tag:theconversation.com,2011:/ca-fr/topics/viral-infections-7133/articlesViral infections – La Conversation2024-03-01T13:33:21Ztag:theconversation.com,2011:article/2244932024-03-01T13:33:21Z2024-03-01T13:33:21ZMeasles is one of the deadliest and most contagious infectious diseases – and one of the most easily preventable<figure><img src="https://images.theconversation.com/files/578746/original/file-20240228-16-96qj3k.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2119%2C1414&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Young children, pregnant people and the immunocompromised are among the most vulnerable to measles.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/measles-royalty-free-image/534079149">CHBD/E+ via Getty Images</a></span></figcaption></figure><p>“You don’t count your children until the measles has passed.” <a href="https://www.nytimes.com/2022/11/05/health/samuel-katz-dead.html">Dr. Samuel Katz</a>, one of the pioneers of the first measles vaccine in the late 1950s to early 1960s, regularly heard this tragic statement from parents in countries where the measles vaccine was not yet available, because they were so accustomed to losing their children to measles.</p>
<p>I am a <a href="https://som.cuanschutz.edu/Profiles/Faculty/Profile/25677">pediatrician and preventive medicine physician</a>, and I have anxiously watched measles cases rise worldwide while <a href="https://www.cdc.gov/media/releases/2023/p1116-global-measles.html">vaccination rates have dropped</a> since the early days of the COVID-19 pandemic due to disruptions in vaccine access and the spread of vaccine misinformation.</p>
<p>In 2022 alone, there were <a href="http://dx.doi.org/10.15585/mmwr.mm7246a3">over 9 million measles cases and 136,000 deaths worldwide</a>, an 18% and 43% increase from the year before, respectively. The World Health Organization warned that <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/more-than-half-world-faces-high-measles-risk-who-says-2024-02-20/">over half the world’s countries</a> are at high risk of measles outbreaks this year.</p>
<p>The U.S. is no exception. The country is on track to have one of the worst measles years since 2019, when Americans experienced the <a href="https://www.cdc.gov/measles/cases-outbreaks.html">largest measles outbreak</a> in 30 years. As of mid-February 2024, <a href="https://www.cdc.gov/measles/cases-outbreaks.html">at least 15 states</a> have reported measles cases and multiple ongoing, uncontained outbreaks.</p>
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<figcaption><span class="caption">Measles is on the rise across the U.S. once again, despite being eliminated in 2000.</span></figcaption>
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<p>While this measles crisis unfolds, U.S. measles vaccination rates are at the <a href="http://dx.doi.org/10.15585/mmwr.mm7245a2">lowest levels in 10 years</a>. Prominent figures like the <a href="https://www.washingtonpost.com/health/2024/02/22/florida-measles-outbreak-ladapo/">Florida surgeon general</a> are responding to local outbreaks in ways that run counter to science and public health recommendations. The spread of <a href="https://www.nbcnews.com/health/health-news/measles-outbreaks-anti-vaccine-misinformation-rcna136994">misinformation and disinformation</a> from anti-vaccine activists online further promotes misguided ideas that measles is not a serious health threat and measles vaccination is not essential. </p>
<p>However, the evidence is clear: Measles is <a href="https://www.cdc.gov/measles/symptoms/complications.html">extremely dangerous</a> for everyone, and especially for young children, pregnant people and people with compromised immune systems. But simple and effective tools are available to prevent it.</p>
<h2>Measles is a serious illness</h2>
<p>Measles is one of the most deadly infectious diseases in human history. Before a vaccine became available in 1963, around 30 million people were infected with measles and <a href="https://doi.org/10.1016/j.eclinm.2024.102502">2.6 million people died from the disease</a> every year worldwide. In the U.S., measles was responsible for an estimated 3 million to 4 million infections. Among reported cases, there were 48,000 hospitalizations, 1,000 cases of encephalitis, or brain swelling, and 500 deaths <a href="https://www.cdc.gov/measles/about/history.html">every year</a>. </p>
<p>Measles is also one of the most contagious infectious diseases. According to the Centers for Disease Control and Prevention, <a href="https://www.cdc.gov/measles/about/parents-top4.html">up to 9 out of 10 people</a> exposed to an infected person will become infected if they don’t have protection from vaccines. The measles virus can stay in the air and infect others for up to two hours after a contagious person has left the room. Measles can also hide in an unknowing victim for <a href="https://www.cdc.gov/vaccines/pubs/surv-manual/chpt07-measles.html">one to two weeks and sometimes up to 21 days</a> before symptoms begin. Infected people can <a href="https://www.cdc.gov/measles/transmission.html">spread measles</a> for up to four days before they develop its characteristic rash, and up to four days after. </p>
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<a href="https://images.theconversation.com/files/578749/original/file-20240228-20-nsp7wf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Close-up of abdomen with red measles rash" src="https://images.theconversation.com/files/578749/original/file-20240228-20-nsp7wf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/578749/original/file-20240228-20-nsp7wf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/578749/original/file-20240228-20-nsp7wf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/578749/original/file-20240228-20-nsp7wf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/578749/original/file-20240228-20-nsp7wf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/578749/original/file-20240228-20-nsp7wf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/578749/original/file-20240228-20-nsp7wf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">One characteristic measles symptom is a rash that spreads from the face to the rest of the body.</span>
<span class="attribution"><a class="source" href="https://phil.cdc.gov/details.aspx?pid=3168">CDC/Heinz F. Eichenwald, MD</a></span>
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<p>The <a href="https://www.cdc.gov/measles/symptoms/signs-symptoms.html">initial symptoms</a> of measles are similar to those of many other common viral illnesses in the U.S.: fever, cough, runny nose and red eyes. Several days after symptoms begin, characteristic tiny white spots develop inside the mouth, and a facial rash spreads to the rest of the body. </p>
<p>While most people’s symptoms improve, 1 in 5 unvaccinated children will be hospitalized, 1 out of every 1,000 will develop brain swelling that can lead to brain damage, and up to <a href="https://www.cdc.gov/measles/symptoms/complications.html#">3 of every 1,000 will die</a>. For unvaccinated people who are pregnant, measles infection can lead to miscarriage, stillbirth, premature birth and low birth weight.</p>
<p>The risk of severe complications from measles persists even after a person appears to be fully recovered. In rare cases, people can experience a brain disease called <a href="https://www.ninds.nih.gov/health-information/disorders/subacute-sclerosing-panencephalitis#">subacute sclerosing panencephalitis</a> that develops seven to 10 years after infection and leads to memory loss, involuntary movements, seizures, blindness and eventually death.</p>
<p>Beyond these individual health effects, the <a href="https://www.idsociety.org/science-speaks-blog/2022/estimating-the-impact-how-much-does-a-measles-outbreak-cost/#/+/0/publishedDate_na_dt/desc/">financial cost</a> to society for containing measles outbreaks is significant. For example, a 2019 measles outbreak in Washington state is estimated to have cost <a href="https://doi.org/10.1542/peds.2020-027037">US$3.4 million</a>. Necessary efforts to control measles outbreaks pull millions of dollars’ worth of critical resources away from other essential public health functions such as ensuring food safety, preventing injuries and chronic diseases, and responding to disasters.</p>
<h2>Vaccines protect against measles</h2>
<p>Why put communities at risk and allow these societal costs from measles when effective and safe tools are available to protect everyone?</p>
<p>Measles vaccines have been so effective, providing lifelong protection to <a href="https://www.cdc.gov/measles/vaccination.html">over 97% of people</a> who receive two vaccine doses, that they are victims of their own success. Initial widespread measles vaccination had reduced measles cases by 99% compared to before the vaccine was available, and consequently, most people in the U.S. are unaware of the seriousness of this disease.</p>
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<a href="https://images.theconversation.com/files/578753/original/file-20240228-7861-io367m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Person looking at Florida Health measles and MMR shot information sheet" src="https://images.theconversation.com/files/578753/original/file-20240228-7861-io367m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/578753/original/file-20240228-7861-io367m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=454&fit=crop&dpr=1 600w, https://images.theconversation.com/files/578753/original/file-20240228-7861-io367m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=454&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/578753/original/file-20240228-7861-io367m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=454&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/578753/original/file-20240228-7861-io367m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=570&fit=crop&dpr=1 754w, https://images.theconversation.com/files/578753/original/file-20240228-7861-io367m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=570&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/578753/original/file-20240228-7861-io367m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=570&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Measles is a highly preventable disease.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/measles-information-sheet-is-seen-posted-at-the-orange-news-photo/1141724959">Paul Hennessy/NurPhoto via Getty Images</a></span>
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<p>Despite the success of highly effective vaccination programs in the U.S., anyone can still come into contact with measles in their community. Measles is most often brought into the U.S. by <a href="https://www.cdc.gov/measles/about/parents-top4.html">unvaccinated American travelers</a> returning home and sometimes from foreign visitors. For people traveling out of the country, the threat of measles exposure is even greater, with widespread outbreaks occurring in <a href="https://wwwnc.cdc.gov/travel/notices/level1/measles-globe">many travel destinations</a>.</p>
<p>Public health leaders who embrace and promote vaccination and follow simple, proven infectious disease containment measures can help prevent measles disease spread. Every single preventable illness, complication, hospitalization or death from measles is one too many.</p><img src="https://counter.theconversation.com/content/224493/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Higgins is affiliated with Immunize Colorado, a nonprofit that works to protect Colorado families, schools and communities from vaccine-preventable diseases (volunteer non-paid board of directors member) and American Academy of Pediatrics (volunteer non-paid chapter immunization representative for the Colorado chapter).</span></em></p>A pediatrician and preventive medicine physician explains how measles vaccines became victims of their own success and the risk that rising outbreaks pose to everyone.David Higgins, Research Fellow and Instructor in Pediatrics, University of Colorado Anschutz Medical CampusLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2201682024-01-17T13:37:40Z2024-01-17T13:37:40ZDengue fever: the tropical disease spreading across Europe<figure><img src="https://images.theconversation.com/files/566586/original/file-20231214-23-8x6yy5.jpg?ixlib=rb-1.1.0&rect=73%2C73%2C5390%2C3563&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The dengue virus is spread through bites from infected Aedes mosquitoes.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/es/image-photo/striped-mosquitoes-eating-blood-on-human-1510102085">Witsawat.S/Shutterstock</a></span></figcaption></figure><p>If you were looking for information on dengue fever and only had access to older textbooks, it would likely be found in the sections on tropical and subtropical diseases.</p>
<p>The disease is, indeed, spreading rapidly in warmer regions: Peru – which has mixed subtropical and tropical climates – has recently recorded some of <a href="https://www.unicef.org/peru/comunicados-prensa/mas-37-mil-ninas-ninos-adolescentes-enfermaron-de-dengue-primeros-meses-2023-recomendaciones-especialista">the highest numbers of the virus</a> (both cases and deaths) within memory. This has led to the declaration of a state of emergency in most of its regions, as cases continue to climb year after year.</p>
<h2>Record numbers of cases in 2023</h2>
<p>We are also seeing more and more new cases outside of Latin America. There have been increasing numbers of locally transmitted cases in the <a href="https://www.cdc.gov/dengue/statistics-maps/historic-data.html">USA</a>, <a href="https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2023.28.37.2300471">Italy</a> and <a href="https://www.santepubliquefrance.fr/en/autochthonous-dengue-in-mainland-france-2022-geographical-expansion-and-increase-in-incidence">France</a>, as well as the first recorded cases in many years in <a href="https://www.sanidad.gob.es/profesionales/saludPublica/ccayes/alertasActual/docs/20230228_ERR_Dengue_autoctono.pdf">Spain</a>.</p>
<p>In 2022, there were <a href="https://www3.paho.org/data/index.php/es/temas/indicadores-dengue/boletin-anual-arbovirosis-2022.html">2.8 million registered cases of dengue</a> on the American continent alone. This was more than double the 1.2 million cases in 2021.</p>
<p>Although the majority of cases affect <a href="https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON448">tropical and subtropical areas of America, Asia and Africa</a>, a significant increase has recently been observed in more temperate areas, such as Europe. This is especially true in the south of the continent, where the disease has been present since the 1970s.</p>
<p>According to statistics from the <a href="https://www.ecdc.europa.eu/en/dengue-monthly">European Centre for Disease Prevention and Control</a>, 71 locally transmitted cases of dengue were reported in 2022 in mainland EU countries. This is an increase of over 20% compared to 2021.</p>
<h2>Small bites, big consequences</h2>
<p><a href="https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue">Dengue</a> is a disease caused by one of the four strains of dengue virus (DENV). It has been reported that all four strains can circulate together, and that they can cause the same set of symptoms. Special attention should be given to severe or haemorrhagic dengue, which is usually caused by exposure to one strain after previous exposure to another.</p>
<p>DENV is <a href="https://www.cdc.gov/dengue/transmission/index.html">transmitted</a> through bites from infected <em>Aedes</em> mosquitoes, primarily <em>Aedes aegypti</em>, but also to a lesser extent <em>Aedes albopictus</em>, also known as the Tiger Mosquito. These insects, which feed on human blood and transmit the virus through their saliva, are found in tropical and subtropical areas. However, in recent decades they have become more and more common in temperate areas.</p>
<p>The virus is not transmitted directly, but works in a cycle, passing from human to mosquito to human. When an infected female <em>Aedes</em> mosquito bites a person, it introduces DENV into their system and begins the cycle. The incubation period is usually between 3 and 10 days, although it can vary depending on external factors such as temperature.</p>
<p>Symptoms then begin to develop, usually fever, headaches, muscle aches, joint pain, nausea and vomiting. In severe cases, it can lead to haemorrhage, organ failure and death.</p>
<p><em>Aedes</em> mosquitoes breed in standing or stagnant water, such as water containers, unused swimming pools, old tyres, and so on. In the absence of vaccines and effective treatments, it is important to eliminate mosquito breeding sites to prevent the transmission of the disease. This can not only prevent the spread of dengue, but also the mosquito-borne viruses that cause Zika and chikungunya.</p>
<h2>The role of climate change and globalisation</h2>
<p>Climate change is one of the <a href="https://pubmed.ncbi.nlm.nih.gov/30884421/">driving forces behind the rise in dengue cases</a>, both in America and Europe. Increased temperatures and longer mosquito breeding seasons (due to warmer and longer summers) may help the spread of <em>Aedes aegypti</em>.</p>
<p>These mosquitoes are able to survive in temperatures above 10C, and thanks to global warming they are able expand their range to more temperate zones. Changes in rainfall patterns – caused by climate change – also increase the volume of standing water, providing an ideal breeding ground.</p>
<p>In addition, increased international travel and trade with areas where dengue fever is common, as well as the growth of cities, make the spread of the disease all the more likely.</p>
<h2>Will dengue become endemic in Europe?</h2>
<p>Against this backdrop, the possibility of dengue becoming endemic in Europe is a real possibility. Environmental conditions such as climate change and globalisation are making it easier for mosquitoes – and the diseases they carry – to spread. These are factors that cannot easily be brought under control, at least for the time being.</p>
<p>If dengue were to become endemic in Europe, it could have a significant impact on public health. For this reason, <a href="https://climate-adapt.eea.europa.eu/en/observatory/evidence/health-effects/vector-borne-diseases/dengue-factsheet">European health authorities are already working</a> to prevent its spread by addressing the factors that can currently be controlled. This includes monitoring cases, educating populations on how to prevent mosquito bites, and taking measures to control new mosquito populations as soon as their presence is detected, as has been happening on the Spanish island of <a href="https://www.ull.es/portal/noticias/2023/sanidad-activa-con-ayuda-de-la-ull-el-protocolo-ante-la-deteccion-de-un-mosquito-aedes-albopictus-en-santa-cruz-de-tenerife/">Tenerife</a>.</p><img src="https://counter.theconversation.com/content/220168/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Raimundo Seguí López-Peñalver no recibe salario, ni ejerce labores de consultoría, ni posee acciones, ni recibe financiación de ninguna compañía u organización que pueda obtener beneficio de este artículo, y ha declarado carecer de vínculos relevantes más allá del cargo académico citado.</span></em></p>Climate change is causing dengue-carrying mosquitoes to spread. Could the disease become endemic in Europe?Raimundo Seguí López-Peñalver, Profesor de Epidemiología en VIU, Universidad Internacional de ValenciaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2134602023-11-23T19:02:31Z2023-11-23T19:02:31ZDrug resistance may make common infections like thrush untreatable<p><em>Antimicrobial resistance is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">one of the biggest global threats</a> to health, food security and development. This month, The Conversation’s experts <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">explore how we got here and the potential solutions</a>.</em></p>
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<p>We’ve all heard about antibiotic resistance. This happens when bacteria develop strategies to avoid being destroyed by an antibiotic. </p>
<p>The consequences of antibiotic resistance mean an antibiotic previously used to cure bacterial infections no longer works effectively because the bacteria have become resistant to the drug. This means it’s getting harder to cure the infections some bacteria cause.</p>
<p>But unfortunately, it’s only one part of the problem. The same phenomenon is also happening with other causes of infections in humans: fungi, viruses and parasites.</p>
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Read more:
<a href="https://theconversation.com/the-rise-and-fall-of-antibiotics-what-would-a-post-antibiotic-world-look-like-213450">The rise and fall of antibiotics. What would a post-antibiotic world look like?</a>
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<p>“Antimicrobial resistance” means the drugs used to treat diseases caused by microbes (bugs that cause infection) no longer work. This occurs with antibacterial agents used against bacteria, antifungal agents used against fungi, anti-parasitic agents used against parasites and antiviral agents used against viruses.</p>
<p>This means a wide range of previously controllable infections are becoming difficult to treat – and may become untreatable. </p>
<h2>Fighting fungi</h2>
<p>Fungi are responsible for a range of infections in humans. Tinea, ringworm and vulvovaginal candidiasis (thrush) are some of the more familiar and common superficial fungal infections. </p>
<p>There are also life-threatening fungal infections such as aspergillosis, cryptococcosis and invasive fungal bloodstream infections including those caused by <em>Candida albicans</em> and <em>Candida auris</em>. </p>
<p>Fungal resistance to antifungal agents is a problem for several reasons. </p>
<p>First, the range of antifungal agents available to treat fungal infections is limited, especially compared to the range of antibiotics available to treat bacterial infections. There are only four broad families of antifungal agents, with a small number of drugs in each category. Antifungal resistance further restricts already limited options.</p>
<p>Life-threatening fungal infections happen less frequently than life-threatening bacterial infections. But they’re rising in frequency, especially among people whose immune systems are compromised, including by <a href="https://7news.com.au/news/qld/first-heart-transplant-patient-to-die-from-fungal-infection-at-brisbanes-prince-charles-hospital-identified-as-mango-hill-gp-muhammad-hussain-c-12551559">organ transplants</a> and chemotherapy or immunotherapy for cancer. The threat of getting a drug-resistant fungal infection makes all of these health interventions riskier.</p>
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Read more:
<a href="https://theconversation.com/how-do-candida-auris-and-other-fungi-develop-drug-resistance-a-microbiologist-explains-203495">How do _Candida auris_ and other fungi develop drug resistance? A microbiologist explains</a>
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<p>The greatest <a href="https://www.frontiersin.org/articles/10.3389/fimmu.2017.00735/full">burden of serious fungal disease</a> occurs in places with limited health-care resources available for diagnosing and treating the infections. Even if infections are diagnosed and antifungal treatment is available, antifungal resistance reduces the treatment options that will work.</p>
<p>But even in Australia, common fungal infections are impacted by resistance to antifungal agents. Vulvovaginal candidiasis, known as thrush and caused by <em>Candida</em> species and some closely related fungi, is usually reliably treated by a topical antifungal cream, sometimes supplemented with an oral tablet. However, instances of <a href="https://www.theage.com.au/national/victoria/they-can-t-sit-properly-doctors-treat-growing-number-of-women-with-chronic-thrush-20230913-p5e499.html">drug-resistant thrush</a> are increasing, and new treatments are needed.</p>
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<h2>Targeting viruses</h2>
<p>Even <a href="https://theconversation.com/why-are-there-so-many-drugs-to-kill-bacteria-but-so-few-to-tackle-viruses-137480">fewer antivirals</a> are available than antibacterial and antifungal agents. </p>
<p>Most antimicrobial treatments work by exploiting differences between the microbe causing the infection and the host (us) experiencing the infection. Since viruses use our cells to replicate and cause their infection, it’s difficult to find antiviral treatments that selectively target the virus without damaging us. </p>
<p>With so few antiviral drugs available, any resistance that develops to one of them significantly reduces the treatment options available. </p>
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Read more:
<a href="https://theconversation.com/why-are-there-so-many-drugs-to-kill-bacteria-but-so-few-to-tackle-viruses-137480">Why are there so many drugs to kill bacteria, but so few to tackle viruses?</a>
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<p>Take COVID, for example. Two antiviral medicines are in widespread use to treat this viral infection: Paxlovid (containing nirmatrelvir and ritonavir) and Lagevrio (molnupiravir). So far, SARS-CoV-2, the virus that causes COVID, has not developed significant resistance to either of these <a href="https://www.cidrap.umn.edu/covid-19/low-levels-resistance-paxlovid-seen-sars-cov-2-isolates">treatments</a>. </p>
<p>But if SARS-CoV-2 develops resistance to either one of them, it halves the treatment options. Subsequently relying on one would likely lead to its increased use, which may heighten the risk that resistance to the second agent will develop, leaving us with no antiviral agents to treat COVID. </p>
<p>The threat of antimicrobial resistance makes our ability to treat serious COVID infections rather precarious.</p>
<h2>Stopping parasites</h2>
<p>Another group of microbes that cause infections in humans are single-celled microbes such as <em>Plasmodium</em>, <em>Giardia</em>, <em>Leishmania</em>, and <em>Trypanosoma</em>. These microbes are sometimes referred to as parasites, and they are becoming increasingly resistant to the very limited range of anti-parasitic agents used to treat the infections they cause. </p>
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Read more:
<a href="https://theconversation.com/antibiotic-resistance-microbiologists-turn-to-new-technologies-in-the-hunt-for-solutions-podcast-217615">Antibiotic resistance: microbiologists turn to new technologies in the hunt for solutions – podcast</a>
</strong>
</em>
</p>
<hr>
<p>Several <em>Plasmodium</em> species cause malaria and anti-parasitic drugs have been the cornerstone of malaria treatment for decades. But their usefulness has been significantly reduced by the <a href="https://www.mmv.org/our-work/mmvs-pipeline-antimalarial-drugs/antimalarial-drug-resistance">development of resistance</a>. </p>
<p><em>Giardia</em> parasites cause an infection called giardiasis. This can resolve on its own, but it can also cause severe gastrointestinal symptoms such as diarrhea, nausea, and bloating. These microbes have <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207226/">developed resistance</a> to the main treatments and patients infected with drug-resistant parasites can have protracted, unpleasant infections. </p>
<figure class="align-center ">
<img alt="3D illustration of Giardia lamblia protozoan" src="https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"><em>Giardia</em> parasites (illustrated here) cause giardiasis.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/giardia-lamblia-protozoan-causative-agent-giardiasis-1038065005">Shutterstock</a></span>
</figcaption>
</figure>
<h2>Resistance is a natural consequence</h2>
<p>Treating infections influences microbes’ evolutionary processes. Exposure to drugs that stop or kill them pushes microbes to either evolve or die. The exposure to antimicrobial agents provokes the evolutionary process, selecting for microbes that are resistant and can survive the exposure. </p>
<p>The pressure to evolve, provoked by the antimicrobial treatment, is called “selection pressure”. While most microbes will die, a few will evolve in time to overcome the antimicrobial drugs used against them. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-do-bacteria-actually-become-resistant-to-antibiotics-213451">How do bacteria actually become resistant to antibiotics?</a>
</strong>
</em>
</p>
<hr>
<p>The evolutionary process that leads to the emergence of resistance is inevitable. But some things can be done to minimise this and the problems it brings. </p>
<p>Limiting the use of antimicrobial agents is one approach. This means reserving antimicrobial agents for when their use is known to be necessary, rather than using them “just in case”.</p>
<p>Antimicrobial agents are precious resources, holding at bay many infectious diseases that would otherwise sicken and kill millions. It is imperative we do all we can to preserve the effectiveness of those that remain, and give ourselves more options by working to discover and develop new ones.</p>
<hr>
<p><em>Read the other articles in The Conversation’s series on the dangers of antibiotic resistance <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">here</a>.</em></p><img src="https://counter.theconversation.com/content/213460/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christine Carson receives funding from state and federal funding agencies, and the CUREator program, a national biotechnology incubator delivered by Brandon BioCatalyst. She has a commercial interest in companies developing diagnostic tests and preventing viral infections.</span></em></p>We’ve all heard of antibiotic resistance. The same thing is happening with other causes of infections in humans: fungi, viruses and parasites. This is making thrush and other infections hard to treat.Christine Carson, Senior Research Fellow, School of Medicine, The University of Western AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2126452023-09-28T15:52:33Z2023-09-28T15:52:33ZHepatitis C: Britons getting tattoos and cosmetic procedures abroad may be at risk – here’s how to avoid it<figure><img src="https://images.theconversation.com/files/550273/original/file-20230926-17-v9qc51.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C6038%2C4010&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">If proper sterilisation procedures are in place, your chances of contracting hepatitis C from a tattoo are extremely low.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/cropped-close-bearded-tattoo-artist-working-2125291073">Hryshchyshen Serhii/ Shutterstock</a></span></figcaption></figure><p>A <a href="https://post.parliament.uk/research-briefings/post-pb-0038/">growing number of people</a> living in the UK are going abroad to have tattoos, piercings and cosmetic surgeries. Any procedure, no matter where it’s performed, can carry the risk of injury and infection. </p>
<p>But people heading abroad for cosmetic procedures may want to be extra cautious – with <a href="https://www.thetimes.co.uk/article/hepatitis-c-70-000-people-are-unaware-they-have-infected-0x7b5l39t">recent reports</a> suggesting thousands of UK residents may have <a href="https://news.sky.com/story/thousands-of-people-may-have-unknowingly-contracted-hepatitis-c-abroad-health-experts-warn-12950888">unknowingly contracted</a> hepatitis C this way.</p>
<p>Over <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667440/">170 million people worldwide</a> are estimated to have hepatitis C. There are approximately one million new infections each year. In England, more than <a href="https://www.gov.uk/government/news/hepatitis-c-prevalence-falls-by-45-in-england#:%7E:text=The%20latest%20data%20published%20by,antivirals%20that%20cure%20the%20infection.">70,000 people</a> had hepatitis C in 2022. But many more could unknowingly be infected, as hepatitis C symptoms can take years to show up.</p>
<p>Hepatitis C can develop into severe and fatal liver disease if undiagnosed. But when caught early, treatment is <a href="https://www.nhs.uk/conditions/hepatitis-c/treatment/">over 95% effective</a> – highlighting just how important timely testing is. </p>
<h2>What is hepatitis C?</h2>
<p>Hepatitis C is caused by a virus that infects the liver. This virus is spread via <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239486/">contact with infected blood</a>. </p>
<p>Most transmission occurs via contact with contaminated implements, such as needles for recreational drug use. In <a href="https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2893.2002.00329.x?sid=nlm%3Apubmed">rare cases</a>, hepatitis C can also be spread through sexual intercourse, or from an infected mother to an infant during childbirth.</p>
<p>Around 80% of people who contract hepatitis C will exhibit no symptoms whatsoever. The 20% that do experience a short, <a href="https://pubmed.ncbi.nlm.nih.gov/29773899/">flu-like illness</a> – with varying symptoms that may include fever, headache and muscle aches, fatigue, vomiting, diarrhoea and jaundice. </p>
<p>Symptoms can occur from <a href="https://www.sciencedirect.com/science/article/pii/S0955395915002042?via%3Dihub">two to 12 weeks</a> after catching the virus. Those who experience symptoms often don’t realise the severity of their illness.</p>
<p>Some people manage to clear the virus without treatment. But up to 85% of those infected develop <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3495628/">chronic hepatitis</a> – where the virus <a href="https://cks.nice.org.uk/topics/hepatitis-c/background-information/definition/">remains in the body</a>. </p>
<p>These people can show no signs of illness for years and are often unaware until more serious damage has occurred – which can take decades. Hepatitis C is still very treatable in chronic form, though treatments have <a href="https://pubmed.ncbi.nlm.nih.gov/34913652">better outcomes</a> the sooner they’re received.</p>
<p>Left untreated for years, <a href="https://www.nhs.uk/conditions/hepatitis-c/complications/">chronic hepatitis C</a> causes <a href="https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-7-13#:%7E:text=Liver%20steatosis%20is%20a%20frequent,both%20epigenetic%20and%20genetic%20factors.">severe liver disease</a>. This can cause symptoms such as jaundice, swollen abdomen and legs, easily bleeding or bruising, intense itching, loss of appetite and nausea. </p>
<p>Cirrhosis (liver scarring) can also lead to <a href="https://www.hepatitis.va.gov/cirrhosis/patient/encephalopathy.asp">brain and nervous system damage</a> due to the build-up of toxins the liver normally removes. This can cause concentration and memory problems.</p>
<p>An estimated <a href="https://www.sciencedirect.com/science/article/pii/S2210740120303624?via%3Dihub">one in five people</a> with chronic hepatitis C develop a severe liver cancer called <a href="https://www.nhs.uk/conditions/hepatitis-c/complications/">hepatocellular carcinoma</a>. This is the second most deadly cancer globally, with a five-year survival rate of <a href="https://pubmed.ncbi.nlm.nih.gov/33579422/">just 10%-20%</a>. </p>
<figure class="align-center ">
<img alt="A digital drawing of a liver being attacked by hepatitis C viruses." src="https://images.theconversation.com/files/550274/original/file-20230926-17-bkcmql.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/550274/original/file-20230926-17-bkcmql.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/550274/original/file-20230926-17-bkcmql.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/550274/original/file-20230926-17-bkcmql.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/550274/original/file-20230926-17-bkcmql.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/550274/original/file-20230926-17-bkcmql.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/550274/original/file-20230926-17-bkcmql.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Hepatitis C can lead to severe complications.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/hepatitis-virus-human-liver-medical-research-2361027201">crystal light/ Shutterstock</a></span>
</figcaption>
</figure>
<p>Age, excessive alcohol consumption, having other infections (such as HIV) and the <a href="https://pubmed.ncbi.nlm.nih.gov/33579422/">strain of hepatitis C virus</a> you’re infected with can all <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577946/">increase your risk</a> of developing hepatocellular carcinoma.</p>
<h2>Risk from medical or cosmetic procedures</h2>
<p>If proper sterilisation procedures are in place, your chances of contracting any infection is extremely low. But if surgical implements were used on someone with hepatitis C and not properly sterilised, you will probably catch it. Improper sterilisation also carries risk of other diseases, such as <a href="https://www.fitfortravel.nhs.uk/advice/disease-prevention-advice/blood-borne-virus-infections-including-hiv#:%7E:text=Hepatitis%20B%2C%20Hepatitis%20C%20and,medical%2C%20dental%20or%20surgical%20equipment">HIV and hepatitis B</a>.</p>
