tag:theconversation.com,2011:/us/topics/antibodies-1911/articlesAntibodies – The Conversation2024-03-17T08:37:05Ztag:theconversation.com,2011:article/2244112024-03-17T08:37:05Z2024-03-17T08:37:05ZSnakebites: we thought we’d created a winning new antivenom but then it flopped. Why that turned out to be a good thing<figure><img src="https://images.theconversation.com/files/579144/original/file-20240301-30-2x5qov.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A _Bothrops asper_ is prepared for its venom to be milked to use in making antivenom.</span> <span class="attribution"><span class="source">Jon G. Fuller/VWPics/Universal Images Group</span></span></figcaption></figure><p>Snakebites kill <a href="https://www.nature.com/articles/nrdp201763">over 100,000 people each year</a>, and hundreds of thousands of survivors are left with long-term disabilities such as amputations.</p>
<p>Africa, Asia and Latin America are <a href="https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0009073">the regions most heavily affected</a>. The most venomous snakes in Africa are the <a href="https://theconversation.com/why-knowing-what-black-mamba-venom-does-to-the-human-body-is-crucial-121386">black mamba</a>, cobras and saw-scaled and carpet vipers. In Asia, the Indian cobra, Russel’s viper, saw-scaled viper and common krait are the most venomous.</p>
<p>In the Central America and northern South America regions, the <a href="https://www.britannica.com/animal/viper-snake">venomous pit viper</a> <em>Bothrops asper</em> <a href="https://pubmed.ncbi.nlm.nih.gov/22146491/">is responsible for most of the fatal and harmful bites</a>.</p>
<p>We are venom and antivenom specialists who spent four years developing a therapeutic antibody to mitigate the effects of the pit viper’s bites. We were certain that we’d met all the standards for an effective, safe and efficacious antivenom. But, at the last hurdle, <a href="https://www.nature.com/articles/s41467-023-42624-5">we realised</a> the antibody didn’t neutralise the snake’s toxins: it enhanced them, worsening the venom’s effects.</p>
<p>Initially this was, of course, very disappointing. But it was also a valuable lesson. By reporting this new way that future antivenoms can fail, we have highlighted a problem with the <a href="https://iris.who.int/bitstream/handle/10665/255657/9789241210133-eng.pdf#page=217">current recommendations for testing antivenoms</a> that was hidden until now.</p>
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Read more:
<a href="https://theconversation.com/mozambique-had-no-data-about-snakebites-our-new-study-filled-the-gap-and-the-results-are-scary-192106">Mozambique had no data about snakebites. Our new study filled the gap -- and the results are scary</a>
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<p>Our lesson is likely to have a much larger impact on the development of snakebite treatments than if the antibody had been a success, because the discovery will help antivenom researchers focus their efforts so they don’t fail at the last hurdle as we did. </p>
<h2>Developing our antivenom</h2>
<p>A large percentage of <em>B. asper’s</em> venom consists of potent muscle-damaging molecules called phospholipases A₂ (PLA₂s) and PLA₂-like toxins. These have <a href="https://pubmed.ncbi.nlm.nih.gov/36632869/">severe effects</a>, often leading to irreversible damage and disability. </p>
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Read more:
<a href="https://theconversation.com/finally-snakebite-is-getting-more-attention-as-a-tropical-health-issue-131016">Finally, snakebite is getting more attention as a tropical health issue</a>
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<p>Myotoxin II, a formidable PLA₂-like toxin within <em>B. asper’s</em> arsenal, is particularly significant. The precise mechanisms that underlie myotoxin II’s action aren’t fully understood. It is known to exert its effects locally, binding to muscle fibres and triggering muscle damage. This localised action poses a challenge for traditional antivenom treatments.</p>
<p>We have attempted to develop human monoclonal antibodies that target and neutralise this membrane-disrupting myotoxin II. For the first four years of our research project, the antibodies we discovered kept showing impressive effects in neutralising myotoxin II. </p>
<p>Even when tested in living mice, using the current gold standard for antivenom testing, the antibodies continuously showed impressive neutralisation. However, for our most promising antibody, we wanted to go a step further and carry out an experiment that more closely resembled a human envenoming, in which the antibody is injected after injection of the venom. </p>
<p>The results of this additional experiment were equal parts disappointing and surprising. Our most promising antibody in this last experiment changed its toxin-neutralising effect to toxin-enhancing instead, as we’ve <a href="https://www.nature.com/articles/s41467-023-42624-5">documented in a research paper</a>. </p>
<p>The results were so surprising that we decided to immediately repeat the experiment. We thought something must’ve gone wrong, like the antibody or other materials having gone bad. However, the results remained the same.</p>
<p>This curious phenomenon, which we termed “antibody-dependent enhancement of toxicity”, represents a novel discovery in toxin immunology. Similar phenomena have been observed in other contexts, such as with <a href="https://pubmed.ncbi.nlm.nih.gov/19307220/">poisonous mushrooms</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/3188055/">bacterial toxins</a>, but never before with toxins from the animal kingdom. </p>
<p>Additional studies will be needed to fully understand what causes antibody-dependent enhancement of toxicity. </p>
<h2>Reassessing preclinical models</h2>
<p>There’s good news about this failure. It’s a chance for antivenom researchers all over the world, no matter what snake species they’re working with, to reassess their preclinical models (like the <a href="https://iris.who.int/bitstream/handle/10665/255657/9789241210133-eng.pdf#page=217">current gold standard model</a>).</p>
<p>We also think antivenom researchers should consider incorporating more sophisticated experiments like the ones used in our study, which more closely resemble a real-life envenoming case. By doing so, the antivenom research community can streamline the drug discovery process. This will expedite the identification and development of safer and more effective snakebite treatments.</p><img src="https://counter.theconversation.com/content/224411/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andreas Hougaard Laustsen receives funding from Wellcome, the European Research Council, the Villum Foundation, and Innovation Fund Denmark. </span></em></p><p class="fine-print"><em><span>Bruno Lomonte receives funding from Vicerrectoría de Investigación, Universidad de Costa Rica, Costa Rica.</span></em></p><p class="fine-print"><em><span>Julián Fernández receives funding from Vicerrectoría de Investigación, Universidad de Costa Rica, Costa Rica. </span></em></p><p class="fine-print"><em><span>Christoffer Vinther Sørensen 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>By reporting this new way that future antivenoms can fail, the research has highlighted a problem with current antivenom testing recommendations.Christoffer Vinther Sørensen, Postdoctoral researcher, Department of Biotechnology and Biomedicine, Center for Antibody Technologies, Technical University of DenmarkAndreas Hougaard Laustsen, Professor & Center Director at the Department of Biotechnology and Biomedicine, Technical University of DenmarkBruno Lomonte, Emeritus Professor, Instituto Clodomiro Picado, Universidad de Costa RicaJulián Fernández, Researcher at Instituto Clodomiro Picado, Universidad de Costa RicaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2250912024-03-07T05:30:28Z2024-03-07T05:30:28ZBabies in WA will soon be immunised against RSV – but not with a vaccine<figure><img src="https://images.theconversation.com/files/580326/original/file-20240307-22-um2200.jpeg?ixlib=rb-1.1.0&rect=142%2C194%2C8471%2C5548&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pediatrician-doctor-examines-newborn-stethoscope-female-2278794293">Dragana Gordic/Shutterstock</a></span></figcaption></figure><p>This week, Western Australia <a href="https://www.wa.gov.au/government/media-statements/Cook-Labor-Government/Western-Australian-children-first-to-access-protection-from-RSV-20240305">announced</a> a state government-funded immunisation program against respiratory syncytial virus (RSV). It’s the first Australian state or territory to do so. </p>
<p>All babies under eight months old and those aged eight to 19 months at increased risk of severe RSV infection will be eligible for the immunisation in WA this year.</p>
<p>RSV can cause serious illness in children, and news headlines have welcomed WA’s impending rollout of “<a href="https://www.dailytelegraph.com.au/lifestyle/health/wa-to-become-the-first-state-offering-rsv-vaccinations-for-babies-in-australia/news-story/ffc9cac0ff8ff9ea98a958ee83ef6de7">vaccinations</a>” against the virus.</p>
<p>But this immunisation differs from other <a href="https://www.health.gov.au/resources/publications/national-immunisation-program-schedule?language=en">routine childhood vaccines</a>.</p>
<h2>Why is RSV important?</h2>
<p>RSV is the <a href="https://pubmed.ncbi.nlm.nih.gov/35636455/">most common cause</a> of respiratory infection in young children. By the age of two, almost all children show <a href="https://www.nature.com/articles/s41598-021-88524-w">evidence</a> they’ve been exposed to the virus.</p>
<p>Estimates suggest <a href="https://pubmed.ncbi.nlm.nih.gov/35013434/">2-3%</a> of infants are hospitalised with RSV with infection involving the airways and lungs. Infants under three months are at <a href="https://pubmed.ncbi.nlm.nih.gov/32031631/">highest risk</a>. RSV can also have long-lasting effects on children – there’s a well-established link between RSV and subsequent <a href="https://pubmed.ncbi.nlm.nih.gov/31370064/">wheezing illnesses</a> and asthma. </p>
