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. 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. PubMed Google Scholar. Science 371, 13791382 (2021). All methods were carried out in accordance with relevant guidelines, and the principles of Good Clinical Practice and the Declaration of Helsinki were adhered to. Boots Dual Defence Nasal Spray is used to dampen the symptoms of cold and flu. Since viral levels during early infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) tend to be highest in the nose and nasopharynx1, a nasal spray with an active substance inhibiting virus entry and replication may stop or delay the progression of the disease to the lower respiratory system and reduce the transmission to uninfected individuals. Patient disposition. COVID-19 vaccines teach the immune system to recognize a particular protein on SARS-CoV-2 that is known as the spike protein. For calibration purposes of quantitative assessments, reference samples were included with each PCR run. The nasal spray is comprised of xylitol and GSE (Grapefruit Seed extract) which provides antibacterial properties as well as preventing viral adhesion in the nasal passage. 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). The reduction in the symptom score was clinically relevant for all three groups. The experimental drug works in mice, and researchers believe it may be effective in humans. Investigators and trial participants were masked to the treatment as investigational medicinal products were identical in appearance. Small differences were found with regard to age and bmi, which were both slightly higher in the azelastine 0.1% group (supplementary Table S1). Pharmacol. 17(2), 19. Prevention is the best medicine, and COVID-19 vaccines block most SARS-CoV-2 infections. A summary of study activities is displayed in Table 2. Expert Opin. 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. But the spike protein may mutate to evade immune response. Virological assessment of hospitalized patients with COVID-2019. This trial was conducted at the Department of Otorhinolaryngology, Head and Neck Surgery of the Faculty of Medicine of the University of Cologne, Germany. Soft mist inhalers are propellant-free devices that are slightly larger than conventional metered dose inhalers. 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. Article HG, MS, and FK declare no conflict of interest. . https://doi.org/10.1001/jama.2021.0202 (2021). Suitable for JPK and CL have received grants from the sponsor URSAPHARM Arzneimittel GmbH for performing this trial. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in A research study at Swansea University is examining the efficacy of Boots Dual Defence - a 5.99 nasal spray containing seaweed - in preventing people becoming ill with Covid and reducing the . Virol. To obtain was responsible for data management activities. Other evidence of viral infection showed similar differences between treated and untreated mice in the protective lining of cells called the, inside the nose, nasal mucosa, and airways., : Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants.. Nature (Nature) Jean, F. (2022). This way, the virus moves on.. performed and supervised sample processing and viral load measurements. Pawar, R. D. et al. were investigators involved in the conduct of the study. Duration of culturable SARS-CoV-2 in hospitalized patients with covid-19. Sirijatuphat, R., Leelarasamee, A., Puangpet, T. & Thitithanyanont, A. You are using a browser version with limited support for CSS. https://doi.org/10.1007/s10787-021-00847-2 (2021). Nat. 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. During the treatment phase, 7 visits (V1V7) took place on days 1, 2, 3, 4, 5, 8 and 11. All authors contributed to the preparation of the manuscript, read and approved the manuscript. 147, 400401. Our study showed both strengths and limitations. Pujadas, E. et al. The product targets a stable site on the spike protein of the virus that is not known to mutate. 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., . Article Thank you for visiting nature.com. Absolute changes in viral copy numbers (log10 cp/mL) from baseline (day 1) over time based on the ORF 1a/b gene (ITT analysis set). 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. volume13, Articlenumber:6839 (2023) COVID-19 Get the latest information from the CDC about COVID-19. Nasopharyngeal swabs were obtained by investigators using nylon-flocked swabs (Biocomma; SW01E, flexible minitip, Biocomma, Shenzen, China). 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. 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. We would like to thank Prof. G.A. You are using a browser version with limited support for CSS. Scientists are working on fast-acting nasal sprays to block coronavirus infections but formulating the sprays is a challenge. All nasal sprays were composed of hypromellose, disodium edetate, citric acid, disodium phosphate dodecahydrate, sodium chloride and purified water. Yang, L. et al. China and India approve nasal COVID vaccines are they a game changer? Thus, it should be kept in mind that treatment started at a time point where the peak of viral load had probably passed. 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. Molecular docking and dynamics simulation of FDA approved drugs with the main protease from 2019 novel coronavirus. Article Early intervention with azelastine nasal spray may reduce viral load in SARS-CoV-2 infected patients. https://doi.org/10.1038/s41591-022-01780-9 (2022). Killingley, B. et al. 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). https://doi.org/10.1016/j.jinf.2021.05.009 (2021). 