<p>Several studies have reported that tattoos done in <a href="https://pubmed.ncbi.nlm.nih.gov/16871571/">non-professional settings</a>, such as those <a href="https://journals.lww.com/ajg/abstract/2005/10000/risk_factors_for_hepatitis_c_on_the_texas_mexico.8.aspx">received in prisons</a>, carry an increased risk of contracting hepatitis C due to improper sterilisation. Even tattoos done in professional tattoo parlours may carry an increased risk if reusable needles aren’t <a href="https://www.sciencedirect.com/science/article/pii/S0140673696911721?via%3Dihub">adequately sterilised between clients</a>.</p>
<p>For piercings, the data is less clear. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613802/">Many studies</a> have shown no increased hepatitis C risk from piercings – but these studies did not ask participants whether they’d had their piercing done in a professional parlour or at home. However, cases have been reported of hepatitis C being <a href="https://pubmed.ncbi.nlm.nih.gov/15243336">contracted from a piercing</a>, as well as from <a href="https://pubmed.ncbi.nlm.nih.gov/16264024/">swapping body piercing jewellery</a> with an infected person – so it’s important to be careful.</p>
<p>Although data is limited, this risk is probably the same for cosmetic and dental procedures. If proper sterilisation practices are in place and you go to an accredited surgeon or dentist, your risk of contracting hepatitis C is very low.</p>
<p><a href="https://www.ageb.be/ageb-journal/ageb-volume/ageb-article/1963/">Certain countries</a> have higher incidences of hepatitis C – such as Egypt, Mali, Malaysia, Italy, Thailand and Mauritius. Certain strains of the hepatitis C virus may also be more prevalent in certain destinations. </p>
<p>For example, the dominant hepatitis C strain in Nigeria has a <a href="https://www.mdpi.com/1999-4915/13/1/41">94-99% treatment success rate</a>. But in Thailand, the dominant strain is associated with <a href="https://pubmed.ncbi.nlm.nih.gov/31584833/">rapid chronic liver disease progression</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/33716089/">poorer treatment outcomes</a>. It’s worth being extra vigilant if you plan to have a procedure done when visiting these places. </p>
<h2>How can you avoid it?</h2>
<p>If you’re having any sort of medical, dental or cosmetic procedure, ask about the decontamination or sterilisation process of the implements. </p>
<p>In the UK, councils require tattoo and piercing parlours to use either single-use needles or have proper sterilisation methods to re-use equipment (most commonly via an <a href="https://www.steris.com/healthcare/knowledge-center/sterile-processing/everything-about-autoclaves#:%7E:text=Autoclaves%20are%20also%20known%20as,placed%20inside%20a%20pressure%20vessel.">autoclave</a>). If in the UK, ask to see the business’s licence to ensure they’re registered with a local council.</p>
<p>Other medical procedures, such as botox or fillers, are <a href="https://www.policybee.co.uk/blog/can-anyone-train-to-give-botox-uk#:%7E:text=The%20UK's%20drought%20of%20laws,can%20train%20to%20give%20Botox.">less tightly regulated</a>. With any injectable, ideally these should be done by a medical professional – such as a nurse or dentist.</p>
<p>If you’re getting a procedure done and are unsure whether the implements are safe, ask to see it before it’s unpacked. Single use, sterile needles are always sealed in a packet. </p>
<p>Poor hygiene can also spread hepatitis C, so check these are being <a href="https://authoritytattoo.com/are-tattoo-needles-reusable">changed between clients</a> and that good hygiene practice is being done (such as washing of hands and changing gloves between clients). If in doubt, I would suggest not getting the procedure done at all. </p>
<p>If you’ve had a procedure done abroad (or in the UK a long time ago), I would recommend ordering a <a href="https://hepctest.nhs.uk/">test kit from the NHS</a>. It’s quick, easy and can be done at home. If it comes back positive, get treated as soon as possible as hepatitis C virus is a highly treatable infection.</p><img src="https://counter.theconversation.com/content/212645/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Grace C Roberts receives funding from the MRC.</span></em></p>Hepatitis C treatments are up to 95% effective when caught early.Grace C Roberts, Research Fellow in Virology, University of LeedsLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2004862023-03-13T12:26:20Z2023-03-13T12:26:20ZMarburg virus outbreaks are increasing in frequency and geographic spread – three virologists explain<figure><img src="https://images.theconversation.com/files/514041/original/file-20230307-20-6vacw1.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2100%2C2190&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Marburg virus spreads through close contact with infected body fluids.</span> <span class="attribution"><a class="source" href="https://flic.kr/p/QPbCNb">NIAID/flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>The World Health Organization confirmed an <a href="https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON444">outbreak of the deadly Marburg virus disease</a> in the central African country of Equatorial Guinea on Feb. 13, 2023. To date, there have been <a href="https://www.rfi.fr/en/international-news/20230228-death-toll-in-e-guinea-marburg-outbreak-rises-to-11">11 deaths suspected to be caused by the virus</a>, with one case confirmed. Authorities are currently monitoring 48 contacts, four of whom have developed symptoms and three of whom are hospitalized as of publication. The WHO and the U.S. Centers for Disease Control and Prevention are assisting Equatorial Guinea in its efforts to stop the spread of the outbreak.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/514050/original/file-20230307-16-7oenhk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of Marburg virus particles" src="https://images.theconversation.com/files/514050/original/file-20230307-16-7oenhk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/514050/original/file-20230307-16-7oenhk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=838&fit=crop&dpr=1 600w, https://images.theconversation.com/files/514050/original/file-20230307-16-7oenhk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=838&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/514050/original/file-20230307-16-7oenhk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=838&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/514050/original/file-20230307-16-7oenhk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1053&fit=crop&dpr=1 754w, https://images.theconversation.com/files/514050/original/file-20230307-16-7oenhk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1053&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/514050/original/file-20230307-16-7oenhk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1053&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Marburg virus is structurally similar to the Ebola virus.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/marburg-virus-is-a-hemorrhagic-fever-virus-first-described-news-photo/1035562466">Photo12/Universal Images Group via Getty Images</a></span>
</figcaption>
</figure>
<p><a href="https://doi.org/10.3390/v4101878">Marburg virus</a> and the <a href="https://doi.org/10.12688/f1000research.17573.1">closely related</a> Ebola virus belong to the <a href="https://doi.org/10.1016/j.jmb.2019.06.029">filovirus family</a> and are <a href="https://doi.org/10.1007/82_2017_16">structurally</a> <a href="https://doi.org/10.3201%2Feid1008.040350">similar</a>. Both viruses cause severe disease and death in people, with fatality rates ranging from 22% to 90% <a href="https://www.cdc.gov/vhf/ebola/index.html">depending on</a> <a href="https://www.cdc.gov/vhf/marburg/index.html">the outbreak</a>. Patients infected by these viruses exhibit a <a href="https://doi.org/10.1016/j.ijid.2020.07.042">wide range of similar symptoms</a>, including fever, body aches, severe gastrointestinal symptoms like diarrhea and vomiting, lethargy and sometimes bleeding.</p>
<p>We are <a href="https://scholar.google.com/citations?user=rUT_g04AAAAJ&hl=en&oi=ao">virologists</a> <a href="https://scholar.google.com/citations?hl=en&user=j9jTdBsAAAAJ">who</a> <a href="https://scholar.google.com/citations?user=PdTPtc8AAAAJ&hl=en&oi=ao">study</a> Marburg, Ebola and related viruses. <a href="https://www.bu.edu/muhlbergerlab/">Our laboratory</a> has a long-standing interest in researching the underlying mechanisms of how these viruses cause disease in people. Learning more about how Marburg virus is transmitted from animals to humans and how it spreads between people is essential to preventing and limiting future outbreaks. </p>
<h2>Marburg virus disease</h2>
<p>Marburg virus spreads between people by close contact only after they show symptoms. It is transmitted through <a href="https://doi.org/10.1016/j.ijid.2020.07.042">infected body fluids</a> such as blood, and is not airborne. Contact tracing is a potent tool to combat outbreaks. The incubation time, or time between infection and the onset of symptoms, ranges from two to 21 days and typically falls between five and 10 days. This means that contacts must be observed for extended periods for potential symptoms. </p>
<p>Marburg virus <a href="https://doi.org/10.1093/infdis/jir299">cannot be detected before patients are symptomatic</a>. One major cause of the spread of Marbug virus disease is <a href="https://doi.org/10.3201/eid0912.030355">postmortem transmission</a> due to traditional burial procedures, where family and friends typically have direct skin-to-skin contact with people who have died from the disease.</p>
<p>There are currently no approved <a href="https://doi.org/10.1016/j.ijid.2020.07.042">treatments</a> or <a href="https://doi.org/10.1016/j.vaccine.2020.11.042">vaccines</a> against Marburg virus disease. The most advanced vaccine candidates in development use strategies that <a href="https://doi.org/10.1016/j.ebiom.2023.104463">have been shown</a> <a href="https://doi.org/10.3390/vaccines10101582">to be effective</a> at <a href="https://doi.org/10.1126/scitranslmed.abq6364">protecting against</a> <a href="https://doi.org/10.1016/S0140-6736(22)02400-X">Ebola virus disease</a>. </p>
<p>Without effective treatments or vaccines, Marburg virus <a href="https://doi.org/10.1086/520548">outbreak control</a> primarily relies on contact tracing, sample testing, patient contact monitoring, quarantines and attempts to limit or modify high-risk activities such as <a href="https://doi.org/10.1086/520544">traditional funeral practices</a>.</p>
<h2>What causes Marburg virus outbreaks?</h2>
<p>Marburg virus outbreaks have an unusual history. </p>
<p>The <a href="https://doi.org/10.1086/520551">first recorded outbreak</a> of Marburg virus disease occurred in Europe. In 1967, laboratory workers in Marburg and Frankfurt in Germany, as well as in Belgrade, Yugoslavia (now Serbia) were <a href="https://doi.org/10.1136/pgmj.49.574.542">infected with a previously unknown pathogen</a> after handling infected monkeys that had been imported from Uganda. This outbreak led to the <a href="https://doi.org/10.1086/520551">discovery of the Marburg virus</a>.</p>
<p>Identifying the virus took only three months, which, at the time, was incredibly fast considering the available research tools. Despite receiving intensive care, <a href="https://doi.org/10.1086/520551">seven of the 32 patients died</a>. This case fatality rate of 22% was relatively low compared to subsequent Marburg virus outbreaks in Africa, which have had a <a href="https://www.cdc.gov/vhf/marburg/outbreaks/chronology.html">cumulative case fatality rate of 86%</a>. It remains unclear if these differences in lethality are due to variability in patient care options or other factors such as distinct viral strains.</p>
<p>Subsequent Marburg virus disease outbreaks occurred in Uganda and Kenya, as well as the Democratic Republic of the Congo and Angola in Central Africa. In addition to the current outbreak in Equatorial Guinea, recent Marburg virus cases in the West African countries of Guinea in 2021 and Ghana in 2022 highlight that the Marburg virus is <a href="https://www.cdc.gov/vhf/marburg/outbreaks/chronology.html">not confined to Central Africa</a>.</p>
<p>Strong evidence shows that the <a href="https://doi.org/10.1371/journal.ppat.1000536">Egyptian fruit bat</a>, a natural animal reservoir of Marburg virus, might play an important role in spreading the virus to people. The location of all Marburg virus outbreaks coincides with the <a href="https://www.iucnredlist.org/species/29730/22043105">natural range of these bats</a>. The large area of Marburg virus outbreaks is unsurprising, given the <a href="https://doi.org/10.3390/v4101878">ecology of the virus</a>. However, the mechanisms of zoonotic, or animal-to-human, spread of Marburg virus still remain poorly understood.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/514042/original/file-20230307-16-m3dkhs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Researchers approaching Bat Cave in Queen Elizabeth National Park" src="https://images.theconversation.com/files/514042/original/file-20230307-16-m3dkhs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/514042/original/file-20230307-16-m3dkhs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=403&fit=crop&dpr=1 600w, https://images.theconversation.com/files/514042/original/file-20230307-16-m3dkhs.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=403&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/514042/original/file-20230307-16-m3dkhs.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=403&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/514042/original/file-20230307-16-m3dkhs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=506&fit=crop&dpr=1 754w, https://images.theconversation.com/files/514042/original/file-20230307-16-m3dkhs.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=506&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/514042/original/file-20230307-16-m3dkhs.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=506&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A number of Marburg virus outbreaks are linked to human activity in caves where Egyptian fruit bats are known to roost.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/jennifer-mcquiston-jonathan-towner-and-brian-amman-approach-news-photo/1073367830">Bonnie Jo Mount/The Washington Post via Getty Images</a></span>
</figcaption>
</figure>
<p>The origin of a number of Marburg virus disease outbreaks is closely linked to human activity in caves where Egyptian fruit bats roost. More than half of the cases in a 1998 outbreak in the northeastern Democratic Republic of the Congo were among <a href="https://doi.org/10.1056/NEJMoa051465">gold miners who had worked in Goroumbwa Mine</a>. Intriguingly, the end of the nearly two-year outbreak coincided with the flooding of the cave and the disappearance of the bats in the same month.</p>
<p>Similarly, in 2007, four men who <a href="https://doi.org/10.1093/infdis/jir312">worked in a gold and lead mine</a> in Uganda where thousands of bats were known to roost became infected with Marburg virus. In 2008, two tourists were infected with the virus after visiting <a href="https://www.cdc.gov/cdctv/diseaseandconditions/outbreaks/uganda-python-cave.html">Python Cave</a> in the Maramagambo Forest in Uganda. Both developed severe symptoms after returning to their home countries – the <a href="https://doi.org/10.3201%2Feid1508.090051">woman from the Netherlands died</a> and the <a href="https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5849a2.htm">woman from the United States survived</a>.</p>
<p>The <a href="https://www.iucnredlist.org/species/29730/22043105">geographic range of Egyptian fruit bats</a> extends to large portions of sub-Saharan Africa and the Nile River Delta, as well as portions of the Middle East. There is potential for <a href="https://theconversation.com/what-is-spillover-bird-flu-outbreak-underscores-need-for-early-detection-to-prevent-the-next-big-pandemic-200494">zoonotic spillover events</a>, to occur in any of these regions.</p>
<h2>More frequent outbreaks</h2>
<p>Although Marburg virus disease outbreaks have historically been sporadic, their <a href="https://www.cdc.gov/vhf/marburg/outbreaks/chronology.html">frequency has been increasing</a> in recent years. </p>
<p>The increasing emergence and reemergence of zoonotic viruses, including filoviruses (such as <a href="https://www.cdc.gov/vhf/ebola/index.html">Ebola</a>, <a href="https://www.cdc.gov/mmwr/volumes/71/wr/mm7145a5.htm">Sudan</a> and <a href="https://www.cdc.gov/vhf/marburg/index.html">Marburg</a> viruses), coronaviruses (which cause <a href="https://www.cdc.gov/sars/index.html">SARS</a>, <a href="https://www.cdc.gov/coronavirus/mers/index.html">MERS</a> and <a href="https://www.cdc.gov/coronavirus/2019-ncov/index.html">COVID-19</a>), henipaviruses (such as <a href="https://www.cdc.gov/vhf/nipah/index.html">Nipah</a> and <a href="https://www.cdc.gov/vhf/hendra/index.html">Hendra</a> viruses) and <a href="https://www.cdc.gov/poxvirus/mpox/index.html">Mpox</a> appear to be influenced by both <a href="https://doi.org/10.1038/s41586-022-05506-2">human encroachment</a> on previously undisturbed animal habitats and alterations to wildlife habitat ranges <a href="https://doi.org/10.1038/s41586-022-04788-w">due to climate change</a>. </p>
<p>Most Marburg virus outbreaks have occurred in remote areas, which has helped to contain the spread of the disease. However, the large geographic distribution of Egyptian fruit bats that harbor the virus raises concerns that future Marburg virus disease outbreaks could happen in new locations and spread to more densely populated areas, as seen by the devastating <a href="https://doi.org/10.1007/82_2017_69">Ebola virus outbreak in 2014 in West Africa</a>, where <a href="https://www.cdc.gov/vhf/ebola/history/2014-2016-outbreak/index.html">over 11,300 people died</a>.</p><img src="https://counter.theconversation.com/content/200486/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Elke Mühlberger receives funding from NIH/NIAID, the Bill and Melinda Gates Foundation, the Howard Hughes
Medical Institute (as coinvestigator on Emerging Pathogens Initiative project). </span></em></p><p class="fine-print"><em><span>Adam Hume and Judith Olejnik do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The Marburg virus, a close cousin of Ebola, currently has no approved treatments or vaccines to protect against it.Adam Hume, Research Assistant Professor of Microbiology, Boston UniversityElke Mühlberger, Professor of Microbiology, Boston UniversityJudith Olejnik, Senior Research Scientist, Boston UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1970092023-01-18T13:38:45Z2023-01-18T13:38:45ZVaccination to prevent dementia? New research suggests one way viral infections can accelerate neurodegeneration<figure><img src="https://images.theconversation.com/files/503691/original/file-20230109-7992-tpch1g.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2190%2C1369&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Many viruses interact with the olfactory system, and can damage other areas of the brain through it.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/brain-viral-infection-on-science-background-royalty-free-image/1352255856">Mohammed Haneefa Nizamudeen/iStock via Getty Images Plus</a></span></figcaption></figure><p>One in nine Americans ages 65 and over had <a href="https://www.alz.org/alzheimers-dementia/facts-figures">Alzheimer’s disease</a> in 2022, and countless others were indirectly affected as caregivers, health care providers and taxpayers. There is currently no cure – available treatments primarily focus on prevention by encouraging protective factors, such as exercise and healthy diet, and reducing <a href="https://doi.org/10.1186/s12929-019-0524-y">aggravating factors</a>, such as diabetes and high blood pressure.</p>
<p>One of these aggravating factors is viral infections. Researchers have identified that certain viruses such as <a href="https://doi.org/10.3389/fnagi.2018.00324">herpes simplex virus type 1</a> (HSV-1, which causes cold sores), <a href="https://doi.org/10.1371/journal.pone.0188490">varicella zoster virus</a> (VZV, which causes chickenpox and shingles) and <a href="https://doi.org/10.3233/JAD-220717">SARS-CoV-2</a> (which causes COVID-19) can lead to a higher risk of Alzheimer’s disease and dementia following infection.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/rTAOX4ahMK0?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">There is increasing evidence supporting the potential role viruses play in Alzheimer’s disease.</span></figcaption>
</figure>
<p>Figuring out how and when these viruses contribute to disease could help scientists develop new therapies to prevent dementia. However, researchers have been <a href="https://doi.org/10.1371/journal.ppat.1008575">unable to consistently detect</a> suspect viruses in brains of people who died of Alzheimer’s. Because the Alzheimer’s disease process can start decades before symptoms, some researchers have proposed that viruses act early in a “<a href="https://doi.org/10.1016/j.neurobiolaging.2003.12.021">hit-and-run</a>” manner; they trigger a cascade of events that lead to dementia but have already taken off. In other words, by the time researchers analyze patient brains, any detectable viral components are gone and causation is difficult to establish.</p>
<p>We are a <a href="https://scholar.google.com/citations?user=rH1ZZcwAAAAJ&hl=en">neurovirologist</a>, <a href="https://scholar.google.com/citations?user=hp81rCYAAAAJ&hl=en">neurologist</a> and <a href="https://scholar.google.com/citations?user=LEcQAR0AAAAJ&hl=en">neuroscientist</a> team interested in the role viruses play in neurodegenerative diseases. In our <a href="https://doi.org/10.1016/j.neurobiolaging.2022.12.004">recently published research</a>, we use new technology to search for the tire tracks of these viruses in Alzheimer’s patients. By focusing on the most vulnerable entry point to the brain, the nose, we discovered a genetic network that provides evidence of a robust viral response.</p>
<h2>Focusing on the olfactory system</h2>
<p>Many of the viruses implicated in dementia, including <a href="https://doi.org/10.1038/ncpneuro0401">herpesviruses</a> and the <a href="https://doi.org/10.1126/sciadv.abc5801">virus that causes COVID-19</a>, enter the nose and interact with the olfactory system.</p>
<p>The <a href="https://www.britannica.com/science/olfactory-system">olfactory system</a> is constantly bombarded with odors, pollutants and pathogens. Particles inhaled through the nostrils bind to specific olfactory receptor cells in the tissue lining the nasal cavity. These receptors send messages to other cells in what’s called the olfactory bulb, which acts like a relay station that transmits these messages down the long nerves of the olfactory tract. These messages are then transferred to the area of the brain responsible for learning and memory, the hippocampus.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/mFm3yA1nslE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Sensory cells translate information from your environment into electrical signals your brain can interpret.</span></figcaption>
</figure>
<p>The hippocampus plays a critical role assigning contextual information to odors, such as danger from the foul smell of propane or comfort from the smell of lavender. This area of the brain is also dramatically damaged in Alzheimer’s disease, causing devastating learning and memory deficits. For as many as 85% to 90% of Alzheimer’s patients, <a href="https://doi.org/10.1016/B978-0-12-819973-2.00030-7">loss of smell</a> is an early sign of disease.</p>
<p>The mechanism leading to smell loss in Alzheimer’s disease is relatively unknown. Like muscles that atrophy from lack of use, <a href="https://doi.org/10.1002/cne.901780310">sensory deprivation</a> is thought to lead to atrophy of the brain regions that specialize in interpreting sensory information. Strong sensory input to these regions is critical to maintain general brain health.</p>
<h2>Olfactory inflammation and Alzheimer’s disease</h2>
<p>We hypothesize that viral infections throughout life are both contributors to and potential drug targets in Alzheimers’s disease. To test this idea, <a href="https://doi.org/10.1016/j.neurobiolaging.2022.12.004">we used emerging, state-of-the-art technology to investigate</a> the mRNA and protein networks of the olfactory system of Alzheimer’s disease patients. </p>
<p>The body uses <a href="https://theconversation.com/what-is-mrna-the-messenger-molecule-thats-been-in-every-living-cell-for-billions-of-years-is-the-key-ingredient-in-some-covid-19-vaccines-158511">mRNA</a>, which is transcribed from DNA, to translate genetic material into proteins. The body uses specific mRNA sequences to produce a network of proteins that are used to fight against certain viruses. In some cases, the body continues to <a href="https://doi.org/10.1038/sj.cr.7310019">activate these pathways</a> even after the the virus is cleared, leading to chronic inflammation and tissue damage. Identifying which mRNA sequences and protein networks are present can allow us to infer, to a degree, whether the body is or was responding to a viral pathogen at some point.</p>
<p>Previously, sequencing mRNA in tissue samples was difficult because the molecules degrade very quickly. However, <a href="https://doi.org/10.1371/journal.pone.0212031">new technology</a> specifically addresses that issue by measuring small subsections of mRNA at a time instead of trying to reconstruct the whole mRNA sequence at once.</p>
<p>We leveraged this technology to sequence the mRNA of olfactory bulb and olfactory tract samples from six people with familial Alzheimer’s, an inherited form of the disease, and six people without Alzheimer’s. We focused on familial Alzheimer’s because there is less variability in disease than in the sporadic, or nonfamilial, form of the disease, which can result from a number of different individual and environmental factors.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/503694/original/file-20230109-15603-tfjiny.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of neurons in mouse olfactory bulb" src="https://images.theconversation.com/files/503694/original/file-20230109-15603-tfjiny.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/503694/original/file-20230109-15603-tfjiny.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/503694/original/file-20230109-15603-tfjiny.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/503694/original/file-20230109-15603-tfjiny.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/503694/original/file-20230109-15603-tfjiny.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/503694/original/file-20230109-15603-tfjiny.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/503694/original/file-20230109-15603-tfjiny.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This image shows neurons in a small cross section of a mouse’s olfactory bulb.</span>
<span class="attribution"><a class="source" href="https://directorsblog.nih.gov/2017/11/16/snapshots-of-life-making-sense-of-smell/">Jeremy McIntyre/University of Florida College of Medicine via National Institutes of Health</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<p>In the familial Alzheimer’s samples, we found altered gene expression indicating signs of a past viral infection in the olfactory bulb, as well as inflammatory immune responses in the olfactory tract. We also found higher levels of proteins involved in demyelination in the olfactory tract of familial Alzheimer’s samples than in the controls. Myelin is a protective fatty layer around nerves that allows electrical impulses to move quickly and smoothly from one area of the brain to another. Damage to myelin stalls signal transduction, resulting in impaired neural communication and, by extension, neurodegeneration.</p>
<p>Based on these findings, we hypothesize that viral infections, and the resulting inflammation and demyelination within the olfactory system, may disrupt the function of the hippocampus by impairing communication from the olfactory bulb. This scenario could contribute to the accelerated neurodegeneration seen in Alzheimer’s disease.</p>
<h2>Implications for patient health</h2>
<p>Epidemiological data supports the role of viral infections in the development of Alzheimer’s disease. For example, the <a href="https://doi.org/10.1371/journal.pone.0188490">varicella zoster virus</a> is linked to a nearly threefold risk of developing dementia within five years of infection for patients with a shingles rash on their face. A recent report also found a <a href="https://doi.org/10.3233/JAD-220717">nearly 70% increased risk</a> of getting diagnosed with Alzheimer’s within a year of a COVID-19 diagnosis for people over 65.</p>
<p>These studies suggest that vaccination may be a potential measure to prevent dementia. For example, vaccination against the <a href="https://doi.org/10.1016/j.arr.2021.101534">seasonal flu virus</a> and <a href="https://doi.org/10.1371/journal.pone.0257405">herpes zoster</a> is associated with an up to 29% and 30% reduced risk of developing dementia, respectively.</p>
<p>Further research investigating how viral infections can trigger neurodegeneration could aid in the development of antiviral drugs and vaccines against the viruses implicated in Alzheimer’s disease.</p><img src="https://counter.theconversation.com/content/197009/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrew Bubak receives funding from the National Institute on Aging. </span></em></p><p class="fine-print"><em><span>Diego Restrepo receives funding from the National Institute of Health and the National Science Foundation </span></em></p><p class="fine-print"><em><span>Maria Nagel receives funding from the National Institutes of Health.</span></em></p>Inflammation and damage to the olfactory system from shingles, COVID-19 and herpes infections may contribute to Alzheimer’s disease.Andrew Bubak, Assistant Research Professor of Neurology, University of Colorado Anschutz Medical CampusDiego Restrepo, Professor of Cell and Developmental Biology, University of Colorado Anschutz Medical CampusMaria Nagel, Professor of Neurology and Ophthalmology, University of Colorado Anschutz Medical CampusLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1937052022-11-22T13:25:50Z2022-11-22T13:25:50ZScientists uncovered the structure of the key protein for a future hepatitis C vaccine – here’s how they did it<figure><img src="https://images.theconversation.com/files/496217/original/file-20221118-14-r6a8me.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1999%2C1499&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Imaging the proteins on the surface of HCV has been challenging because of the virus's shape-shifting nature.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/hepatitis-c-virus-particles-illustration-royalty-free-illustration/1042127452">Juan Gaertner/Science Photo Library via Getty Images</a></span></figcaption></figure><p>The <a href="https://www.cdc.gov/hepatitis/hcv/index.htm">hepatitis C virus, or HCV</a>, causes a chronic liver infection that can lead to permanent liver scarring and, in dire cases, cancer. It affects around <a href="https://doi.org/10.1007/s42399-020-00588-3">71 million people worldwide</a> and causes approximately 400,000 deaths each year. While <a href="https://www.uptodate.com/contents/direct-acting-antivirals-for-the-treatment-of-hepatitis-c-virus-infection">treatments are available</a> for HCV-related infections, they are expensive, hard to access and do not protect against reinfection. A vaccine that can help prevent HCV infection is a major unmet medical and public health need. </p>
<p>One major reason there hasn’t been an HCV vaccine yet is that scientists have yet to identify the proper antigen, or the part of the virus would trigger a protective immune response in the body.</p>
<p>Decades of research have pinpointed <a href="https://doi.org/10.1038/nrmicro3098">HCV E1E2</a>, the only protein on the surface of the virus, as the most promising vaccine candidate. However, developing an HCV vaccine based on that protein is limited by uncertainty around what it looks like. Knowing the structure of the protein is necessary to figure out how the immune system responds to the virus.</p>
<p>So how do researchers capture the structure of single protein on a shape-shifting virus? </p>
<p>We are researchers who specialize in <a href="https://scholar.google.com/citations?user=Xejfx54AAAAJ&hl=en">microscopy</a> and <a href="https://scholar.google.com/citations?user=iQj9rSwAAAAJ&hl=en">vaccine design</a>. With new technology, we were able to <a href="https://doi.org/10.1126/science.abn9884">visualize the molecular details</a> of this elusive protein, unlocking key insights into how this virus works and offering a potential blueprint for a future vaccine.</p>
<p>This is how we did it.</p>
<h2>Challenges of capturing a shape-shifting virus</h2>
<p>One reason it has been so difficult to capture the structure of the HCV E1E2 protein is that it is both <a href="https://doi.org/10.1016/j.celrep.2022.110859">flexible and fragile</a>. It changes its shape so often and is so easily broken that it’s challenging to purify. </p>
<p>As an analogy, imagine a bowl of spaghetti drenched in tomato sauce. Now imagine trying to take a picture of each individual piece of spaghetti in the same position over time while the bowl is shaking. Hard to do, right? That’s what it was like to image the full E1E2 protein.</p>
<p>There were also <a href="https://doi.org/10.1126/science.1251652">technological barriers</a>. Until recently, available imaging techniques were limited in their ability to view microscopic proteins. <a href="https://chem.libretexts.org/Bookshelves/Analytical_Chemistry/Supplemental_Modules_(Analytical_Chemistry)/Instrumentation_and_Analysis/Diffraction_Scattering_Techniques/X-ray_Crystallography">X-ray crystallography</a>, for instance, is unable to capture molecules that frequently change and shape-shift, like HCV. Moreover, other options, such as <a href="https://chem.libretexts.org/Bookshelves/Analytical_Chemistry/Physical_Methods_in_Chemistry_and_Nano_Science_(Barron)/04%3A_Chemical_Speciation/4.07%3A_NMR_Spectroscopy">nuclear magnetic resonance spectroscopy</a>, required cutting large parts of the protein or chemically manipulating it in a way that would transform its physiological state and potentially alter its function.</p>
<p>So to examine the structure of E1E2, we needed a way to extract and purify, stabilize and trap the entire shape-shifting protein into one configuration.</p>
<h2>How to take a picture of protein</h2>
<p><a href="https://doi.org/10.1038/d41586-020-01658-1">Cryo-EM, or cryo-electron microscopy</a>, is a type of imaging technique that views specimens at cryogenic temperatures, in this case the boiling point of nitrogen: minus 320.8 degrees Fahrenheit (minus 196 Celsius). With temperatures that cold, ice freezes so quickly that it doesn’t have time to crystallize. That creates a beautiful glasslike frame around the protein of interest, allowing an unhindered view of every structural detail. Cryo-EM also requires very little protein to work, reducing the amount of material we would need to purify. </p>
<p>Winner of the <a href="https://www.nobelprize.org/prizes/chemistry/2017/press-release/">2017 Nobel Prize in chemistry</a> and <a href="https://doi.org/10.1038/nmeth.3730">Nature magazine’s 2015 “Method of the Year</a>” award, cryo-EM is superb for imaging biological macromolecules in their native, or natural, state in the aqueous environment of human blood. Cryo-EM was also pivotal for characterizing the <a href="https://doi.org/10.1038/nature17200">structure of the COVID-19 virus</a> and its variants.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/Qq8DO-4BnIY?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Cryo-EM has allowed researchers to see complex proteins they weren’t able to before.</span></figcaption>
</figure>
<p>So how do you take a picture of a protein? </p>
<p>First, we embedded the genetic code to make E1E2 in human cells in a petri dish so we would have sufficient amounts of protein to study. After purifying the protein, we <a href="https://caic.bio.cam.ac.uk/electron-microscopy/SpecimenPrep/PlungeFreezing">plunged it into liquid ethane</a> followed by liquid nitrogen. Liquid ethane is used to freeze the protein because it has a higher boiling point than liquid nitrogen. This means it is able to capture more heat before turning to a gas, allowing the protein to freeze much more quickly than it would in liquid nitrogen and avoid structural damage. </p>