<p>RSV can also be a problem for the <a href="https://theconversation.com/an-rsv-vaccine-has-been-approved-for-people-over-60-but-what-about-young-children-221311">elderly</a> and people with underlying health conditions such as those with weakened immune systems. </p>
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Read more:
<a href="https://theconversation.com/an-rsv-vaccine-has-been-approved-for-people-over-60-but-what-about-young-children-221311">An RSV vaccine has been approved for people over 60. But what about young children?</a>
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<h2>How do we protect children against RSV?</h2>
<p>Antibodies are a key part of the immune system that protect people against many viral infections, including RSV. They’re usually generated in response to infection or a vaccine, and work by attaching to proteins on the surface of RSV, therefore preventing the virus from invading the cells that line the airways and lungs. </p>
<p>The problem in newborn babies (who are at the highest risk of severe RSV infection) is that previous vaccines have not generated sufficient antibodies to provide protection.</p>
<p>So, two strategies have been developed to protect young children against RSV. These strategies are both referred to as <a href="https://immunisationhandbook.health.gov.au/contents/fundamentals-of-immunisation#passive-immunisation">passive immunisation</a>, because children receive protective antibodies from outside the body. This is different to active immunisation where we give a child a vaccine so they can generate their own antibodies.</p>
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<img alt="A pregnant woman sits on a couch with her daughter, with a laptop on her lap." src="https://images.theconversation.com/files/580324/original/file-20240307-18-9hxern.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/580324/original/file-20240307-18-9hxern.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/580324/original/file-20240307-18-9hxern.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/580324/original/file-20240307-18-9hxern.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/580324/original/file-20240307-18-9hxern.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/580324/original/file-20240307-18-9hxern.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/580324/original/file-20240307-18-9hxern.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">
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<span class="caption">Vaccinating pregnant women is one way to protect babies against RSV.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pregnant-black-woman-working-on-laptop-1817195420">Ground Picture/Shutterstock</a></span>
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<h2>Vaccination in pregnancy</h2>
<p>One way to deliver passive immunity to young infants is by vaccinating their mothers during pregnancy. Maternal immunisation has been shown to be effective at protecting infants from other infections, including <a href="https://pubmed.ncbi.nlm.nih.gov/34446538/">influenza, whooping cough</a> (pertussis), <a href="https://www.who.int/initiatives/maternal-and-neonatal-tetanus-elimination-(mnte)/the-strategies">tetanus</a> and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9974935/">COVID</a>. </p>
<p>By delivering a single RSV vaccine to pregnant women, antibodies are generated by the mother and transported across the placenta, providing passive immunity and protection to the baby for around the first six months of life. In a <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2216480">clinical trial</a>, giving an RSV vaccine in late pregnancy reduced RSV in young infants by approximately 70%. But RSV vaccines for pregnant women are <a href="https://ncirs.org.au/ncirs-fact-sheets-faqs-and-other-resources/respiratory-syncytial-virus-rsv-frequently-asked#:%7E:text=The%20current%20maternal%20RSV%20vaccine,not%20currently%20available%20in%20Australia">not yet available</a> in Australia.</p>
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Read more:
<a href="https://theconversation.com/rsv-is-everywhere-right-now-what-parents-need-to-know-about-respiratory-syncytial-virus-208855">RSV is everywhere right now. What parents need to know about respiratory syncytial virus</a>
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<h2>What are monoclonal antibodies?</h2>
<p>The other passive immunisation strategy relies on manufactured long-acting antibodies (known as “monoclonal antibodies”), which can be delivered by injection to young children. </p>
<p>This is what will be offered in WA. Nirsevimab (also known as Beyfortus) is a long-acting antibody that Australia’s Therapeutic Goods Administration (TGA) <a href="https://www.tga.gov.au/resources/auspmd/beyfortus">approved</a> in November 2023. </p>
<p>Nirsevimab binds specifically to RSV and remains in the body for several months after injection. In a key <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2110275">clinical trial</a> nirsevimab was shown to reduce RSV infections by about 75% for up to five months. </p>
<p>Several European countries have recently implemented infant programs with nirsevimab and are <a href="https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2024.29.6.2400046">reporting</a> significantly lower RSV hospitalisation rates in babies. </p>
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<img alt="A baby's leg with a bandaid on it." src="https://images.theconversation.com/files/580323/original/file-20240307-28-tdjxvt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/580323/original/file-20240307-28-tdjxvt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/580323/original/file-20240307-28-tdjxvt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/580323/original/file-20240307-28-tdjxvt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/580323/original/file-20240307-28-tdjxvt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/580323/original/file-20240307-28-tdjxvt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/580323/original/file-20240307-28-tdjxvt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&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">For babies, the injection will normally be given in the thigh.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/bandaid-on-baby-after-shot-leg-774258127">Allen Mercer/Shutterstock</a></span>
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<p>Antibody therapies in various forms have been used for more than a century for the prevention and treatment of a range of conditions, dating from “<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898362/">serotherapy</a>” for tetanus, diphtheria and snake bite in the late 1800s.</p>
<p>Licensed antibody products are rigorously tested in clinical trials and through post-marketing surveillance to ensure their safety. </p>
<p>For <a href="https://pubmed.ncbi.nlm.nih.gov/36634694/">nirsevimab</a> specifically, the <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2110275">clinical trial</a> mentioned above included over 1,400 infants. Adverse events were reported at similar rates in the nirsevimab and placebo groups, and no serious adverse events relating to treatment were reported. No significant safety concerns have been identified in the real-world rollout in the northern hemisphere either.</p>
<h2>When does RSV occur?</h2>
<p>RSV <a href="https://pubmed.ncbi.nlm.nih.gov/35083489/">usually takes hold</a> just before the flu season in southern states, and circulates year-round in tropical areas. While influenza almost disappeared during the <a href="https://pubmed.ncbi.nlm.nih.gov/32986804/">COVID</a> pandemic, there were <a href="https://www.nature.com/articles/s41467-022-30485-3">ongoing cases</a> of RSV, albeit with a disruption to the normal seasonal pattern. </p>
<p>Since 2022, RSV has resumed its normal seasonal pattern. The WA government says the immunisations will be available <a href="https://www.wa.gov.au/government/media-statements/Cook-Labor-Government/Western-Australian-children-first-to-access-protection-from-RSV-20240305">from April</a>, which is timely in anticipation of the 2024 season.</p>
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Read more:
<a href="https://theconversation.com/rsv-is-a-common-winter-illness-in-children-why-did-it-see-a-summer-surge-in-australia-this-year-156492">RSV is a common winter illness in children. Why did it see a summer surge in Australia this year?</a>
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<h2>What about other states and territories?</h2>
<p>Free access to an immunisation against RSV should significantly benefit young children and families in WA, keeping children out of hospital this winter. </p>
<p>Whether other states will follow WA’s lead is uncertain at this stage, and we don’t yet know whether nirsevimab will in time become part of the <a href="https://www.health.gov.au/our-work/national-immunisation-program">National Immunisation Program</a>, meaning it would be available for free nation-wide. </p>
<p>Ensuring equitable access, particularly for those at greatest risk of severe RSV infection, must be prioritised to ensure maximum benefit for all children and families.</p>
<p>Nirsevimab is likely to be the first of many tools to prevent RSV in children. A maternal RSV vaccine is currently under assessment <a href="https://ncirs.org.au/ncirs-fact-sheets-faqs-and-other-resources/respiratory-syncytial-virus-rsv-frequently-asked#:%7E:text=The%20current%20maternal%20RSV%20vaccine,not%20currently%20available%20in%20Australia.">by the TGA</a> and Pharmaceutical Benefits Advisory Committee (PBAC). A vaccine for older Australians, <a href="https://www.tga.gov.au/resources/auspmd/arexvy">Arexvy</a>, is registered and is also being assessed by the <a href="https://ncirs.org.au/ncirs-fact-sheets-faqs-and-other-resources/respiratory-syncytial-virus-rsv-frequently-asked#:%7E:text=The%20current%20maternal%20RSV%20vaccine,not%20currently%20available%20in%20Australia">PBAC</a>, with additional vaccines expected to be available in the future. </p>