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. Public Health 3, 21. https://doi.org/10.1007/BF02959944 (1995). https://doi.org/10.1089/088318703322751327 (2004). Antiviral efficacy was observed at an EC50 of~6M, which is an approximately 400-fold lower concentration compared to commercially available azelastine nasal sprays. Google Scholar. 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. Information on individual variants was obtained through the original laboratory reports, when available. How nasal-spray vaccines could change the pandemic, How much virus does a person with COVID exhale? Similarly, when given 2 or 4 hours after SARS-CoV-2 had already infected the epithelium, TriSb92 was linked to a complete lack of the virus's RNA in the lungs. The patient status was assessed at V1V7 and at V9 by the investigators with a 11-category ordinal score proposed by the WHO11. Get the most important science stories of the day, free in your inbox. 8, e70. 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. Various studies have looked at the role of different foods in preventing coronavirus infection severe Covid-19 These include seaweed and grapefruit-based nasal sprays, dark chocolate, tuna. Pediatr. SARS-CoV-2 infection progression starts with viral entrance mediated by the spike glycoproteins interaction with the host ACE2 receptor molecule. was the deputy investigator. Lancet Respir. Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults. Antiviral activity was subsequently verified in cell culture. PubMed During visits, nasopharyngeal swabs were taken for quantitative PCR measurements, and investigators assessed the patient status in accordance with the WHO clinical progression scale11. But vaccines are fighting a changing opponent. ICE-COVID, will investigate whether Dual Defence can either prevent Covid-19 infection or reduce . 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. 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. https://doi.org/10.1001/jamaoto.2020.5490 (2021). On days 1, 5, 8 and 11, patients completed the standardized SF-36 questionnaire of quality of life. Slider with three articles shown per slide. 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. Health-related quality of life in patients with COVID-19; international development of a patient-reported outcome measure. Viral load and disease severity in COVID-19. 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. Article This is exemplified by the emergence of the highly immune evasive omicron variant that is resistant to many monoclonal antibodies authorized for clinical use34. Google Scholar. 03:08. 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. Performance of self-collected saliva testing compared with nasopharyngeal swab testing for the detection of SARS-CoV-2. 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. The shown effects of azelastine nasal spray may thus be suggestive of azelastines potential as an antiviral treatment. It also appears to . Resource-efficient internally controlled in-house real-time PCR detection of SARS-CoV-2. 538, 173179. The WHO clinical progression scale progressively decreased in all treatment groups during the study. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. & Ware, J. Although it may be expected that the azelastine might be most efficacious during very early time points after infection, its application in the current study setting could only be started during the symptomatic phase of the disease. All tests were performed two-sided and the type 1 error () was set to 5%. 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. 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). Shapira, T., Monreal, I. A study led by an expert from The University of Western Australia has found a virus-killing nasal spray could be effective in reducing the spread of COVID-19. What the science says, Racial inequalities deepened in US prisons during COVID, The WHO at 75: what doesnt kill you makes you stronger, White House to tap cancer leader Monica Bertagnolli as new NIH director, Massive mosquito factory in Brazil aims to halt dengue, Seeks to identify an outstanding Scientific Director to lead its Division of Preclinical Innovation (DPI) in Rockville, Maryland. 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). 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. Since the start of the COVID-19 pandemic, its treatment via the nasal route has been studied for a range of drugs17. Comirnaty may help your body develop immunity to SARS-CoV-2, the virus that causes COVID-19. Liu, L. et al. Early intervention with azelastine nasal sprays reduces viral load in SARS-CoV-2 infected patients. identified azelastine as an anti-viral candidate and demonstrated pronounced anti-SARS-CoV-2 activity in vitro10. Patients were visited and tested at home on regular basis by the investigators, physicians specialised in otorhinolaryngology, medical hygiene, or general medicine. JAMA Otolaryngol. Topol is also editor-in-chief of Medscape, WebMD's sister site for medical professionals. 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). 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 The trial protocol and the data are however available from the authors upon reasonable request and with permission of URSAPHARM Arzneimittel GmbH. Med. PubMed After having given informed consent, patients tested positively for SARS-CoV-2 were examined to assess eligibility according to inclusion/non-inclusion criteria and subsequently randomized to one of the three study groups. The researchers compared mice treated with TriSb92 before and after exposure to SARS-CoV-2. The sprays would be fast-acting and would be applied frequently, perhaps once or. 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. Within this context it is important to point out that in vitro data indicate efficacy of azelastine against various SARS-CoV-2 variants tested10. 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). Cornell Daily Sun. 