<p>Once the protein was vitrified, or in a glasslike ice state, we were able not just to see its overall structure, but also to capture multiple individual configurations of the protein that it takes when it shape-shifts, including its less stable forms.</p>
<p>At this point, our protein was ready for its close-up. We employed a microscope that <a href="https://www.ccber.ucsb.edu/ucsb-natural-history-collections-botanical-plant-anatomy/transmission-electron-microscope">uses a beam of focused, high energy electrons</a> and a very fancy camera that detects how the elections bounce off the protein’s surface. This created a 2D image that we then mathematically transformed into a 3D model. And that was how we got the coveted “close-up” of HCV’s surface protein. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/jgEQ6A2-liU?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">This video shows the newly identified 3D structure of the E1E2 protein on the surface of the hepatitis C virus. The two main subunits of the protein are colored in pink and blue. Sugar molecules are colored in green.</span></figcaption>
</figure>
<p>Our next step was then to assess the location of each amino acid, or building block of the protein, in 3D space. Because every amino acid has a unique shape, we used a computer program that could identify each one in our 3D map. This allowed us to manually reconstruct a high-resolution model of the protein, one building block at a time.</p>
<h2>A new tool to design an HCV vaccine</h2>
<p>Our 3D map and model of the HCV E1E2 protein supports previous research describing its structure while providing new insights into features that will help pave the way for a long-sought vaccine design against this virus. </p>
<p>For example, our structure reveals that the interface between the two main parts of the protein is stabilized by sugars and hydrophobic patches, or areas that push out water molecules. This creates sticky binding hubs along the protein and keeps it from falling apart – a potential site for protective antibodies and new drugs to target. </p>
<p>Researchers now have the tools to design antiviral drugs and vaccines against HCV infection.</p><img src="https://counter.theconversation.com/content/193705/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Lisa Eshun-Wilson receives funding from the National Science Foundation. </span></em></p><p class="fine-print"><em><span>Alba Torrents de la Peña receives funding from Netherlands Organization for Scientific Research (NWO) Rubicon Grant 45219118. </span></em></p>Using a Nobel Prize-winning technique called cryo-EM, researchers were able to identify potential areas on the hepatitis C virus that a vaccine could target.Lisa Eshun-Wilson, Postdoctoral Scholar in Molecular and Cell Biology, The Scripps Research InstituteAlba Torrents de la Peña, Postdoctoral Fellow in Integrative Structural and Computational Biology, The Scripps Research InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1944032022-11-18T16:46:55Z2022-11-18T16:46:55ZRSV: experts explain why rates of this virus are surging this year<figure><img src="https://images.theconversation.com/files/495104/original/file-20221114-4815-3ntrfj.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3994%2C2658&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">RSV is most common in children under two.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/mother-measuring-temperature-her-ill-kid-493198735">Aleksandra Suzi/ Shutterstock</a></span></figcaption></figure><p><a href="https://www.youtube.com/watch?v=MDhTlSqev8k&t=3s">Respiratory syncytial virus</a> (RSV) is a very common virus, typically causing infection in children during the colder months. In most cases, RSV causes a mild illness, with symptoms similar to that of a regular cold. </p>
<p>But it can also cause lung infections, such as <a href="https://www.nhs.uk/conditions/bronchiolitis/">bronchiolitis</a> or <a href="https://www.nhs.uk/conditions/pneumonia/">pneumonia</a>, especially in <a href="https://publications.aap.org/pediatrics/article-abstract/132/2/e341/31332/Respiratory-Syncytial-Virus-Associated">infants, premature babies and children</a> with underlying health problems. It is the most common cause of hospital admission in young children, with around <a href="https://bmjopen.bmj.com/content/6/6/e009337">26,000 children</a> under the age of two admitted to hospital with RSV every year in the UK alone.</p>
<p>Cases tend to rise in October and hit a peak in December before beginning to fall from February. But this year, <a href="https://theconversation.com/covid-flu-rsv-how-this-triple-threat-of-respiratory-viruses-could-collide-this-winter-191822">cases are particularly high</a> and are already at levels that clinicians wouldn’t normally expect to see until later in the season. And it’s not only the UK that’s seeing a rise in case numbers – the <a href="https://www.cdc.gov/surveillance/nrevss/rsv/natl-trend.html">US</a> and <a href="https://www.ecdc.europa.eu/sites/default/files/documents/Communicable-disease-threats-report-29-oct-2022.pdf">Europe</a> are also currently experiencing an early and high rise in RSV.</p>
<p>Alongside the spike in case numbers, there are <a href="https://edition.cnn.com/2022/11/03/health/rsv-hospitalizations-high-levels/index.html">also reports</a> that <a href="https://www.mirror.co.uk/news/uk-news/urgent-warning-parents-number-brit-28404348?_ga=2.205297237.431766559.1668421707-1206984722.1650463124">hospitalisations have rapidly risen</a>. With <a href="https://theconversation.com/covid-flu-rsv-how-this-triple-threat-of-respiratory-viruses-could-collide-this-winter-191822">cases of influenza and COVID-19</a> also on the rise, there are concerns that the NHS and other health services may be unable to cope with this increased pressure. </p>
<h2>What has changed?</h2>
<p><a href="https://theconversation.com/covid-flu-rsv-how-this-triple-threat-of-respiratory-viruses-could-collide-this-winter-191822">Changes in the pattern</a> of this usually winter virus have been seen both during and since the pandemic. </p>
<p>Throughout 2020-2021, very <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00525-4/fulltext">few cases of RSV</a> were recorded. In June and July 2021, cases rose to a small summer peak in England, and then unusually there were far fewer children with RSV during the normal winter season. </p>
<p>This year, cases of RSV rose again a little during the summer months. But now there has been an <a href="https://theconversation.com/covid-flu-rsv-how-this-triple-threat-of-respiratory-viruses-could-collide-this-winter-191822">increase in cases</a> sooner than had been expected.</p>
<p>Part of the reason for this change in pattern – and for the early and rapid rise in cases this year – are the measures used to prevent COVID-19 transmission. These measures – such as wearing masks and socially distancing – were also effective at <a href="https://www.gov.uk/government/statistics/annual-flu-reports/surveillance-of-influenza-and-other-seasonal-respiratory-viruses-in-winter-2021-to-2022#influenza-in-the-uk">decreasing the spread of other respiratory viruses</a> such as the common cold, flu and RSV while they were in place. </p>
<p>But decreased exposure to these viruses means that a child’s immunity has not been boosted naturally. This means fewer children have protection against them. So, as COVID-19 restrictions were lifted and people began to mix normally, respiratory viruses began to <a href="https://academic.oup.com/cid/article/73/9/e2829/6140790">spread again</a>, at all times of year.</p>
<figure class="align-center ">
<img alt="Two young girls play with an abacus at daycare or school together." src="https://images.theconversation.com/files/495106/original/file-20221114-12-h0lj1v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/495106/original/file-20221114-12-h0lj1v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/495106/original/file-20221114-12-h0lj1v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/495106/original/file-20221114-12-h0lj1v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/495106/original/file-20221114-12-h0lj1v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/495106/original/file-20221114-12-h0lj1v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/495106/original/file-20221114-12-h0lj1v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Viruses began to spread again when pandemic restrictions were lifted.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/white-dark-skinned-children-sit-together-1789633022">ShineTerra/ Shutterstock</a></span>
</figcaption>
</figure>
<p>Many adults also weren’t exposed to many viruses during the pandemic, meaning they have lower levels of antibodies to RSV. This is particularly important for young infants, since they have not been exposed to viruses before. This means they rely on the immunity of those around them to protect them from infection. It also means that babies born during the pandemic or just after restrictions ended received fewer protective antibodies from their mother while in the womb. As a result, they may have lower levels of protection against RSV in the first months of life.</p>
<p>Other family members will also have less specific protective immunity and are therefore more likely to get infected and pass RSV to the infant.</p>
<p>This difference between expected immunity levels in a population and the immunity levels we’re seeing now is termed the “immunity gap” or “<a href="https://www.magonlinelibrary.com/doi/abs/10.12968/hmed.2022.0349?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%253Arid%253Acrossref.org">immunity debt</a>”. This doesn’t mean that people’s immune systems are weaker or unable to respond normally to infections. Rather, it means that people may have reduced protection to specific viruses (such as RSV), making them more likely to catch and spread the virus.</p>
<h2>Global fight against RSV</h2>
<p>We’ll likely see RSV peaks return to normal in a couple of years. But tackling the virus remains a high priority – as even in years with normal seasonal patterns, RSV is associated with <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00478-0/fulltext">over 100,000 deaths</a> globally in children under five.</p>
<p>There has been promising news in the development of vaccines to prevent RSV. Pfizer has recently announced positive results of a <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-top-line-data-phase-3-global">phase 3 clinical trial</a> of a single-dose vaccine given to pregnant women. The vaccine proved to be 82% effective against severe infection from RSV in the first three months of an infant’s life and 69% through to six months of life. The vaccine was safe for both mothers and babies. This is a major breakthrough as until now, RSV vaccines have not been available.</p>
<p>The <a href="https://www.sanofi.com/en/media-room/press-releases/2022/2022-11-04-07-00-00-2548492">European Union</a> and UK have also approved an antibody treatment for use in young infants following successful <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2110275">phase 3 studies</a>. Only one dose of this treatment is needed to provide immediate, long-lasting protection against RSV. </p>
<p>Researchers are <a href="https://rsvharmoniestudy.com/en-gb">currently enrolling infants</a> in the UK, France and Germany to see whether the treatment can reduce the number of RSV hospital admissions. If the trial is successful, this antibody treatment would be far more effective at tackling RSV in infants and cheaper than the <a href="https://www.england.nhs.uk/south/wp-content/uploads/sites/6/2021/07/phe-ref-ra-21.035-palivizumab-passive-immunisation-against-respiratory-syncytial-virus-rsv-in-at-risk-pre-term.pdf">only antibody treatment</a> used in the UK for RSV.</p>
<p>Both vaccines and antibody treatments could help to prevent dangerous RSV infections in young infants in the future, reducing the impact on families and easing pressures on the NHS. But until they’re available, there are many things parents and those who work with young children can do to <a href="https://www.cdc.gov/rsv/high-risk/infants-young-children.html">reduce the risk</a> of passing on infection – such as washing your hands often or cleaning and disinfecting surfaces. </p>
<p>Parents should also know the <a href="https://www.nhs.uk/conditions/bronchiolitis/">symptoms of serious RSV infection</a> in young babies – which include problems with breathing or difficulties feeding. If you recognise these symptoms, seek immediate medical attention.</p><img src="https://counter.theconversation.com/content/194403/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Chrissie Jones conducts studies on behalf of the University of Southampton and University Hospital Southampton NHS Foundation Trust funded by vaccine manufacturers, including Novavax (maternal RSV vaccine), Pfizer, Minervax, Moderna and Medicago, she received no personal funding from these activities. She has also provided consultative advice to Moderna and Sanofi (including for their RSV portfolio), she received financial payment for this work. </span></em></p><p class="fine-print"><em><span>Saul Faust acts on behalf of University Hospital Southampton NHS Foundation Trust as an Investigator and/or providing consultative advice on clinical trials and studies of COVID-19 and other vaccines and antimicrobials funded or sponsored by vaccine manufacturers including Sanofi (including for the HARMONIE trial), Janssen, Pfizer, AstraZeneca, GlaxoSmithKline, Novavax, Seqirus, Medimmune, Merck and Valneva. He receives no personal financial payment for this work (all monies are paid to UHS NHS FT).</span></em></p>Respiratory syncytial virus may be common, but it can lead to severe infection in some children.Chrissie Jones, Associate Professor of Paediatric Infectious Diseases, University of SouthamptonSaul Faust, Professor of Paediatric Immunology and Infectious Diseases, University of SouthamptonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1888992022-09-18T20:15:03Z2022-09-18T20:15:03ZI’ve had COVID and am constantly getting colds. Did COVID harm my immune system? Am I now at risk of other infectious diseases?<figure><img src="https://images.theconversation.com/files/483171/original/file-20220907-24-ekxrkx.jpg?ixlib=rb-1.1.0&rect=2%2C2%2C1914%2C1276&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.pexels.com/photo/photo-of-a-cold-woman-6753163/">Pavel Danilyuk/Pexels</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>So you’ve had COVID and have now recovered. You don’t have ongoing symptoms and luckily, you don’t seem to have developed <a href="https://theconversation.com/long-covid-how-researchers-are-zeroing-in-on-the-self-targeted-immune-attacks-that-may-lurk-behind-it-169911">long COVID</a>. </p>
<p>But what impacts has COVID had on your overall immune system?</p>
<p>It’s early days yet. But growing evidence suggests there are changes to your immune system that may put you at risk of other infectious diseases.</p>
<p>Here’s what we know so far.</p>
<h2>A round of viral infections</h2>
<p>Over this past winter, many of us have had what seemed like a <a href="https://theconversation.com/why-do-i-and-my-kids-get-so-many-colds-and-with-all-this-covid-around-should-we-be-isolating-too-179302">continual round</a> of viral illness. This may have included COVID, <a href="https://www.who.int/health-topics/influenza-seasonal#tab=tab_1">influenza</a> or infection with <a href="https://www.mayoclinic.org/diseases-conditions/respiratory-syncytial-virus/symptoms-causes/syc-20353098">respiratory syncytial virus</a>. We may have recovered from one infection, only to get another.</p>
<p>Then there is the re-emergence of infectious diseases globally such as <a href="https://theconversation.com/we-need-to-talk-about-monkeypox-without-shame-and-blame-188295">monkeypox</a> or <a href="https://theconversation.com/the-latest-polio-cases-have-put-the-world-on-alert-heres-what-this-means-for-australia-and-people-travelling-overseas-188989">polio</a>.</p>
<p>Could these all be connected? Does COVID somehow weaken the immune system to make us more prone to other infectious diseases?</p>
<p>There are <a href="https://www.sciencedirect.com/science/article/pii/B9780128009475000168?via%3Dihub">many reasons</a> for infectious diseases to emerge in new locations, after many decades, or in new populations. So we cannot jump to the conclusion COVID infections have given rise to these and other viral infections.</p>
<p>But evidence is building of the negative impact of COVID on a healthy <em>individual’s</em> immune system, several weeks after symptoms have subsided.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-latest-polio-cases-have-put-the-world-on-alert-heres-what-this-means-for-australia-and-people-travelling-overseas-188989">The latest polio cases have put the world on alert. Here's what this means for Australia and people travelling overseas</a>
</strong>
</em>
</p>
<hr>
<h2>What happens when you catch a virus?</h2>
<p>There are three possible outcomes after a viral infection:</p>
<p>1) your immune system clears the infection and you recover (for instance, with <a href="https://www.healthychildren.org/English/health-issues/conditions/ear-nose-throat/Pages/Rhinovirus-Infections.aspx">rhinovirus</a> which causes the common cold)</p>
<p>2) your immune system fights the virus into “latency” and you recover with a virus dormant in our bodies (for instance, <a href="https://www.healthdirect.gov.au/chickenpox">varicella zoster virus</a>, which causes chickenpox) </p>
<p>3) your immune system fights, and despite best efforts the virus remains “chronic”, replicating at very low levels (this can occur for <a href="https://www.who.int/news-room/fact-sheets/detail/hepatitis-c">hepatitis C virus</a>).</p>
<p>Ideally we all want option 1, to clear the virus. In fact, most of us <a href="https://biosignaling.biomedcentral.com/articles/10.1186/s12964-022-00856-w">clear SARS-CoV-2</a>, the virus that causes COVID. That’s through a complex process, using many different parts of our immune system.</p>
<p>But international evidence suggests changes to our immune cells after SARS-CoV-2 infection may have other impacts. It may affect our ability to fight other viruses, as well as other pathogens, such as bacteria or fungi. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/no-the-extra-hygiene-precautions-were-taking-for-covid-19-wont-weaken-our-immune-systems-143690">No, the extra hygiene precautions we're taking for COVID-19 won't weaken our immune systems</a>
</strong>
</em>
</p>
<hr>
<h2>How much do we know?</h2>
<p>An <a href="https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-02228-6">Australian study</a> has found SARS-CoV-2 alters the balance of immune cells up to 24 weeks after clearing the infection. </p>
<p>There were changes to the relative numbers and types of immune cells between people who had recovered from COVID compared with healthy people who had not been infected.</p>
<p>This included changes to cells of the <a href="https://www.khanacademy.org/test-prep/mcat/organ-systems/the-immune-system/a/innate-immunity">innate immune system</a> (which provides a non-specific immune response) and the <a href="https://www.ncbi.nlm.nih.gov/books/NBK21070/">adaptive immune system</a> (a specific immune response, targeting a recognised foreign invader).</p>
<p><a href="https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009742">Another study</a> focused specifically on <a href="https://www.immunology.org/public-information/bitesized-immunology/cells/dendritic-cells">dendritic cells</a> – the immune cells that are often considered the body’s “first line of defence”.</p>
<p>Researchers found fewer of these cells circulating after people recovered from COVID. The ones that remained were less able to activate white blood cells known as <a href="https://www.britannica.com/science/T-cell">T-cells</a>, a critical step in activating anti-viral immunity.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/483176/original/file-20220907-16-x3asae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Dendritic cells (red) attacking viruses (green)" src="https://images.theconversation.com/files/483176/original/file-20220907-16-x3asae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/483176/original/file-20220907-16-x3asae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/483176/original/file-20220907-16-x3asae.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/483176/original/file-20220907-16-x3asae.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/483176/original/file-20220907-16-x3asae.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/483176/original/file-20220907-16-x3asae.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/483176/original/file-20220907-16-x3asae.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Fewer dendritic cells (red) were circulating after COVID.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/antiviral-immunity-dendritic-cells-binding-viruses-1781314607">Shutterstock</a></span>
</figcaption>
</figure>
<p>Other studies have found different impacts on T-cells, and other types of white blood cells known as <a href="https://askabiologist.asu.edu/b-cell">B-cells</a> (cells involved in producing antibodies).</p>
<p>After SARS-CoV-2 infection, one study <a href="https://doi.org/10.1172/JCI140491">found evidence</a> many of these cells had been activated and “exhausted”. This suggests the cells are dysfunctional, and might not be able to adequately fight a subsequent infection. In other words, sustained activation of these immune cells after a SARS-CoV-2 infection may have an impact on other inflammatory diseases.</p>
<p><a href="https://www.nature.com/articles/s41392-021-00749-3#citeas">One study</a> found people who had recovered from COVID have changes in different types of B-cells. This included changes in the cells’ metabolism, which may impact how these cells function. Given B-cells are critical for producing antibodies, we’re not quite sure of the precise implications.</p>
<p>Could this influence how our bodies produce antibodies against SARS-CoV-2 should we encounter it again? Or could this impact our ability to produce antibodies against pathogens more broadly – against other viruses, bacteria or fungi? The study did not say.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-what-is-the-immune-system-19240">Explainer: what is the immune system?</a>
</strong>
</em>
</p>
<hr>
<h2>What impact will these changes have?</h2>
<p>One of the main concerns is whether such changes may impact how the immune system responds to other infections, or whether these changes
might worsen or cause other chronic conditions. </p>
<p>So more work needs to be done to understand the long-term impact of SARS-CoV-2 infection on a person’s immune system.</p>
<p>For instance, we still don’t know how long these changes to the immune system last, and if the immune system recovers. We also don’t know if SARS-CoV-2 triggers other chronic illnesses, such as <a href="https://www.healthdirect.gov.au/chronic-fatigue-syndrome-cfs-me">chronic fatigue syndrome</a> (myalgic encephalomyelitis). Research into this is ongoing.</p>
<p>What we do know is that having a healthy immune system and being vaccinated (when a vaccine has been developed) is critically important to have the best chance of fighting any infection.</p><img src="https://counter.theconversation.com/content/188899/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Lara Herrero receives funding from NHMRC.</span></em></p>Evidence is growing there are changes to your immune system that may put you at risk of other infectious diseases.Lara Herrero, Research Leader in Virology and Infectious Disease, Griffith UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1899492022-09-15T12:25:40Z2022-09-15T12:25:40ZViruses may be ‘watching’ you – some microbes lie in wait until their hosts unknowingly give them the signal to start multiplying and kill them<figure><img src="https://images.theconversation.com/files/484664/original/file-20220914-25-l0cplf.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2309%2C1299&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Phages can sense bacterial DNA damage, which triggers them to replicate and jump ship.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/bacteriophage-infecting-bacterium-royalty-free-image/992263464">Design Cells/iStock via Getty Images Plus</a></span></figcaption></figure><p>After more than two years of the COVID-19 pandemic, you might picture a virus as a nasty spiked ball – a mindless killer that gets into a cell and hijacks its machinery to create a gazillion copies of itself before bursting out. For many viruses, including the <a href="https://doi.org/10.1038/s41579-020-00468-6">coronavirus that causes COVID-19</a>, the “mindless killer” epithet is essentially true.</p>
<p>But there’s more to virus biology than meets the eye.</p>
<p>Take HIV, the virus that causes <a href="https://doi.org/10.1002/eji.200737441">AIDS</a>. HIV is a <a href="https://doi.org/10.1101%2Fcshperspect.a006882">retrovirus</a> that does not go directly on a killing spree when it enters a cell. Instead, it integrates itself into your chromosomes and chills, waiting for the right moment to command the cell to make copies of it and burst out to infect other immune cells and eventually cause AIDS.</p>
<p>Exactly what moment HIV is waiting for is still an <a href="https://doi.org/10.1016/j.cell.2018.04.005">area of active study</a>. But research on other viruses has long hinted that these pathogens can be quite “thoughtful” about killing. Of course, viruses cannot think the way you and I do. But, as it turns out, evolution has endowed them with some pretty elaborate decision-making mechanisms. Some viruses, for instance, will choose to leave the cell they have been residing in if they detect DNA damage. Not even viruses, it appears, like to stay in a sinking ship.</p>
<p><a href="https://scholar.google.com/citations?user=T1I1sNAAAAAJ&hl=en">My</a> <a href="https://erilllab.umbc.edu/">laboratory</a> has been studying the molecular biology of <a href="https://doi.org/10.4161%2Fbact.1.1.14942">bacteriophages</a>, or phages for short, the viruses that infect bacteria, for over two decades. Recently, my colleagues and I <a href="https://doi.org/10.3389/fmicb.2022.918015">have shown</a> that phages can listen for key cellular signals to help them in their decision-making. Even worse, they can use the cell’s own “ears” to do the listening for them.</p>
<h2>Escaping DNA damage</h2>
<p>If the enemy of your enemy is your friend, phages are certainly your friends. Phages <a href="https://doi.org/10.4161%2Fbact.1.1.14942">control bacterial populations</a> in nature, and clinicians are increasingly using them to <a href="https://doi.org/10.1038/s41591-019-0437-z">treat bacterial infections</a> that do not respond to antibiotics.</p>
<p>The best studied phage, <a href="https://doi.org/10.1016/j.virol.2015.02.010">lambda</a>, works a bit like HIV. Upon entering the bacterial cell, lambda decides whether to replicate and kill the cell outright, like most viruses do, or to integrate itself into the cell’s chromosome, as HIV does. If the latter, lambda harmlessly replicates with its host each time the bacteria divides. </p>
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<figcaption><span class="caption">This video shows a lambda phage infecting <em>E. coli</em>.</span></figcaption>
</figure>
<p>But, like HIV, lambda is not just sitting idle. It uses a special protein called CI like a stethoscope to listen for signs of DNA damage within the bacterial cell. If the bacterium’s DNA gets compromised, that’s bad news for the lambda phage nested within it. Damaged DNA leads straight to evolution’s landfill because it’s useless for the phage that needs it to reproduce. So lambda turns on its replication genes, makes copies of itself and bursts out of the cell to look for more undamaged cells to infect.</p>
<h2>Tapping the cell’s communication system</h2>
<p>Some phages, instead of gathering intel with their own proteins, tap the infected cell’s very own DNA damage sensor: LexA.</p>
<p>Proteins like CI and LexA are <a href="https://doi.org/10.1016/j.jmb.2019.04.011">transcription factors</a> that turn genes on and off by binding to specific genetic patterns within the DNA instruction book that is the chromosome. Some phages like Coliphage 186 have figured out that they don’t need their own viral CI protein if they have a short DNA sequence in their chromosomes that bacterial LexA can bind to. Upon detecting DNA damage, LexA will activate the phage’s replicate-and-kill genes, essentially double-crossing the cell into committing suicide while allowing the phage to escape.</p>
<p>Scientists first reported CI’s role in phage decision-making <a href="https://doi.org/10.1038/294217a0">in the 1980s</a> and Coliphage 186’s counterintelligence trick <a href="https://doi.org/10.1074/jbc.273.10.5708">in the late 1990s</a>. Since then, there have been a few other reports of phages tapping bacterial communication systems. One example is <a href="https://doi.org/10.1038/sj.emboj.7600826">phage phi29</a>, which exploits its host’s transcription factor to detect when the bacterium is getting ready to generate a spore, or a kind of bacterial egg <a href="https://doi.org/10.1023/A:1020561122764">capable of surviving extreme environments</a>. Phi29 instructs the cell to package its DNA into the spore, killing the budding bacteria once the spore germinates.</p>
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<figcaption><span class="caption">Transcription factors turn genes on and off.</span></figcaption>
</figure>
<p>In our <a href="https://doi.org/10.3389/fmicb.2022.918015">recently published research</a>, my colleagues and I show that several groups of phages have independently evolved the ability to tap into yet another bacterial communication system: the CtrA protein. CtrA integrates multiple internal and external signals to set in motion different developmental processes in bacteria. Key among these is the production of bacterial appendages called <a href="https://doi.org/10.1007/s12275-017-7369-4">flagella and pili</a>. Turns out, these phages attach themselves to the pili and flagella of bacteria in order to infect them.</p>
<p>Our leading hypothesis is that phages use CtrA to guesstimate when there will be enough bacteria nearby sporting pili and flagella that they can readily infect. A pretty smart trick for a “mindless killer.”</p>
<p>These are not the only phages that make elaborate decisions – all without the benefit of even having a brain. Some phages that infect <em>Bacillus</em> bacteria produce a small molecule each time they infect a cell. The phages can sense this molecule and use it to <a href="https://doi.org/10.1016/j.cub.2021.08.072">count the number of phage infections</a> taking place around them. Like alien invaders, this count helps decide when they should switch on their replicate-and-kill genes, killing only when hosts are relatively abundant. This way, the phages make sure that they never run out of hosts to infect and guarantee their own long-term survival.</p>
<h2>Countering viral counterintelligence</h2>
<p>You may be wondering why you should care about the counterintelligence ops run by bacterial viruses. While bacteria are very different from people, the viruses that infect them are <a href="https://doi.org/10.1128/MMBR.00193-20">not that different</a> from the viruses that infect humans. Pretty much <a href="https://doi.org/10.1016/j.virol.2012.09.017">every single trick</a> played by phages has later been shown to be used by human viruses. If a phage can tap bacterial communication lines, why wouldn’t a human virus tap yours?</p>
<p>So far, researchers don’t know what human viruses could be listening for if they hijack these lines, but plenty of options come to mind. I believe that, like phages, human viruses could potentially be able to count their numbers to strategize, detect cell growth and tissue formation and even monitor immune responses. For now, these possibilities are only speculation, but scientific investigation is underway.</p>
<p>Having viruses listening to your cells’ private conversations is not the rosiest of pictures, but it’s not without a silver lining. As intelligence agencies all around the world know well, counterintelligence works only when it’s covert. Once detected, the system can very easily be exploited to feed misinformation to your enemy. Similarly, I believe that future antiviral therapies may be able to combine conventional artillery, like antivirals that prevent viral replication, with information warfare trickery, such as making the virus believe the cell it is in belongs to a different tissue. </p>
<p>But, hush, don’t tell anybody. Viruses could be listening!</p><img src="https://counter.theconversation.com/content/189949/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ivan Erill receives funding from the US National Science Foundation</span></em></p>Phages, or viruses that infect bacteria, can lie dormant within chromosomes until they’re triggered to replicate and burst out of their hosts.Ivan Erill, Associate Professor of Biological Sciences, University of Maryland, Baltimore CountyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1870562022-08-17T12:38:37Z2022-08-17T12:38:37ZWhen COVID-19 or flu viruses kill, they often have an accomplice – bacterial infections<figure><img src="https://images.theconversation.com/files/479451/original/file-20220816-9774-ss8ukw.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2059%2C1454&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Bacteria can team up with viruses to cause coinfections.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/microscopic-view-of-bacteria-or-virus-moving-in-a-royalty-free-image/1328434309">Erlon Silva - TRI Digital/Moment via Getty Images</a></span></figcaption></figure><p>The <a href="https://www.cdc.gov/flu/pandemic-resources/1918-pandemic-h1n1.html">1918 influenza pandemic</a> resulted in the loss of over 3% of the world’s population – at least 50 million people. But it wasn’t the flu virus that caused the majority of these deaths.</p>
<p>An <a href="https://doi.org/10.1086/591708">analysis of lung samples</a> collected during that flu pandemic indicated that most of the deaths were likely due to bacterial pneumonia, which ran rampant in the absence of antibiotics. Even in more recent history, like the <a href="https://doi.org/10.1016/S0140-6736(58)90060-6">1957 H2N2</a> and <a href="https://doi.org/10.1378/chest.10-1396">2009 H1N1</a> flu pandemics, nearly 18% of patients with viral pneumonia had additional bacterial infections that increased their risk of death. And the <a href="https://doi.org/10.1186/s41479-021-00083-w">COVID-19 pandemic</a> is no different.</p>
<p>With yet another flu season fast approaching in the midst of the ongoing COVID-19 pandemic, lessening the harm caused by these viruses is important to prevent deaths and reduce infections. However, many deaths associated with the flu and COVID-19 don’t occur at the hand of the virus alone. Instead, it’s a <a href="https://doi.org/10.3390/v13091725">secondary bacterial infection</a> that is often at the root of the devastating consequences attributed to an initial viral infection.</p>
<p>I am an <a href="https://medicine.tufts.edu/people/faculty/hayley-muendlein">immunologist</a> who studies why and how cells die during bacterial and viral infections. Understanding the synergy between these microbes is critical not only for effective diagnosis and treatment, but also for managing current pandemics and preventing future ones. My colleagues and I <a href="https://doi.org/10.1073/pnas.2113872119">published a study</a> showing how an immune system protein crucial to fighting against viruses also plays an indispensable role in fighting bacteria.</p>
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<figcaption><span class="caption">One Texas man who died in March 2020 tested positive for COVID-19, strep throat and the flu.</span></figcaption>
</figure>
<h2>Viruses and bacteria team up</h2>
<p>Multiple pathogens can cause multiple infections in different ways. Scientists distinguish each type <a href="https://doi.org/10.1186/s41479-021-00083-w">based on the timing</a> of when each infection occurs. <a href="https://www.biomedcentral.com/collections/CIS">Coinfection</a> refers to two or more different pathogens causing infections at the same time. <a href="https://www.mountsinai.org/health-library/special-topic/secondary-infections#">Secondary or superinfections</a>, on the other hand, refer to sequential infections that occur after an initial infection. They’re often caused by pathogens resistant to antibiotics used to treat the primary infection.</p>
<p>How viral and bacterial infections interact with each other increases the potential harm they can cause. Viral respiratory infections can increase the likelihood of bacterial infections and lead to worse disease. The reason why this happens is often multifaceted.</p>
