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COVID nasal sprays may one day prevent and treat infection

<p>We have vaccines to boost our immune response to SARS-CoV-2, the virus that causes COVID. We have medicines you can take at home (and in hospital) to treat COVID. Now researchers are trialling something new.</p> <p>They want to develop drugs that stop the virus getting into the body in the first place. That includes nasal sprays that stop the virus attaching to cells in the nose.</p> <p>Other researchers are looking at the potential for nasal sprays to stop the virus replicating in the nose, or to make the nose a hostile place to enter the body.</p> <p>Here’s where the science is up to and what we can expect next.</p> <h2>How could we block the virus?</h2> <p>“Viral blockade”, as the name suggests, is a simple premise based on blocking SARS-CoV-2. In other words, if something gets in its way, the virus cannot attach to a cell and it can’t infect you.</p> <p>As SARS-CoV-2 is a respiratory virus, it makes sense to deliver this type of medicine where the virus mainly enters the body – via the nose, in a nasal spray.</p> <p>There are various groups around the world working on this concept. Some research is still being conducted in the lab. Some agents have progressed to preliminary human trials. None are yet available for widespread use.</p> <p><strong>Heparin</strong></p> <p>Heparin is a common medicine that’s been used for decades to thin the blood. Studies in mice show that when heparin is delivered via the nose, <a href="https://link.springer.com/article/10.1007/s11095-022-03191-4" target="_blank" rel="noopener">it’s safe</a> and <a href="https://journals.asm.org/doi/10.1128/JVI.01987-20" target="_blank" rel="noopener">effective</a> in preventing the virus binding to nose cells. Researchers believe heparin binds to the virus itself and stops the virus attaching to the cells it’s trying to infect.</p> <p>A <a href="https://clinicaltrials.gov/ct2/show/NCT05204550" target="_blank" rel="noopener">clinical trial</a> is being <a href="https://www.premier.vic.gov.au/covid-nasal-spray-treatment-clinical-trials-begin" target="_blank" rel="noopener">conducted in Victoria</a> in collaboration between multiple Melbourne-based research centres and the University of Oxford.</p> <p><strong>Covixyl-V</strong></p> <p>Covixyl-V (ethyl lauroyl arginine hydrochloride) is another nasal spray <a href="https://assets.researchsquare.com/files/rs-911449/v1/0577f1f1-56f8-476f-97f6-d27d332ea9ca.pdf?c=1643375660" target="_blank" rel="noopener">under development</a>. It aims to prevent COVID by blocking or modifying the cell surface to prevent the virus from infecting.</p> <p>This compound has been explored for use in various viral infections, and <a href="https://assets.researchsquare.com/files/rs-911449/v1/0577f1f1-56f8-476f-97f6-d27d332ea9ca.pdf?c=1643375660" target="_blank" rel="noopener">early studies</a> in cells and small animals has shown it can prevent attachment of SARS-CoV-2 and reduce the overall viral load.</p> <p><strong>Iota-carrageenan</strong></p> <p>This molecule, which is extracted from seaweed, acts by blocking virus entry into <a href="https://www.frontiersin.org/articles/10.3389/fviro.2021.746824/full" target="_blank" rel="noopener">airway cells</a>.</p> <p>One study of about 400 health-care workers suggests a nasal spray may reduce the incidence of COVID <a href="https://www.dovepress.com/efficacy-of-a-nasal-spray-containing-iota-carrageenan-in-the-postexpos-peer-reviewed-fulltext-article-IJGM" target="_blank" rel="noopener">by up to 80%</a>.</p> <p><strong>IGM-6268</strong></p> <p>This is <a href="https://www.nature.com/articles/s41586-021-03673-2" target="_blank" rel="noopener">an engineered antibody</a> that binds to SARS-CoV-2, <a href="https://www.sciencedaily.com/releases/2021/06/210603171306.htm" target="_blank" rel="noopener">blocking</a> the virus from attaching to cells in the nose.</p> <p>A nasal and oral (mouth) spray are in a clinical trial <a href="https://clinicaltrials.gov/ct2/show/NCT05184218?term=IGM-6268&amp;draw=2&amp;rank=2" target="_blank" rel="noopener">to assess safety</a>.