<p>These developments highlight the future of RSV prevention and also the significant potential for monoclonal antibodies to play a greater role in preventing infections as part of public health programs.</p><img src="https://counter.theconversation.com/content/225091/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Chris Blyth receives funding from the Australian Department of Health and Aged Care, National Health and Medical Research Council and the Perron Trust for RSV-related research. He has previously been a member of the Australian Technical Advisory Group on Immunisation.</span></em></p><p class="fine-print"><em><span>Allen Cheng receives funding from the Australian Department of Health and Aged Care and the National Health and Medical Research Council. He is a member of the Australian Technical Advisory Group on Immunisation.</span></em></p>The RSV shot children in WA will get is a monoclonal antibody. Here’s what that means.Christopher Blyth, Paediatrician, Infectious Diseases Physician and Clinical Microbiologist, Telethon Kids Institute, The University of Western AustraliaAllen Cheng, Professor of Infectious Diseases, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2246642024-03-05T16:05:39Z2024-03-05T16:05:39ZWe’re a step closer to having a universal antivenom for snake bites – new study<p>If you’re bitten by a venomous snake, the medicine you need is antivenom. Unfortunately, antivenoms are species specific, meaning you need to have the right antivenom for the snake that bit you. Most of the time, people have no idea what species of snake has bitten them. And for some snakes, antivenoms are simply not available. </p>
<p><a href="https://www.science.org/doi/full/10.1126/scitranslmed.adk1867">New research</a> my colleagues and I conducted provides a significant step forward in enabling the development of an antivenom that will neutralise the effects of venom from any venomous snake: a so-called “universal antivenom”. </p>
<p>In our paper, published in Science Translational Medicine, we describe the discovery and development of a laboratory-made antibody that can neutralise a neurotoxin (a toxin that acts on the nervous system) found in the venom of many types of snake around the world.</p>
<p>Venomous snakes kill as many as <a href="https://www.who.int/news-room/fact-sheets/detail/snakebite-envenoming#:%7E:text=An%20estimated%205.4%20million%20people,are%20caused%20by%20snakebites%20annually.">138,000 people</a> each year, with many more survivors suffering from life-changing injuries and mental trauma. Children and farmers make up the bulk of the victims. </p>
<p>The active ingredients in antivenoms are anti-toxin antibodies. They are made by injecting horses with small quantities of snake venom and harvesting the antibodies. This method of making antivenom has remained the same for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9634357/#b0005">over a century</a> – and it has substantial drawbacks. </p>
<p>In addition to antivenoms being species specific, they are also not very potent, so you need lots of antivenom to neutralise the venom from a bite. </p>
<p>Also, because antivenoms are made in horses, you are highly likely to experience severe side-effects when administered, as your body’s immune system will detect and react to the “foreign” horse antibodies circulating in your bloodstream. </p>
<p>Antibodies that are made in the laboratory using genetically modified cells are routinely used in humans to treat <a href="https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/monoclonal-antibodies#how-do-monoclonal-antibodies-work-against-cancer">cancers</a> and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775886/">immune disorders</a>. A long-held hope is that the technology used to produce these antibodies can be used to make antivenom and eventually replace traditional antivenoms, thereby solving many of the issues current antivenoms face.</p>
<p>The antibodies in lab-made antivenoms could be “humanised”, a process that tricks your immune system into thinking foreign antibodies are your own antibodies. This might reduce the rate of severe side-effects that are commonly encountered with horse-derived antivenoms. </p>
<h2>Paralysis and death avoided</h2>
<p>One of the most important families of toxins in snake venoms are neurotoxins. </p>
<p>These toxins prevent nerve signals from travelling from your brain to your muscles, paralysing them. This includes paralysing the muscles that inflate and deflate your lungs, so prey and human victims quickly stop breathing and die. </p>
<p>These neurotoxins are in the venoms of some of the world’s most deadly snakes, including the African black mamba, the Asian monocled cobra and king Cobra, and the deadly kraits of the Indian subcontinent. </p>
<p>In our research, we describe the discovery and development of a lab-made humanised antibody that can neutralise key venom neurotoxins from diverse snakes from diverse regions. </p>
<p>The lab-made antibody is called 95Mat5 and was discovered after examining 50 billion unique antibodies to find ones capable of not only recognising the neurotoxin in the venoms of many species but also able to neutralise its deadly effects. </p>
<p>When injected into mice that had received lethal doses of venom, 95Mat5 was able to prevent paralysis and death in all the venoms tested. </p>
<p>These results are particularly exciting as they show that generating lab-made antibodies that can broadly neutralise the effects of venoms from many species is feasible, making the development of a universal antivenom a realistic prospect. </p>
<p>However, 95Mat5 is a single antibody that only works against neurotoxins. As we said earlier, to make a universal antivenom you will require a handful of antibodies. This is because snake venoms don’t just consist of neurotoxins. </p>
<p>Some snake venoms have haemotoxins, which make you bleed, and some have cytotoxins, which destroy skin and bone. To create a universal antivenom, capable of treating any bite from any snake, we still need to identify additional antibodies that can broadly and potently neutralise the other toxin types, in the same manner as 95Mat5. </p>
<p>We hope that once identified, these antibodies can be mixed with 95Mat5 to make an antivenom that is capable of neutralising the venom of any snake, no matter what toxin types it possesses. </p>
<figure class="align-center ">
<img alt="Person milking a snake" src="https://images.theconversation.com/files/579412/original/file-20240303-24-3b1s50.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/579412/original/file-20240303-24-3b1s50.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/579412/original/file-20240303-24-3b1s50.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/579412/original/file-20240303-24-3b1s50.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/579412/original/file-20240303-24-3b1s50.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/579412/original/file-20240303-24-3b1s50.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/579412/original/file-20240303-24-3b1s50.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 universal antivenom would make milking snakes a thing of the past.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/milking-cobra-snake-venom-thailand-1580384338">Ali _Cobanoglu/Shutterstock</a></span>
</figcaption>
</figure>
<p>The requirement for antibodies for other venom toxins and also the need to ensure any new lab-made antivenom for effectiveness and safety in human trials means it will still take many years for a universal antivenom to become available to snakebite victims. </p>
<p>Other hurdles need to be overcome. These new antivenoms will probably need to be stored in a fridge to prevent loss of effectiveness, so it will need to be shown that they can be distributed in often warm regions of the world that don’t have reliable electricity for refrigeration. </p>
<p>Lab-made antibodies are some of the most expensive drugs on the planet. While we are hopeful, it remains to be seen if lab-made antivenoms will be affordable for most snakebite victims, who are usually some of the poorest people in the world.</p><img src="https://counter.theconversation.com/content/224664/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Stuart Ainsworth receives funding from United Kingdom Research and Innovation and the National Centre for the Replacement, Reduction and Refinement of Animals in Research. </span></em></p><p class="fine-print"><em><span>Camille Abada receives funding from the Medical Research Council, UK.</span></em></p>We’re still using century-old technology to make snake antivenom. A method fit for the 21st century is on the horizon.Stuart Ainsworth, Senior Lecture and UKRI Future Leader Fellow, University of LiverpoolCamille Abada, PhD Candidate, Antibodies, Liverpool School of Tropical MedicineLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2161392023-11-21T13:26:58Z2023-11-21T13:26:58ZHow do viruses get into cells? Their infection tactics determine whether they can jump species or set off a pandemic<figure><img src="https://images.theconversation.com/files/560185/original/file-20231117-23-zg89fr.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2309%2C1299&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Surface proteins on a virus enable it to attach to and get inside a cell to start replicating.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/new-omicron-sub-variant-bq-1-1-royalty-free-image/1435658319">koto_feja/E+ via Getty Images</a></span></figcaption></figure><p>COVID-19, flu, mpox, noroviral diarrhea: How do the viruses that cause these diseases actually infect you?</p>
<p>Viruses <a href="https://www.khanacademy.org/science/biology/biology-of-viruses/virus-biology/a/intro-to-viruses">cannot replicate on their own</a>, so they must infect cells in your body to make more copies of themselves. The life cycle of a virus can thus be roughly described as: get inside a cell, make more virus, get out, repeat. </p>