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. A closer look at single symptoms confirmed moderate expression of symptoms (supplementary Figure S1) and the general decrease of symptoms over time (supplementary Figure S2). Short intervals of swab collection time points, particularly during early days of infection, and high number of PCR tests aimed to monitor SARS-CoV-2 viral loads as closely as possible, considering that only limited knowledge regarding details of viral clearance was publicly available at the time of the study development. 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. [1] Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants. Struct. Thank you for visiting nature.com. Biophys. EN, VS and GN are shareholders in CEBINA GmbH, RK and EN are inventors on related patent applications. Chem. Whether the current data can be extrapolated to other SARS-CoV-2 variants needs to be investigated. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Overall, none of the participating patients had clinically relevant increased values of body temperature (data not shown). 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. For data analysis, negative PCR results were replaced with the Ct value 45 and the cp/mL value 1, respectively. Ther. 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. Now, researchers at Swansea University will test Boots' Dual Defence Nasal Spray, which costs 5.99 for 20ml, against Covid-19. 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%. 1). was responsible for the patient disposition. The current proof-of-concept study served to investigate if nasally applied azelastine may have the potential to reduce the viral load (via blocking viral entry and viral replication) in patients tested positively for SARS-CoV-2. Nasal defence sprays Products such as Vicks First Defence nasal spray claim to trap and neutralise viruses in the nose before they have a chance to develop and spread. Now, researchers at Swansea University will test it against Covid-19. It would be desirable to extend the investigation of azelastine nasal spray as potential antiviral treatment with in vitro culture experiments. 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.. Gottlieb, R. L. et al. KaplanMeier survival analyses with log-rank test were performed to display the occurrence of negative PCR test results upon treatment. the epithelium, to recreate the first line of defense against respiratory viruses. Trial registration: The study was registered in the German Clinical Trial Register (DRKS-ID: DRKS00024520; Date of Registration in DRKS: 12/02/2021). An essential round-up of science news, opinion and analysis, delivered to your inbox every weekday. 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. Approval of the study by the German Federal Institute for Drugs and Medical Devices (BfArM) was given on 3rd February 2021. . By blocking that access, compounds that target TMPRSS2 have the potential to be effective against both current and future variants. 20, e192e197. Open Access funding enabled and organized by Projekt DEAL. SARS-CoV-2 viral load predicts COVID-19 mortality. 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. PubMed By Dr. Ramya Dwivedi, Ph.D. Jul 19 2021. 1). Pharmaceutics 14, 2059. https://doi.org/10.3390/pharmaceutics14102059 (2022). Future studies will help understanding the impact of azelastine hydrochloride in treating SARS-CoV-2 infected patients. Subgroups were analysed exploratorily (e.g., subgroups regarding gender, age, symptom severity, etc.). Associate Professor Peter Friedland, from UWA's Medical School, was lead author of the study In vivo . Med. 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. A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic. 31(6), 113. 2 and supplementary Table S2). TMPRSS2 is a protein in mouse and human cells that SARS-CoV-2 uses as a gateway to infect humans. Ku Z, Xie X, Hinton PR, Liu X, Ye X, Muruato AE, Ng DC, Biswas S, Zou J, Liu Y, Pandya D, Menachery VD, Rahman S, Cao . . J.P.K. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. https://doi.org/10.1016/s1081-1206(10)63465-5 (1996). It would be desirable to study azelastine treatment in a greater COVID-19 population to get further insights on azelastines effects on individual symptoms and to determine its potential on long-term symptoms. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. Currently, the jury is out on their effectiveness and evidence is still limited, but it's possible they could act as a prophylactic for a short period of time. 24 COVID-19 status classified as negative, asymptomatic, mild, or severe. https://cornellsun.com/2022/04/27/cornell-research-team-to-develop-covid-19-nose-spray-treatment/, Shapira, T., Monreal, I. However, the overall small number of participants limits conclusions, and results should be interpreted with care. 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. and showed they could neutralize the SARS-CoV-2 virus. ITTintention to treat. Amdal, C. D. et al. 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. Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. Viruses 12, 1384. https://doi.org/10.3390/v12121384 (2020). Monoclonal antibodies can block SARS-CoV-2 from . E.N., V.S., G.N., R.K., A.B., M.F. Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2. Evaluation of AUC values (reflecting baseline adjusted decreases of viral load over 11days) showed that the 0.1% azelastine group exhibited a greater AUC value of 24.1413.12 (referring to greater decrease) compared to the placebo group with an AUC value of 18.894.70 (p=0.007, Fig. 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. During the course of the treatment, all study groups showed clear improvements of symptoms (Fig.
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