the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in A pilot study of 0.4% povidone-iodine nasal spray to eradicate SARS-CoV-2 in the nasopharynx. Nature 581, 465469. The antiviral also could offer an alternative to people who cannot or do not respond to a vaccine. 6). 538, 173179. 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.. 19(10), 16. https://doi.org/10.1001/jamaoto.2020.5490 (2021). Our study results provide the first human data showing that azelastine hydrochloride nasal spray used in a 0.1% concentration may be effective in accelerating the reduction of virus load in the nasal cavity and improving symptoms reported by COVID-19 patients. The overall AUC of the Azelastine 0.1% group (red area) was significantly greater than that of placebo (green area), p=0.007. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Anna R. Mkel, PhD, senior scientist, Department of Virology, University of Helsinki, Finland. 11, 25262533. Nasopharyngeal swabs were obtained by investigators using nylon-flocked swabs (Biocomma; SW01E, flexible minitip, Biocomma, Shenzen, China). 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). A Boots nasal spray for cold and flu has shown positive results during testing to see if it could help tackle coronavirus infections. 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. 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. C.A. Elife 10, e69302. The researchers first tried one dose a day for seven days, starting a day before SARS-CoV-2 infection. Nat. SARS-CoV-2 infection progression starts with viral entrance mediated by the spike glycoproteins interaction with the host ACE2 receptor molecule. drafted the manuscript. Postdoctoral Associate- Immunology, T Cells, GVHD, Bone Marrow Transplantation, Postdoctoral Fellows in the VU Department of Biochemistry. To infect a cell, the virus tricks several of that cells proteins, including one called TMPRSS2, to gain entry. Hypromellose-based nasal spray solution containing human IgG1 anti-SARS-CoV-2 antibody cocktail is a medical device innovated to provide the dual-action physical barrier on nasal mucosa that aids the natural defence in which the mucus layer is fortified by a steric barrier-forming agent HPMC and invading viral particles of all major SARS-CoV-2 To evaluate the total load during the study, AUC was calculated using a linear equation. The study was funded by URSAPHARM Arzneimittel GmbH, Saarbruecken, Germany and CEBINA GmbH Vienna, Austria. Kalle Saksela, MD, PhD, virologist, University of Helsinki, Nature Communications: Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants.. 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. 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). Reznikov et al. Virological assessment of hospitalized patients with COVID-2019. When treated with N-0385, 70% of the mice survived and had little to no lung damage. CAS If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Chem. Thus, eligibility criteria were designed carefully to investigate a clearly defined, homogeneous study population of low-risk patients with a narrow age range. Ther. Ghahremanpour et al. Cornell research team to develop COVID-19 nose spray treatment. Informed consent was obtained from all participants prior to involvement in the study. reported that a low pH hypromellose nasal powder spray containing common components of nasal sprays could reduce SARS-CoV-2 infection rates19. 15, 75297536. Levine-Tiefenbrun, M. et al. Small differences were found with regard to age and bmi, which were both slightly higher in the azelastine 0.1% group (supplementary Table S1). FH is the CEO of URSAPHARM Arzneimittel GmbH. D.G., C.S. Med. EudraCT number: 2020-005544-34. Patient Rep. Outcomes 6, 26. https://doi.org/10.1186/s41687-022-00434-1 (2022). PM, MF, DG, CS and BS are employed at URSAPHARM Arzneimittel GmbH. Reznikov, L. R. et al. The surface of SARS-CoV-2, the virus that causes COVID-19, is covered with spike proteins. How nasal-spray vaccines could change the pandemic, How much virus does a person with COVID exhale? The sample size calculation was based on the expected reduction of virus load during the treatment considering 3 treatment arms. About 388 participants were included in the study Recently, Shmuel et al. 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. Yang, L. et al. Mitze, T. & Rode, J. Early-stage spatial disease surveillance of novel SARS-CoV-2 variants of concern in Germany with crowdsourced data. 24 COVID-19 status classified as negative, asymptomatic, mild, or severe. Ann. 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: https://doi.org/10.1038/s41586-021-04388-0 (2022). 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 authors contributed to the preparation of the manuscript, read and approved the manuscript. Odhar, H. A. et al. https://cornellsun.com/2022/04/27/cornell-research-team-to-develop-covid-19-nose-spray-treatment/, Shapira, T., Monreal, I. 