<p>Within your respiratory tract, the epithelial cells lining your airways and lungs serve as the first line of defense against inhaled pathogens and debris. However, <a href="https://doi.org/10.1164/rccm.200909-1420OC">viruses can kill these cells</a> and disrupt this protective barrier, allowing inhaled bacteria to invade. They can also <a href="https://doi.org/10.1164/arrd.1986.134.5.1040">change the surface of epithelial cells</a> to make them easier for bacteria to attach to. </p>
<p>Viruses can also alter the surface of <a href="https://doi.org/10.1164/rccm.201406-1101PP">epithelial and immune cells</a> by <a href="https://doi.org/10.1159/000335548">reducing the number of receptors</a> that help these cells recognize and mount a response against pathogens. This reduction means fewer immune cells report to the viral infection site, giving bacteria an opening to launch another infection.</p>
<h2>Influenza, COVID-19 and bacterial infections</h2>
<p>Patients who have a bacterial infection at the same time they’re battling the seasonal flu are more likely to wind up in a hospital. <a href="https://doi.org/10.1111/j.1750-2659.2012.00360.x">Nearly a quarter</a> of patients admitted to the ICU with severe influenza also have a bacterial infection. One study on the 2010 to 2018 flu seasons found that <a href="https://doi.org/10.1016/j.jiac.2018.10.014">nearly 20% of patients</a> admitted to the hospital with flu-associated pneumonia had acquired bacterial infections.</p>
<p><a href="https://doi.org/10.1016/j.eclinm.2021.100955">Another study</a> of patients hospitalized with viral or bacterial infections found that nearly half had a coinfection with another pathogen. These patients also had nearly double the risk of dying within 30 days compared to those with only a single infection. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/479453/original/file-20220816-8398-d1lnpm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscopy image of Staphylococcus aureus (MRSA) bacteria" src="https://images.theconversation.com/files/479453/original/file-20220816-8398-d1lnpm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/479453/original/file-20220816-8398-d1lnpm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=407&fit=crop&dpr=1 600w, https://images.theconversation.com/files/479453/original/file-20220816-8398-d1lnpm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=407&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/479453/original/file-20220816-8398-d1lnpm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=407&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/479453/original/file-20220816-8398-d1lnpm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=512&fit=crop&dpr=1 754w, https://images.theconversation.com/files/479453/original/file-20220816-8398-d1lnpm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=512&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/479453/original/file-20220816-8398-d1lnpm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=512&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption"><em>Staphylococcus aureus</em>, or MRSA, is a common source of bacterial coinfections.</span>
<span class="attribution"><a class="source" href="https://phil.cdc.gov/Details.aspx?pid=10046">Janice Haney Car/Centers for Disease Control and Prevention</a></span>
</figcaption>
</figure>
<p>Interestingly, the <a href="https://doi.org/10.1111/irv.12398">two bacteria species</a> most commonly involved in coinfections with the influenza virus are <em>Streptococcus pneumoniae</em> and <em>Staphylococcus aureus</em>, which normally exist in the respiratory tract without causing disease. However, the influenza virus can damage the cell barrier of the lungs and disrupt immune function enough to make patients susceptible to infection by these otherwise benign bacteria.</p>
<p>Secondary bacterial infections are also exacerbating the COVID-19 pandemic. A 2021 review estimated that <a href="https://doi.org/10.1371/journal.pone.0251170">16% to 28% of adults</a> hospitalized for COVID-19 also had a bacterial infection. These patients stayed in the hospital for twice as long, were four times more likely to need mechanical ventilation and had three times greater odds of dying compared to patients with only COVID-19.</p>
<h2>Addressing secondary and coinfections</h2>
<p>The immune system <a href="https://courses.lumenlearning.com/suny-ap2/chapter/the-immune-response-against-pathogens/">responds differently</a> to viruses and bacteria. <a href="https://theconversation.com/why-are-there-so-many-drugs-to-kill-bacteria-but-so-few-to-tackle-viruses-137480">Antivirals</a> don’t work on bacteria, and antibiotics don’t work on viruses. A better understanding of what pathways the body uses to regulate both antiviral and antibacterial infections is critical to addressing secondary and coinfections.</p>
<p><a href="https://doi.org/10.1073/pnas.2113872119">Recent work</a> by my colleagues and me may provide a clue. We <a href="https://doi.org/10.1101/pdb.top084970">sequenced the RNA</a> of one type of immune cell, macrophages, in mice to identify what molecules were present in cells that were either protected from or died due to bacterial infection. </p>
<p>We identified <a href="https://doi.org/10.1007/82_2019_190">Z-DNA binding protein (ZBP1)</a>, a molecule already known to play a regulatory role in how the immune system responds to influenza. Specifically, ZBP1 <a href="https://doi.org/10.1007/82_2019_190">detects influenza viruses</a> within the lungs and signals infected epithelial and immune cells to self-destruct. This induced cell death eliminates the virus and promotes recruitment of additional immune cells to the infection site.</p>
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<figcaption><span class="caption">Programmed cell death takes a number of forms, two of which include apoptosis and necrosis.</span></figcaption>
</figure>
<p>Building off this finding that ZBP1 is important for fighting viral infection, we found that macrophages infected with <em>Yersinia pseudotuberculosis</em>, a type of bacteria that causes foodborne illness, also use this protein to initiate <a href="https://doi.org/10.1038/s41467-020-20357-z">cell death</a>. This limits bacterial replication while also sending <a href="https://doi.org/10.1073/pnas.2113872119">inflammatory signals</a> that help clear bacteria.</p>
<p>These findings raise the possibility that ZBP1 may play a dual role in how the body responds to viral and bacterial infections. It’s possible that treatments that increase ZBP1 in certain types of cells may be useful in managing bacterial and viral coinfections.</p><img src="https://counter.theconversation.com/content/187056/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Hayley Muendlein does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Coinfections with bacteria can make viral infections even deadlier. Researchers have identified a protein in immune cells that may play a role in fighting both types of pathogens.Hayley Muendlein, Research Assistant Professor of Immunology, Tufts UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1869702022-08-04T12:23:36Z2022-08-04T12:23:36ZLong COVID-19 and other chronic respiratory conditions after viral infections may stem from an overactive immune response in the lungs<figure><img src="https://images.theconversation.com/files/477255/original/file-20220802-23-r6z7fj.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2297%2C1292&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The immune system usually stays dormant in the lungs in times of health.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/lung-virus-infection-royalty-free-image/1205199983">wildpixel/iStock via Getty Images</a></span></figcaption></figure><p>Viruses that cause respiratory diseases like the flu and COVID-19 can lead to mild to severe symptoms within the first few weeks of infection. These symptoms typically resolve within a few more weeks, sometimes with the help of treatment if severe. However, some people go on to experience persistent symptoms that last several months to years. Why and how respiratory diseases can develop into chronic conditions like <a href="https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html">long COVID-19</a> are still unclear.</p>
<p>I am a <a href="https://scholar.google.com/citations?hl=en&user=BNGZA1MAAAAJ">doctoral student</a> working in the <a href="https://www.immunology.virginia.edu/Sun/">Sun Lab</a> at the University of Virginia. We study how the immune system sometimes goes awry after fighting off viral infections. We also develop ways to target the immune system to prevent further complications without weakening its ability to protect against future infections. Our <a href="https://doi.org/10.1126/sciimmunol.abm7996">recently published review</a> of the research in this area found that it is becoming clearer that it might not be an active viral infection causing long COVID-19 and similar conditions, but an overactive immune system.</p>
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<figcaption><span class="caption">Long COVID-19 patients can experience persistent respiratory, cognitive and neurological symptoms.</span></figcaption>
</figure>
<h2>The lungs in health and disease</h2>
<p>Keeping your immune system dormant when there isn’t an active infection is essential for your lungs to be able to function optimally. </p>
<p>Your respiratory tract is in constant contact with your external environment, sampling around <a href="https://www.acepnow.com/article/avoid-airway-catastrophes-extremes-minute-ventilation/">5 to 8 liters (1.3 to 2 gallons) of air</a> – and the toxins and microorganisms in it – every minute. Despite continuous exposure to potential pathogens and harmful substances, your body has evolved to <a href="https://doi.org/10.1164/ajrccm.162.supplement_3.15tac6">keep the immune system dormant in the lungs</a>. In fact, allergies and conditions such as asthma are byproducts of an <a href="https://doi.org/10.1513/AnnalsATS.201401-028AW">overactive immune system</a>. These excessive immune responses can cause your airways to constrict and make it difficult to breathe. Some severe cases may require treatment to suppress the immune system. </p>
<p>During an active infection, however, the immune system is absolutely essential. When viruses infect your respiratory tract, immune cells are recruited to your lungs to fight off the infection. Although these cells are crucial to eliminate the virus from your body, their activity often results in collateral damage to your lung tissue. After the virus is removed, your body <a href="https://doi.org/10.1007%2Fs00281-016-0560-6">dampens your immune system</a> to give your lungs a chance to recover.</p>
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<figcaption><span class="caption">An overactive immune system, as in the case of asthma, can damage the lungs.</span></figcaption>
</figure>
<p>Over the past decade, researchers have identified a variety of <a href="https://doi.org/10.1016/j.stem.2020.03.009">specialized stem cells in the lungs</a> that can help regenerate damaged tissue. These stem cells can turn into almost all the different types of cells in the lungs depending on the signals they receive from their surrounding environment. <a href="https://doi.org/10.1126/scitranslmed.abo5254">Recent</a> <a href="https://doi.org/10.1016/j.stem.2020.06.020">studies</a> <a href="https://doi.org/10.1016/j.stemcr.2019.02.013">have highlighted</a> the prominent role the immune system plays in providing signals that facilitate lung recovery. But these signals can produce more than one effect. They can not only activate stem cells, but also perpetuate damaging inflammatory processes in the lung. Therefore, your body tightly regulates when, where and how strongly these signals are made in order to prevent further damage.</p>
<p>While the reasons are still unclear, some people are unable to turn off their immune system after infection and <a href="https://doi.org/10.1126/sciimmunol.abk1741">continue to produce tissue-damaging molecules</a> <a href="https://doi.org/10.1038/s41590-021-01113-x">long after</a> the virus has been flushed out. This not only further damages the lungs, but also interferes with regeneration via the lung’s resident stem cells. This phenomenon can result in chronic disease, as seen in several respiratory viral infections including <a href="https://doi.org/10.1016/j.immuni.2022.01.017">COVID-19</a>, <a href="https://doi.org/10.2340/16501977-2694">Middle East Respiratory Syndrome (MERS)</a>, <a href="https://doi.org/10.1056/NEJMoa1211917">respiratory syncytial virus (RSV)</a> and the <a href="https://doi.org/10.1016/j.jaci.2005.06.024">common cold</a>.</p>
<h2>The immune system’s role in chronic disease</h2>
<p>In our review, my colleagues and I found that many <a href="https://doi.org/10.1126/sciimmunol.abm7996">different types of immune cells</a> are involved in the development of chronic disease after respiratory viral infections, including long COVID-19.</p>
<p>Scientists so far have identified one particular type of immune cells, <a href="https://doi.org/10.1126/sciimmunol.abk1741">killer T cells</a>, as potential contributors to chronic disease. Also known as cytotoxic or CD8+ T cells, they specialize in killing infected cells either by interacting directly with them or by producing damaging molecules called cytokines. </p>
<p>Killer T cells are essential to curbing the virus from spreading in the body during an active infection. But their persistence in the lungs after the infection has resolved is linked to extended <a href="https://doi.org/10.1126/sciimmunol.abc4557">reduced respiratory function</a>. Moreover, animal studies have shown that <a href="https://doi.org/10.1126/sciimmunol.abk1741">removing killer T cells from the lungs</a> after infection may improve lung function and tissue repair.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/PSRJfaAYkW4?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">A legion of immune cells work together to remove invading pathogens.</span></figcaption>
</figure>
<p>Another type of immune cells called monocytes are also involved in fighting respiratory infections, serving among the first responders by producing virus- and tissue-damaging cytokines. Research has found that these cells also <a href="https://doi.org/10.1016/j.immuni.2022.01.017">continue to accumulate</a> in the lungs of long COVID-19 patients and promote a pro-inflammatory environment that can cause further damage.</p>
<p>Understanding the immunological mechanisms underlying long COVID-19 is the first step to addressing a <a href="https://www.kff.org/policy-watch/what-are-the-implications-of-long-covid-for-employment-and-health-coverage/">quickly worsening public health problem</a>. Identifying the subtle differences in how the same immune cells that protect you during an active infection can later become harmful could lead to earlier diagnosis of long COVID-19. Moreover, based on our findings, my team and I believe treatments that target the immune system could be an effective approach to manage long COVID-19 symptoms. We believe that this strategy may turn out to be useful not only for COVID-19, but also for other respiratory viral infections that lead to chronic disease as well.</p><img src="https://counter.theconversation.com/content/186970/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Harish Narasimhan does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>While a strong immune response is essential to fight against viral infection, an immune system that continues to stay active long after the virus has been cleared can lead to lung damage.Harish Narasimhan, PhD Candidate in Immunology, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1840852022-06-06T19:40:43Z2022-06-06T19:40:43ZMonkeypox: ‘This is an entirely new spread of the disease’<figure><img src="https://images.theconversation.com/files/467198/original/file-20220606-20-5nho1v.png?ixlib=rb-1.1.0&rect=0%2C8%2C2901%2C1770&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Electron micrograph of monkeypox virus particles isolated in 2003 in the United States from human samples (left, mature, oval viruses; right, immature, round viruses).</span> <span class="attribution"><a class="source" href="https://phil.cdc.gov/Details.aspx?pid=22664">Cynthia S. Goldsmith, Russell Regner / CDC / AP</a></span></figcaption></figure><p><em>One thousand confirmed cases of monkeypox, a disease originating in Africa, have been recorded since early May across at least 30 non-endemic countries such as the United Kingdom, Spain, Portugal, France, the United States, Australia, United Arab Emirates and Israel. But what is this virus? Who is affected? And should we be worried about the recent surge in cases? In a bid to answer such questions, we caught up with Camille Besombes, a medical doctor specialist in infectious diseases, who has been involved for the past three years in <a href="https://research.pasteur.fr/fr/project/afripox/">Afripox</a>, a project that aims to gain a better understanding of the virus in its endemic region. She is currently conducting PhD research within the unit headed by the project’s coordinator, Arnaud Fontanet, a leading medical epidemiologist and emerging infectious disease specialist at the Pasteur Institute.</em></p>
<hr>
<p><strong>The Conversation: What exactly is the monkeypox virus?</strong></p>
<p><strong>Camille Besombes:</strong> Monkeypox is a virus belonging to the genus Orthopoxvirus, a family that also includes smallpox. Like smallpox, it is a large DNA virus with a particular appetite for skin tissue. However, smallpox only affected humans, which meant that we were able to eradicate it through worldwide mass vaccination, whereas monkeypox is carried by an animal viral reservoir. And despite its name, the natural reservoir is not actually monkeys.</p>
<p>The term “monkeypox” was coined when the virus was first identified in captive primates (in Denmark back in 1958), but in nature, the virus is most often found in squirrels and other rodents. In 1970, the first human case of monkeypox was documented in a nine-month-old child in the Democratic Republic of the Congo, amid increasing efforts in the campaign to eradicate smallpox.</p>
<p><a href="https://pubmed.ncbi.nlm.nih.gov/35148313/">There are two strains of monkeypox that we know of</a>. The type that affects Nigeria, Liberia, Sierra Leone, and Côte d’Ivoire is the so-called West African strain, with a case-fatality rate between 1 to 3%. This is the one that was detected in the recent cases in Europe. The second is the “Congo Basin” strain, which circulates in the Democratic Republic of the Congo (DRC), the Republic of the Congo, the Central African Republic (CAR), and Gabon. Both strains are now circulating in Cameroon: recently, cases of infections implying the West African strain – imported from Nigeria – have been reported. Associated with more severe clinical forms, the Congo Basin strain has a case-fatality rate of around 10%.</p>
<p>We must also keep in mind that these figures are taken from countries where medical care is somewhat lacking, particularly in more remote regions. As for Europe, several patients are currently in hospital with the disease, but no death and no severe form of it have been detected on the continent.</p>
<p><strong>TC: What are the symptoms of this disease?</strong></p>
<p><strong>CB:</strong> Following a relatively long incubation (usually lasting around 6 to 13 days, and up to 21 days), it presents its first onset symptoms during a two-day period known as the “prodromal” phase. These symptoms may include high fever, headaches, swollen lymph nodes (which are a sign that distinguishes it from smallpox), muscle pain, and fatigue. It is at this stage that patients are considered to be contagious.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/464537/original/file-20220520-18-ynskxc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Photo of monkeypox lesions" src="https://images.theconversation.com/files/464537/original/file-20220520-18-ynskxc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/464537/original/file-20220520-18-ynskxc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=800&fit=crop&dpr=1 600w, https://images.theconversation.com/files/464537/original/file-20220520-18-ynskxc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=800&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/464537/original/file-20220520-18-ynskxc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=800&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/464537/original/file-20220520-18-ynskxc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1005&fit=crop&dpr=1 754w, https://images.theconversation.com/files/464537/original/file-20220520-18-ynskxc.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1005&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/464537/original/file-20220520-18-ynskxc.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1005&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Monkeypox causes lesions that gradually spread over the infected person’s body.</span>
<span class="attribution"><span class="source">Jean-Marc Zokoé</span>, <span class="license">Fourni par l'auteur</span></span>
</figcaption>
</figure>
<p>Next, the patient develops a rash, <a href="https://www.cdc.gov/poxvirus/monkeypox/symptoms.html">usually starting on the face</a> and gradually spreading over the rest of the body. This rash causes pain and intense itching due to the inflammation that occurs around the skin lesions. In the West African strain, these lesions can be initially rather infrequent and discreet, and may therefore go unnoticed. The disease typically lasts two to four weeks and tends to go away spontaneously in the majority of cases.</p>
<p>The main complications of monkeypox include dehydration due to water loss from numerous and more widespread lesions, secondary bacterial infection of the lesions, sepsis, and corneal or other ocular lesions that may lead to vision loss. On top of these, cases of encephalitis (<em>ed. note: “inflammation of the brain”</em>) have also been documented, most notably in a <a href="https://pubmed.ncbi.nlm.nih.gov/15499541/">child during the 2003 US outbreak</a>.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/464538/original/file-20220520-18-ig02wa.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt=" Photo of an infant covered with lesions due to monkeypox virus " src="https://images.theconversation.com/files/464538/original/file-20220520-18-ig02wa.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/464538/original/file-20220520-18-ig02wa.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/464538/original/file-20220520-18-ig02wa.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/464538/original/file-20220520-18-ig02wa.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/464538/original/file-20220520-18-ig02wa.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/464538/original/file-20220520-18-ig02wa.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/464538/original/file-20220520-18-ig02wa.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Children are more at risk of developing more severe forms of the disease.</span>
<span class="attribution"><span class="source">Jean-Marc Zokoé</span>, <span class="license">Fourni par l'auteur</span></span>
</figcaption>
</figure>
<p>Children who have been infected with monkeypox are more likely to experience complications and therefore have a higher fatality rate than adults. It is also assumed that immunocompromised individuals (particularly those who are HIV-positive) have a higher risk of developing a severe form of the disease, but there is not enough data yet to know this for certain. During the 2017-18 Nigerian outbreak, <a href="https://pubmed.ncbi.nlm.nih.gov/31285143/">four out of seven people who died from the disease were HIV-positive</a>. Pregnant women could also be affected by less moderate forms and we noted instances of mother-to-child transmission.</p>
<p>Treatment of the disease is largely symptom-based and involves methods like disinfecting the lesions, administering antibiotics in cases of secondary infection, and rehydration. Research is currently being conducted into whether certain antiviral molecules (such as <a href="https://www.ema.europa.eu/en/medicines/human/EPAR/tecovirimat-siga">tecovirimat</a> could be effective against monkeypox, but the results are not yet conclusive.</p>
<p><strong>TC: Is this the first time that the virus has spread outside of the African continent? How many cases have been recorded so far, and where?</strong></p>
<p><strong>CB:</strong> No, it isn’t the first time. Although the Congo Basin strain has never travelled beyond Africa, the West African strain managed to reach the United States in 2003 by way of imported animals that had been infected. More recently, however, a number of countries have reported several cases brought in by humans.</p>
<p>Back in 2003, <a href="https://www.cdc.gov/poxvirus/monkeypox/outbreak/us-outbreaks.html">number of individuals in the United States</a> caught the virus from infected prairie dogs purchased from pet shops where the animals had been in contact with monkeypox-carrying Gambian pouched rats (<em>Cricetomys gambianus</em>) imported from Ghana. A total of 47 suspected cases of human infection were recorded, all the result of zoonotic (i.e., animal-to-human) transmission. There were no instances of interhuman transmission. At the time, the US authorities were concerned that the virus might take over a reservoir of local species, but this did not happen.</p>
<p>Then, in September 2017, a more severe outbreak occurred in Nigeria, which had not experienced any monkeypox epidemic in the preceding 39 years. This particular epidemic is still ongoing, sustained by sporadic, regular transmissions that are both zoonotic and interhuman. To date, at least 500 suspected cases have been declared (215 of which have been confirmed). Reassuringly, albeit regrettably, only 8 deaths have been documented in the past 5 years.</p>
<p>However, the Nigerian epidemic had marked a major change in monkeypox epidemiology and should have acted as a warning to us. Whereas the virus had tended to thrive in forest regions with little connection, in 2017, it hit the country’s more urban areas and at a larger scale. This is how it managed to spread more easily beyond the continent, with cases popping up in 2018 <a href="https://pubmed.ncbi.nlm.nih.gov/32880628/">in Singapore, Israel, and England, brought back by travellers returning from Nigeria</a>.</p>
<p>In the case of England, a local human-to-human transmission occurred when a British healthcare worker <a href="https://jglobalbiosecurity.com/article/10.31646/gbio.22/">became infected while cleaning a patient’s bed</a>. There was no endemic viral circulation at the time, but more infections emerged in 2021, again linked to travellers coming back from Nigeria and occurring both in the UK and in the United States (where two cases were recorded).</p>
<p>In the UK in 2018, scientists also studied the risk of emergence of an endemic animal reservoir. Species such as the common squirrel (<em>Sciurus vulgaris</em>) and domestic mouse (<em>Mus musculus</em>) were thought to be particularly prone to the virus, while other rodents (voles, dormice, other mice) or still hedgehogs were also considered <a href="https://www.gov.uk/government/publications/hairs-risk-assessment-monkeypox/qualitative-assessment-of-the-risk-to-the-uk-human-population-of-monkeypox-infection-in-a-canine-feline-mustelid-lagomorph-or-rodent-uk-pet">as potential reservoirs</a>.</p>
<p><strong>TC: What is different about the current context?</strong></p>
<p><strong>CB:</strong> <a href="https://www.bmj.com/content/377/bmj.o1274">The situation</a> is <a href="https://www.nature.com/articles/d41586-022-01421-8">very different</a> this time around. We know that the first case of the current epidemic, recorded on 7 May in the UK, was that of an individual travelling back from Nigeria. However, several other UK cases have since been confirmed that are apparently unrelated to one another or to this 7th May case. No instance of foreign travel (to African countries) associated with the infections has yet been proven and the direct chains of transmission have not been identified, suggesting the existence of several chains of transmission and a local circulation of the virus.</p>
<p>As of 6th June, 1,000 cases had been detected in at least 30 different countries, worldwide, with the largest number of cases located in the United Kingdom (<a href="https://www.gov.uk/government/news/monkeypox-cases-confirmed-in-england-latest-updates">287 confirmed</a>), Spain (189 confirmed), Portugal (143 confirmed). French authorities have reported 51 confirmed cases. For now, all of the recorded infections outside of Africa have been mild. Only a few patients have been hospitalised and no death or vital threat has been reported. A non-negligible proportion of cases were reported among HIV+ patients.</p>
<iframe src="https://ourworldindata.org/explorers/monkeypox?tab=map&facet=none&hideControls=true&Metric=Confirmed+cases&Frequency=Cumulative&Shown+by=Date+of+confirmation&country=~OWID_WRL" loading="lazy" style="width: 100%; height: 600px; border: 0px none;" width="100%" height="400"></iframe>
<p>That said, these local circulations of the disease are unprecedented. Another new aspect is that the cases have almost exclusively been reported among young males, primarily among homosexual men (<a href="https://www.gov.uk/government/news/ukhsa-latest-findings-into-monkeypox-outbreak">in the UK, the authorities emphasised that “currently most cases have been in men who are gay, bisexual or have sex with men”</a>). Only six suspected and confirmed women were declared in Spain, Czech Republic, Italy, the United States and United Arab Emirates. These last two women were not linked to the European cluster following mass gathering events, but returned from Western Africa, suggesting something is up with the Nigerian epidemic that is exporting the virus.</p>
<p><strong>TC: Why is this new? What are the usual channels of infection?</strong></p>
<p><strong>CB:</strong> Monkeypox epidemics most often arise from animal-to-human transmission, although the exact details of how they occur are unclear and it has not yet been possible to isolate the same viral strain in animals and in humans. It may come from direct contact with a living animal when hunting or eating bush meat.</p>
<p>One thing we have noticed from our research in the CAR is that the outbreaks tend to be seasonal. This would suggest a link with certain seasonal activities like the harvesting of edible caterpillars, which involves individuals entering the forest, where they would be more exposed to local wildlife.</p>
<p>Even though scientists have been tracking the viral reservoir since the 1970s, it has, as of yet, only rarely been isolated in wild animals. The first instance was in <a href="https://pubmed.ncbi.nlm.nih.gov/2867342/">1985 in the DRC</a> and involved a species known as a Thomas’s rope squirrel (<em>Funisciurus anerythrus</em>), thought to be the reservoir of the virus. The next was that of a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036778/">sooty mangabey monkey in 1992</a> (<em>Cercocebus atys</em>) in Côte d’Ivoire. Then, two decades later, the virus was isolated <a href="https://www.researchsquare.com/article/rs-414280/v1(2021)%20doi:10.21203/rs.3.rs-414280/v1">in a Gambian pouched rat and another rodent species</a> (<em>Stochomys longicaudatus</em>), as well as in another rope squirrel (<em>Funisciurus _bayonii</em>) and a shrew (<em>Corcidura litoralis</em>). As things stand, the prime suspects for the viral reservoir are rodents, including squirrels.</p>
<figure class="align-center ">
<img alt="Image of the squirrel _Funisciurus anerythrus_" src="https://images.theconversation.com/files/464550/original/file-20220520-22-ycsfnc.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/464550/original/file-20220520-22-ycsfnc.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/464550/original/file-20220520-22-ycsfnc.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/464550/original/file-20220520-22-ycsfnc.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/464550/original/file-20220520-22-ycsfnc.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/464550/original/file-20220520-22-ycsfnc.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/464550/original/file-20220520-22-ycsfnc.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The <em>Funisciurus anerythrus</em> squirrel is the suspected reservoir of the monkeypox virus.</span>
<span class="attribution"><a class="source" href="https://www.naturalista.mx/observations/91613867">cherifikoukomon</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<p>Interestingly, monkeypox was also <a href="https://pubmed.ncbi.nlm.nih.gov/32341480/">found in chimpanzee feces</a> in Taï National Park, Côte d’Ivoire, during an outbreak among primates, which implies the possibility of environmental contamination.</p>
<p>Aside from zoonotic transmission, there’s also human-to-human transmission, which occurs as a result of direct and prolonged contact with infected individuals through exposure to bodily fluids or contaminated materials (e.g. clothing, bedding, or surfaces). Such infections most often take place within the home.</p>
<p>Transmission through inhalation of respiratory droplets has also been considered, but this point is difficult to ascertain. Generally speaking, infections take place within the family home, where there is closer human proximity and modes of contact are numerous and diverse. Africa has also seen some cases of hospital-acquired infection.</p>
<p>In a detailed case description of the 2017 Nigerian outbreak, a large proportion of individuals suffered genital infections (68%), suggesting for the first time that the virus could be <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214229">transmitted through close skin-to-skin contact during sex</a>. Our data also shows that the rate of such infections is very high among cases recorded in the CAR.</p>
<p>Close, intimate contact during intercourse may be behind the new increased frequency in interhuman transmission of monkeypox, a virus that is usually thought to present low transmissibility. This theory is supported by the fact that – at the time of writing – the “non-African” cases of recent weeks <a href="https://www.nature.com/articles/d41586-022-01421-8">have mainly affected young men who have sex with men</a> or who identify as homosexual. It should be noted, though, that such transmissions could also occur during heterosexual intercourse.</p>
<p>Italian researchers have recently detected <a href="https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2022.27.22.2200421dNOqOXpB6UZW0!-e5CvHkNDnLULK2likc_KiXJc1imufkf_T4VXcf9ioTyz3ec33AGy6YKlMeS7NWNXGRNl1EH$">significant amount of monkeypox virus in the semen of 3 patients</a>. However, the authors stressed that these findings “cannot be considered definitive evidence of infectivity”. The implications for transmission are not clear either.</p>
<p><strong>TC: Should we be worried about this disease becoming widespread? What can we do to prevent this?</strong></p>
<p><strong>CB:</strong> For now, we can’t say for certain what will happen. The problem is that the chain of transmission of these new cases has yet to be identified. As indicated by the daily evolution of the virus, and due to its relatively long incubation period, there is a real risk that new infections could emerge within the coming days and weeks, whether in countries that are already affected or elsewhere.</p>
<p>Numerous cases in Spain and Europa <a href="https://www.dailymail.co.uk/news/article-10839877/Monkeypox-outbreak-Europes-biggest-100-cases-reported.html">appear to be linked to two festivals, one in Belgium between 4 and 9 May and one</a> that took place in the Canary Islands between 5 and 15 May. The latter was <a href="https://www.dailymail.co.uk/news/article-10839877/Monkeypox-outbreak-Europes-biggest-100-cases-reported.html">attended by 80,000 people</a>, potentially making it a “super-spreading” event.</p>
<p>In order to prevent the spread of the virus, we need to raise awareness among the communities and individuals concerned, and among doctors, so that we can quickly identify each case and trace their contacts. One difficulty facing doctors is that monkeypox lesions resemble those caused by chickenpox and, when they occur on the genitals, they can be mistaken for symptoms of some STIs (like syphilis and herpes). A monkeypox diagnosis can be confirmed by a PCR test and isolation of the virus, but only a few specialist laboratories are equipped for these types of analysis.</p>
<p>Nevertheless, we can find some reassurance in the fact that monkeypox outbreaks resolve spontaneously and relatively quickly. The longest chain of transmission ever identified was carried over <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880088/">seven generations, meaning that seven humans passed on the disease consecutively before transmission ceased</a>.</p>