</p> <p><strong>Cold atmospheric plasma</strong></p> <p>This is a gas that contains charged particles. At cold temperatures, it can <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0165322" target="_blank" rel="noopener">alter the surface</a> of a cell.</p> <p>A <a href="https://www.thno.org/v12p2811.htm" target="_blank" rel="noopener">lab-based study</a> shows the gas changes expression of receptors on the skin that would normally allow the virus to attach. This results in less SARS-CoV-2 attachment and infection.</p> <p>Scientists now think this technology could be adapted to a nasal spray to prevent SARS-CoV-2 infection.</p> <h2>How could we stop the virus replicating?</h2> <p>Another tactic is to develop nasal sprays that stop the virus replicating in the nose.</p> <p>Researchers are designing genetic fragments that bind to the viral RNA. These fragments – known as “<a href="https://www.nature.com/articles/s41467-022-32216-0" target="_blank" rel="noopener">locked nucleic acid antisense oligonucleotides</a>” (or LNA ASOs for short) – put a proverbial spanner in the works and stop the virus from replicating.</p> <p>A spray of these genetic fragments delivered into the nose <a href="https://www.nature.com/articles/s41467-022-32216-0" target="_blank" rel="noopener">reduced virus replication in the nose</a> and prevented disease in small animals.</p> <h2>How could we change the nose?</h2> <p>A third strategy is to change the nose environment to make it less hospitable for the virus.</p> <p>That could be by using a nasal spray to change moisture levels (with saline), alter the pH (making the nose more acidic or alkaline), or adding a virus-killing agent (iodine).</p> <p>Saline can reduce the amount of <a href="https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2768627" target="_blank" rel="noopener">SARS-CoV-2 in the nose</a> by simply washing away the virus. One study has even found that saline nasal irrigation <a href="https://journals.sagepub.com/doi/10.1177/01455613221123737" target="_blank" rel="noopener">can lessen COVID disease</a> severity. But we would need further research into saline sprays.</p> <p>An Australian-led study has found that an iodine-based nasal spray <a href="https://www.theajo.com/article/view/4466/html" target="_blank" rel="noopener">reduced the viral load</a> in the nose. Further <a href="https://www.uwa.edu.au/news/Article/2022/February/Study-finds-nasal-spray-could-aid-battle-against-COVID" target="_blank" rel="noopener">clinical trials</a> are planned.</p> <p><a href="https://www.sciencedirect.com/science/article/pii/S1386653222001809#!" target="_blank" rel="noopener">One study</a> used a test spray – containing ingredients including eucalyptus and clove oils, potassium chloride and glycerol. The aim was to kill the virus and change the acidity of the nose to prevent the virus attaching.</p> <p>This novel formulation has been tested in the lab and in a <a href="https://www.sciencedirect.com/science/article/pii/S1386653222001809#!" target="_blank" rel="noopener">clinical trial</a> showing it to be safe and to reduce infection rate from about 34% to 13% when compared to placebo controls.</p> <h2>Barriers ahead</h2> <p>Despite promising data so far on nasal sprays for COVID, one of the <a href="https://www.nature.com/articles/d41586-022-03341-z" target="_blank" rel="noopener">major barriers</a> is keeping the sprays in the nose.</p> <p>To overcome this, most sprays need multiple applications a day, sometimes every few hours.</p> <p>So based on what we know so far, nasal sprays will not singlehandedly beat COVID. But if they are shown to be safe and effective in clinical trials, and receive regulatory approval, they might be another tool to help prevent it.</p> <p><strong>This article originally appeared on <a href="https://theconversation.com/covid-nasal-sprays-may-one-day-prevent-and-treat-infection-heres-where-the-science-is-up-to-193840" target="_blank" rel="noopener">The Conversation</a>.</strong></p> <p><em>Image: Shutterstock</em></p>

