmbH but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. By submitting a comment you agree to abide by our Terms and Community Guidelines. ADS From hydroxychloroquine and veterinarian doses of the antiparasitic drug ivermectin, questionableand potentially harmfultreatments for COVID-19 have circulated the internet. 17(2), 19. Nationwide effectiveness of five SARS-CoV-2 vaccines in - PubMed Jain, R. & Mujwar, S. Repurposing metocurine as main protease inhibitor to develop novel antiviral therapy for COVID-19. Nasal antiviral blocks SARS-CoV-2 infection in mice, Finding Effective Treatments for SARS-CoV-2 Variants, Understanding the Range of Reactions to SARS-CoV-2, Lee, K. (2022, April 27). Additionally, 0.02% azelastine nasal spray and 0.1% azelastine nasal spray were formulated by the addition of 0.2mg/mL or 1mg/mL azelastine hydrochloride, respectively. 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. https://doi.org/10.1016/s1473-3099(20)30483-7 (2020). Identification of 14 known drugs as inhibitors of the main protease of SARS-CoV-2. 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. Intern. 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. 76, 469475. Treatment of COVID-19 with a hypertonic solution containing seawater, xylitol, panthenol and lactic acid was shown to reduce the viral shedding time in patients with asymptomatic or mild COVID-1920, whereas application of povidone iodine nasal spray showed only poor influence on SARS-CoV-2 viral titres21,22. 11, 25262533. During visits, nasopharyngeal swabs were taken for quantitative PCR measurements, and investigators assessed the patient status in accordance with the WHO clinical progression scale11. 8, 701709. Since azelastine has been shown to inhibit viral replication by 99.9% in Vero E6 cell culture and in reconstituted human nasal tissue cultures, it was assumed that a reduction of 3-log in virus load would be seen within 3days in actively treated patients, while no effect on virus load reduction would be seen in placebo treated patients. Importantly, this scenario corresponds to current COVID-19 treatment regimens (e.g., with monoclonal antibodies or antiviral substances), which are usually started at57days upon start of symptoms but are still efficacious. Google Scholar. The overall AUC of the Azelastine 0.1% group (red area) was significantly greater than that of placebo (green area), p=0.007. Patients aged 18 to 60years were eligible to participate if tested positive for SARS-CoV-2 in a Corona test centre by PCR test within 48h prior to inclusion and had to quarantine at home due to instructions of the local health authority. Reznikov, L. R. et al. 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. Thank you for visiting nature.com. The Coronavirus Immunotherapy Consortium identified new candidate drugs based on monoclonal antibodies in work funded by NIAID. Boots Dual Defence Nasal Spray Family Bundle - 4 x 20ml Boots Dual Defence Nasal Spray Family Bundle - 4 x 20ml 20.00 Save 3.96 Worth 23.96 when bought separately 1486004 Maximum quantity reached Add to basket Add to favourites Collect 80 Boots Advantage Card points with this purchase Product details In this bundle: Thus, antibody therapy (bamlanivimab and etesevimab) in positively tested, non-hospitalized patients demonstrated that treatment resulted in decreased SARS-CoV-2 viral load by log100.57 on day 11, which was significantly greater compared to placebo (p=0.01)33. AB is employed at Ursatec GmbH, supplier of primary packing materials to Ursapharm. D.G., C.S. The trial medication (placebo nasal spray, 0.02% azelastine nasal spray or 0.1% azelastine nasal spray (the latter being identically composed as the commercial anti-allergic product Pollival) was manufactured at URSAPHARM Arzneimittel GmbH, Saarbruecken, Germany). Area under the curve (AUC) reflecting changes in viral copy numbers (log10 cp/mL) from baseline (day 1) over time (until day 11) based on the ORF 1a/b gene (ITT analysis set). Hamasaki, Y. et al. While comparison of categorial variables between groups were performed by Chi square testing, continuous variables were compared using ANCOVA with the factors baseline, visit, and treatment group. Article Generally, treatment with azelastine appeared safe in SARS-CoV-2 positive patients: no serious adverse events were reported in the current study, and the number of adverse events was comparable between groups. Provided by the Springer Nature SharedIt content-sharing initiative. 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. You are using a browser version with limited support for CSS. Nasal spray that protects against COVID-19 is also effective against the common cold . Patient Rep. Outcomes 6, 26. https://doi.org/10.1186/s41687-022-00434-1 (2022). Rev. EudraCT number: 2020-005544-34. China and India approve nasal COVID vaccines are they a game changer? 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. https://doi.org/10.21203/rs.3.rs-864566/v1. 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). BR, SMS, HS, CA, NW, SA, and RM are employees of ClinCompetence Cologne, the CRO which organized this trial. Data on virus variants was available for 59 patients and 54 (92%) of those carried the alpha (B.1.1.7) variant. 83, 237279. The reduction of the symptom score from baseline to day 11 was 8.389.42 in the 0.02% azelastine group and 11.129.45 in the placebo group. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access funding enabled and organized by Projekt DEAL. PubMed Central Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological . 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). Upon treatment, a gradual decline of viral load from baseline (day 1) to day 11 of treatment was observed in all three study groups. It also appears to . Identification of antiviral antihistamines for COVID-19 repurposing. 2 and supplementary Table S2). Infect. 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 this context, it is interesting to note that publications indicate that individuals vaccinated against SARS-CoV-2 have lower viral loads and are less contagious24,25. Quantifying the relationship between SARS-CoV-2 viral load and infectiousness. https://cornellsun.com/2022/04/27/cornell-research-team-to-develop-covid-19-nose-spray-treatment/, Shapira, T., Monreal, I. Overall, no significant differences were observed between treatment groups regarding gender, age and body mass index (bmi, supplementary Table S1). About 388 participants were included in the study Postdoctoral Associate- Immunology, T Cells, GVHD, Bone Marrow Transplantation, Postdoctoral Fellows in the VU Department of Biochemistry. The Sponsor designed a dual chamber nasal spray bottle for NORS administration. At V1, a comparable distribution of patients with a score of 1 (14.8% in the 0.1% azelastine group, 14.3% in the 0.02% azelastine group and 23.1% in the placebo group) or 2 (85.2% in the 0.1% azelastine group, 85.7% in the 0.02% azelastine group and 76.9% in the placebo group) was observed. 10, 294. https://doi.org/10.3389/fphar.2019.00294 (2019). Loading Twitter content. . Researchers have looked for ways to prevent SARS-CoV-2 infection that the virus cant learn to dodge or evade by mutating. Can Nasal Sprays Treat or Prevent COVID-19? - GoodRx To infect a cell, the virus tricks several of that cells proteins, including one called TMPRSS2, to gain entry. Betadine as COVID-19 Prevention Risks - Health Med. Article A nasal and mouth spray called "IGM-6268" is in the early stages of clinical trials. KaplanMeier survival analyses underlined those findings, indicating that mean times of a PCR result to turn negative was 9.96days (95% CI: 9.0210.90) in the 0.1% azelastine group, 10.21days (95% CI: 9.5710.86) in the 0.02% azelastine group and 11.00 (95% CI: 10.0010.77) in the placebo group (Fig. Lancet Infect. Jean, F. (2022). Of note, in vitro tests carried out prior to the current study did not indicate any interaction between the study products and the PCR reaction (see supplementary PCR data). 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. Nature (Nature) First report on a double-blind placebo-controlled phase II clinical trial. https://doi.org/10.1007/s11739-021-02786-w (2021). C.L. Samples of day 1 represent pre-treatment baseline samples. Only one of the 20 mice given saline survived. Whereas PCR data of individual days served for daily comparisons between treatment groups, the area under the curve (AUC) value was used for the evaluation of the overall development of viral kinetics. 384, 671673. COVID-19 Get the latest information from the CDC about COVID-19. For clarity reason, only cp/mL values of the ORF 1a/b gene are shown in the main text of the manuscript. An essential round-up of science news, opinion and analysis, delivered to your inbox every weekday. The sprays generally require multiple doses per day, whereas a single dose of a nasal vaccine may protect for months, he said. Struct. A final safety follow-up and assessment of the patient status (WHO scale) by phone call was done on day 60 (V9) for all patients. Zapor, M. Persistent detection and infectious potential of SARS-CoV-2 virus in clinical specimens from COVID-19 patients. Other evidence of viral infection showed similar differences between treated and untreated mice in the protective lining of cells called theepithelium inside the nose, nasal mucosa, and airways.. Dis. Patients were visited and tested at home on regular basis by the investigators, physicians specialised in otorhinolaryngology, medical hygiene, or general medicine. SARS-CoV-2 viral load predicts COVID-19 mortality. Now, researchers at Swansea University will test it against Covid-19 Now, researchers at Swansea University. Patient disposition. New methods of fast-acting COVID-19 prevention are being researched to make it safer to be in large public gatherings like sporting events or concerts. Rep. 12, 899. https://doi.org/10.1038/s41598-021-04573-1 (2022). PubMed In addition, patient's quality of life was evaluated by the SF-36 questionnaire, covering 36 items divided into the 8 quality of life domains physical functioning; role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, and general health12. B.R. Internet Explorer). Google Scholar. J. 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. 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., . Front. Med. TMPRSS2 is a protein in mouse and human cells that SARS-CoV-2 uses as a gateway to infect humans. The aim of our study was to support the preclinical evidence for azelastines antiviral activity in patients tested positive for SARS-CoV-2. PubMed Central PubMedGoogle Scholar. It should be noted that the SARS-CoV-2 alpha variant (B.1.1.7) was the dominant variant in Germany during the enrolment phase of the current study16. https://doi.org/10.7554/eLife.69302 (2021). 6). 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). 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.. Sirijatuphat, R., Leelarasamee, A., Puangpet, T. & Thitithanyanont, A. H.G., M.S., and F.K. 538, 173179. Overall, no statistical differences between groups were determined. To obtain Negative PCR results appeared earlier and more frequently in the azelastine treated groups: being 18.52% and 21.43% in the 0.1% and 0.02% groups, respectively, compared to 0% for placebo on day 8. https://doi.org/10.1038/s41591-021-01316-7 (2021).