<p>It is unclear why spreads simply stop like this. One hypothesis is that, until recently, these outbreaks would occur in small villages within restricted communities where some individuals might have already been immune, so the virus would contaminate only those who had never been in contact with it. But the 2003 epidemic in the United States also ended quickly and without any secondary human-to-human infection.</p>
<p>It remains to be seen where this new outbreak will take us.</p>
<p><strong>TC: Could the smallpox vaccine protect against this virus?</strong></p>
<p><strong>CB:</strong> We know that a natural infection of smallpox offers cross-protection against monkeypox. In the 1980s, it was shown that the smallpox vaccine could also provide cross-protection at a rate of around 85%. However, these estimates were made just a few years after the mass-vaccination campaign to eradicate smallpox. It is now believed that its efficacy is <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2168110/">closer to around 63% against severe disease</a>.</p>
<p>Moreover, smallpox vaccination was suspended in the 1980s once the disease was wiped out. Today, only a handful of healthcare professionals are vaccinated (in case of bioterrorist threats, while the virus is stored under high surveillance at a number of laboratories) and the <a href="https://www.mesvaccins.net/web/diseases/29-variole">first generation</a> of the vaccine is no longer used, due to significant side effects.</p>
<p>At present, if ever necessary, the most suitable vaccine for a roll-out would be the “third-generation” version known as Imvamune (or Imvanex or Jynneos). This is an <a href="https://www.sciencedirect.com/topics/immunology-and-microbiology/attenuated-vaccine">attenuated vaccine</a> that can be administered to immunocompromised people, unlike older vaccines. It has already been given to healthcare professionals and contact cases in Israel, Singapore, and the UK, and its effectiveness is <a href="https://pubmed.ncbi.nlm.nih.gov/30445121/">currently being assessed among healthcare professionals in the DRC</a>.</p>
<p>There are also a number of fourth-generation “subunit” vaccines in development. These do not contain the attenuated virus and instead have only fragments of it. They are also being assessed for their effectiveness.</p>
<p>Vaccines can be administered as either a pre-exposure (i.e., before contact with the virus) or a post-exposure treatment. With regards to the latter, US guidelines recommend that it be given preferably within 4 days and up to 14 days after exposure. On 27 May two French individuals received post-exposure vaccination for the first time after a high-risk contact with confirmed cases.</p>
<p><strong>TC: Could we see other variants of monkeypox emerging? Is the genome of the virus currently circulating in Europe identical to the West African strain?</strong></p>
<p><strong>CB:</strong> Monkeypox is a DNA virus, which means that it is less likely to mutate than an RNA virus like SARS-CoV-2.</p>
<p>It is actually quite simple to determine whether we are dealing with a West African or Congo Basin strain. We just need to sequence out short sections of its DNA. But given the large size of the viral genome, it takes time and effort to obtain a complete sequence. We need this complete sequence in order to detect differences in sequences more precisely, which would allow us to identify chains of transmission and find out how cases are linked. However, if our experience with SARS-CoV-2 has taught us anything, it’s that a large-scale global effort can be of great help in moving things along.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/464738/original/file-20220523-16-m4igxt.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Chart showing relationships between different monkeypox strains" src="https://images.theconversation.com/files/464738/original/file-20220523-16-m4igxt.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/464738/original/file-20220523-16-m4igxt.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=502&fit=crop&dpr=1 600w, https://images.theconversation.com/files/464738/original/file-20220523-16-m4igxt.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=502&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/464738/original/file-20220523-16-m4igxt.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=502&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/464738/original/file-20220523-16-m4igxt.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=631&fit=crop&dpr=1 754w, https://images.theconversation.com/files/464738/original/file-20220523-16-m4igxt.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=631&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/464738/original/file-20220523-16-m4igxt.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=631&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Phylogenetic tree depicting the ‘family’ relationships between the different strains of monkeypox virus responsible for outbreaks.</span>
<span class="attribution"><a class="source" href="https://nextstrain.org/monkeypox">Nextrain.org</a></span>
</figcaption>
</figure>
<p>Initial sequencing carried out on samples from a Portuguese and a Belgian patient have shown the genetic proximity of the virus to strains isolated <a href="https://virological.org/t/first-draft-genome-sequence-of-monkeypox-virus-associated-with-the-suspected-multi-country-outbreak-may-2022-confirmed-case-in-portugal/799">in Nigeria and during the previous out-of-African spread of the virus in 2018</a>, with genomes of the ongoing outbreak <a href="https://virological.org/t/belgian-case-of-monkeypox-virus-linked-to-outbreak-in-portugal/801#post_2">being highly similar</a>. This is in favour of a single introduction followed by community spread in Western countries after superspreading events.</p>
<p>More detailed genomic analyses comparing 2022 strains to those of 2018 identified around 40 mutations (fivefold the expected rate of mutations) with a pattern specific of the action of an antiviral enzyme called APOBEC which may reveal the sustained circulation of the virus <a href="https://virological.org/t/initial-observations-about-putative-apobec3-deaminase-editing-driving-short-term-evolution-of-mpxv-since-2017/830">in a new animal intermediate host, or in humans</a>. This observation, possibly indicating a recent increase in viral circulation in Nigeria, matches the documentation of cases in peri-urban areas of Nigeria like Abuja, together with increased frequencies of overseas exportation of cases.</p>
<p>A recent article hypothesises that Nigerian synanthropic rodent populations (<em>i.e., undomesticated rodents that live in close association with people and benefits from their surroundings</em>) <a href="https://www.ijidonline.com/article/S1201-9712(22)00322-8/fulltext">have increased in recent years as</a> a result of land conversion and high urbanisation leading to increased human-rodent contact.</p>
<p>Further sequencing is required to address remaining questions, like genome adaptation toward increased viral transmissibility. But, for the time being, there has been no evidence to suggest this.</p>
<p>In a more exceptional way, what looks like a relapse of the monkeypox disease <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00228-6/fulltext">was reported among one of the 2018 UK patients</a>, with an increased lymphadenopathy, a recurrence of rash and a transient shedding of monkeypox viral DNA following initial complete recovery. This hypothesis requires further study to be exploited.</p>
<p><strong>TC: In 2019, the Institut Pasteur came together with partners in France and the CAR to launch the <a href="https://research.pasteur.fr/fr/project/afripox/">Afripox project</a>, driven by a goal to increase understanding of the monkeypox virus and its spread. What exactly does the project involve?</strong></p>
<p><strong>CB:</strong> Afripox is a cross-disciplinary project that was set up in light of an increasing number of monkeypox outbreaks in the CAR, as reported by Emmanuel Yandoko Nakoune, Director of the Laboratory for Arboviruses, Viral Haemorrhagic Fevers, Emerging Viruses, and Zoonoses at the Institut Pasteur in Bangui, the country’s capital.</p>
<p>In the past few decades, monkeypox outbreaks have been more numerous and frequent in Africa overall, with the disease also expanding into areas where it was not endemic before. Improved medical monitoring and reduced immunity (following the end of smallpox vaccinations in 1980) are likely to have contributed to this figure, but the phenomenon may also reflect a growing viral circulation in a region of the world currently experiencing major ecological disturbances.</p>
<p>Faced with the many uncertainties surrounding the epidemiology of monkeypox, the idea for this project was to rely on the CAR’s existing national medical monitoring system to develop a <a href="https://theconversation.com/le-concept-one-health-doit-simposer-pour-permettre-lanticipation-des-pandemies-139549">One Health</a> approach toward the monkeypox virus, encompassing all its aspects in epidemiology, ecology, zoology, anthropology, and virology.</p>
<p>For instance, through our partnership with researchers from the French National Museum of Natural History, we are attempting to identify its animal reservoir. Meanwhile, along with the <a href="https://sesstim.univ-amu.fr/">SESSTIM</a> team in Marseille, we are exploring the disease’s ecology in order to better understand why it spreads more in forest areas, pinpoint how deforestation affects outbreaks, determine whether or not there is a seasonal aspect, and so on.</p>
<figure class="align-center ">
<img alt="Emmanuel Nakoune and Camille Besombes investigating an outbreak of monkeypox." src="https://images.theconversation.com/files/464556/original/file-20220520-20-wnzq6c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/464556/original/file-20220520-20-wnzq6c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/464556/original/file-20220520-20-wnzq6c.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/464556/original/file-20220520-20-wnzq6c.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/464556/original/file-20220520-20-wnzq6c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/464556/original/file-20220520-20-wnzq6c.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/464556/original/file-20220520-20-wnzq6c.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Emmanuel Nakoune and Camille Besombes investigating an outbreak of monkeypox in Zoméa, Lobaye, CAR.</span>
<span class="attribution"><span class="source">Jean Marc Zokoé</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>In the near future, the Afripox project also hopes to use on-the-ground PCR diagnostic tests that are currently being developed by the Emergency Biological Response Unit (“Cibu”) team at the Institut Pasteur in Paris. For now, suspected case samples are analysed in Bangui, but these tests would allow for reduced diagnosis time and quicker implementation of the appropriate measures.</p>
<p>Lastly, the epidemiological and anthropological aspects of the virus are being explored by the teams at the Institut Pasteur Paris (namely, the Emerging Diseases Epidemiology Unit and the Emerging Diseases Anthropology and Ecology Unit), in collaboration with local researchers. Their goal is to precisely determine the risk factors of zoonotic or interhuman transmission and ascertain why monkeypox has been on the rise since the 1980s.</p>
<p>While it is essential to identify the mechanics of this latest human-to-human epidemic of a relatively new format, it is also vital to understand how monkeypox emerges and circulates in its continent of origin.</p>
<p>When Afripox was launched three years ago, few could have imagined that this disease would one day spread beyond the African continent and across the planet. The current epidemic has highlighted once more the importance of investing in scientific research over the long term, so that we can be better prepared for any and all eventualities.</p>
<hr>
<p><em>Translated from the French by Enda Boorman for <a href="http://www.fastforword.fr/en">Fast ForWord</a>.</em></p><img src="https://counter.theconversation.com/content/184085/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Camille Besombes has received funding from the French National Research Agency (ANR).</span></em></p><p class="fine-print"><em><span>Arnaud Fontanet has received funding from the French National Research Agency (ANR), the SCOR Research Foundation and the Institut Pasteur.</span></em></p>This is not the first time that the monkeypox virus has spread beyond Africa, its continent of origin. But the current epidemic is unprecedented for a number of reasons.Camille Besombes, Médecin infectiologue - Epidémiologie - Unité d'épidémiologie des maladies émergentes, Institut PasteurArnaud Fontanet, Médecin, directeur de l’Unité d’épidémiologie des maladies émergentes à l’Institut Pasteur de Paris, professeur de santé publique, Conservatoire national des arts et métiers (CNAM)Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1822502022-05-04T13:03:13Z2022-05-04T13:03:13ZMeasles: global increase in cases likely driven by COVID pandemic<figure><img src="https://images.theconversation.com/files/461275/original/file-20220504-13-c76318.jpg?ixlib=rb-1.1.0&rect=46%2C0%2C5184%2C3453&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In the first two months of 2022, 17,000 cases were already reported worldwide.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/viral-diseases-hand-infected-foot-mouth-693857683">fotohay/ Shutterstock</a></span></figcaption></figure><p>A report by the World Health Organization (WHO) and Unicef warns that there could be a significant increase in the number of measles cases around the world. More than 17,000 cases have already been reported globally in January and February, an increase of nearly 80% from the 9,665 cases reported in the <a href="https://www.who.int/news/item/27-04-2022-unicef-and-who-warn-of--perfect-storm--of-conditions-for-measles-outbreaks--affecting-children">same period last year</a>. The report cites low global vaccination rates in the past few years as the main driver of this increase. Given measles is a preventable disease, it’s worrying to see cases rising.</p>
<p>Measles is a disease caused by infection by the <a href="https://www.nature.com/articles/nrdp201649">measles virus</a>, which is spread through respiratory droplets when a person with the virus coughs or sneezes. Symptoms can include fever, cough, red eyes and a rash. Measles is extremely contagious, and is one of the <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30307-9/fulltext">most easily spread viruses</a> that infect humans. It is particularly dangerous for children, who may develop severe complications (such as pneumonia or brain swelling) as a result of measles.</p>
<p>But measles is easily prevented with a double vaccine dose which is usually administered by the time a child is four years old. This vaccine provides lifelong protection against measles. In places where measles vaccination is high, there are <a href="https://www.sciencedirect.com/science/article/pii/S0264410X14001571">low numbers of infections and deaths</a>. Despite this, cases of measles are still seen in nearly every country in the world. </p>
<p>According to the report, cases are rising most quickly in countries where vaccination rates are the lowest in the world. The countries that experienced the most significant increases in case numbers last year were Somalia, Yemen, Afghanistan, Nigeria and Ethiopia. In these countries, only 46-68% of the population is vaccinated against measles. Typically, it’s recommended that 95% of the population needs to be vaccinated to protect children.</p>
<p>The low vaccination rates in many of these countries are likely caused by a number of factors – including low investment in healthcare systems as well as conflicts and natural disasters that disrupt vaccination programmes. But the pandemic has only worsened measles vaccine rollout, due to such health programmes being halted and greater funding and effort being diverted to COVID-19 vaccination programmes. This means many children didn’t receive their first or second doses of the measles vaccine during the pandemic – making it even more difficult to reduce outbreaks and stop the spread of this virus.</p>
<p>Other reasons – such as ongoing conflicts and refugee migrations – also make it difficult to track patients and administer double doses on time. With a contagious disease like measles, these can spread rapidly in crowded camps and houses, making immunisation even more important. </p>
<h2>Global cases rising</h2>
<p>The WHO reports also show that case numbers are rising in almost all countries around the world – the UK included. </p>
<p>In 2019, 119 of the 194 WHO member states had over 90% first dose vaccination coverage. In 2020, this dropped to <a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm7045a1.htm?s_cid=mm7045a1_w">only 75 countries</a> with the largest decreases seen in the <a href="https://www.frontiersin.org/articles/10.3389/fmed.2021.798031/full">Netherlands, Armenia and Romania</a>. In the UK alone, only <a href="https://www.nuffieldtrust.org.uk/resource/chart-of-the-week-how-do-mmr-vaccination-rates-vary-across-england">around 87%</a> of people are fully vaccinated against measles – though this number varies depending on the region, with some areas such as London only having a vaccination rate of around 75%. It’s a similar story in the US, where case numbers are increasing despite measles being <a href="https://www.nature.com/articles/s41598-020-80214-3">declared eliminated in 2000</a>.</p>
<figure class="align-center ">
<img alt="A doctor or nurse administers a vaccine to a child." src="https://images.theconversation.com/files/461276/original/file-20220504-15-hl0x06.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/461276/original/file-20220504-15-hl0x06.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/461276/original/file-20220504-15-hl0x06.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/461276/original/file-20220504-15-hl0x06.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/461276/original/file-20220504-15-hl0x06.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/461276/original/file-20220504-15-hl0x06.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/461276/original/file-20220504-15-hl0x06.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The measles vaccine can offer lifelong protection against the virus.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pediatrician-makes-vaccination-small-boy-542046412">adriaticfoto/ Shutterstock</a></span>
</figcaption>
</figure>
<p>Again, it’s likely that the rise in cases many countries have seen is because fewer vaccines are being administered. While the pandemic is one reason for this, vaccine hesitancy is another factor. A <a href="https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002578">direct relationship</a> has been observed between increased hesitancy and increased cases of measles. </p>
<p>Children and pregnant people are at greatest risk from these increases in measles cases. This is because they’re more likely to suffer severe side effects as a <a href="https://www.who.int/news-room/fact-sheets/detail/measles">result of measles</a>. But anyone who isn’t vaccinated is at risk of contracting the disease – and more importantly, they’re more likely to pass it on to any other unvaccinated people they come into contact with. </p>
<p>Mass vaccination programmes are still the best way to combat the rise in measles cases globally – especially given 95% of the population needs to be vaccinated with both doses to achieve herd immunity. While ensuring these programmes have the funding needed to provide these vaccines is important, it may also be important to put efforts into educating people on the importance of measles vaccination and that the vaccine is safe.</p>
<p>Global support must also be given to countries experiencing low vaccination rates – especially if this is due to natural disasters or refugee crises. This is especially important given that measles is highly contagious and local outbreaks can quickly spread globally.</p>
<p>Given the increase in case numbers seen at the beginning of this year, it’s likely numbers will only continue to rise throughout 2022. This resurgence is just one example of the knock-on effect that the COVID-19 pandemic has had on other diseases – and the importance of getting regular vaccination programmes back on track to prevent further spread of harmful viruses.</p><img src="https://counter.theconversation.com/content/182250/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Conor Meehan does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The latest report from the WHO and Unicef found cases have increased nearly 80% worldwide.Conor Meehan, Senior Lecturer in Microbiology, Nottingham Trent UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1772382022-03-10T20:57:37Z2022-03-10T20:57:37ZShould public health measures like masking continue beyond the pandemic? Data on viral infections shows their benefits<figure><img src="https://images.theconversation.com/files/450321/original/file-20220307-84100-jira1v.jpg?ixlib=rb-1.1.0&rect=166%2C98%2C2717%2C1675&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A woman wears a face mask as she walks by the sculpture ‘The Illuminated Crowd’ on a street in Montréal. Vulnerable people may benefit from measures like face masks even after the COVID-19 pandemic.</span> <span class="attribution"><span class="source">THE CANADIAN PRESS/Graham Hughes</span></span></figcaption></figure><p>Public health measures, such as masking and physical distancing, that have been a high-profile part of the COVID-19 response for the past two years <a href="https://www.cbc.ca/news/canada/edmonton/jason-kenney-copping-alta-covid-restrictions-lift-1.6368297">are now</a> <a href="https://www.cbc.ca/news/canada/toronto/covid19-ontario-march-9-mask-mandates-1.6378148">beginning to lift</a>. However, surprisingly little attention has been paid to the remarkable effects of these measures on other respiratory illnesses that are caused or exacerbated by viral infections.</p>
<p>These effects are a valuable research discovery from the pandemic. It’s a discovery that suggests that selective, non-mandated use of public health measures like masking, physical distancing and hand-washing may have a continued role as we enter the endemic phase of COVID-19. Collectively, these measures are known as non-pharmacologic public health interventions (NPIs).</p>
<h2>Decreases in acute care</h2>
<p>Following the onset of the pandemic in March 2020, many regions around the world reported a dramatic decrease in demand for <a href="https://doi.org/10.1371/journal.pone.0252441">acute health-care services</a>, including urgent care visits to emergency departments and inpatient hospital stays.</p>
<p>Early on, this was likely driven by stringent lockdown measures, patients avoiding health-care settings due to fears of contracting COVID-19 or the perception that hospitals were overwhelmed and unable to accommodate non-emergency cases. </p>
<p>However, as public health measures were relaxed over the following months, there was a rapid rebound in health-care services for conditions such as heart disease and appendicitis. Meanwhile, the decrease persisted for respiratory illnesses attributed to <a href="http://doi.org/10.1007/s11739-022-02932-y">non-COVID-19 viruses</a>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/450460/original/file-20220307-126102-ix8ztx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A sign above a row of sinks shows an image of a man washing his hands with the message 'Clean hands keep you healthy. Wash your hands with soap and water for at least 20 seconds. Life is better with clean hands.'" src="https://images.theconversation.com/files/450460/original/file-20220307-126102-ix8ztx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/450460/original/file-20220307-126102-ix8ztx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/450460/original/file-20220307-126102-ix8ztx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/450460/original/file-20220307-126102-ix8ztx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/450460/original/file-20220307-126102-ix8ztx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/450460/original/file-20220307-126102-ix8ztx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/450460/original/file-20220307-126102-ix8ztx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Public health measures such as masking, hand-washing and physical distancing are collectively known as non-pharmacologic public health interventions (NPIs).</span>
<span class="attribution"><span class="source">(AP Photo/David Zalubowski)</span></span>
</figcaption>
</figure>
<p>In Canada, the usual annual surge in influenza infections has not occurred during the <a href="https://doi.org/10.1016/j.lana.2021.100015">two winters since the beginning of the pandemic</a>. </p>
<p>Our research group — all front-line health-care workers — analyzed nationwide admissions data. Our analysis revealed that hospital admissions for major respiratory illnesses dropped sharply in the year following the start of the first lockdown. </p>
<p>Specifically, flare-ups of chronic obstructive pulmonary disease (COPD), a severe lung disease related to long-term smoking, and community-acquired non-COVID-19 pneumonia decreased by nearly 40 per cent across Canada <a href="http://doi.org/10.1007/s11739-022-02932-y">following the implementation of NPIs like masking and physical distancing</a>. </p>
<p>These findings were supported by another study of 15,677 patients from nine countries. That study reported a 50 per cent reduction in the hospital admissions for COPD <a href="https://doi.org/10.1371/journal.pone.0255659">following the onset of the pandemic</a>. This is not entirely surprising as <a href="https://doi.org/10.1111/resp.12780">both COPD and non-COVID-19 pneumonia</a> are often triggered by <a href="https://doi.org/10.1007/s10741-017-9614-7">common cold viruses</a>. If you are like most Canadians, you have not caught a cold in nearly two years. </p>
<h2>Impact on vulnerable patients</h2>
<p>So, what’s the big fuss about a few runny noses and colds? While a viral infection such as the common cold or influenza is unlikely to significantly harm a healthy individual, it can be <a href="https://doi.org/10.1503/cmaj.201748">debilitating and sometimes deadly</a> for someone who is <a href="https://dx.doi.org/10.1016%2FS2213-2600(18)30496-X">elderly, immunocompromised or suffering from a lung disease</a>. It can result in the need for acute care in the hospital, or even the ICU in severe cases, and some patients do not survive. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/450462/original/file-20220307-84591-12fhn71.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Two people in masks sitting on a park bench." src="https://images.theconversation.com/files/450462/original/file-20220307-84591-12fhn71.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/450462/original/file-20220307-84591-12fhn71.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=456&fit=crop&dpr=1 600w, https://images.theconversation.com/files/450462/original/file-20220307-84591-12fhn71.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=456&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/450462/original/file-20220307-84591-12fhn71.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=456&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/450462/original/file-20220307-84591-12fhn71.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=573&fit=crop&dpr=1 754w, https://images.theconversation.com/files/450462/original/file-20220307-84591-12fhn71.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=573&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/450462/original/file-20220307-84591-12fhn71.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=573&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A viral infection, such as the common cold or influenza, is unlikely to significantly harm a healthy individual, but it can be debilitating and sometimes deadly for someone who is elderly, immunocompromised or living with a lung disease.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Graham Hughes</span></span>
</figcaption>
</figure>
<p>In Canada, acute and chronic respiratory diseases are the third greatest cause of death, trailing behind only <a href="https://www150.statcan.gc.ca/n1/daily-quotidien/201126/t001b-eng.htm">cancer and heart disease</a>. This also means virally linked respiratory illnesses place a substantial burden on limited health-care resources. </p>
<p>There were several periods during the pandemic when our <a href="https://cmajnews.com/2022/01/11/covid-update-beds-duong-1095984/">health-care systems</a> were <a href="https://www.cbc.ca/news/health/tam-omicron-more-restrictions-better-masks-1.6293347">over capacity</a>, and there was a fear that hospitals would need to <a href="https://www.theglobeandmail.com/canada/article-alberta-preps-critical-care-triage-plan-amid-surge-in-covid-19-cases/">triage resources</a> and deny ICU care to some critically ill patients. </p>
<p>Thankfully, this did not come to pass, and it seems that the likely reason was the significant additional capacity that became available due to hospitalizations avoided for other <a href="http://doi.org/10.1007/s11739-022-02932-y">virally linked respiratory illnesses</a>.</p>
<h2>Ending COVID-19 prevention measures</h2>
<p>As the pandemic drags on, people have become fatigued with ongoing public health restrictions. With <a href="https://ourworldindata.org/covid-vaccinations">vaccination rates in Canada among the highest in the world</a> and expected to reach even higher with the <a href="https://www.canada.ca/en/public-health/services/vaccination-children/making-decisions-5-11-years-age.html">approval of vaccinations for pediatric populations</a>, many are looking forward to a time when NPIs may no longer be needed. </p>
<p>However, before dispensing with the measures entirely, it is important to consider whether their demonstrated benefits warrant continued use. The fact that hospitalizations for non-COVID-19 respiratory illnesses have remained low, despite the relaxation of stringent lockdown measures, suggests that these benefits may be sustained with the use of masking and practices such as frequent hand-washing. </p>
<figure class="align-center ">
<img alt="Close-up image of a red social distancing circle on asphalt, with two shoe-prints and the message 'Please keep 2M distance'" src="https://images.theconversation.com/files/450465/original/file-20220307-109743-4ln58a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/450465/original/file-20220307-109743-4ln58a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=420&fit=crop&dpr=1 600w, https://images.theconversation.com/files/450465/original/file-20220307-109743-4ln58a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=420&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/450465/original/file-20220307-109743-4ln58a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=420&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/450465/original/file-20220307-109743-4ln58a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=528&fit=crop&dpr=1 754w, https://images.theconversation.com/files/450465/original/file-20220307-109743-4ln58a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=528&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/450465/original/file-20220307-109743-4ln58a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=528&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">There is no consensus on which specific NPIs may be most effective in preventing disease spread.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Jonathan Hayward</span></span>
</figcaption>
</figure>
<p>Even prior to the pandemic, <a href="https://www.asiapacific.ca/publication/great-mask-divide-lessons-asia">public masking was a common practice</a> in many Asian countries. With this now being the norm in Canada as well, continuing these practices may have significant merit and offer protection to the most vulnerable demographics of our society. </p>
<p>This will certainly be challenging given <a href="https://www.reuters.com/world/americas/canadian-cities-brace-more-anti-vaccine-mandate-protests-2022-02-05/">opposition from a vocal minority</a> and the lack of awareness among the general public about the benefits of continuing use of NPIs. Currently, most available evidence is largely observational, as no randomized trials have yet evaluated the efficacy of NPIs for reducing non-COVID-19 viral respiratory illnesses at a population level. </p>
<p>Additionally, there is no consensus on which specific NPIs may be most effective in preventing disease spread. It’s also unknown whether reductions in acute care use have translated into a reduction in mortality rates for specific conditions. </p>
<h2>Future prevention</h2>
<p>These limitations are currently being addressed in a large-scale Albertan study of over 500,000 patients. The preliminary results — which will be published in the proceedings of the 2022 American Thoracic Society International Conference — show that NPIs are an effective strategy for preventing both acute care visits and mortality related to respiratory illnesses. </p>
<p>However, in the interim, public policy-makers should consider this compelling evidence and weigh in on whether the continued use of masking and other NPI measures is warranted, especially for individuals at high-risk for serious illness from viral respiratory infections and those close to them. </p>
<p>Recommendations, policies or, if deemed necessary, mandates can be amended in the future as new evidence emerges. Until then, NPI use, even on an interim basis, may reduce the strain on our health-care system and help protect the most vulnerable members of our society.</p><img src="https://counter.theconversation.com/content/177238/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Decreases in respiratory infections during the pandemic suggest there may be a continued role for the selective, non-mandated use of measures like masks and social distancing even post-COVID-19.Rutvij A. Khanolkar, Medical Student, University of CalgaryEddy S. Lang, Professor, Cumming School of Medicine, University of CalgaryLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1584612021-04-07T09:36:11Z2021-04-07T09:36:11ZThe common cold might protect you from coronavirus – here’s how<figure><img src="https://images.theconversation.com/files/393556/original/file-20210406-17-tqm7q8.jpg?ixlib=rb-1.1.0&rect=131%2C122%2C5299%2C3432&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The common cold is usually caused by a rhinovirus.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/ill-african-young-woman-covered-blanket-1444224857">Shutterstock/fizkes</a></span></figcaption></figure><p>We often assume that viral infections are caused by individual virus types. But in reality, we’re exposed to many viruses on a day to day basis, and co-infection – where someone is simultaneously infected by two or more virus types – is quite common. </p>
<p>The cells lining our throat and lower airways are exposed to the environment around us, making them a prime target for co-infection by respiratory viruses. These range from common-cold-causing rhinoviruses to the more serious influenza viruses, which are often the cause of global pandemics.</p>
<p>One of the most frequent outcomes of co-infection is viral interference, a phenomenon where one virus out-competes and suppresses the replication of <a href="https://cmr.asm.org/content/31/4/e00111-17">the other co-infecting viruses</a>. Interestingly, a growing body of evidence suggests rhinoviruses may interfere with the replication of other respiratory viruses that tend to be more serious. They may even offer the host temporary protection from them.</p>
<p>The good news is that this appears to include SARS-CoV-2 – the virus responsible for COVID-19. In <a href="https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab147/6179975">a new study</a>, rhinoviruses have been shown to suppress the replication of this virus. </p>
<h2>Rhinoviruses</h2>
<p>The majority of respiratory viruses that infect humans are rhinoviruses (from the Greek “rhino” for “of the nose”). First identified in 1953, rhinoviruses are extremely small respiratory viruses that are present all over the world. As far as we know, they are only capable of infecting humans. </p>
<p>Rhinovirus infections can be serious in some cases. However, they usually infect us to cause the common cold, a relatively mild disease. In response to such an infection, our immune system produces virus-killing molecules called interferons.</p>