<p>Getting inside a cell, or <a href="https://doi.org/10.1016/j.jmb.2018.03.034">viral entry</a>, is the part of the cycle that most vaccines target, as well as a key barrier for viruses jumping from one species to another. <a href="https://scholar.google.com/citations?user=OQ7vzu0AAAAJ&hl=en">My lab</a> and many others study this process to better anticipate and combat emerging viruses.</p>
<h2>How viruses enter cells</h2>
<p>Different viruses travel into the body in <a href="https://www.oregon.gov/oha/ph/diseasesconditions/communicabledisease/pages/transmission.aspx">various ways</a> – via airborne droplets, on food, through contact with mucous membranes or through injection. They typically first infect host cells near their site of entry – the cells lining the respiratory tract for most airborne viruses – then either remain there or spread throughout the body.</p>
<p>Viruses <a href="https://doi.org/10.1016/j.jmb.2018.06.024">recognize specific proteins or sugars</a> on host cells and stick to them. Each virus gets only one shot at putting its genome inside a cell – if their entry machinery misfires, they risk becoming inactivated. So they <a href="https://doi.org/10.1016/j.virol.2015.02.037">use several mechanisms</a> to prevent triggering entry prematurely.</p>
<p>After the virus binds to the cell, specific molecules on the cell’s surface or within the cell’s recycling machinery <a href="https://doi.org/10.1111/tra.12389">activate viral coat proteins for entry</a>. An example is the SARS-CoV-2 spike that COVID-19 vaccines target. These proteins need to modify the cell membrane to allow the viral genome to get through without killing the cell in the process. Different viruses use different tricks for this, but most work like cellular secretion – how cells release materials into their environment – in reverse. Specialized viral proteins help <a href="https://doi.org/10.1146/annurev-virology-111821-093413">merge the membranes of the virus and the cell</a> together and release the viral core into the interior of the cell.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/i__QSjC-pt0?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">This animation depicts HIV fusing its membrane with a cell in order to release its contents inside.</span></figcaption>
</figure>
<p>At this point, the viral genome can enter the cell and <a href="https://doi.org/10.1016%2FB978-0-12-800947-5.00004-1">start replicating</a>. Some viruses use only the cell’s machinery to replicate, while others carry along portions of their own replication machinery and borrow some parts from the cell. After replicating their genomes, viruses assemble the components required to make new viruses.</p>
<p>Two central questions scientists are studying about viral entry are how your body’s defenses can disrupt it and what determines whether a virus from other species can infect people.</p>
<h2>Immune defenses against viruses</h2>
<p>Your body has a multilayered defense system against viral threats. But the part of your immune system called the <a href="https://doi.org/10.1016/j.jaci.2009.12.980">antibody response</a> is generally thought to be most effective at <a href="https://doi.org/10.1016/j.immuni.2022.10.017">sterilizing immunity</a> – preventing an infection from taking hold in the first place as opposed to just limiting its scope and severity. </p>
<p>For many viruses, antibodies target the part of the virus that binds to cells. This is the case not just for current COVID-19 vaccines but also the majority of immunity against influenza, whether from vaccines or from prior infection. </p>
<p>However, some antibodies target the entry machinery instead: Rather than preventing the virus from sticking, they prevent the virus from working altogether. Such antibodies are often harder for the viruses to escape from but are difficult to reproduce with vaccines. For that reason, developing antibodies that inhibit cell entry has the been the goal of many <a href="https://doi.org/10.1016/j.coviro.2016.02.002">next-generation vaccine efforts</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of the mechanisms of four classes of HIV antivirals" src="https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=496&fit=crop&dpr=1 600w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=496&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=496&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=623&fit=crop&dpr=1 754w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=623&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/551885/original/file-20231003-25-cv0pnn.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=623&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 diagram shows how four different classes of antiviral drugs inhibit HIV. One stops viruses from entering cells, and three inhibit different viral enzymes.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:HIV-drug-classes.svg">Thomas Splettstoesser/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>Species-hopping and pandemics</h2>
<p>The other key question researchers are asking about viral entry is <a href="https://www.cdc.gov/flu/pandemic-resources/national-strategy/risk-assessment.htm">how to tell when</a> a virus from another species poses a threat to people. This is particularly important because many viruses are first identified in animals such as bats, birds and pigs before they spread to humans, but it’s unclear which ones may cause a pandemic.</p>
<p>The part of viruses that stick to human cells varies the most across species, while the part that gets the virus into cells <a href="https://doi.org/10.1016/bs.aivir.2016.08.004">tends to stay mostly the same</a>. Many researchers have thought that viruses changing in ways that bind better to human cells, like influenza viruses that bind to cells in the nose and throat, are some of the most important warning signs for pandemic risk. </p>
<p>However, coronaviruses – the family of viruses containing SARS-CoV-2 – are prompting re-examination of that idea. This is because several animal coronaviruses can actually <a href="https://doi.org/10.1038/s41564-020-0688-y">bind to human cells</a>, but only a few seem to be able to transmit well between people.</p>
<p>Only time will tell whether researchers need to broaden their pandemic prevention horizons or if their current prioritization of risky viruses is correct. The one grim reality of pandemic research, like earthquake research, is that there will always be another one – we just don’t know when or where, and we <a href="https://www.niaid.nih.gov/sites/default/files/pandemic-preparedness-plan.pdf">want to be ready</a>.</p><img src="https://counter.theconversation.com/content/216139/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Peter Kasson receives funding from the National Institutes of Health, the National Science Foundation, the Commonwealth Health Research Board, and the Knut and Alice Wallenberg Foundation. He is affiliated with the University of Virginia, Uppsala University, and Georgia Institute of Technology.</span></em></p>Viruses can get into cells in several ways. Figuring out how to stop them from entering in the first place is a key to developing better vaccines and stopping future pandemics.Peter Kasson, Professor of Molecular Physiology and Biomedical Engineering, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2085382023-09-21T21:27:36Z2023-09-21T21:27:36ZLyme disease: The pathogen’s cunning strategies for persistent infection offer clues for vaccine development<figure><img src="https://images.theconversation.com/files/547386/original/file-20230911-25-n5os9t.JPG?ixlib=rb-1.1.0&rect=65%2C23%2C1709%2C1158&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The black-legged tick is the vector that spreads Lyme disease. Its bite can infect humans with the Borrelia burgdorferi bacterium.</span> <span class="attribution"><span class="source">(Jim Gathany/CDC)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/lyme-disease-the-pathogens-cunning-strategies-for-persistent-infection-offer-clues-for-vaccine-development" width="100%" height="400"></iframe>
<p>Lyme disease is the leading <a href="https://www.who.int/news-room/fact-sheets/detail/vector-borne-diseases">vector-borne disease</a> — meaning diseases that are transmitted to humans from another organism like a tick or mosquito — in <a href="https://doi.org/10.1186/s12889-019-7069-6">North America and Europe</a>. </p>
<p><a href="https://doi.org/10.3201/eid2702.202731">New human cases are estimated</a> at over <a href="http://dx.doi.org/10.15585/mmwr.ss6622a1">400,000 in the United States each year</a>. Canada has experienced a drastic increase in human cases, <a href="https://www.canada.ca/en/public-health/services/diseases/lyme-disease/surveillance-lyme-disease.html#a5">from 266 cases in 2011 to 3,147 in 2021</a>, as the habitat of its vector, a tick, expands north. </p>
<p>The initial symptoms of human Lyme disease can be vague, such as fever, headache, fatigue and often rash. It is a potentially serious condition that can affect multiple systems in the body — including the heart, nervous system and joints — and can become a chronic illness.</p>
<p>Lyme disease is caused by a unique, spiral-shaped (spirochete) bacterium called <a href="https://doi.org/10.1099/00207713-34-4-496"><em>Borrelia burgdorferi</em></a>. <em>B. burgdorferi</em> cannot survive in the environment on its own. For <a href="https://doi.org/10.21775/cimb.042.473">survival and transmission</a>, it requires susceptible hosts (usually small mammals or birds) and a <a href="https://doi.org/10.1056/NEJM198303313081301">specific vector</a>: the black-legged tick, also called the deer tick.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=420&fit=crop&dpr=1 600w, https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=420&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=420&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=528&fit=crop&dpr=1 754w, https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=528&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/535388/original/file-20230703-257464-m0lz6y.png?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">Lyme disease infectious cycle: Adult ticks lay egg sacs that can hatch thousands of tick larvae. Larvae are not born with Borrelia burgdorferi but can acquire the bacterium when they feed on an infected host. After feeding, larvae molt to nymphs which must feed once to molt to adults. Female adult ticks also feed once before laying the egg sac. Nymphs and adult ticks can transmit B. burgdorferi to susceptible hosts while feeding.</span>