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). Viruses 12, 1384. https://doi.org/10.3390/v12121384 (2020). By submitting a comment you agree to abide by our Terms and Community Guidelines. 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. Internet Explorer). When treated with N-0385, 70% of the mice survived and had little to no lung damage. https://doi.org/10.1016/j.bbrc.2020.11.095 (2021). Thank you for visiting nature.com. 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. Postdoctoral fellowship in vascular biology at UT Southwestern, studying the endothelial basis of cardiometabolic disease. Comirnaty is FDA-approved as a 2-dose series for the prevention of COVID-19 in individuals 12 years of age and older. Google Scholar. Many elderly people as well asindividuals who are immunodeficient for various reasons do not respond to vaccines, and are in the need of other protective measures, said Kalle Saksela, MD, PhD, senior author of the study and a virologist at the University of Helsinki. Public Health 3, 21. https://doi.org/10.1007/BF02959944 (1995). This is similar to the natural SARS-CoV-2 clearance time of approximately 2weeks. Slider with three articles shown per slide. identified azelastine as an anti-viral candidate and demonstrated pronounced anti-SARS-CoV-2 activity in vitro10. P eople who receive a Covid booster dose in the UK next month will be among the first in the world to receive Moderna's dual-variant vaccine, which protects against two strains of the virus.But . Further endpoints include infection. https://doi.org/10.1016/s1081-1206(10)63465-5 (1996). The Sponsor designed a dual chamber nasal spray bottle for NORS administration. Study endpoints were presented by descriptive statistics, aiming to compare the course of viral load between the three treatment groups. Researchers are developing coronavirus vaccines that will be sprayed up the nose. The sprays generally require multiple doses per day, whereas a single dose of a nasal vaccine may protect for months, he said. We are aware that this limited the capture of COVID-19 specific issues as questions were not specifically aimed for COVID-19 patients. Kim, M.-C. et al. It's a type of antibody that targets the coronavirus' spike protein. Sin. At the end of the study, patients and investigators assessed the overall tolerability and efficacy of the treatment as very good (3), good (2), moderate (1) or poor (0). Patient reported outcomes were documented by patient diaries and questionnaires. Early intervention with azelastine nasal sprays reduces viral load in SARS-CoV-2 infected patients. 31(6), 113. The researchers first tried one dose a day for seven days, starting a day before SARS-CoV-2 infection. 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. https://doi.org/10.1007/s11224-020-01605-w (2020). 13, 861295. https://doi.org/10.3389/fphar.2022.861295 (2022). . Expert. One puff of the respective nasal spray was applied per nostril, 3 times a day (morning, midday, evening). 83, 237279. Thank you for visiting nature.com. Clinical efficacy of nitric oxide nasal spray (NONS) for the treatment of mild COVID-19 infection. 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. Comirnaty is the FDA-approved monovalent COVID-19 (coronavirus 2019) vaccine made by Pfizer for BioNTech. 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. and B.S. Ralph Msges. PubMed Smell retraining therapy (SRT) is a treatment for loss of smell, also referred to as hyposmia or anosmia. Of note, we cannot rule out the possibility that the placebo (nasal spray buffer) contributed to viral clearance. Antiviral activity was subsequently verified in cell culture. Viral load and disease severity in COVID-19. 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. However, a rinsing and diluting effect of the placebo formulation would have led to an underestimation of the effect of the use of the azelastine nasal spray. Vitiello, A., Ferrara, F., Troiano, V. & La Porta, R. COVID-19 vaccines and decreased transmission of SARS-CoV-2. 59.3% (0.1% azelastine treatment), 50.0% (0.02% azelastine treatment) and 80.8% (placebo treatment) of patients assessed the overall tolerability of the treatment as very good, which mirrored the tolerability judgement of the investigators, which was assessed as very good for 59.3% (0.1% azelastine treatment), 50.0% (0.02% azelastine treatment) and 80.8% (placebo treatment) of patients. 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. 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. A study of frontline workers is looking into how a Boots nasal spray could prevent Covid-19. The team will enrol 480 healthworkers, including nurses and doctors . H.S. 