<p>Interferons are produced in response to infections by all types of viruses, but they’re produced much <a href="https://doi.org/10.1093/infdis/jiab147">faster and in greater quantities</a> in response to rhinovirus compared to other respiratory viruses. Despite this, rhinoviruses have evolved complex mechanisms that allow them to evade interferons and replicate efficiently. It’s widely accepted that the rhinovirus-induced interferon response is what produces the <a href="https://doi.org/10.1016/j.coviro.2012.03.008">symptoms of the common cold</a>, rather than the virus itself.</p>
<figure class="align-center ">
<img alt="A computer generated illustration of rhinoviruses." src="https://images.theconversation.com/files/393561/original/file-20210406-23-1jiqhx4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/393561/original/file-20210406-23-1jiqhx4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/393561/original/file-20210406-23-1jiqhx4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/393561/original/file-20210406-23-1jiqhx4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/393561/original/file-20210406-23-1jiqhx4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/393561/original/file-20210406-23-1jiqhx4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/393561/original/file-20210406-23-1jiqhx4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Rhinos without horns.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/molecular-model-rhinovirus-virus-that-causes-1054047338">Shutterstock/Kateryna Kon</a></span>
</figcaption>
</figure>
<p>While rhinoviruses are pretty resistant to interferons, some other respiratory viruses are extremely sensitive to them. Influenza viruses, for example, can’t replicate properly in the presence of interferons.</p>
<p>Since rhinovirus infections trigger such a huge interferon response, researchers had the idea that they might offer protection against infection by more deadly, interferon-sensitive viruses, such as influenza. </p>
<p>In recent years, several research groups have investigated this phenomenon in the lab. They found that when cells are infected with rhinovirus, it triggers an interferon response which prevents them from being <a href="https://doi.org/10.1073/pnas.1911083116">infected with</a> the influenza virus. </p>
<p>If rhinovirus infections block the replication of other respiratory viruses, this could affect their spread and patterns of distribution. For instance, <a href="https://doi.org/10.1016/S2666-5247(20)30114-2">evidence suggests</a> that rhinovirus may have interrupted the spread of the H1N1, or “swine flu”, influenza virus during the 2009 global pandemic.</p>
<h2>The cold and COVID-19</h2>
<p>If rhinovirus infections can interfere with the replication and spread of pandemic influenza viruses, could it do the same for interferon-sensitive coronaviruses, such as SARS-CoV-2? </p>
<p>A team of scientists at the University of Glasgow recently set out to answer this question. They infected lab-grown layers of cells that replicates the conditions in the human respiratory tract with rhinovirus, SARS-CoV-2 and both viruses simultaneously. </p>
<p>Interestingly, SARS-CoV-2 replicated much slower in the co-infection scenario. But rhinovirus replication didn’t change in the presence or absence of SARS-CoV-2. </p>
<p>To better replicate real-life conditions, the authors also infected the cells with either rhinovirus or SARS-CoV-2 24 hours prior to co-infecting them with the other virus. Rhinovirus was able to suppress the replication of SARS-CoV-2 regardless of whether it was added before or after SARS-CoV-2, suggesting that rhinovirus infection actively protects the cells from SARS-CoV-2. </p>
<p>Next, the authors wanted to confirm that the inhibitory effect on SARS-CoV-2 replication was specifically caused by a rhinovirus-induced interferon response. They co-infected cells with both rhinovirus and SARS-CoV-2 in the presence of a drug which blocks the virus-killing properties of interferons, called BX795. </p>
<p>In this part of the experiment, BX795 allowed SARS-CoV-2 to replicate at a level comparable to that of a single SARS-CoV-2 infection. This confirmed that a rhinovirus-induced interferon response is indeed responsible for the block in SARS-CoV-2 replication seen in the co-infection experiments without BX795. </p>
<p>Using mathematical simulations, the authors also found that more frequent rhinovirus infections among the population would result in a reduced rate of SARS-CoV-2 infection. Taken together, these results confirm that rhinovirus infections suppress the replication of SARS-CoV-2, which may in turn reduce the number of new cases among the population.</p>
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Read more:
<a href="https://theconversation.com/the-end-of-the-pandemic-is-coming-just-dont-set-a-date-for-the-party-157205">The end of the pandemic is coming – just don't set a date for the party</a>
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<p>So, can rhinoviruses protect us from infection by SARS-CoV-2? The short answer is yes. However, it’s essential to note that the rhinovirus-induced interferon response is an example of innate immunity, meaning that its effect only lasts as long as the invading rhinovirus is in your body.</p>
<p>If you recover from a cold and then come into contact with SARS-CoV-2 a week later, it’s unlikely you will have enough interferons to successfully block the SARS-CoV-2 infection. Long-term immunity, which involves the production of highly specific antibodies, is only obtained by coming into direct contact with the virus in question – either in the wild or by vaccination. </p>
<p>So, if you’re someone who has not yet had COVID-19 or are unvaccinated, you’ll only be protected if you are lucky enough to be infected at the same time that you’re experiencing a cold. Rhinoviruses may play a critical role in controlling the spread of SARS-CoV-2 among the human population. The most effective way, however, probably remains vaccination.</p><img src="https://counter.theconversation.com/content/158461/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Matthew James receives funding from the Department for the Economy, Asthma UK and the Medical Research Foundation. </span></em></p>Rhinoviruses may play a critical role in controlling the spread of SARS-CoV-2 among the human population.Matthew James, Research Assistant, Wellcome-Wolfson Institute for Experimental Medicine, Queen's University BelfastLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1552132021-03-08T13:35:53Z2021-03-08T13:35:53ZA year into the pandemic, the coronavirus is messing with our minds as well as our bodies<figure><img src="https://images.theconversation.com/files/387617/original/file-20210303-14-1pt7xvk.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C4193%2C2797&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">It's not a stretch to say asymptomatic spreaders unwittingly engage in zombielike behaviors. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/hordes-of-angry-walking-dead-zombies-royalty-free-image/908122164?adppopup=true">gremlin via Getty Images</a></span></figcaption></figure><p>COVID-19 has hijacked people’s lives, families and work. And, it has hijacked their bodies and minds in ways that they may not even be aware of. </p>
<p>As we see it, SARS-CoV-2, the virus that causes COVID-19, is a sort of zombie virus, turning people not into the undead but rather into the unsick. By interfering with our bodies’ normal immune response and blocking pain, the virus keeps the infected on their feet, spreading the virus. </p>
<p>People typically think of zombies as the stuff of science fiction. But in the biological world, <a href="https://doi.org/10.1016/S0031-9384(03)00163-X">zombies are all over the place</a>, from the <a href="https://doi.org/10.1186/s12862-014-0166-3">Ophiocordyceps</a> fungus that perpetuates itself by zombifying ants; to <a href="https://doi.org/10.1371/journal.pone.0023277">Toxoplasma gondii</a>, a single-celled parasite that completes its life cycle by leading rodents into the jaws of predators. <a href="https://doi.org/10.1016/S0031-9384(03)00163-X">Zombie viruses are also a real thing, influencing</a> their host’s behavior in ways that enhance the viruses’ <a href="https://doi.org/10.1016/j.beproc.2004.06.010">evolutionary fitness</a>.</p>
<p>One of us is a <a href="http://www.athenaaktipis.org/">professor of psychology</a>. The other is <a href="https://evolutionmedicine.com/about-joe-alcock-author-of-this-blog/">an emergency physician</a>. Both of us are evolutionary medicine researchers. And we suggest to you that SARS-CoV-2, the virus that causes COVID-19, is yet another zombie virus, a master manipulator operating under the radar. This pandemic may have unleashed a horde of the unsick: infected and unwitting victims of a manipulative virus. </p>
<figure class="align-center ">
<img alt="An image of the coronavirus." src="https://images.theconversation.com/files/387651/original/file-20210304-14-q616d7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/387651/original/file-20210304-14-q616d7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=365&fit=crop&dpr=1 600w, https://images.theconversation.com/files/387651/original/file-20210304-14-q616d7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=365&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/387651/original/file-20210304-14-q616d7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=365&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/387651/original/file-20210304-14-q616d7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=459&fit=crop&dpr=1 754w, https://images.theconversation.com/files/387651/original/file-20210304-14-q616d7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=459&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/387651/original/file-20210304-14-q616d7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=459&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">The novel coronavirus, which first appeared in China in late 2019.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/corona-virus-close-up-royalty-free-image/1212213050?adppopup=true">Radoslav Zilinsky via Getty Images</a></span>
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<h2>How the virus turns us into the unsick</h2>
<p>It is the unsick who spread the virus most readily. About 40% of those with SARS-CoV-2 are asymptomatic spreaders, never showing symptoms at all. And those who do show symptoms are <a href="https://doi.org/10.1038/s41591-020-0869-5">most contagious in the two days before symptoms appear</a>. Why people don’t feel sick earlier – or sick at all – might be part of the <a href="https://doi.org/10.1073/pnas.2009787117">evolutionary strategy of SARS-CoV-2</a>. </p>
<p>A look under the hood of the virus reveals more about that manipulative machinery. SARS-CoV-2 interferes with a person’s <a href="https://doi.org/10.1101/2020.08.18.256776">immune response</a>; this is why people don’t necessarily feel sick and withdrawn as they would in a typical viral infection. Instead, SARS-CoV-2 silences the body’s alarm signals that otherwise would orchestrate <a href="https://doi.org/10.1101/2020.08.18.256776">anti-viral defenses</a>. It blocks interferons, a set of molecules that help fight viruses. Interferon activity makes people feel more <a href="https://doi.org/10.1038/s41423-020-0402-2">depressed and socially withdrawn</a> – so when the novel coronanvirus impedes interferon activity, mood is lifted, sociality is increased and you feel less sick. </p>
<p>The virus also <a href="https://doi.org/10.1101/2020.07.17.209288">decreases pain perception</a>. Normally, pain <a href="https://doi.org/10.1146/annurev.psych.51.1.29">motivates us to hunker down</a> when we need to heal. But SARS-CoV-2 blocks this response by preventing <a href="https://doi.org/10.1101/2020.07.17.209288">the transmission of pain signals</a>. This is why people feel fine even when they are teeming with virus before the onset of symptoms. </p>
<p>At the same time, SARS-CoV-2 dampens the body’s response to infection. It <a href="https://doi.org/10.1101/2020.05.24.111823">hinders pro-inflammatory cytokines</a>, molecules that help spur the immune response. This too makes hosts feel better than they should. Typically, feeling sick helps our bodies prioritize healing by making us reduce our energy expenditure. With SARS-CoV-2, unsick hosts have the energy to do as much as they used to, maybe more. </p>
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<figcaption><span class="caption">3D Animation: SARS-CoV-2 virus transmission leading to COVID-19.</span></figcaption>
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<h2>An evolutionary leg up</h2>
<p>How SARS-CoV-2 evolved to manipulate humans is still speculation. The virus could have first evolved in other mammals, like pangolins. There, it may have acquired its immune-evading, manipulative machinery before jumping to humans. </p>
<p>No intent or thought is involved; SARS-CoV-2 is not scheming to take over your body. This is simply evolution at work, nothing personal. The virus evolves because of variation and selection. And in a pandemic involving hundreds of millions of infections and trillions of viral replications, plenty of <a href="https://doi.org/10.1016/j.plrev.2005.11.002">genetic variants could give it an evolutionary leg up</a>. </p>
<p>More research is needed to determine whether new variants make people feel unsick for longer. That, of course, would make it even easier for the virus spread during the asymptomatic phase. For example, a paper in the Journal of Transnational Medicine reported that the <a href="https://doi.org/10.1186/s12967-020-02535-1">GZ69 variant</a> is associated with high shedding rates in asymptomatic patients, meaning that people are highly contagious even when they are feeling fine. </p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p>
<p>It’s possible that SARS-CoV-2 might make people feel even better than they would without infection from the virus. One study found people did not reduce their time out in public even when they had COVID-19 symptoms. If anything, they <a href="https://doi.org/10.1101/2020.04.19.20065219">went out more</a>. Any variant that does this clearly has an evolutionary advantage when it comes to transmission. Using surveys and social media data, <a href="https://www.cooperationintheapocalypse.org/">our research team</a> is now testing whether people are more social during their most infectious days. </p>
<h2>Things to consider</h2>
<p>We must take seriously the possibility that the virus is zombifying us – altering our behavior in ways that help perpetuate it. By keeping people feeling good when they are capable of spreading the virus, SARS-CoV-2 spreads under the radar, <a href="https://theconversation.com/how-the-coronavirus-escapes-an-evolutionary-trade-off-that-helps-keep-other-pathogens-in-check-140706">more like a sexually transmitted disease</a> than a respiratory virus. </p>
<p>Many of us have unwittingly acted as vehicles for its propagation, with stunning implications. Our behavior might not be in our own evolutionary interests. Instead, the unsick may be serving the virus.</p>
<p>Researchers often ignore the impact that viruses might have on our moods and behaviors. But like ants and rodents, humans are not exempt from the neural and behavioral hijacking that’s widespread in the natural world. </p>
<p>We believe that it is critical to consider the possible “anti-symptoms” of this virus: temporary reduction in pain, feeling more energetic than normal and perhaps even wanting to be around people more than usual. With all this in mind, here’s some advice, likely the most ironic you’ve heard in the last year: If you’ve been feeling surprisingly good the last few days, you might want to get a COVID-19 test.</p><img src="https://counter.theconversation.com/content/155213/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>SARS-CoV-2 is much like a zombie virus. It interferes with normal sickness behavior and blocks pain, turning its victims into unsick spreaders of the virus.Athena Aktipis, Associate Professor of Psychology, Center for Evolution and Medicine, Arizona State UniversityJoe Alcock, Professor of Emergency Medicine, University of New MexicoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1475472020-11-17T15:50:55Z2020-11-17T15:50:55ZAntibiotics in cold and flu season: Potentially harmful and seldom helpful<figure><img src="https://images.theconversation.com/files/368064/original/file-20201107-17-ynhp4y.jpg?ixlib=rb-1.1.0&rect=677%2C201%2C5432%2C3884&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Antibiotics do not shorten or reduce the severity of colds or flu, but they could produce adverse effects that make you feel even worse.</span> <span class="attribution"><span class="source">(Pexels/Andrea Piacquadio)</span></span></figcaption></figure><p>Antibiotics are <a href="https://doi.org/10.1503/cmaj.109-5742">over-prescribed in Canada</a> and <a href="https://doi.org/10.1001/jama.2016.4151">worldwide</a>, often for infections that do not need their help, <a href="https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6034a1.htm">particularly respiratory conditions</a>. While these unnecessary prescriptions may contribute to the development of <a href="https://theconversation.com/antibiotic-resistant-infections-could-destroy-our-way-of-life-new-report-126670">resistant bacteria</a>, there is another reason to be cautious about antibiotics: Direct harms caused by these drugs.</p>
<p>Our group — a family physician, an infectious disease specialist and a health sciences student — has published <a href="https://www.cfp.ca/content/66/9/651">a review of the evidence about adverse effects of antibiotics commonly used in the community</a>. Even though two of us are experienced physicians, and knew about many problems with drugs, we were surprised by the frequency and severity of some of these effects.</p>
<h2>Gut reactions, allergies and skin rashes</h2>
<p>The review showed that for many antibiotics, over 10 per cent of patients get gut reactions, such as stomach pain, discomfort or diarrhea. This is particularly common in children given antibiotics for ear and throat infections.</p>
<p>Every antibiotic causes allergic reactions in some people. A few allergic reactions cause swelling of the mouth and airways, needing immediate treatment with adrenalin and other drugs. </p>
<p>Other allergic reactions are just a skin rash, but this is often very irritating, and in some it may progress to cause severe blistering. Such severe reactions can be caused by sulfonamide drugs, often used to treat urinary tract infections. In Canada, a medication combining the antibiotic trimethoprim and a sulfa drug is often used for this purpose. However, using trimethoprim alone — a common practice in Europe — reduces the risk of allergic reactions.</p>
<figure class="align-center ">
<img alt="Red and white pill capsules scattered on a white surface beside a glass of water." src="https://images.theconversation.com/files/368066/original/file-20201107-17-a4sy62.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/368066/original/file-20201107-17-a4sy62.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/368066/original/file-20201107-17-a4sy62.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/368066/original/file-20201107-17-a4sy62.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/368066/original/file-20201107-17-a4sy62.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/368066/original/file-20201107-17-a4sy62.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/368066/original/file-20201107-17-a4sy62.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">In mononucleosis patients, amoxycillin can cause a severe skin rash that looks just like an allergy.</span>
<span class="attribution"><span class="source">(Piqsels)</span></span>
</figcaption>
</figure>
<p>A severe skin rash occurs in as many as one-third of people given amoxycillin for infectious mononucleosis (glandular fever), a common cause of sore throat in adolescents and young adults. This looks just like an allergy, so these people may be told they are allergic, which prevents use of penicillins even when they would be the best drug to use. A skin test can show that it is not an allergy, in which case penicillins may be used in future.</p>
<p>In rare cases, antibiotics cause other serious reactions, including some that are fatal. They can cause serious damage to lungs, liver, kidneys, nerves and joints. For example quinolones, a common group of antibiotics (the most well known is ciprofloxacin), can cause ruptured tendons and damage to nerves that causes tingling and numbness. Minocycline, often used to treat acne, can cause <a href="https://doi.org/10.1503/cmaj.200012">dark pigmentation of the face, as well as neurological effects</a>.</p>
<h2>Benefits vs. risks</h2>
<p>With antibiotics, the likelihood of benefit must be balanced against the chance of harm they may cause. When someone has a serious infection, it is worth taking the risk of harms, to gain the benefits of cure. But for a mild infection that the immune system will defeat by itself, there is no benefit from the antibiotic, only a chance of harm. So a prescription for antibiotics can be worse than useless.</p>
<p>Antibiotics are among our most commonly used drugs. However, they should not be thought of as necessary to cure any infection. For most infections, they only help to tip the balance in favour of our immune system.</p>
<p>Antibiotics work on bacterial infections such as pneumonia or cellulitis, and these illnesses improve faster with the right antibiotic.</p>
<figure class="align-right ">
<img alt="Half-sphere cross-section of a flu virus showing interior and exterior." src="https://images.theconversation.com/files/368065/original/file-20201107-17-l5tdr9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/368065/original/file-20201107-17-l5tdr9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=793&fit=crop&dpr=1 600w, https://images.theconversation.com/files/368065/original/file-20201107-17-l5tdr9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=793&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/368065/original/file-20201107-17-l5tdr9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=793&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/368065/original/file-20201107-17-l5tdr9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=997&fit=crop&dpr=1 754w, https://images.theconversation.com/files/368065/original/file-20201107-17-l5tdr9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=997&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/368065/original/file-20201107-17-l5tdr9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=997&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">3-D illustration of a flu virus. There is no value in taking antibiotics for viral infections.</span>
<span class="attribution"><span class="source">(NIAID)</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>But most coughs and colds, sinusitis, influenza and even COVID-19 are viral infections that the immune system will overcome. While some bacteria may be present, they are not the cause, so there is no value in taking an antibiotic. They do not shorten these infections, nor do they reduce their severity, but they could produce adverse effects that only make matters worse. For coughs and colds, it’s better to seek advice from a physician or pharmacist about treatments that reduce fever, aches and pains, and coughs, while the immune system does its job.</p>
<p>As the fall and winter <a href="https://www.cp24.com/news/doctors-brace-for-viral-overload-between-cold-and-flu-season-and-covid-19-1.5070966">respiratory infection season approaches</a>, both prescribers and patients must remember how harmful these drugs can be. Antibiotic use should be minimized, and used only when there is good reason. They must be chosen carefully, and when prescribed, they should be taken for the minimum effective time. So rather than visiting a doctor asking for antibiotics, ask whether one could help, and what other treatments will soothe symptoms and reduce the misery.</p>
<p>Using antibiotics cautiously not only means decreasing the risk of allergic reactions or other harms, but also decreasing the risk of bacterial resistance. That means that when an antibiotic is really needed, the appropriate drug will be safe and effective.</p><img src="https://counter.theconversation.com/content/147547/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>James Dickinson receives funding from Alberta Health to run the Alberta community Influenza surveillance program. </span></em></p><p class="fine-print"><em><span>Ranjani Somayaji has received funding from Cystic Fibrosis Canada, Cystic Fibrosis Foundation, Canadian Institute for Health Research and Alberta Innovates-Health Solutions. </span></em></p><p class="fine-print"><em><span>Samiha Tarek Ah Mohsen does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Resistant bacteria aren’t the only risk posed by overprescribing antibiotics. A more immediate risk is side-effects and reactions, which a new review shows are surprisingly frequent and often severe.James Dickinson, Professor of Family Medicine, University of CalgaryRanjani Somayaji, Assistant Professor in the Department of Medicine, University of CalgarySamiha Tarek Ah Mohsen, Research Assistant at Department of Critical Care Medicine, University of CalgaryLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1482102020-10-28T13:31:12Z2020-10-28T13:31:12ZMultiple sclerosis: some patients may already hold the key to protecting the brain against viruses<figure><img src="https://images.theconversation.com/files/366148/original/file-20201028-19-37e7ta.jpg?ixlib=rb-1.1.0&rect=21%2C0%2C4671%2C2729&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In patients with MS, the body's immune system attacks the nerve cells.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/nerve-cells-291476537">adike/ Shutterstock</a></span></figcaption></figure><p>Usually our immune system protects us from harmful microbes such as bacteria or viruses. It does this either by directly attacking a microbe, or producing an antibody which recognises and removes microbes from the body. But, in patients with multiple sclerosis (MS), their <a href="https://www.nationalmssociety.org/What-is-MS/Types-of-MS/Relapsing-remitting-MS">immune response is overactive</a>, resulting in the body attacking it’s own cells – namely those in the central nervous system (including the brain and spinal cord). This results in damage to the central nervous system, which leads to impaired sensory and motor function. </p>
<p>A lot of <a href="https://pubmed.ncbi.nlm.nih.gov/26250739/">research</a> has gone into determining why the immune cells of MS patients attack the brain. Researchers are especially interested in understanding why MS patients make so many <a href="https://pubmed.ncbi.nlm.nih.gov/30071507/">antibodies</a>, which are important for protecting the body from viral infections. Large quantities of antibodies are found in their <a href="https://pubmed.ncbi.nlm.nih.gov/30071507/">cerebrospinal</a> fluid (the liquid barrier that surrounds the brain). </p>
<p>In researching this phenomenon, we have actually identified that some of these antibodies <a href="https://www.biomedcentral.com/epdf/10.1186/s40478-020-01011-7?sharing_token=yS-J8TofyQWAvXx9twlXzW_BpE1tBhCbnbw3BuzI2RMDzbL_HgsGvFF2Mw0MGZE0b1n0FGZo3Iubs_rCa5YKpFU1gB3AsrTPfXTtIGYMk8czL88GFHitjPjx_AUByzRIZdlPcuwsaI3kYq60zHTPqkKaj-OVdVr-fxH3zUs_sok%3D">can be beneficial</a> as they enhance immunity against viruses. This stronger immune response could help protect these people from certain viral infections. </p>
<p>We don’t yet fully understand all aspects of the abnormal immune response in MS patients. However, many drug treatments now focus on <a href="https://pubmed.ncbi.nlm.nih.gov/29470968/">suppressing</a> this overactive immune system to prevent further brain damage. For many patients, these drugs are very <a href="https://pubmed.ncbi.nlm.nih.gov/28209331/">effective</a>.</p>
<p>But suppressing the immune system can cause other problems. One such problem is that these treatments can leave patients vulnerable to viral infections. Patients are particularly susceptible to infection of the brain by <a href="https://www.mssociety.org.uk/about-ms/treatments-and-therapies/disease-modifying-therapies/natalizumab">John Cunningham virus (JCV)</a>. If John Cunningham virus infects the brain, it can cause a disease called <a href="https://www.nejm.org/doi/10.1056/NEJMoa1107829?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed">progressive multifocal leukoencephalopathy</a>. This can cause lasting disability or even death. There are currently no antiviral treatments available for it.</p>
<h2>Immunoglobulin M</h2>
<p>Recently, researchers found that <a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.24345">around 40% of MS patients</a> do not seem to get these viral brain infections, even when taking immunosuppressive drugs. To understand what was protecting these patients, researchers observed that those who didn’t develop any viral brain infections had a particular type of antibody in their cerebrospinal fluid. These antibodies, called immunoglobulin M (or IgM antibodies), can bind to lipids (fat) on cells rather than binding to microbes, as antibodies normally do with viruses. This suggested to us that these antibodies were protecting the brain against viruses in a different way, one that does not involve binding the virus directly.</p>
<p>As such, we wanted to test if these IgM antibodies may be able to prevent viral infections. To do this, we used a unique cell culture system that we call a “brain-in-a-dish”. This contained all the major cell types of the central nervous system that integrated together like a miniature brain. We added the IgM antibodies to these cultures and then infected them with different viruses, such as Semliki Forest virus and Bunyamwera virus, to test whether the antibody would protect against these viral infections.</p>
<p>We were able to show that indeed the antibodies <a href="https://rdcu.be/b8Inh">prevented these virus from replicating</a> in the cultures, effectively stopping the viral infections in their tracks. To further investigate how this works, we looked at the ways the immune response was affected by these antibodies. We found that the antibodies specifically activated parts of the immune system that are involved in developing immunity to viruses. </p>
<p>To see which brain cells might be protected by these antibodies, we used a microscope to look at the different cells that make up the central nervous system. At the same time, we used fluorescent probes (a type of molecule that absorbs light, and is used to study biological samples) that bound to the specific parts of the immune response that we had identified. Fluorescent probe molecules absorb light of a specific wavelength and emit it in a different, longer wavelength. This allows researchers to study changes in biological samples and detect antibodies in cells. </p>
<p>By merging the two images – of the cell types and the immune response – we could see that this protective antiviral immune response was activated in <a href="https://rdcu.be/b8Inh">all the major cell types</a> of the central nervous system. This is very important, as many different viruses can infect the brain, each by attacking different cell types within the central nervous system. Our findings suggest that this specific type of antibody protects some MS patients against many different viruses that infect the brain by enhancing their immune response. This finding has a major impact for those with MS, and for future antiviral research and treatment.</p>
<p>Caution is taken when prescribing immunosuppresive therapies to MS patients to prevent the patient from developing a potentially life-threatening viral infection. Using these specific IgM antibodies, we can understand which patients may be more vulnerable to viral infections, while allowing more patients to use these drugs, especially those who have this protective antibody. </p>
<p>The antibodies identified in this study highlight an alternative way of protecting the brain against viruses. Most antiviral drugs target a specific virus. These antibodies act by enhancing the brain’s own antiviral defences, offering protection to all major cell types of the central nervous system. This mechanism can pave the way for the generation of new antiviral therapies that can treat and prevent viral brain infections. But more investigation will be needed to see how these antibodies work.</p><img src="https://counter.theconversation.com/content/148210/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Marieke Pingen receives funding from the BBSRC, the MRC, and the Multiple Sclerosis Society. </span></em></p><p class="fine-print"><em><span>Lorna Hayden does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>This antibody protects patients from viruses, even while on immunosuppressant drugs.Lorna Hayden, PhD Candidate in Neuroimmunology, University of GlasgowMarieke Pingen, Research Associate in Immunology, University of GlasgowLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1342262020-05-12T15:29:36Z2020-05-12T15:29:36ZHuman activities are responsible for viruses crossing over from bats and causing pandemics like coronavirus<figure><img src="https://images.theconversation.com/files/332082/original/file-20200502-42923-1jb2q4v.jpg?ixlib=rb-1.1.0&rect=16%2C0%2C5542%2C3700&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The Egyptian pipistrelle bat is one of seven bat species associated with spreading the coronavirus Middle East Respiratory Syndrome.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Viruses are naturally occurring entities. <a href="http://doi.org/10.1126/sciadv.1500527">Viruses have existed on Earth long before humans</a> and <a href="https://doi.org/10.1038/nrmicro2644">vastly outnumber humans</a>. There are <a href="https://doi.org/10.1038/nature19094">more viruses on Earth</a> than there are <a href="https://doi.org/10.1139/gen-2013-0152">stars in the universe</a> or <a href="https://www.tandfonline.com/doi/abs/10.3109/03014460.2013.807878">cells in the human body</a>. </p>
<p>As a cellular microbiologist who has studied <a href="http://dx.doi.org/10.1128/jmbe.v15i1.707">the origin and development of infectious diseases and their prevention</a>, understanding where infectious agents come from is as important, if not more important, to understanding how to combat the rampant spread of diseases within the human population. </p>
<p>Fortunately, only a small fraction — <a href="http://doi.org/10.1098/rstb.2011.0354">about 200</a> — of this vast array of viruses can infect humans. Some of the better-known human viral infections include measles, varicella, polio, human papilloma virus, influenza and rhinoviruses, which are typically responsible for the common cold. </p>
<p>An even smaller number of viruses are responsible for the deadliest human infections that we have experienced. In recent decades these include rabies virus, human immunodeficiency virus (HIV), Ebola virus and now, infamously, coronaviruses. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/327416/original/file-20200413-174608-omeq7p.jpg?ixlib=rb-1.1.0&rect=9%2C0%2C2035%2C2026&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/327416/original/file-20200413-174608-omeq7p.jpg?ixlib=rb-1.1.0&rect=9%2C0%2C2035%2C2026&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/327416/original/file-20200413-174608-omeq7p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/327416/original/file-20200413-174608-omeq7p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/327416/original/file-20200413-174608-omeq7p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/327416/original/file-20200413-174608-omeq7p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/327416/original/file-20200413-174608-omeq7p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/327416/original/file-20200413-174608-omeq7p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A colour-enhanced image of SARS-CoV-2 virus particles, isolated from a patient.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/niaid/49597020648/in/album-72157712914621487/">(National Institute of Allergy and Infectious Diseases Integrated Research Facility)</a></span>
</figcaption>
</figure>
<p>Viruses that circulate in other animals can enter a human population when <a href="https://dx.doi.org/10.1086%2F652860">a variety of human activities</a> allow for consistent and regular interaction with naturally occurring reservoirs. These events involve repeated and routine <a href="http://doi.org/10.1056/NEJMra1108296">interaction of humans with these animal hosts</a>. </p>
<p>Some of these interactions take place through the following <a href="https://www.unenvironment.org/news-and-stories/story/six-nature-facts-related-coronaviruses">human activities</a>: hunting, butchering and farming (husbandry), as well as the global trade of animals and domestication of exotic animals as pets. Population growth, global travel and <a href="https://www.who.int/globalchange/summary/en/index5.html">climate change</a> that cause the disruption of habitats further provide opportunities for cross-species transfer.</p>