<span class="attribution"><span class="source">(BioRender)</span></span>
</figcaption>
</figure>
<h2>Evading the immune system</h2>
<p><em>B. burgdorferi</em> must survive extremely diverse conditions over the course of its transmission and infection cycle: from host to tick vector, and then into new hosts. </p>
<p>This bacterium senses and responds to its surroundings, most notably by <a href="https://doi.org/10.1128/iai.70.7.3382-3388.2002">modifying its appearance</a> by changing the <a href="https://doi.org/10.1073/pnas.92.7.2909" title="). _B. burgdorferi_ has over [50 surface-exposed proteins](https://doi.org/10.1128/jb.00658-16 "">proteins on its outer surface</a> to <a href="https://doi.org/10.1111/j.1574-695X.2012.00980.x">help it survive</a> in either <a href="https://doi.org/10.1038/s41467-023-35897-3">the tick</a> or the host.</p>
<p>When a tick infected by <em>B. burgdorferi</em> bites and feeds on a vertebrate host, it provides a signal for the bacteria to switch its proteins to those required to infect the host, and to begin migrating through the tick and into the bite site. This process takes between <a href="https://doi.org/10.4269/ajtmh.1995.53.397">36 and 72 hours</a>. </p>
<p>However, many of these proteins are recognized by the host as foreign, and the host’s immune system works to try to clear the infection. This includes a strong, antibody response targeted against <em>B. burgdorferi</em>. </p>
<p>Despite these immune responses, <em>B. burgdorferi</em> is able to cause long-term infections. In natural host reservoirs — the animals that the bacterium usually finds itself in via tick bites, such as small rodents — these infections do not cause diseases like those seen in humans and other <a href="https://doi.org/10.1016/j.idc.2007.12.013">non-natural reservoirs</a>. </p>
<p>In fact, the bacteria itself does not produce any products that would be <a href="https://doi.org/10.1016/j.cll.2015.07.004">toxic to its hosts</a>, either natural or non-natural. Yet chronic infection in humans can lead to <a href="https://doi.org/10.1038/nrdp.2016.90">Lyme neuroborreliosis, carditis and Lyme arthritis</a>.</p>
<figure class="align-center ">
<img alt="Bacteria that look like bright green and yellow squiggles against a dark green background" src="https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=612&fit=crop&dpr=1 600w, https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=612&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=612&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=770&fit=crop&dpr=1 754w, https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=770&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/548570/original/file-20230915-23-4ysjok.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=770&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Microscopic image of Lyme disease bacteria Borrelia burgdorferi. In this photo, immunofluorescent antibodies have been used to change the colour of spirochetes that express different outer surface proteins.</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>How then, are these bacteria able to cause such a devastating disease in humans and other animals, but not in their natural host reservoirs?</p>
<p>While there is still much to learn about <em>B. burgdorferi</em>, we know of several factors that play a role in the <a href="https://doi.org/10.1038/nrdp.2016.90">range of disease it causes</a>. These include:</p>
<ul>
<li>its genetic make-up, </li>
<li>its ability to access various tissues (such as the joints, heart and nervous system) due to its <a href="https://doi.org/10.1128/iai.01228-12">ability to move around (motility)</a>, and </li>
<li>the immune response of the host. </li>
</ul>
<p>Apart from motility, <em>B. burgdorferi</em> also protects itself from the strong <em>B. burgdorferi</em>-specific targeted antibody response of its host’s immune system by changing the appearance of the main outer surface protein expressed during persistent infection in a process called <a href="https://doi.org/10.1128/iai.66.8.3698-3704.1998">antigenic variation</a>.</p>
<h2>How Lyme disease is perpetuated</h2>
<p>In addition to antigenic variation, <em>B. burgdorferi</em> bacteria can also change their DNA by <a href="https://doi.org/10.1073/pnas.0402745101">exchanging genetic information, a process also known as gene transfer</a>. This process allows these bacteria to further alter their <a href="https://doi.org/10.1128/mbio.00153-10">appearance</a> <a href="https://doi.org/10.1534/genetics.111.130773">during infection</a> to avoid the host immune system.</p>
<p>This process works so well that these <em>B. burgdorferi</em> bacteria appear different enough to allow <a href="https://doi.org/10.7326/0003-4819-127-2-199707150-00006">re-infection</a> or even <a href="https://doi.org/10.1128/iai.01817-14">co-infection</a> (where multiple strains of B. burgdorferi infect a single host at the same time) of a vertebrate host, like a mouse or a human, despite the presence of specific antibodies to fight the bacterium.</p>
<p>In fact, in nature, the majority of host reservoirs and the ticks that carry the bacterium are infected with <a href="https://doi.org/10.1128/AEM.02296-15">multiple strains of <em>B. burgdorferi</em></a>. The ability of <em>B. burgdorferi</em> to reinfect and co-infect both ticks and hosts increases the spread of the bacteria in the environment as well as the chances that humans will encounter Lyme disease.</p>
<h2>Human cases of Lyme disease are increasing</h2>
<p>As a vector-borne pathogen, <em>B. burgdorferi</em> only infects individuals that are bitten by an infected tick. It is not transmitted from <a href="https://doi.org/10.1093/cid/ciz872">person to person</a>.</p>
<p>Environments that support black-legged/deer ticks are at risk of harbouring <em>B. burgdorferi</em>. In North America, these species of ticks are widely distributed throughout the eastern and midwestern United States. Recent <a href="https://doi.org/10.1093/jme/tjy104">geographic expansion</a> to the north is increasing the prevalence of Lyme disease <a href="https://doi.org/10.1503/cmaj.080148">in Canada</a>. </p>
<p>The increase of human Lyme disease cases highlights the failure of existing preventive strategies — such as minimizing exposure to tick habitats, performing diligent tick checks, and wearing suitable clothing when performing activities in known tick habitats — and emphasizes the need for an effective <a href="https://doi.org/10.21775/cimb.042.191">human vaccine</a>.</p>
<h2>A One Health approach</h2>
<p>At <a href="https://www.vido.org/">Vaccine and Infectious Disease Organization</a> at the University of Saskatchewan, we are taking a <a href="https://ipac-canada.org/one-health">One Health</a> approach by recognizing that human health is closely related to the health of animals and the shared environment. We are investigating the role of <em>B. burgdorferi</em>, ticks, and susceptible animals on the spread and survival of the Lyme disease bacterium. </p>
<p>It is important to mimic the natural infectious cycle as much as possible when identifying potential vaccine and drug targets. This is because the way host animals are infected (for example, artificial needle infection or natural tick bite) can produce drastic differences in the resulting infection. </p>
<p>Additionally, despite the prevalence of this disease, there are still many aspects of the infectious cycle that remain unknown due to the uniqueness of <em>B. burgdorferi</em> and a lack of knowledge about the tick vector. </p>
<p>For example, we recently learned that a <em>B. burgdorferi</em> protein is responsible for regulating the components necessary for the bacterium to infect vertebrates, including humans. The absence of this protein, among other things, leads to the <a href="https://doi.org/10.1038/s41467-023-35897-3">death of <em>B. burgdorferi</em> in ticks</a>, making it an exciting target for research investigation. </p>
<p>By learning more about the molecular mechanisms that change or reduce the severity of the disease caused by this bacterium, we can identify new targets for the prevention of human Lyme disease.</p><img src="https://counter.theconversation.com/content/208538/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jenny Wachter 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 bacterium that causes Lyme disease is a master of disguise, changing its appearance to evade the immune system as it moves from the ticks that carry it to humans or animals.Jenny Wachter, Research scientist/Adjunct professor, University of SaskatchewanLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2080892023-07-03T12:05:53Z2023-07-03T12:05:53ZVaccination in pregnancy greatly reduces risk of severe illness and death from COVID-19, and protects babies up to 6 months after birth<figure><img src="https://images.theconversation.com/files/534923/original/file-20230629-17-ey9jrq.jpg?ixlib=rb-1.1.0&rect=100%2C191%2C6438%2C4275&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Extensive evidence shows COVID-19 vaccinations in pregnancy are safe, when given at any time during the pregnancy.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>From the early days of the pandemic, it has been evident that a COVID-19 infection in pregnancy can be serious. Hundreds of studies from around the world have consistently shown that a COVID-19 infection in pregnancy carries <a href="https://doi.org/10.1093/cid/ciac544">significantly higher risk</a> for <a href="https://doi.org/10.1136/bmj.m3320">admission to intensive care units (ICU), invasive ventilation, preeclampsia and death</a>, compared to other COVID-19 patients. </p>