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. 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. 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. R.M., S.M.S., S.A. and P.M. designed the study protocol. Allergy Asthma Immunol. Guenezan, J. et al. Three-group comparisons were analysed with KruskalWallis test. KaplanMeier analysis results regarding the ORF 1a/b gene from baseline (day 1) until day 11 of treatment (ITT analysis set). We acknowledge support for the Article Processing Charge from the DFG (German Research Foundation, 491454339). J. Med. 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. The researchers compared mice treated with TriSb92 before and after exposure to SARS-CoV-2. 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. Xlear have developed and patented a xylitol containing nasal spray for the treatment of upper-respiratory tract infections. De Vries, R. D. et al. During the course of the treatment, all study groups showed clear improvements of symptoms (Fig. Gottlieb, R. L. et al. The hope is the vaccines will build immunity in one spot the coronavirus often invades . Rep. 117 https://doi.org/10.1007/s43440-023-00463-7. Topol is also editor-in-chief of Medscape, WebMD's sister site for medical professionals. Applied treatment regimens aimed to explore differences regarding viral carriage upon treatment with azelastine compared to placebo. 62, 50937, Cologne, Germany, CEBINA GmbH, Karl-Farkas-Gasse 22, 1030, Vienna, Austria, Eszter Nagy,Valria Szijrt&Gbor Nagy, Department of Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, Dr.-Bohr-Gasse 9, 1030, Vienna, Austria, Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital, University of Cologne, Kerpener Str. This observational study (HUN-VE: Hungarian Vaccine Effectiveness) estimated vaccine effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related mortality in 3.7 million . Researchers supported in part by the National Institute of Allergy and Infectious Diseases (NIAID) have developed a nasal spray that has the potential to not only treat COVID-19 but also prevent SARS-CoV-2 infection in a way that the virus cant mutate to avoid. https://doi.org/10.1038/s41586-022-04661-w. Read stories about the efforts underway to prevent, detect, and treat COVID-19 and its effects on our health. J. Rep. 12, 899. https://doi.org/10.1038/s41598-021-04573-1 (2022). And she wished she could feel confident that she could see her immunocompromised relatives without inadvertently spreading the novel coronavirus to them. Those compounds were tested in human lung and colon cells that were then exposed to SARS-CoV-2. CAS 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. Intern. 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. 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 viral load reduction of the ORF 1a/b gene from baseline to day 11 was log10 5.042.05 in the 0.1% azelastine group, log10 4.391.74 in the 0.02% azelastine and log10 4.151.34 in the placebo group. Researchers at Swansea University will begin human trials this week following a successful study suggests the 5.99 remedy, Dual Defence, could help reduce infections thanks to its special ingredient - seaweed . 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%. https://doi.org/10.1007/s10787-021-00847-2 (2021). Trial registration: The study was registered in the German Clinical Trial Register (DRKS-ID: DRKS00024520; Date of Registration in DRKS: 12/02/2021). Both descriptive and exploratory statistics were performed. Lee, C. & Corren, J. Now, researchers at Swansea University will test it against Covid-19. J.P.K. 4). Get the most important science stories of the day, free in your inbox. Since the start of the COVID-19 pandemic, its treatment via the nasal route has been studied for a range of drugs17. Overall, no statistical differences between groups were determined. For pairwise comparisons between treatment groups, Mann Whitney U test was performed, and significance levels were adjusted to p<0.0167 based on the Bonferroni correction. A nasal and mouth spray called "IGM-6268" is in the early stages of clinical trials. 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. Correspondence to Similarly, no clinically relevant differences regarding blood oxygen saturation values were detected between groups (data not shown). ITTintention to treat. 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., . 62, 50937, Cologne, Germany, Medical Faculty, Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne, Kerpener Str. The current study was a randomized, parallel, double-blind, placebo-controlled trial. The 0.02% azelastine group showed an AUC value of 22.6412.56, which was not significantly different from the placebo group (p=0.022, Fig. In a study funded by NIAID, researchers are using mice to look for genes that account for different COVID-19 symptoms. Anti. *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). 