<h2>Cross-species transfer</h2>
<p>Many of the viruses that have affected us over the past 20 years have emerged from non-human reservoirs. Reservoirs are the source of viruses and other pathogens and can be located in animal populations or the natural environment. What is of note is that <a href="https://doi.org/10.1038/cddiscovery.2016.48">the original reservoir for many of these viruses are bats</a>. </p>
<p>Bats have been shown to be the <a href="https://dx.doi.org/10.1128%2FCMR.00017-06">natural reservoir</a> of numerous deadly human viruses. The specialized immune systems of bats allow multiple different types of viruses to persist within these hosts. The coexistence of these <a href="https://dx.doi.org/10.1098%2Frspb.2012.2753">viruses within the same host</a> in combination with the molecular makeup of viruses further allows for the emergence of deadly human diseases. Bats aren’t all bad though; they have an <a href="https://theconversation.com/its-wrong-to-blame-bats-for-the-coronavirus-epidemic-134300">important role in our ecosystem</a>. </p>
<h2>Current COVID-19 pandemic</h2>
<p>The current <a href="https://doi.org/10.1016/S0140-6736(03)15329-9">coronavirus pandemic has been traced to a wet market, called the Huanan Seafood Wholesale Market, in Wuhan, China</a>. Within these wet markets, numerous animals are held together in confined spaces and small cages. This setting is inherently stressful and can allow for the exchange and mixing of multiple different bodily fluids. Human handling of these animals allows for <a href="http://doi.org/10.1097/01.qco.0000244043.08264.fc">the viruses contained within these reservoirs to spill over into the human population</a>. This is further facilitated by the long working hours and stress of the handlers themselves, as well as cuts, scratches, bites or other wounds inflicted by the animals on their handlers. </p>
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Read more:
<a href="https://theconversation.com/coronavirus-live-animals-are-stressed-in-wet-markets-and-stressed-animals-are-more-likely-to-carry-diseases-135479">Coronavirus: live animals are stressed in wet markets, and stressed animals are more likely to carry diseases</a>
</strong>
</em>
</p>
<hr>
<p>A similar confluence of factors was attributed to the 2002 outbreak of SARS, <a href="https://doi.org/10.1007/978-3-540-70962-6_13">which has been attributed to the virus crossing over from bats to civets</a>. The related MERS-CoV was <a href="http://dx.doi.org/10.3201/eid1911.131172">attributed to a bat reservoir in Saudi Arabia</a>.</p>
<h2>Ebola outbreaks</h2>
<p>Outbreaks of Ebola in West Africa (2014-16 and 2018-present) have been attributed <a href="https://dx.doi.org/10.1007%2F82_2017_11">to human interaction with bats</a>. Three subfamilies of fruit bats — <em>Hypsignathus monstrosus</em>, <em>Epomops franqueti</em> and <em>Myonycteris torquata</em> — <a href="https://doi.org/10.1038/438575a">have been identified as natural reservoirs for the Ebola virus</a>. </p>
<p>These bats <a href="https://www.sciencemag.org/news/2017/06/hunting-ebola-among-bats-congo">inhabit caves deep within the Ebola River Valley</a>. Cross-species transmission of the Ebola virus from bats to humans can occur either directly or via intermediary hosts such as non-human primates, horses or pigs. </p>
<p>Global travel allowed for the virus to <a href="https://www.who.int/csr/disease/ebola/en/">spread from Central Africa to West Africa, and subsequently Europe and North America</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/332081/original/file-20200502-42908-1oteam2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/332081/original/file-20200502-42908-1oteam2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/332081/original/file-20200502-42908-1oteam2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=339&fit=crop&dpr=1 600w, https://images.theconversation.com/files/332081/original/file-20200502-42908-1oteam2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=339&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/332081/original/file-20200502-42908-1oteam2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=339&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/332081/original/file-20200502-42908-1oteam2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=427&fit=crop&dpr=1 754w, https://images.theconversation.com/files/332081/original/file-20200502-42908-1oteam2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=427&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/332081/original/file-20200502-42908-1oteam2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=427&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A sign in Makoua, Congo, warns visitors that Ebola is present in the area, and to avoid handling any animals found dead.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<h2>The Hendra virus</h2>
<p>The Hendra virus (HeV) has been a persistent infection of <a href="https://doi.org/10.5694/j.1326-5377.1995.tb126050.x">horses and humans in Australia since 1994</a>. Transmission into the equine population has been attributed to <a href="https://doi.org/10.1016/S1473-3099(12)70158-5">food or water contaminated with bat feces, urine or saliva</a>. HeV originated in black flying foxes, and its transmission to horses and humans results in a severe respiratory disease. </p>
<p>Subsequent transmission from horses to humans involves the close contact of humans with the <a href="https://www.cdc.gov/vhf/hendra/transmission/index.html">bodily fluids of infected horses</a>. Fortunately, <a href="http://doi.org/10.1016/j.coviro.2016.02.004">horse-to-horse, human-to-horse and bat-to-human transmission of hendra virus (HeV) is currently limited</a>. As a result, <a href="https://www.who.int/health-topics/hendra-virus-disease">this viral infection has not lead to widespread infections or fatalities</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/327418/original/file-20200413-109081-fryzhj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/327418/original/file-20200413-109081-fryzhj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/327418/original/file-20200413-109081-fryzhj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=447&fit=crop&dpr=1 600w, https://images.theconversation.com/files/327418/original/file-20200413-109081-fryzhj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=447&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/327418/original/file-20200413-109081-fryzhj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=447&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/327418/original/file-20200413-109081-fryzhj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=562&fit=crop&dpr=1 754w, https://images.theconversation.com/files/327418/original/file-20200413-109081-fryzhj.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=562&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/327418/original/file-20200413-109081-fryzhj.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=562&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Black flying foxes (<em>Pteropus alecto</em>) roosting in the Redcliffe Botanical Garden in Brisbane, Australia.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/niaid/49597020648/in/album-72157712914621487/">(gailhampshire/flickr)</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>The Nipah virus</h2>
<p>Nipah virus (NiV) infections have been occurring <a href="https://doi.org/10.1007/s00281-002-0106-y">in Bangladesh and Malaysia since 1998</a>. This virus causes respiratory disease and swelling of the brain — encephalitis — in pigs. Human contact with infected pigs results in severe encephalitis, fever and eventually death. This virus also emerged from fruit bats through a spill-over event with the <a href="https://doi.org/10.1007/s11908-006-0036-2">close proximity of living conditions</a> between humans, domesticated animals and the natural reservoir. </p>
<p>Altogether, it is clear that human activities play a role in the emergence or re-emergence of infectious diseases. The role of <a href="http://dx.doi.org/10.1038/cddiscovery.2016.48">bats as natural reservoirs</a> to numerous deadly human diseases is also very clear.</p>
<p>The uncertainty of subsequent outbreaks or pandemics is not related to how or why but rather a question of when.</p><img src="https://counter.theconversation.com/content/134226/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Narveen Jandu does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Bats have been the reservoir for recent disease outbreaks, including SARS and the current COVID-19 pandemic. But it’s human activity that allows the virus to cross over.Narveen Jandu, School of Public Health & Health Studies, University of WaterlooLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1358702020-04-20T17:20:05Z2020-04-20T17:20:05ZThere is no evidence that the coronavirus was created in a laboratory<figure><img src="https://images.theconversation.com/files/326087/original/file-20200407-91406-46z6bt.jpg?ixlib=rb-1.1.0&rect=0%2C305%2C12000%2C7706&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">No, this person is not creating a deadly virus.</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/_HvUN5xlv7I">CDC / Unsplash</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>The <a href="https://en.wikipedia.org/wiki/2019%E2%80%9320_coronavirus_pandemic">Covid-19</a> pandemic, which is disrupting our lives and shaking our health systems and economies, is at the root of what Dr. Sylvie Briand, director of the Department of Pandemic and Epidemic Diseases of the World Health Organization (WHO), rightly described as an <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30461-X/fulltext">infodemic</a> – the viral circulation of rumours and false information.</p>
<h2>The Covid-19 infodemic</h2>
<p><a href="https://www.msn.com/it-it/video/amici/paolo-liguori-questo-virus-nasce-in-un-laboratorio/vi-BBZjDhw">Journalists</a> and <a href="https://www.washingtontimes.com/news/2020/jan/26/coronavirus-link-to-china-biowarfare-program-possi/">so-called experts</a> have seriously suggested that the SARS-CoV-2 coronavirus at the heart of the epidemic could have been produced in the <a href="https://en.wikipedia.org/wiki/Biosafety_level">Level 4 Biosafety Laboratory</a> (BL4) in China’s Wuhan region, the epicentre of the epidemic.</p>
<p>These theories have gone viral, to the point that <a href="https://jean-jaures.org/sites/default/files/redac/commun/productions/2020/2803/117275_rapport_covid_19.pdf">recent polls</a> show that 23% of Americans and 17% French believe that the new coronavirus was made intentionally in a laboratory.</p>
<p>The wave of conspiracy theories surrounding the Covid-19 epidemic has also been spurred on by a few governments waging a veritable information war by politicizing the epidemic. In a speech on March 11, 2020, US president Donald Trump called Covid-19 the “Chinese virus”. In response, a spokesperson for the Chinese Ministry of Foreign Affairs posted on <a href="https://twitter.com/zlj517/status/1238269193427906560?s=20">his Twitter account</a> an article allegedly demonstrating that SARS-CoV-2 was already present in 2019 in the United States and was brought to China by American soldiers.</p>
<p>The spread of such false information can hamper the response to real epidemics, and it is therefore crucial to establish the verifiable facts about SARS-CoV-2 virus.</p>
<h2>What do we know about the origins of Covid-19?</h2>
<p>The results of the <a href="https://www.nature.com/articles/s41591-020-0820-9">genomic analysis of SARS-CoV-2</a> are clear: its sequence is 96% identical to that of the RaTG13 coronavirus isolated from a bat collected in the Chinese province of Yunan. The sequence of the receptor binding domain (RBD) present on the surface of SARS-CoV-2 that allows it to infect human cells, however, diverges strongly from the equivalent sequence observed in RaTG13. On the other hand, the RBD sequence of SARS-CoV-2 is very close (99%) to that of a coronavirus isolated in the pangolin. This suggests that SARS-CoV-2 is the result of the <a href="https://theconversation.com/coronavirus-origins-genome-analysis-suggests-two-viruses-may-have-combined-134059">recombination of two viruses</a>. This recombination mechanism has <a href="https://jvi.asm.org/content/84/7/3134">already been observed</a> in coronaviruses.</p>
<p>Comparison of coronavirus sequences present in nature supports a natural origin for SARS-CoV-2. Furthermore, SARS-CoV-2 contains no trace of any human-mediated genetic manipulation. More specifically, it does not contain residual sequences related to <a href="https://en.wikipedia.org/wiki/Genetic_engineering">vector systems</a> conventionally used for genetic manipulation, which suggests that it is indeed the product of natural random selection.</p>
<h2>BL4 laboratory, genetic manipulation: reality and myths</h2>
<p>There is indeed a BL4 laboratory in Wuhan: the Wuhan National Biosafety Laboratory. Built in partnership with France, it obtained certification in 2017. Following the SARS epidemics of 2002-2004 and H1N1 in 2009, China wanted to improve its capacity to fight epidemics. The laboratory primarily carries out research on Ebola, Crimean-Congo hemorrhagic fever and SARS. The only documented accident linked to a laboratory working on coronaviruses in China was the <a href="https://www.cdc.gov/sars/media/2004-05-19.html">infection of nine individuals in April 2004 with the SARS-CoV-1 virus</a> responsible for the SARS epidemic of 2002-2004. The people infected were two students working at the National Institute of Virology Laboratory and their relatives.</p>
<p>There are almost 30 BL4 laboratories listed worldwide. Their operations have always been a source of controversy and suspicion, in particular because some were previously involved in the manufacture of biological weapons. With the signing of the 1972 <a href="https://en.wikipedia.org/wiki/Biological_Weapons_Convention">Convention on the Prohibition of Biological Weapons</a>, which banned the development, acquisition, stockpiling and use of biological weapons, the purpose of the laboratories changed. They now officially work to fight epidemics and biological weapons. However, it has been shown that certain countries, including the former Soviet Union, continued to fund biological-weapons research programs, such as <a href="https://en.wikipedia.org/wiki/Biopreparat">Biopreparat</a>, despite having signed the convention.</p>
<p>These BL4 laboratories have indeed already been linked to accidents. For example, the <a href="https://en.wikipedia.org/wiki/Sverdlovsk_anthrax_leak">1979 Sverdlovsk disaster</a>, which involved the <a href="https://science.sciencemag.org/content/266/5188/1202">accidental spread of spores of the bacterium <em>Bacillus anthracis</em></a> that causes anthrax, caused dozens of deaths. The <a href="https://en.wikipedia.org/wiki/2001_anthrax_attacks">2001 anthrax attacks</a> in the United States were linked to a microbiologist, <a href="https://en.wikipedia.org/wiki/Bruce_Edwards_Ivins">Bruce Ivins</a>, who was working in a US Army BL4 laboratory. These high security laboratories have thus provided fertile ground for the development of highly extravagant conspiracy theories.</p>
<p>It is also true that ancient deadly viruses have been resuscitated in the laboratory, that new viruses are created by genetic manipulation for research purposes, and that some viruses have already been disseminated in the wild by countries. In 2005, the <a href="https://en.wikipedia.org/wiki/Spanish_flu">1918 Spanish influenza virus</a> was <a href="https://science.sciencemag.org/content/310/5745/77.long">genetically engineered and tested in the laboratory</a> to <a href="https://www.sciencedirect.com/science/article/pii/S0042682218302502?via%3Dihub">better understand its exceptional virulence</a>. In 2012, the H5N1 flu virus was modified in the laboratory to give it the ability to <a href="https://www.nature.com/articles/nature10831">infect ferrets by air</a> to understand how the virus could mutate to infect humans by the same route. In 2017, the Australian government authorised the spread of a <a href="https://www.agric.wa.gov.au/biological-control/rabbit-biocontrol-rhdv1-k5-national-release">strain of rabbit hemorrhagic disease virus</a> (RHDV1 K5) to reduce the population of wild rabbits on its territory. These well-documented events have also provided good fodder for an infinite variety of scenarios.</p>
<h2>Russel’s teapot and Covid-19</h2>
<p>What do a “celestial teapot” and the conspiracy theories surrounding Covid-19 have in common? More than you might think at first glance.</p>
<p>The <a href="https://en.wikipedia.org/wiki/Russell%27s_teapot">metaphor of the celestial teapot</a> was proposed by the philosopher <a href="https://en.wikipedia.org/wiki/Bertrand_Russell">Bertrand Russell</a> to challenge the idea that it is up to the sceptic to refute the unverifiable bases of religion and to affirm that the burden of proof falls instead to the believer. Russell suggested that a teapot is in orbit around the sun, precisely between Earth and the planet Mars. We cannot demonstrate that this teapot does not exist, so we have to believe it is there. Russel’s teapot is the cosmic version of <a href="https://en.wikipedia.org/wiki/Occam%27s_razor">Ockham’s razor</a>, also known as the principle of parsimony or simplicity. This principle recommends eliminating complex explanations for a phenomenon from reasoning if simpler explanations prove plausible. There remains a fundamental principle of logical reasoning in science: it does not state that the simplest explanation is necessarily true, only that it must be considered first.</p>
<p>In the case of Covid-19, there is no verifiable fact to support the hypothesis that SARS-CoV-2 was intentionally manufactured in a laboratory. Various conspiracy theories are only supported by correlations, such as the existence of a BL4 in Wuhan. The RBD sequences of the virus could, in theory, result from an adaptation of the virus in the laboratory when cultured in human cells. But the existence of an RBD sequence that is 99% identical in a coronavirus infecting the pangolin supports a more parsimonious hypothesis: the infection of a bat or a pangolin with two coronaviruses that recombined to form a new virus that in turn infected a human, who would then be the famous and still unknown patient zero behind the Covid-19 epidemic.</p>
<p>The success of conspiracy theories about Covid-19 reveals much about our visceral need to reassure ourselves by inventing simplistic explanations for terrifying natural phenomena. Which hypothesis is the most unbearable – that mad scientists subsidised by a foreign power sparked an epidemic capable of shaking our modern societies, or that new epidemics emerge because of our invasion and destruction of natural ecosystems? In the first case, it would be easy to end the nightmare. In the second, it is our way of life and our economic system that must change.</p><img src="https://counter.theconversation.com/content/135870/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Eric Muraille received funding from Fonds de la Recherche Scientifique (FNRS-FRS), Belgium.</span></em></p>The conspiracy theory that Covid-19 was created in a laboratory has been widely reported, yet there is no evidence to support it. Why such theories thrive can easily be explained, however.Eric Muraille, Biologiste, Immunologiste. Maître de recherches au FNRS, Université Libre de Bruxelles (ULB)Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1357902020-04-20T13:31:01Z2020-04-20T13:31:01ZDrug-resistant superbugs: A global threat intensified by the fight against coronavirus<figure><img src="https://images.theconversation.com/files/328554/original/file-20200416-192731-1hcrz6l.jpg?ixlib=rb-1.1.0&rect=5%2C32%2C1272%2C848&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Methicillin-resistant Staphylococcus aureus (MRSA) bacteria (coloured yellow) enmeshed within a human white blood cell (coloured red). MRSA is a major cause of hospital-associated infections.</span> <span class="attribution"><a class="source" href="https://phil.cdc.gov/Details.aspx?pid=18125">(NIAID)</a></span></figcaption></figure><p>With the world’s attention on COVID-19, I believe that now is the time to talk about another pandemic that’s been happening right under our noses: antimicrobial resistance (AMR). </p>
<p>When infections caused by bacteria, parasites, viruses or fungi stop responding to the medicines designed to treat them, that’s AMR. Resistance builds over time through overexposure to antimicrobial drugs, such as antibiotics, or disinfectants. With ineffective treatments, these infections persist in the body and ultimately spread to others.</p>
<h2>A major public health and economic risk</h2>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/327321/original/file-20200412-51445-1qir6kq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/327321/original/file-20200412-51445-1qir6kq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=628&fit=crop&dpr=1 600w, https://images.theconversation.com/files/327321/original/file-20200412-51445-1qir6kq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=628&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/327321/original/file-20200412-51445-1qir6kq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=628&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/327321/original/file-20200412-51445-1qir6kq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=789&fit=crop&dpr=1 754w, https://images.theconversation.com/files/327321/original/file-20200412-51445-1qir6kq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=789&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/327321/original/file-20200412-51445-1qir6kq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=789&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Two methicillin-resistant Staphylococcus aureus (MRSA) bacteria, being enveloped by a white blood cell.</span>
<span class="attribution"><a class="source" href="https://phil.cdc.gov/Details.aspx?pid=18168">(NIAID)</a></span>
</figcaption>
</figure>
<p>AMR is a slower-moving pandemic than COVID-19, but one that is worsening every day. A <a href="https://cca-reports.ca/reports/the-potential-socio-economic-impacts-of-antimicrobial-resistance-in-canada/">recent report by the Council of Canadian Academies</a> said that in 2018, more than a quarter of all infections in Canada were resistant to first-line drugs. In that one year alone, 5,400 people died as a direct result of resistant infections. </p>
<p>Drug-resistant infections lead to longer hospital stays and potentially greater complications. Doctors might need to use alternative medicines with more side effects. These issues cost the Canadian health-care system 1.4 billion dollars, and this will only increase.</p>
<p><a href="https://theconversation.com/newsletter"><img src="https://images.theconversation.com/files/320030/original/file-20200312-116261-a6ugi0.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=90&fit=crop&dpr=2" alt="Sign up to The Conversation" width="100%"></a></p>
<p>The <a href="https://www.un.org/press/en/2016/ga11825.doc.htm">United Nations</a>, the <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">World Health Organization</a> and even the <a href="https://www.worldbank.org/en/topic/health/publication/drug-resistant-infections-a-threat-to-our-economic-future">World Bank</a> recognize AMR as a public health and economic disaster waiting to happen. In 2016, United Kingdom economist Jim O’Neill and his team published <a href="https://amr-review.org">a report</a> stating that if we do not address the growing threat of AMR, by 2050 more people will die from drug-resistant infections than from cancer. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/327754/original/file-20200414-117587-rhjhzk.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/327754/original/file-20200414-117587-rhjhzk.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=480&fit=crop&dpr=1 600w, https://images.theconversation.com/files/327754/original/file-20200414-117587-rhjhzk.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=480&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/327754/original/file-20200414-117587-rhjhzk.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=480&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/327754/original/file-20200414-117587-rhjhzk.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=603&fit=crop&dpr=1 754w, https://images.theconversation.com/files/327754/original/file-20200414-117587-rhjhzk.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=603&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/327754/original/file-20200414-117587-rhjhzk.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=603&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">If left unsolved, AMR will cause more global deaths than cancer by 2050.</span>
<span class="attribution"><span class="source">(Christy Groves, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University)</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>If left unsolved, AMR will cost the health-care system trillions of dollars and, more importantly, it will cost millions of people their lives. </p>
<h2>Lessons from SARS-CoV-2</h2>
<p>We can learn from COVID-19. The current pandemic shows that despite all of our medical advances, we remain incredibly vulnerable to infections for which we have no therapies. However, it shows that if sufficiently motivated, we can make huge changes in short timeframes. </p>
<p>While there is inspiring work being done in different parts of the world to address the issues surrounding AMR — including here at <a href="https://iidr.mcmaster.ca">McMaster University’s Institute for Infectious Disease Research</a>, where my group is based — there is a long road ahead of us.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/327756/original/file-20200414-117573-1azvjmw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/327756/original/file-20200414-117573-1azvjmw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/327756/original/file-20200414-117573-1azvjmw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/327756/original/file-20200414-117573-1azvjmw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/327756/original/file-20200414-117573-1azvjmw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/327756/original/file-20200414-117573-1azvjmw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/327756/original/file-20200414-117573-1azvjmw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The author at work in the lab at McMaster University’s Institute for Infectious Disease Research.</span>
<span class="attribution"><span class="source">(J.D. Howell, McMaster University)</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Despite significant efforts to educate policymakers and the public about the AMR crisis and offer possible solutions, it remains low on the priority list for many jurisdictions. On top of that, <a href="https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf">research on AMR is woefully underfunded compared to other areas of medicine</a>, such as cancer and cardiac disease. </p>
<p>Another major hurdle for the AMR response is loss of interest by big pharmaceutical companies. The need for expensive clinical trials and the risk of AMR rendering their products useless after a few years mean <a href="https://www.nytimes.com/2019/12/25/health/antibiotics-new-resistance.html">it’s challenging for them to recover their investment</a> into antibiotic research and development. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/327324/original/file-20200412-196246-g0e86m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/327324/original/file-20200412-196246-g0e86m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=464&fit=crop&dpr=1 600w, https://images.theconversation.com/files/327324/original/file-20200412-196246-g0e86m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=464&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/327324/original/file-20200412-196246-g0e86m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=464&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/327324/original/file-20200412-196246-g0e86m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=583&fit=crop&dpr=1 754w, https://images.theconversation.com/files/327324/original/file-20200412-196246-g0e86m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=583&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/327324/original/file-20200412-196246-g0e86m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=583&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Drug-resistant Salmonella serotype Typhi bacteria, from the Centers for Disease Control and Prevention publication <em>Antibiotic Resistance Threats in the United States</em>.</span>
<span class="attribution"><a class="source" href="https://phil.cdc.gov/Details.aspx?pid=23251">(Illustration by James Archer)</a></span>
</figcaption>
</figure>
<p>Fortunately, antibiotics are only one strategy for fighting bacterial infections. Another common and highly successful approach is vaccination (think about routine <a href="https://link.springer.com/chapter/10.1007/978-94-007-7624-1_11">childhood immunizations against diphtheria</a> and <a href="http://www.health.gov.on.ca/en/pro/programs/immunization/docs/hcp_fact_sheets_hoemophilus_influenzae_typeb.pdf"><em>Haemophilus</em> <em>influenzae</em></a>), but vaccines are also challenging to develop and deliver in the face of a <a href="https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2020-46/issue-2-3-february-6-2020/article-5-best-practices-addressing-vaccine-hesitancy.html">growing hesitancy movement</a>. Novel treatments such as <a href="https://www.nature.com/articles/nrd.2017.162">immune boosters</a>, <a href="https://doi.org/10.1016/j.drudis.2019.03.002">therapeutic antibodies</a> or natural predators of bacteria called <a href="https://www.id-hub.com/2019/11/21/bacteriophages-2-0-old-solution-modern-problem/">bacteriophages</a> all show promise but are still in the early days of development.</p>
<h2>Antibacterial products contribute to AMR</h2>
<p>While the key players in the global response to AMR undoubtedly include researchers, food producers, policymakers and health-care professionals, the truth is every single person has a role to play.</p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/327317/original/file-20200412-32369-1kpxyl9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/327317/original/file-20200412-32369-1kpxyl9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/327317/original/file-20200412-32369-1kpxyl9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/327317/original/file-20200412-32369-1kpxyl9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/327317/original/file-20200412-32369-1kpxyl9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/327317/original/file-20200412-32369-1kpxyl9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/327317/original/file-20200412-32369-1kpxyl9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Antibacterial soaps and disinfectant cleansers can contribute to antimicrobial resistance.</span>
<span class="attribution"><span class="source">(Kelly Sikkema/Unsplash)</span></span>
</figcaption>
</figure>
<p>One thing we can all do to help combat the spread of AMR is to use regular — not “antibacterial” — soap. Good old-fashioned regular soap is antibacterial and antiviral; it dissolves the greasy membranes that surround bacteria and viruses such as SARS-CoV-2, killing them. </p>
<p>Conversely, antibacterial soaps usually contain additional chemicals that don’t add much in the way of hygiene, but can activate a microorganism’s efflux pumps. The pumps force disinfectants out before they can cause harm (picture someone bailing water out of a leaky boat so it doesn’t sink). They increase the ability of bacteria to fend off multiple types of toxic compounds, including antibiotics, and hasten the spread of AMR. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/327325/original/file-20200412-51445-16eao6a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/327325/original/file-20200412-51445-16eao6a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=628&fit=crop&dpr=1 600w, https://images.theconversation.com/files/327325/original/file-20200412-51445-16eao6a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=628&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/327325/original/file-20200412-51445-16eao6a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=628&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/327325/original/file-20200412-51445-16eao6a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=789&fit=crop&dpr=1 754w, https://images.theconversation.com/files/327325/original/file-20200412-51445-16eao6a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=789&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/327325/original/file-20200412-51445-16eao6a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=789&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Multidrug-resistant Klebsiella pneumoniae bacteria, which are known to cause severe hospital acquired nosocomial infections.</span>
<span class="attribution"><a class="source" href="https://phil.cdc.gov/Details.aspx?pid=18170">(David Dorward/NIAID)</a></span>
</figcaption>
</figure>
<p>While COVID-19 in its own right is indeed terrifying, its implications for the future of AMR might be even worse. Widespread use of antibacterial soaps and disinfectants aside, <a href="https://doi.org/10.1016/S0140-6736(20)30566-3">early studies out of China</a> show that almost all severely ill COVID-19 patients were given antibiotics (sometimes multiple antibiotics) to prevent or treat the secondary bacterial infections to which many ultimately succumbed. Unfortunately, the more antibiotics we use, the more we select for AMR. </p>
<p>But I choose to be an optimist. I hope that COVID-19 is a learning experience. I hope it will open the eyes of many to the life-altering power of microbes. I hope it teaches us that we need better (and faster) surveillance infrastructure for outbreaks. I hope it highlights the need for the rapid development, approval and scale up of effective diagnostics and new therapies.</p>
<p>To me, these steps would be encouraging progress in the global response to AMR.</p><img src="https://counter.theconversation.com/content/135790/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Lori L. Burrows receives research grants from the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, Glyconet, and the Ontario Research Fund. </span></em></p>Antimicrobial resistance is a public health and economic disaster waiting to happen. If we do not address this threat, by 2050 more people will die from drug-resistant infections than from cancer.Lori L. Burrows, Professor of Biocchemistry and Biomedical Sciences, McMaster UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1351362020-03-31T11:32:24Z2020-03-31T11:32:24ZCoronavirus weekly: as the world stays at home, where is the pandemic heading?<p>From New York to Moscow, Johannesburg to Buenos Aires, the novel coronavirus continues its global journey. On March 30, almost three months after China announced the discovery of COVID-19, the disease associated with the coronavirus, <a href="https://coronavirus.jhu.edu/map.html">more than 780,000 people</a> have been infected and at least 37,000 have died. </p>
<p>While the epidemic appears to be under control in China, the US is now the country most affected by the pandemic. In Europe, it would appear containment measures and lockdowns are beginning to bear fruit: in Italy, the figures indicate a slowdown in the number of infections.</p>
<p>All over the world countries are locking themselves off one after the other, closing their borders and confining their populations more and more drastically. The World Health Organization has welcomed these efforts. The world is slowing down and holding its breath. For how long?</p>
<p>As researchers around the world continue to decipher the consequences of this unprecedented situation and to seek solutions to the crisis, The Conversation’s international network continues to work with them to inform you as best as possible.</p>
<hr>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/320716/original/file-20200316-18073-ruhw8b.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/320716/original/file-20200316-18073-ruhw8b.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/320716/original/file-20200316-18073-ruhw8b.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/320716/original/file-20200316-18073-ruhw8b.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/320716/original/file-20200316-18073-ruhw8b.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/320716/original/file-20200316-18073-ruhw8b.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/320716/original/file-20200316-18073-ruhw8b.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