<p>The data is stark: there is a <a href="https://doi.org/10.1001/jamapediatrics.2021.1050">five times higher risk of ICU admission and 22 times higher risk of maternal mortality</a> due to COVID-19 infections in pregnancy. There are also <a href="https://doi.org/10.1016/j.xagr.2021.100049">considerable risks to the fetus</a>, with a higher risk of preterm delivery, low birth weight as well as serious fetal outcomes such as stillbirth, and neonatal mortality. </p>
<p>Interestingly, and not entirely surprisingly, studies have found that stillbirths and neonatal deaths occurred predominantly in <a href="https://doi.org/10.1038/s41591-021-01666-2">those who were unvaccinated </a> against SARS-CoV-2 at the time of infection. The same study also showed that 90 per cent of all hospitalizations and 98 per cent of critical care hospitalizations in pregnancy due to COVID-19 infection were also in the unvaccinated.</p>
<h2>Safety of COVID-19 vaccines in pregnancy</h2>
<p>As a science communicator and a Doctor of Public Health student, a lot of my work has focused specifically on understanding vaccine hesitancy. Despite the overwhelming data on the risks of COVID-19 infection in pregnancy, many have still been reluctant to get vaccinated, <a href="https://doi.org/10.1186/s12889-022-14617-4">citing safety concerns</a>.</p>
<p>We now have extensive evidence that shows COVID-19 vaccinations in pregnancy are safe, when given at any time during the pregnancy. </p>
<p>Globally, multiple meta-analyses have confirmed that there is <a href="https://doi.org/10.1038/s41467-022-30052-w">no evidence of a higher risk of adverse outcomes</a> in either the pregnant person or the infant. No differences were found in miscarriage, earlier gestation at birth, placental abruption, postpartum hemorrhage, maternal death, lower birthweight or neonatal intensive care unit admission with a COVID-19 vaccine given in pregnancy. </p>
<p>In fact, most of these studies found that <a href="https://doi.org/10.1001/jamapediatrics.2022.3456">vaccination offered positive</a> health outcomes: those who were vaccinated had a lower risk for stillbirths, preterm births and neonatal intensive care unit admission and more favourable <a href="https://www.aboutkidshealth.ca/Article?contentid=427&language=English">Apgar scores</a>.</p>
<h2>Infants protected by transfer of antibodies across placenta</h2>
<p>Several <a href="https://doi.org/10.1016/j.ajogmf.2021.100481">studies</a> have documented the presence of SARS-CoV-2 antibodies in umbilical cord blood after <a href="https://doi.org/10.1172/jci150319">maternal vaccination</a>. This confirms that there is an added benefit of vaccination, with SARS-CoV-2 IgG antibodies - which are the most common type of antibody found in blood, and protect against infections - <a href="https://doi.org/10.1038/s41467-022-32188-1">transferring across the placenta from mother to fetus</a>, particularly when vaccination occurs <a href="https://doi.org/10.1093/cid/ciac135">in the third trimester of pregnancy</a>.</p>
<figure class="align-center ">
<img alt="An infant in arms" src="https://images.theconversation.com/files/534932/original/file-20230629-27-krbk5b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/534932/original/file-20230629-27-krbk5b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=444&fit=crop&dpr=1 600w, https://images.theconversation.com/files/534932/original/file-20230629-27-krbk5b.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=444&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/534932/original/file-20230629-27-krbk5b.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=444&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/534932/original/file-20230629-27-krbk5b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=558&fit=crop&dpr=1 754w, https://images.theconversation.com/files/534932/original/file-20230629-27-krbk5b.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=558&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/534932/original/file-20230629-27-krbk5b.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=558&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">There is an added benefit of COVID-19 vaccination in pregnancy: SARS-CoV-2 IgG antibodies transfer across the placenta from mother to fetus, particularly when vaccination occurs in the third trimester of pregnancy.</span>
<span class="attribution"><span class="source">(Unsplash)</span></span>
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<p>What was unknown until very recently, however, is whether vaccination in pregnancy generates functional antibodies that are detectable in the infant post-birth and, if so, do they confer any benefit to the infant in terms of protection from COVID-19 infection or severity of infection. </p>
<p>Recent studies have shown that these IgG antibodies transferred to the fetus can remain in the baby for several months after birth. One study showed <a href="https://doi.org/10.1001/jama.2022.1206">57 per cent of infants</a> born to vaccinated mothers had detectable antibodies at six months. </p>
<p>A study conducted by the Centers for Disease Control and Prevention (CDC) published in the <em>Morbidity and Mortality Weekly Report</em> (MMWR) showed that COVID-19 mRNA vaccination during pregnancy was <a href="https://doi.org/10.15585/mmwr.mm7107e3">61 per cent effective</a> in preventing COVID-19-related hospitalization in infants aged less than six months. </p>
<p>A recently published study from Ontario assessed the effectiveness of maternal mRNA COVID-19 vaccination during pregnancy against Delta and Omicron variants in preventing hospital admission in infants younger than six months of age. </p>
<p>The study found that vaccine effectiveness against hospital admission in infants from two maternal doses was <a href="https://doi.org/10.1136/bmj-2022-074035">97 per cent for Delta variant and 53 per cent for Omicron</a>. Vaccine effectiveness against infant Omicron infection was found to be highest for the first eight weeks of life, but then declined in a stepwise manner. </p>
<p>While COVID-19-related infections in the pediatric population are generally mild, there is considerable variability and a small — but real — number of children get <a href="https://doi.org/10.1080/24694193.2021.1930288">moderate or severe disease</a>. </p>
<p>Children younger than six months have the highest risk for <a href="https://doi.org/10.3389/fped.2021.674899">severe outcomes</a> associated with COVID-19 infections, including <a href="https://data.cdc.gov/NCHS/Provisional-COVID-19-Death-Counts-by-Age-in-Years-/3apk-4u4f/data">hospitalizations and death</a>. </p>
<h2>Benefits of a COVID-19 booster in pregnancy</h2>
<p>Recently the <a href="https://cdn.who.int/media/docs/default-source/immunization/sage/2023/march-2023/sage_march_2023_meeting_highlights.pdf?sfvrsn=a8e5be9_3">World Health Organization</a> recommended a COVID-19 booster during pregnancy if the last dose was over six months ago. </p>
<p>It is abundantly clear that COVID-19 infection in pregnancy carries considerable risk to the pregnant person and the fetus. Given the high efficacy of COVID-19 vaccinations in preventing severe illness in the pregnant woman, as well as the substantive benefits for the infant, there is a robust and evidence-driven indication to recommend a COVID-19 booster routinely in all pregnancies, particularly if the last dose was more than six months ago. </p>
<p>Recommending additional boosters will allow families a superior opportunity to protect themselves and their babies in the fourth year of the pandemic. We have in our arsenal an intervention that has the potential to make a meaningful impact on maternal and infant health. So I ask, what are we waiting for?</p><img src="https://counter.theconversation.com/content/208089/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sabina Vohra-Miller 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>COVID-19 vaccination has been shown to be safe in pregnancy, and protects both the mother and infant from severe disease. It’s now also clear that infants’ antibody protection continues after birth.Sabina Vohra-Miller, Doctor of Public Health Student, University of TorontoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2074482023-06-15T12:33:36Z2023-06-15T12:33:36Z96.4% of Americans had COVID-19 antibodies in their blood by fall 2022<figure><img src="https://images.theconversation.com/files/532214/original/file-20230615-15-koig6o.jpg?ixlib=rb-1.1.0&rect=110%2C30%2C6530%2C4403&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Infection and vaccination both leave their mark in your blood.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/covid-19-positive-test-tubes-on-the-pink-background-royalty-free-image/1225071884">Yulia Reznikov/Moment via Getty Images</a></span></figcaption></figure><figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/532033/original/file-20230614-21-a1dd6k.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="graphic of text '96.4%: Share of Americans who had coronavirus antibodies in their blood by September 2022.'" src="https://images.theconversation.com/files/532033/original/file-20230614-21-a1dd6k.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/532033/original/file-20230614-21-a1dd6k.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=255&fit=crop&dpr=1 600w, https://images.theconversation.com/files/532033/original/file-20230614-21-a1dd6k.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=255&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/532033/original/file-20230614-21-a1dd6k.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=255&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/532033/original/file-20230614-21-a1dd6k.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=321&fit=crop&dpr=1 754w, https://images.theconversation.com/files/532033/original/file-20230614-21-a1dd6k.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=321&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/532033/original/file-20230614-21-a1dd6k.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=321&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="attribution"><a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<p>Antibodies to SARS-CoV-2, the virus that causes COVID-19, were present in the blood of <a href="http://dx.doi.org/10.15585/mmwr.mm7222a3">96.4% of Americans over the age of 16</a> by September 2022. That’s according to <a href="https://theconversation.com/covid-19-official-counts-can-miss-mild-cases-heres-how-serosurveys-that-analyze-blood-for-signs-of-past-infection-can-help-182112">a serosurvey</a> – an analysis testing for the presence of these immune defense molecules – conducted on samples from blood donors.</p>