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Keep your nose out of it: why saliva tests could offer a better alternative to nasal COVID-19 swabs

<p>Saliva is one of our biggest foes in the COVID-19 pandemic, because of its role in spreading the virus. But it could be our friend too, because it potentially offers a way to diagnose the disease without using invasive nasal swabs.</p> <p>Our research review, <a href="https://www.mdpi.com/2075-4418/10/5/290">published in the journal Diagnostics</a>, suggests saliva could offer a readily accessible diagnostic tool for detecting the presence of SARS-CoV-2, the virus that causes COVID-19, and might even be able to reveal whether someone’s immune system has already encountered it.</p> <p>COVID-19 testing is a crucial part of the pandemic response, especially now countries are gradually lifting social distancing restrictions. This requires widespread, early, accurate and sensitive diagnosis of infected people, both with and without symptoms.</p> <p>Our review looked at the results of three different studies, in Hong Kong, the nearby Chinese mainland city of Shenzhen, and Italy. All three studies found SARS-CoV-2 is indeed present in the saliva of COVID-19 patients (at rates of 87%, 91.6%, and 100% of patients, respectively). This suggests saliva is a potentially very useful source of specimens for detecting the virus.</p> <p>Saliva <a href="https://www.sciencedirect.com/science/article/pii/S016041202031254X">spreads the SARS-CoV-2 virus</a> via breathing, coughing, sneezing, and <a href="https://www.nap.edu/catalog/25769/rapid-expert-consultation-on-the-possibility-of-bioaerosol-spread-of-sars-cov-2-for-the-covid-19-pandemic-april-1-2020">conversation</a>, which is why guidelines suggest we maintain a distance of at least 1.5 metres from one another. We also know <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094991/">SARS-CoV-2 can survive in tiny droplets of saliva</a> in an experimental setting.</p> <p>Saliva is an attractive option for detecting SARS-CoV-2, compared with the <a href="https://www.healthdirect.gov.au/coronavirus-covid-19-seeing-a-doctor-getting-tested-faqs#diagnosis">current tests</a> which involve taking swabs of mucus from the upper respiratory tract. Saliva is easy to access, which potentially makes the tests cheaper and less invasive. Saliva can hold up a <a href="https://www.ncbi.nlm.nih.gov/pubmed/19726214">mirror to our health</a>, not just of our mouth but our whole body.</p> <p>For this reason, saliva has already been widely investigated as a diagnostic tool for chronic systemic diseases, as well as for oral ailments such as periodontal disease and oral cancers. But less attention has been given to its potential usefulness in acute infectious diseases such as COVID-19, perhaps because researchers and clinicians don’t yet appreciate its full potential.</p> <p><strong>What a mouthful</strong></p> <p>When we get sick, much of the evidence is present in our saliva – from the germs themselves, to the antibodies and immune system proteins we use to fight them off. Saliva also contains genetic material and other cellular components of pathogens after we have broken them down (for the full biochemical breakdown of the weird and wonderful things in our saliva, see pages 51-61 of our <a href="https://www.mdpi.com/2075-4418/10/5/290">review</a>).</p> <p>Saliva is also hardy. It can be <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=High-yield+RNA-extraction+method+for+saliva">stored at –80℃ for several years with little degradation</a>.</p> <p>This means it would be relatively straightforward to track the progression of COVID-19 in individual patients, by collecting saliva at various times during the disease and recovery. Saliva tests from recovered patients could also tell us if they have encountered the disease for a second time, and how strong their immune response is.</p> <p>However, there is no research yet available on using saliva to monitor immune responses. This will be well worth investigating, given the pressing need for a reliable and cost-effective way to monitor the population for immunity to COVID-19 as the outbreak continues.</p> <p><strong>Could saliva testing replace nasal swabs?</strong></p> <p>An ideal saliva test would be a disposable, off-the-shelf device that could be used at home by individuals, without exposing them or others to the risk of visiting a clinic.</p> <p>One drawback with the research so far is that it has involved small numbers of patients (each of the three studies we reviewed involved no more than 25 people), and there is little published detail on exactly how these studies collected the saliva – whether from the mouth or throat, whether by spitting, drooling or swabbing, and whether collected by the patient or by a clinician.</p> <p>Nevertheless, based on the modest amount of research done so far, saliva looks like a promising candidate for COVID-19 testing. More research is now needed, in larger groups of people, to learn more about how to confidently test for SARS-CoV-2 in the saliva of both symptomatic and non-symptomatic people.</p> <p>Earlier this month the US Food and Drug Administration <a href="https://www.nytimes.com/2020/05/08/health/fda-coronavirus-spit-test.html">approved the sale</a> of saliva-based COVID-19 test kits that will allow people to collect their own samples and send them to a lab for analysis.</p> <p>A reliable test would offer a cheaper, less invasive and potentially even more accurate way to detect the virus, which would also reduce the risk posed by routine COVID-19 checks to both patients and front-line medical professionals.</p> <p><em>Written by Pingping Han. Republished with permission of </em><a href="https://theconversation.com/keep-your-nose-out-of-it-why-saliva-tests-could-offer-a-better-alternative-to-nasal-covid-19-swabs-138816"><em>The Conversation.</em></a></p> <p><em> </em></p>

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Doctors uncover disgusting find in man’s unbearably blocked nose

<p>Zhang Binsheng, 30, went to the doctors after struggling to breathe for the last three months. His symptoms were so severe that he could not sleep properly at night and reported smelling “decay” out of one nostril.</p> <p>The doctors advised him to undergo an X-ray, where a shadow of ‘high density’ material was uncovered at the back of his nasal cavity.</p> <p>Zhang was left stunned when medics explained that it was his own tooth.</p> <p>“(It) looked a lot like a tooth,” Dr Bai Zhibang, a deputy director at the hospital’s ear, nose and throat department, told <em><a rel="noopener" href="https://www.pearvideo.com/video_1620810" target="_blank" title="www.pearvideo.com">Pear Video</a></em>.</p> <p>The tooth had been knocked out of Zhang’s mouth when he fell from the fourth floor of a mall at the age of ten and had managed to root and grow in his nasal cavity.</p> <p>This means that the tooth had been growing in Zhang’s nose for the last twenty years.</p> <p>Doctor Guo Longmei explained that the reason that the body hadn’t rejected the tooth was because it was Zhangs and not a ‘foreign object’.</p> <p><img style="width: 0px; height: 0px;" src="https://oversixtydev.blob.core.windows.net/media/7832417/tooth-body.jpg" alt="" data-udi="umb://media/05204a0162064ff59685b602d25dcaea" /></p> <p>The tooth measured at 1cm and was removed from <span>Zhang’s nose in a 30-minute surgery. He is said to be recovering well.</span></p> <p>According to<span> </span><em><a rel="noopener" href="https://metro.co.uk/2019/11/11/mans-blocked-nose-caused-tooth-growing-nostril-11080867/" target="_blank">Metro</a>,<span> </span></em>having a tooth growing inside your nose is considered to be rare, with less than 0.1 per cent of the population likely to be affected.</p>

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