</figcaption>
</figure>
<p><strong>This is our weekly roundup of expert info about the <a href="https://theconversation.com/topics/covid-19-82431">coronavirus</a>.</strong><br>
<em>The Conversation, a not-for-profit group, works with a wide range of academics across its global network. Together we produce evidence-based analysis and insights. The articles are free to read – there is no paywall – and to <a href="http://theconversation.com/republishing-guidelines">republish</a>. Keep up to date with the latest research by <a href="http://theconversation.com/newsletter">reading our free newsletter</a>.</em></p>
<hr>
<h2>The fate of the epidemic</h2>
<p>How long will we have to live with COVID-19? Could it possibly return? The history and modelling of epidemics can help find the answers. </p>
<ul>
<li><a href="https://theconversation.com/four-graphs-that-show-how-the-coronavirus-pandemic-could-now-unfold-133979"><strong>Modelling past major epidemics</strong></a> can show how this one will unfold. This is what Adam Kleczkowski at the University of Strathclyde and Rowland Raymond Kao at the University of Edinburgh have done.</li>
</ul>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/322291/original/file-20200323-112688-1vsktee.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/322291/original/file-20200323-112688-1vsktee.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/322291/original/file-20200323-112688-1vsktee.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/322291/original/file-20200323-112688-1vsktee.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/322291/original/file-20200323-112688-1vsktee.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/322291/original/file-20200323-112688-1vsktee.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/322291/original/file-20200323-112688-1vsktee.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">An example of a disease progress curve for a long-term scenario following the initial outbreak: quick eradication. The number of cases and duration of the epidemic for illustrative purpose only.</span>
</figcaption>
</figure>
<ul>
<li><p><strong>Mathematical models.</strong> Christian Yates at the University of Bath explains how epidemiologists create the models to <a href="https://theconversation.com/how-to-model-a-pandemic-134187">predict the course of an epidemic</a>, which are essential tools for informing governments’ actions.</p></li>
<li><p><strong>Anticipating epidemics.</strong> According to Éric Muraille at the Université Libre de Bruxelles, history teaches us epidemics are inevitable. This is why <a href="https://theconversation.com/les-epidemies-sont-inevitables-apprenons-a-les-anticiper-133888">it is essential to know how to anticipate them</a> <em>(in French)</em>.</p></li>
</ul>
<p>The fate of the pandemic will obviously depend on the weapons at our disposal to fight the coronavirus.</p>
<ul>
<li><p><strong>Chloroquine?</strong> Parastou Donyai from the University of Reading explains that although much has been written about the anti-malarial drug, there is as yet <a href="https://theconversation.com/chloroquine-and-hydroxychloroquine-no-proof-these-anti-malarial-drugs-prevent-novel-coronavirus-in-humans-134703">no evidence of its effectiveness in preventing COVID-19</a>.</p></li>
<li><p><strong>Therapies and vaccines.</strong> Ignacio López-Goñi at the University of Navarra lists the different therapeutic trials currently underway and says there is hope for <a href="https://theconversation.com/coronavirus-treatments-and-vaccines-research-on-3-types-of-antivirals-and-10-different-vaccines-is-being-fast-tracked-134613">therapies to treat patients or vaccines to prevent infection</a>. </p></li>
</ul>
<p>The coronavirus pandemic must not be allowed to overshadow other deadly diseases. </p>
<ul>
<li><strong>Tuberculosis and AIDS.</strong> Emily Wong at the University of KwaZulu-Natal draws attention to the fact that in South Africa, COVID-19 is adding to existing epidemics. Experts are concerned these patients are <a href="https://theconversation.com/tb-hiv-and-covid-19-urgent-questions-as-three-epidemics-collide-134554">more at risk of developing severe forms</a> of the disease. </li>
</ul>
<h2>A disease of biodiversity</h2>
<p>Like many infectious diseases that affect humans, the COVID-19 pandemic is a zoonosis: the virus that comes from animals.</p>
<ul>
<li><p><strong>Bats?</strong> - Once again, this new virus probably originated from a bat. Eric Leroy at the Institut de recherche pour le développement explains why these mammals <a href="https://theconversation.com/les-chauves-souris-source-inepuisable-de-virus-dangereux-pour-les-humains-134332">are a “usual suspect”</a> for the transmission of viruses to humans <em>(in French)</em>. </p></li>
<li><p><strong>But it’s unfair to blame them</strong>, because they <a href="https://theconversation.com/its-wrong-to-blame-bats-for-the-coronavirus-epidemic-134300">do us important services and must be protected</a>, says Peter Alagona at the University of California, Santa Barbara.</p></li>
</ul>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/324103/original/file-20200330-172952-1ahz37p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/324103/original/file-20200330-172952-1ahz37p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/324103/original/file-20200330-172952-1ahz37p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/324103/original/file-20200330-172952-1ahz37p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/324103/original/file-20200330-172952-1ahz37p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/324103/original/file-20200330-172952-1ahz37p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/324103/original/file-20200330-172952-1ahz37p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">There are over 1,200 different species of bats.</span>
<span class="attribution"><a class="source" href="https://ccsearch.creativecommons.org/photos/d08bdf84-47d1-47d4-9bc8-0ceb6d037ea9">mmariomm/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span>
</figcaption>
</figure>
<p>Rather than blaming these flying mammals, we’d be better off questioning our relationship to nature and biodiversity.</p>
<ul>
<li><p><a href="https://theconversation.com/covid-19-ou-la-pandemie-dune-biodiversite-maltraitee-134712"><strong>The symptom of a global environmental crisis?</strong></a> It could well be, write Philippe Grandcolas and Jean-Lou Justine at the Muséum national d’histoire naturelle (MNHN) <em>(in French)</em></p></li>
<li><p><strong>“This is not a tragedy for everyone.</strong> Some of our neighbours are doing better since we have retired to our apartments”, writes Jérôme Sueur at MNHN. Less human activity means less noise, which is actually a good thing for <a href="https://theconversation.com/dans-le-silence-du-virus-quels-effets-sur-les-etres-vivants-134073">birds in our cities, in particular</a> <em>(in French)</em>.</p></li>
</ul>
<h2>Lockdown left behind</h2>
<p>More and more of us are being confined in the hope of limiting the spread of the virus and relieving the unbearable strain on health systems. But not everyone is equal when it comes to lockdown and quarantine measures. Some groups are particular at risk.</p>
<ul>
<li><p><strong>Elderly or disabled people.</strong> In medical-social institutions, those who are already vulnerable <a href="https://theconversation.com/confinement-quel-impact-dans-les-etablissements-pour-personnes-agees-et-handicapees-134561">are the big losers of containment measures</a>, writes Emmanuelle Fillion at École des hautes études en santé publique <em>(in French)</em>.</p></li>
<li><p><a href="https://theconversation.com/coronavirus-la-prison-en-etat-critique-134359"><strong>Prisoners.</strong></a> <em>(in French)</em> This is also the case of prisoners, whose fate worries the prison administration because of their proximity to the prison. </p></li>
<li><p><strong>Those who can’t be confined.</strong> Alex Broadbent and Benjamin Smart at the University of Johannesburg point out that some cannot be locked down, or even implement <a href="https://theconversation.com/why-a-one-size-fits-all-approach-to-covid-19-could-have-lethal-consequences-134252">adequate social distancing measures</a>.</p></li>
</ul>
<p>In addition to the risk of lockdown, heads of state face political risk: their every move is scrutinised and commented upon.</p>
<ul>
<li><p>The South African President Cyril Ramaphosa <a href="https://theconversation.com/all-world-leaders-face-mega-covid-19-crises-how-ramaphosa-is-stacking-up-134682">is no exception</a>, explains Richard Calland at the University of Cape Town, but so far his government’s lockdown measures <a href="https://theconversation.com/reality-of-exponential-growth-of-covid-19-shows-south-africas-lockdown-is-right-134572">seem adequate</a>, writes Philip Machanick at Rhodes University.</p></li>
<li><p>Conversely, as the epidemic is just entering a phase of exponential growth in Indonesia, Iqbal Elyazar at the Eijkman-Oxford Clinical Research Unit and his colleagues are urging the government <a href="https://theconversation.com/without-major-intervention-indonesia-could-have-71-000-covid-19-cases-by-aprils-end-134239">to take tougher measures to avoid disaster</a>.</p></li>
<li><p>In France, Catherine Le Bris at the Université Paris 1 Panthéon-Sorbonne wonders how to reconcile emergency situations, the limitation of freedoms and the rule of law. The balance lies in <a href="https://theconversation.com/la-sauvegarde-des-libertes-en-temps-de-guerre-contre-le-coronavirus-134913">the respect of human rights</a> she argues <em>(in French)</em>.</p></li>
</ul>
<p>– Finally, Michael Baker at the University of Otago returns to the essential point of all these efforts: to control the pandemic. He is a professor of public health and is <a href="https://theconversation.com/overjoyed-a-leading-health-expert-on-new-zealands-coronavirus-shutdown-and-the-challenging-weeks-ahead-134395">“overjoyed” that shutdowns are happening</a>.</p>
<h2>Revealing inequalities</h2>
<p>The current pandemic is also exacerbating inequalities. </p>
<ul>
<li><p><strong>Panic buying.</strong> James Lappeman at the University of Cape Town has focused on the panic buying triggered by the coronavirus panic. But this <a href="https://theconversation.com/panic-buying-in-the-wake-of-covid-19-underscores-inequalities-in-south-africa-134172">sheds a harsh light on economic inequality</a>.</p></li>
<li><p><strong>Inequality.</strong> Pandemics reveal inequality as never before, and <a href="https://theconversation.com/pandemics-dont-heal-divisions-they-reveal-them-south-africa-is-a-case-in-point-134002">South Africa is a textbook case</a> of this, according to Steven Friedman at the University of Johannesburg. </p></li>
</ul>
<p>But the current crisis could also be an opportunity to explore ways to reduce inequalities and to test new approaches, particularly economic ones.</p>
<ul>
<li><strong>“Helicopter money”</strong>, a theory coined by the economist Milton Friedman in the 1970s, <a href="https://theconversation.com/lhelicoptere-monetaire-un-outil-de-lutte-contre-les-inegalites-134670">could be used to reduce inequality</a> by distributing money directly to the population, explains Baptiste Massenot at TBS Business School <em>(in French)</em>. </li>
</ul>
<p>And finally, as a tribute to the “heroes in white coats”, The Conversation has published a <a href="https://theconversation.com/im-a-family-doctor-fighting-against-fear-and-struggling-with-distancing-while-trying-to-keep-my-patients-healthy-134342">series of testimonies</a> from clinicians and researchers operating on the front lines of the pandemic – and providing advice on the conversations <a href="https://theconversation.com/coronavirus-the-conversation-we-should-have-with-our-loved-ones-now-leading-medic-134337">we should now be having with our loved ones</a>.</p>
<hr>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/320718/original/file-20200316-18056-1umaqbp.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/320718/original/file-20200316-18056-1umaqbp.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=90&fit=crop&dpr=1 600w, https://images.theconversation.com/files/320718/original/file-20200316-18056-1umaqbp.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=90&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/320718/original/file-20200316-18056-1umaqbp.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=90&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/320718/original/file-20200316-18056-1umaqbp.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=113&fit=crop&dpr=1 754w, https://images.theconversation.com/files/320718/original/file-20200316-18056-1umaqbp.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=113&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/320718/original/file-20200316-18056-1umaqbp.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=113&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<p><em>Get the latest news and advice on <a href="https://theconversation.com/topics/covid-19-82431">COVID-19</a>, direct from the experts in your inbox. Join hundreds of thousands who trust experts by <a href="http://theconversation.com/newsletter"><strong>subscribing to our newsletter</strong></a>.</em></p><img src="https://counter.theconversation.com/content/135136/count.gif" alt="The Conversation" width="1" height="1" />
Since the pandemic began, the new coronavirus has infected more than 780,000 people and killed at least 37,000. The experts at The Conversation offer its readers insights from every continent.Lionel Cavicchioli, Chef de rubrique Santé + Médecine, The Conversation FranceLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1337012020-03-20T12:09:43Z2020-03-20T12:09:43ZCOVID-19 treatment might already exist in old drugs – we’re using pieces of the coronavirus itself to find them<figure><img src="https://images.theconversation.com/files/321806/original/file-20200319-22632-ia4tnn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">There are 20,000 FDA approved drugs. One of them might fight COVID-19, if we can find it. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/close-up-of-prescription-drugs-royalty-free-image/506115031?adppopup=true"> Peter Dazeley/The Image Bank via Getty Images</a></span></figcaption></figure><p>Why don’t we have drugs to treat COVID-19 and how long will it take to develop them? </p>
<p>SARS-CoV-2 – the coronavirus that causes the disease COVID-19 – is completely new and attacks cells in a novel way. Every virus is different and so are the drugs used to treat them. That’s why there wasn’t a drug ready to tackle the new coronavirus that only emerged a few months ago.</p>
<p>As a systems biologist who studies how cells are affected by viruses during infections, I’m especially interested in the second question. Finding points of vulnerability and <a href="https://www.medicinenet.com/script/main/art.asp?articlekey=9877">developing a drug to treat a disease typically takes years</a>. But the new coronavirus isn’t giving the world that kind of time. With most of the world on lockdown and the <a href="https://www.worldometers.info/coronavirus/">looming threat of millions of deaths</a>, researchers need to find an effective drug much faster.</p>
<p>This situation has presented my colleagues and me with the challenge and opportunity of a lifetime: to help solve this huge public health and economic crisis posed by the global pandemic of SARS-CoV-2. </p>
<p>Facing this crisis, we assembled a team here at the Quantitative Biosciences Institute (QBI) at the University of California, San Francisco, to discover how the virus attacks cells. But instead of trying to create a new drug based on this information, we are first looking to see if there are any drugs available today that can disrupt these pathways and fight the coronavirus. So far, we’ve identified <a href="https://www.biorxiv.org/content/10.1101/2020.03.22.002386v1?referringSource=articleShare">27 FDA-approved drugs</a> that we hope will narrow and speed up the search.</p>
<p><a href="http://qbi.ucsf.edu/COVID-19">The team of 22 labs</a>, that we named the QCRG, is working at breakneck speed – literally around the clock and in shifts – seven days a week. I imagine this is what it felt like to be in <a href="https://www.britannica.com/topic/Enigma-German-code-device">wartime efforts like the Enigma code-breaking group</a> during World War II, and our team is similarly hoping to disarm our enemy by understanding its inner workings. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/321813/original/file-20200320-22627-536fpp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/321813/original/file-20200320-22627-536fpp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/321813/original/file-20200320-22627-536fpp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/321813/original/file-20200320-22627-536fpp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/321813/original/file-20200320-22627-536fpp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/321813/original/file-20200320-22627-536fpp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/321813/original/file-20200320-22627-536fpp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/321813/original/file-20200320-22627-536fpp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The coronavirus is simple biologically, but complicated in how it infects a host.</span>
<span class="attribution"><a class="source" href="https://phil.cdc.gov/Details.aspx?pid=23354">CDC/ Hannah A Bullock; Azaibi Tamin</a></span>
</figcaption>
</figure>
<h2>A stealthy opponent</h2>
<p>Compared with human cells, viruses are <a href="https://www.livescience.com/53272-what-is-a-virus.html">small and can’t reproduce on their own</a>. <a href="https://dx.doi.org/10.1007%2F978-1-4939-2438-7_1">The coronavirus has about 30 proteins</a>, whereas a human cell has more than 20,000.</p>
<p>To get around this limited set of tools, the virus cleverly turns the human body against itself. The pathways into a human cell are normally locked to outside invaders, but the coronavirus uses its own proteins like keys to open these “locks” and enter a person’s cells.</p>
<p>Once inside, the virus binds to proteins the cell normally uses for its own functions, essentially <a href="https://www2.mrc-lmb.cam.ac.uk/viruswars/viruses.php">hijacking the cell and turning it into a coronavirus factory</a>. As the resources and mechanics of infected cells get retooled to produce thousands and thousands of viruses, the cells start dying.</p>
<p>Lung cells are particularly vulnerable to this because they express high amounts of the “lock” protein SARS-CoV-2 uses for entry. A large number of a person’s lung cells dying causes the respiratory symptoms associated with COVID-19. </p>
<p>There are two ways to fight back. First, drugs could attack the virus’s own proteins, preventing them from doing jobs like entering the cell or copying their genetic material once they are inside. This is how <a href="https://www.drugtargetreview.com/news/56798/mechanism-of-action-revealed-for-remdesivir-potential-coronavirus-drug/">remdesivir – a drug currently in clinical trials for COVID-19 – works</a>.</p>
<p>A problem with this approach is that viruses mutate and change over time. In the future, the coronavirus could evolve in ways that render a drug like remdesivir useless. This arms race between drugs and viruses is <a href="https://theconversation.com/influenza-the-search-for-a-universal-vaccine-68947">why you need a new flu shot every year</a>.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/321787/original/file-20200319-22610-nr27ao.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/321787/original/file-20200319-22610-nr27ao.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/321787/original/file-20200319-22610-nr27ao.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=800&fit=crop&dpr=1 600w, https://images.theconversation.com/files/321787/original/file-20200319-22610-nr27ao.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=800&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/321787/original/file-20200319-22610-nr27ao.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=800&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/321787/original/file-20200319-22610-nr27ao.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1005&fit=crop&dpr=1 754w, https://images.theconversation.com/files/321787/original/file-20200319-22610-nr27ao.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1005&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/321787/original/file-20200319-22610-nr27ao.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1005&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The first step to discovering a treatment is to understand the virus. Jiewei Xu at the Krogan lab prepares samples for the mass spectrometer.</span>
<span class="attribution"><span class="source">Jacqueline Fabius</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Alternatively, a drug can work by blocking a viral protein from interacting with a human protein it needs. This approach – essentially protecting the host machinery – has a big advantage over disabling the virus itself, because the human cell doesn’t change as fast. Once you find a good drug, it should keep working. This is the approach that our team is taking. And it may also work against other emergent viruses.</p>
<h2>Learning the enemy’s plans</h2>
<p>The first thing our group needed to do was identify every part of the cellular factory that the coronavirus relies on to reproduce. We needed to find out what proteins the virus was hijacking.</p>
<p>To do this, a team in <a href="https://kroganlab.ucsf.edu/krogan-lab*">my lab</a> went on a molecular fishing expedition inside human cells. Instead of a worm on a hook, they used <a href="https://kroganlab.ucsf.edu/protein-protein-interaction-analysis">viral proteins with tiny chemical tags attached to them - termed a “bait.”</a> We put these baits into lab-grown human cells and then pulled them out to see what we caught. Anything that stuck was a human protein that the virus hijacks during infection. </p>
<p>By March 2, we had a partial list of the human proteins that the coronavirus needs to thrive. These were the first clues we could use. A team member sent a message to our group, “First iteration, just 3 baits … next 5 baits coming.” The fight was on.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/321807/original/file-20200319-22598-1xajqd4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/321807/original/file-20200319-22598-1xajqd4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/321807/original/file-20200319-22598-1xajqd4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/321807/original/file-20200319-22598-1xajqd4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/321807/original/file-20200319-22598-1xajqd4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/321807/original/file-20200319-22598-1xajqd4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/321807/original/file-20200319-22598-1xajqd4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/321807/original/file-20200319-22598-1xajqd4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Once the first protein targets where found, we needed to search the massive FDA drug database for potential matches.</span>
<span class="attribution"><span class="source">Alexa Rocourt</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>Counterattack</h2>
<p>Once we had this list of molecular targets the virus needs to survive, members of the team raced to identify known compounds that might bind to these targets and prevent the virus from using them to replicate. If a compound can prevent the virus from copying itself in a person’s body, the infection stops. But you can’t simply interfere with cellular processes at will without potentially causing harm to the body. Our team needed to be sure the compounds we identified would be safe and nontoxic for people.</p>
<p>The traditional way to do this would involve <a href="http://dx.doi.org/10.1038/d41591-019-00008-7">years of pre-clinical studies and clinical trials costing millions of dollars</a>. But there is a fast and basically free way around this: looking to the <a href="https://www.fda.gov/about-fda/fda-basics/fact-sheet-fda-glance">nearly 2,000 FDA-approved drugs that have already been safety-tested</a>. Maybe there is a drug in this large list that can fight the coronavirus. </p>
<p><a href="http://shokatlab.ucsf.edu/">Our</a> <a href="http://www.bkslab.org/">chemists</a> used a massive database to match the approved drugs and proteins they interact with to the proteins on our list. They found 10 candidate drugs last week. For example, one of the hits was a cancer drug called JQ1. While we cannot predict how this drug might affect the virus, it has a good chance of doing something. Through testing, we will know if that something helps patients.</p>
<p>Facing the <a href="https://www.theguardian.com/world/2020/mar/18/what-a-coronavirus-lockdown-might-mean-for-london">threat of global border shutdowns</a>, we immediately shipped boxes of these 10 drugs to three of the few labs in the world working with live coronavirus samples: <a href="https://research.pasteur.fr/en/member/olivier-schwartz/">two at</a> the <a href="http://www.vignuzzilab.eu/">Pasteur Institute in Paris</a> and <a href="https://labs.icahn.mssm.edu/garcia-sastre/">Mount Sinai in New York</a>. By March 13, the drugs were being tested in cells to see if they prevent the virus from reproducing.</p>
<h2>Dispatches from the battlefield</h2>
<p>Our team will soon learn from our collaborators at Mt. Sinai and the Pasteur Institute whether any of these first 10 drugs work against SARS-CoV-2 infections. Meanwhile, the team has continued fishing with viral baits. So far we have found 332 human proteins that the coronavirus co-opts, and there are drugs that interact with 66 of those proteins. We <a href="https://doi.org/10.1101/2020.03.22.002386">published the results of our work, which has not yet been peer-reviewed, on March 22</a> in the hope that labs around the world can start to test these drugs and find a treatment as fast as possible.</p>
<p>The good news is that so far, our team has found 69 existing drugs that bind the human proteins we’ve identified. 27 of these are FDA approved, and 42 are in clinical or pre-clinical trials. This large number makes me hopeful that we’ll be able to find a drug to treat COVID-19. If we find an approved drug that even slows down the virus’s progression, doctors should be able to start getting it to patients quickly and save lives. </p>
<p><em>This is an updated version of an article originally published on March 20, 2020.</em></p>
<p>[<em>You need to understand the coronavirus pandemic, and we can help.</em> <a href="https://theconversation.com/us/newsletters?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=upper-coronavirus-help">Read our newsletter</a>.]</p><img src="https://counter.theconversation.com/content/133701/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nevan Krogan receives funding from NIH, DARPA, Roche Pharmaceuticals. </span></em></p>Among the more than 20,000 drugs approved by the FDA, there may be some that can treat COVID-19. A team at the University of California, San Francisco, is identifying possible candidates.Nevan Krogan, Professor and Director of Quantitative Biosciences Institute & Senior Investigator at the Gladstone Institutes, University of California, San FranciscoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1340592020-03-18T14:32:47Z2020-03-18T14:32:47ZCoronavirus origins: genome analysis suggests two viruses may have combined<figure><img src="https://images.theconversation.com/files/321324/original/file-20200318-37397-1h0do17.jpg?ixlib=rb-1.1.0&rect=543%2C325%2C3996%2C2584&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The origin of the Covid-19 virus is still unclear: a cave, the forest...</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/LWnztQq-b8E">Michal Ico/Unsplash</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>In the space of a few weeks, we have all learned a lot about COVID-19 and the virus that causes it: SARS-CoV-2. But there have also been a lot of rumours. And while the number of scientific articles on this virus is increasing, there are still many grey areas as to its origins.</p>
<p>In which animal species did it occur? A bat, a pangolin or another wild species? Where does it come from? From a cave or a forest in the Chinese province of Hubei, or elsewhere?</p>
<p>In December 2019, 27 of the first 41 people hospitalised (66%) passed through a market located in the heart of Wuhan city in Hubei province. But, according to a <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30183-5/fulltext#%20">study conducted at Wuhan Hospital</a>, the very first human case identified did not frequent this market. Instead, <a href="https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.25731">a molecular dating estimate based on the SARS-CoV-2 genomic sequences</a> indicates an origin in November. This raises questions about the link between this COVID-19 epidemic and wildlife.</p>
<h2>Genomic data</h2>
<p>The <a href="https://www.nature.com/articles/s41586-020-2008-3">SARS-CoV-2 genome</a> was rapidly sequenced by Chinese researchers. It is an <a href="https://www.britannica.com/science/RNA">RNA</a> molecule of about 30,000 bases containing 15 genes, including the S gene which codes for a protein located on the surface of the viral envelope (for comparison, our genome is in the form of a double helix of DNA about 3 billion bases in size and contains about 30,000 genes).</p>
<p>Comparative <a href="https://www.nature.com/articles/s41586-020-2008-3">genomic analyses</a> have shown that SARS-CoV-2 belongs to the group of <em>Betacoronaviruses</em> and that it is very close to <a href="https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome">SARS-CoV</a>, responsible for an epidemic of acute pneumonia which appeared in November 2002 in the Chinese province of Guangdong and then spread to 29 countries in 2003. A total of 8,098 cases were recorded, including 774 deaths. It is known that bats of the genus <em>Rhinolophus</em> (potentially several cave species) were the <a href="https://science.sciencemag.org/content/310/5748/676.pdf-extract">reservoir of this virus</a> and that a small carnivore, the palm civet (<em>Paguma larvata</em>), may have served as an <a href="https://www.nature.com/articles/nm.3985">intermediate host</a> between bats and the first human cases.</p>
<p>Since then, many <em>Betacoronaviruses</em> have been discovered, mainly in bats, but also in humans. For example, RaTG13, isolated from a bat of the species <em>Rhinolophus affinis</em> collected in China’s Yunan Province, has recently been described as very similar to SARS-CoV-2, with <a href="https://www.nature.com/articles/s41586-020-2012-7">genome sequences identical to 96%</a>. These results indicate that bats, and in particular species of the genus <em>Rhinolophus</em>, constitute the reservoir of the SARS-CoV and SARS-CoV-2 viruses.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/321013/original/file-20200317-60915-28xqp7.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/321013/original/file-20200317-60915-28xqp7.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=586&fit=crop&dpr=1 600w, https://images.theconversation.com/files/321013/original/file-20200317-60915-28xqp7.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=586&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/321013/original/file-20200317-60915-28xqp7.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=586&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/321013/original/file-20200317-60915-28xqp7.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=736&fit=crop&dpr=1 754w, https://images.theconversation.com/files/321013/original/file-20200317-60915-28xqp7.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=736&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/321013/original/file-20200317-60915-28xqp7.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=736&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Bat, <em>Rhinolophus affinis</em>.</span>
<span class="attribution"><span class="source">Alexandre Hassanin</span>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>But how do you define a reservoir? A reservoir is one or several animal species that are not or not very sensitive to the virus, which will naturally host one or several viruses. The absence of symptoms of the disease is explained by the effectiveness of their immune system, which allows them to fight against too much viral proliferation.</p>
<h2>Recombination mechanism</h2>
<p>On February 7, 2020, we learned that a virus even closer to SARS-CoV-2 had been discovered in pangolin. With 99% of <a href="https://www.nature.com/articles/d41586-020-00364-2">genomic concordance reported</a>, this suggested a more likely reservoir than bats. However, a <a href="https://www.biorxiv.org/content/10.1101/2020.02.17.951335v1">recent study under review </a> shows that the genome of the coronavirus isolated from the Malaysian pangolin (<em>Manis javanica</em>) is less similar to SARS-Cov-2, with only 90% of genomic concordance. This would indicate that the virus isolated in the pangolin is not responsible for the COVID-19 epidemic currently raging. </p>
<p>However, the coronavirus isolated from pangolin is similar at 99% in a specific region of the S protein, which corresponds to the 74 amino acids involved in the ACE (Angiotensin Converting Enzyme 2) receptor binding domain, the one that allows the virus to enter human cells to infect them. By contrast, the virus RaTG13 isolated from bat <em>R. affinis</em> is highly divergent in this specific region (only 77 % of similarity). This means that the coronavirus isolated from pangolin is capable of entering human cells whereas the one isolated from bat <em>R. affinis</em> is not. </p>
<p>In addition, these genomic comparisons suggest that the SARS-Cov-2 virus is the result of a recombination between two different viruses, one close to RaTG13 and the other closer to the pangolin virus. In other words, it is a chimera between two pre-existing viruses.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/321295/original/file-20200318-37382-1asjmm0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/321295/original/file-20200318-37382-1asjmm0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/321295/original/file-20200318-37382-1asjmm0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/321295/original/file-20200318-37382-1asjmm0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/321295/original/file-20200318-37382-1asjmm0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/321295/original/file-20200318-37382-1asjmm0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/321295/original/file-20200318-37382-1asjmm0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A coronavirus from the pangolin could be one of the sources for COVID-19.</span>
<span class="attribution"><a class="source" href="https://flickr.com/photos/wildlifealliance/9449651631/in/photolist-fp2Wd8-fp2VPr-dvdFMe-WuPH93-fayKr-2fu82Xk-XwNXdj-fp2Wo4-2417s1k-bjPb7R-5rdv65-4FJyvL-fPQBEB-JeETqX-ENZk8a-aeF2U-fPPZVg-bisnrv-bzdfNF-bmdsZc-brcacR-aJL6Xt-borQcx-2gF5mH8-2h6UBJN-2hu8phU-2huxjLS-fp2W7r-fphc71-bomDhx-byaRGB-bj7msn-bmduig-fphbYU-4Dyku-fp2VT8-fp2VFF-fp2War-KCV1Hw-fp2VHr-fp2VAZ-bF1ERj-6GE2wq-bLwNde-6675ZU-PbrBAo-anqs2u-anqp6q-g8QZ9K-9xiPdG">Wildlife Alliance/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>This recombination mechanism had <a href="https://jvi.asm.org/content/84/7/3134">already been described</a> in coronaviruses, in particular to explain the origin of SARS-CoV. It is important to know that recombination results in a new virus potentially capable of infecting a new host species. For recombination to occur, the two divergent viruses must have infected the same organism simultaneously.</p>
<p>Two questions remain unanswered: in which organism did this recombination occur? (a bat, a pangolin or another species?) And above all, under what conditions did this recombination take place?</p><img src="https://counter.theconversation.com/content/134059/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Alexandre Hassanin ne travaille pas, ne conseille pas, ne possède pas de parts, ne reçoit pas de fonds d'une organisation qui pourrait tirer profit de cet article, et n'a déclaré aucune autre affiliation que son organisme de recherche.</span></em></p>The SARS-CoV-2 virus responsible for the COVID-19 pandemic is undergoing extensive genetic analysis around the world to understand its origin and evolution.Alexandre Hassanin, Maître de Conférences (HDR) à Sorbonne Université, ISYEB - Institut de Systématique, Evolution, Biodiversité (CNRS, MNHN, SU, EPHE, UA), Muséum national d’histoire naturelle (MNHN)Licensed as Creative Commons – attribution, no derivatives.