<p>A serosurvey like this one helps researchers estimate how many people have been exposed to any part of the coronavirus, whether via vaccination or infection. Both can trigger the generation of antibodies to SARS-CoV-2. And by identifying which kind of antibodies someone has in their blood, researchers can break down the 96.4% into different types of immunity: infection-derived, vaccine-derived and hybrid.</p>
<p><iframe id="XVVEY" class="tc-infographic-datawrapper" src="https://datawrapper.dwcdn.net/XVVEY/2/" height="400px" width="100%" style="border: none" frameborder="0"></iframe></p>
<p>COVID-19 vaccines used in the United States are <a href="https://theconversation.com/how-do-mrna-vaccines-work-and-why-do-you-need-a-second-dose-5-essential-reads-157198">based on only one part of the virus</a> – the spike, or S, protein. Researchers can tell that a person has been vaccinated and has not been infected if their blood has only anti-S antibodies that target that spike protein. If someone has anti-N antibodies, which target the virus’s nucleocapsid protein, it’s a sign that they’ve been infected by SARS-CoV-2. To reliably identify someone with hybrid immunity, a researcher would need to match someone who has anti-N antibodies to an official vaccination database.</p>
<h2>What about the 3.6% without antibodies?</h2>
<p>Immunologists know that <a href="https://theconversation.com/how-long-does-protective-immunity-against-covid-19-last-after-infection-or-vaccination-two-immunologists-explain-177309">antibody levels decrease in the months after</a> a COVID-19 infection or vaccination, and this is <a href="https://doi.org/10.1093/infdis/jiac039">true for many pathogens</a>. It’s possible some people did have antibodies at one point, but they’re no longer detectable. And not every infection leads to a detectable antibody response, particularly if the case was mild or asymptomatic.</p>
<p>Another factor is <a href="https://theconversation.com/coronavirus-tests-are-pretty-accurate-but-far-from-perfect-136671">the accuracy of the antibody test</a>. No test is perfect, so a small percentage of people who truly have antibodies might come up negative.</p>
<p>Together, these considerations mean that the 96.4% number is likely an underestimate. It seems reasonable to conclude that almost no one in this population has neither been infected by SARS-CoV-2 nor received a COVID-19 vaccine.</p>
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<figcaption><span class="caption">Here’s how antibodies help your body fight against an invader like the coronavirus.</span></figcaption>
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<h2>A clearer picture of a virus’s spread</h2>
<p>Serosurveys are useful for understanding how likely different types of people – of varying ages or races, for example – were to have been infected. For this purpose, a serosurvey can be much more reliable than using data on people who received a positive PCR test, or who report having had a positive rapid antigen test, because getting a positive test is heavily influenced by access to care, health care behavior and how severe your illness is. These are sources of what is called bias.</p>
<p>This bias has two effects: It leads to large underestimation of the proportion of the overall population infected, and it can lead to spurious differences between groups. For example, people with mild symptoms are less likely to get tested and are also likely to be younger. Researchers might draw the wrong conclusion that because they’re not getting tested these people aren’t actually catching the virus.</p>
<p>Looking at antibodies as a marker of infection is not biased by such behavioral factors. Many serosurveys, including ones that <a href="https://doi.org/10.1093/aje/kwad103">we worked on in Chennai, India</a>, and <a href="https://doi.org/10.1371/journal.pmed.1004093">Salvador, Brazil</a>, found similar or even higher seroprevalence in children compared with young adults, contradicting an early narrative that children were less susceptible to the virus. Instead, our results suggested that infections in children were less likely to be detected.</p>
<h2>What does this statistic mean for future waves?</h2>
<p>Antibodies are not just a marker of previous infection; part of their job is to help prevent future infection with the same pathogen. So, serosurveys can be used to understand levels of immunity in the population.</p>
<p>For some diseases, like measles, immunity is essentially lifelong, and having antibodies means you are protected. However, for SARS-CoV-2 this is not the case, because the virus has continually evolved new variants that are able to reinfect people despite their antibodies.</p>
<p>Nevertheless, <a href="https://doi.org/10.1016/S1473-3099(22)00140-2">many studies have shown</a> <a href="https://doi.org/10.1371/journal.pmed.1004136">that individuals with hybrid immunity</a> <a href="https://doi.org/10.1016/S1473-3099(22)00143-8">will be more protected</a> against future infection and variants than those with vaccine- or infection-derived immunity alone. It may be useful to know the proportion of the population with single-source immunity in order to target certain groups with vaccination campaigns.</p><img src="https://counter.theconversation.com/content/207448/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Matt Hitchings receives funding from Merck, Sharp and Dohme, US-CDC, National Science Foundation, US National Institutes of Health. </span></em></p><p class="fine-print"><em><span>Derek Cummings receives funding from US NIH, US CDC, US NSF, and Merck, Sharp and Dohme.</span></em></p>There’s pretty much no one left in the US who hasn’t been exposed to the coronavirus, whether by vaccination, infection or both.Matt Hitchings, Assistant Professor of Biostatistics, University of FloridaDerek Cummings, Professor of Biology, the Emerging Pathogens Institute, University of FloridaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2014062023-03-24T09:34:57Z2023-03-24T09:34:57ZCOVID testing led to new techniques of disease diagnosis: progress mustn’t stop now<figure><img src="https://images.theconversation.com/files/514637/original/file-20230310-142-f88cb4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Covid-19 exposed critical shortcomings of existing diagnostic techniques</span> <span class="attribution"><span class="source">Michael Tewelde/Xinhua via Getty Images</span></span></figcaption></figure><p>In March 2020, weeks before the World Health Organization (WHO) declared COVID-19 a pandemic, its director-general Tedros Adhanom Ghebreyesus delivered <a href="https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---16-march-2020">a speech</a> in which he emphasised the importance of testing:</p>
<blockquote>
<p>… the most effective way to prevent infections and save lives is breaking the chains of transmission. And to do that, you must test and isolate. You cannot fight a fire blindfolded. And we cannot stop this pandemic if we don’t know who is infected. We have a simple message for all countries: test, test, test.</p>
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<p>The pandemic exposed critical shortcomings of existing diagnostic techniques. It revealed an urgent need for tests that are faster, simpler, cheaper and more scalable than existing methods, and just as accurate. </p>
<p>Three years on, the global face of diagnostics has changed. New techniques of disease diagnosis have been developed that can be applied to other emerging zoonotic pathogens such as “<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367867/">disease X</a>” – a hypothetical infectious disease that has the potential to develop into a pandemic.</p>
<p>As a molecular scientist with a keen interest in veterinary disease diagnostics, I have closely followed developments in the diagnostic space since the start of the pandemic. These emerging technologies, together with conventional tests, have the potential to overcome bottlenecks in the current diagnostic procedures. By incorporating these tests into a country’s healthcare system, clinicians and policy makers are better equipped to practise precision medicine and to react to potential outbreaks.</p>
<h2>How the tests changed</h2>
<p>The first diagnostic tests for SARS-CoV-2 (the virus that causes COVID disease) used established molecular techniques such as reverse transcription polymerase reaction (RT-PCR). These techniques detect and identify organisms by amplifying their genetic material millions of times. Running the tests however requires trained technicians and expensive equipment.</p>
<p>As the pandemic became more severe, other ways to test for the virus had to be developed. Substances and compounds needed to effectively run diagnostic tests were in short supply and many countries did not have the kinds of sophisticated laboratories needed for the existing tests. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178421/">Low- and middle-income countries</a> like those throughout the African continent had limited finances too and not enough trained specialists to handle the demand.</p>