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. It can be used to help return your sense of smell if it was lost during a viral infection or minor head trauma. First report on a double-blind placebo-controlled phase II clinical trial. Subgroups were analysed exploratorily (e.g., subgroups regarding gender, age, symptom severity, etc.). The mean bmi of participants was 24.915.27. Nature 602, 676681. Pawar, R. D. et al. For male patients, the assessment was done via phone call. June 16, 2022, U.S. Department of Health and Human Services, The researchers first tried one dose a day for seven days, starting a day before SARS-CoV-2 infection. Now, researchers at Swansea University will test Boots' Dual Defence Nasal Spray, which costs 5.99 for 20ml, 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. Treatment kits were manufactured by URSAPHARM Arzneimittel GmbH, Saarbruecken, Germany, according to the randomization list (as sequentially numbered containers). Virol. Ghahremanpour, M. M. et al. and showed they could neutralize the SARS-CoV-2 virus. Res. Asthma Allergy Immunol. Eric Topol, MD, director and founder, Scripps Research Translational Institute, La Jolla, CA; editor-in-chief, Medscape. 00:00. 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., . Investigators and trial participants were masked to the treatment as investigational medicinal products were identical in appearance. 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. As expected, a continuous decrease in the mean virus load was observed in all study groups during the 11 treatment days. 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). 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. Only one of the 20 mice given saline survived. 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. N. Engl. 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). Sci Rep 13, 6839 (2023). Even in cases where the antiviral does not prevent coronavirus infection, the treatment could slow infection. Now, researchers at Swansea University will test it against Covid-19 Now, researchers at Swansea University. Since the start of the Coronavirus Disease 2019 (COVID-19) pandemic, several independent research groups revealed azelastines potential as a promising candidate for drug repurposing to reduce SARS-CoV-2 viral load and infection rates5,6,7,8,9,10. Google Scholar. 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. https://doi.org/10.1080/14787210.2021.1908127 (2021). When the treatment course was shortened to four days, starting one day before infection, all 10 of the mice treated with N-0385. C.L. Resource-efficient internally controlled in-house real-time PCR detection of SARS-CoV-2. 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. You are using a browser version with limited support for CSS. Preliminary results of the current study have been published as preprint15. Thus, it should be kept in mind that treatment started at a time point where the peak of viral load had probably passed. Within the subgroup of patients with baseline Ct values below 25, a similar progression of viral load data was observed (Fig. 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. Article Health-related quality of life in patients with COVID-19; international development of a patient-reported outcome measure. It would be desirable to extend the investigation of azelastine nasal spray as potential antiviral treatment with in vitro culture experiments. 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.. were involved in data management. & Ware, J. performed the statistical analysis. 62, 50937, Cologne, Germany, Jens Peter Klussmann,Maria Grosheva,Paula Aguiar de Arago,Henning Morr&Helal Al Saleh, URSAPHARM Arzneimittel GmbH, Industriestrae 35, 66129, Saarbruecken, Germany, Peter Meiser,Michael Flegel,Frank Holzer,Dorothea Gro,Charlotte Steinmetz&Barbara Scherer, Department I of Internal Medicine, Division of Infectious Diseases, University of Cologne, Kerpener Str. 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. Article Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological . An essential round-up of science news, opinion and analysis, delivered to your inbox every weekday. Google Scholar. New research has answers, COVID's future: mini-waves rather than seasonal surges, Are repeat COVID infections dangerous? 384, 671673. Therefore, the primary analysis for the viral loads was conducted non-parametrically. Of note, pharmacometric analyses of our data indicate that more frequent applications of the nasal spray may be more appropriate for efficient treatment35. Struct. EN, VS and GN are shareholders in CEBINA GmbH, RK and EN are inventors on related patent applications.
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