<p>Isothermal amplification techniques helped to address the need. This is a simple process which rapidly and effectively amplifies DNA and RNA (genetic material) at constant temperature. </p>
<p>Immunological assays also helped. These tests can be used on-site or in the lab and are able to detect specific molecules such as antibodies and antigens. Antibodies are generated in a person’s body when a foreign molecule (antigen) invades the body.</p>
<p>These cost-effective tests provide rapid results and can be used on a big scale even where resources are scarce. The <a href="https://www.mdpi.com/2075-4418/11/2/182">major challenge</a> of these tests is that they are less accurate. Unlike molecular tests, which amplify the genetic material of the virus, immunological assays do not amplify their protein signal. This makes them <a href="https://www.science.org/content/article/coronavirus-antigen-tests-quick-and-cheap-too-often-wrong">less sensitive</a>. The risk is high that an infected person might incorrectly be told that they don’t have the virus.</p>
<p>The global diagnostic community realised it was time to look at methods that were as accurate as conventional molecular tests but could be used outside laboratories and on a large scale. </p>
<h2>Big strides</h2>
<p>Scientists needed a new generation of rapid, accurate, accessible and affordable diagnostic tests. The National Institutes of Health in the US set up the Rapid Acceleration of Diagnostics programme (<a href="https://www.nih.gov/research-training/medical-research-initiatives/radx/radx-programs">RADx</a>) in 2020 to fund innovative point-of-care and home-based tests and to speed up the development, validation and commercialisation of these tests.</p>
<p>One particularly interesting change in this space is the use of <a href="https://www.sciencedirect.com/science/article/pii/S1046202321000992">CRISPR</a>. The technology was previously known for its use in gene editing. But now it has revolutionised diagnostics with the launch of SHERLOCK and DETECTR, two innovative CRISPR-based kits used for the detection of SARS-CoV-2. These are particularly sensitive and specific and provide a visual colour readout using a commercially available paper dipstick, making them suitable for use as a point-of-care test. </p>
<p>The versatility of these techniques enables researches to apply the same principles to the detection of other infectious diseases too.</p>
<p>There have also been advances in using <a href="https://www.mdpi.com/1467-3045/44/10/325">biosensors</a>, <a href="https://luminostics.com/">nanotechnology</a>, <a href="https://nicoyalife.com/blog/nicoya-covid-19-diagnostic-test-2/?utm_campaign=COVID-19">smartphone-based tests</a> and <a href="https://www.nature.com/articles/s41591-020-1123-x">wearable technologies</a> for diagnostics.</p>
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Read more:
<a href="https://theconversation.com/what-is-crispr-the-gene-editing-technology-that-won-the-chemistry-nobel-prize-147695">What is CRISPR, the gene editing technology that won the Chemistry Nobel prize?</a>
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<p>Overall, in the past three years, the <a href="https://pubs.rsc.org/en/content/articlelanding/2023/lc/d2lc00662f">focus of disease testing</a> has moved from simple detecting and understanding to incorporating speed, efficiency and portability of the tests.</p>
<h2>Problems remain</h2>
<p>While there is a lot to celebrate in the diagnostic space, problems remain. There are barriers in developing and disseminating tests, particularly in poorer countries. <a href="https://www.finddx.org/wp-content/uploads/2022/12/20221210_rep_democratizing_testing_FV_EN.pdf">Fairer</a> access to quality testing and improved data sharing between countries is needed to eliminate the inequity in diagnostics.</p>
<p>The lack of resources to deliver a robust regulatory system in low- and middle-income countries also poses a serious challenge. Companies have less incentive to develop and commercialise products where there is weak regulation. Thus countries still depend on tests that are manufactured elsewhere. </p>
<p>As the world moves out of its pandemic response phase, it is likely that investment in diagnostics will fall. With a reduced need for tests, the economic return of investing in developing tests will diminish.</p>
<p>This is unfortunate as there are still so many healthcare challenges worldwide and unless disease surveillance is proactive, it won’t be possible to predict where the next pandemic might emerge from. The momentum created by the COVID pandemic offers an opportunity and should be used to build on the things that worked well in the diagnostic industry and to improve on the things that didn’t.</p><img src="https://counter.theconversation.com/content/201406/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Angelika Loots 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 pandemic spurred the diagnostics industry to consider aspects like scale, affordability, speed and portability of tests.Angelika Loots, Postdoctoral Fellow, University of PretoriaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1925672022-12-14T13:14:47Z2022-12-14T13:14:47ZNasal vaccines promise to stop the COVID-19 virus before it gets to the lungs – an immunologist explains how they work<figure><img src="https://images.theconversation.com/files/493959/original/file-20221107-19718-xu583n.jpg?ixlib=rb-1.1.0&rect=0%2C11%2C7360%2C4891&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Nasal vaccines for COVID-19 are still in early development.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/little-cute-blonde-boy-getting-vaccinated-covid-19-royalty-free-image/1282728128?phrase=COVID-19%20nasal%20vaccine&adppopup=true">Paul Biris/Moment via Getty Images</a></span></figcaption></figure><p><em>The Pfizer-BioNTech and Moderna mRNA vaccines have played a large role in preventing deaths and severe infections from COVID-19. But researchers are still in the process of developing alternative approaches to vaccines to improve their effectiveness, including how they’re administered. Immunologist and microbiologist <a href="https://www.researchgate.net/profile/Michael-Russell-10">Michael W. Russell</a> of the University at Buffalo explains how nasal vaccines work, and where they are in the development pipeline.</em></p>
<h2>How does the immune system fight pathogens?</h2>
<p>The immune system has two distinct components: mucosal and circulatory.</p>
<p>The <a href="http://dx.doi.org/10.1016/B978-0-12-415847-4.00001-X">mucosal immune system</a> provides protection at the mucosal surfaces of the body. These include the mouth, eyes, middle ear, the mammary and other glands, and the gastrointestinal, respiratory and urogenital tracts. Antibodies and a variety of other anti-microbial proteins in the <a href="https://theconversation.com/slime-is-all-around-and-inside-you-new-research-on-its-origins-offers-insight-into-genetic-evolution-189278">sticky secretions</a> that cover these surfaces, as well as immune cells located in the lining of these surfaces, directly attack invading pathogens.</p>
<p>The <a href="https://doi.org/10.1186/1741-7007-8-84">circulatory part of the immune system</a> generates antibodies and immune cells that are delivered through the bloodstream to the internal tissues and organs. These circulating antibodies do not usually reach the mucosal surfaces in large enough amounts to be effective. Thus mucosal and circulatory compartments of the immune system are largely <a href="http://dx.doi.org/10.3389/fimmu.2022.957107">separate and independent</a>.</p>
<h2>What are the key players in mucosal immunity?</h2>
<p>The immune components people may be most familiar with are proteins known as <a href="https://www.ncbi.nlm.nih.gov/books/NBK513460/">antibodies, or immunoglobulins</a>. The immune system generates antibodies in response to invading agents that the body identifies as “non-self,” such as viruses and bacteria.</p>
<p>Antibodies bind to specific antigens: the part or product of a pathogen that induces an immune response. Binding to antigens allows antibodies to either inactivate them, as they do with toxins and viruses, or kill bacteria with the help of additional immune proteins or cells.</p>
<p>The mucosal immune system generates a specialized form of antibody called <a href="http://dx.doi.org/10.1038/mi.2011.39">secretory IgA, or SIgA</a>. Because SIgA is located in mucosal secretions, such as saliva, tears, nasal and intestinal secretions, and breast milk, it is resistant to digestive enzymes that readily destroy other forms of antibodies. It is also superior to most other immunoglobulins at neutralizing viruses and toxins, and at preventing bacteria from attaching to and invading the cells lining the surfaces of organs.</p>
<p>There are also many <a href="http://dx.doi.org/10.1002/9780470015902.a0000942.pub2">other key players</a> in the mucosal immune system, including different types of anti-microbial proteins that kill pathogens, as well as immune cells that generate antibody responses.</p>
<figure>
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<figcaption><span class="caption">Mucus is one of the central secretions of the mucosal immune system.</span></figcaption>
</figure>
<h2>How does the COVID-19 virus enter the body?</h2>
<p>Almost all infectious diseases in people and other animals are <a href="https://www.ncbi.nlm.nih.gov/books/NBK209710/">acquired through mucosal surfaces</a>, such as by eating or drinking, breathing or sexual contact. Major exceptions include infections from wounds, or pathogens delivered by insect or tick bites.</p>
<p>The virus that causes COVID-19, SARS-CoV-2, enters the body via droplets or aerosols that get into your <a href="http://dx.doi.org/10.1038/s41385-020-00359-2">nose, mouth or eyes</a>. It can cause severe disease if it descends deep into the lungs and causes an <a href="https://theconversation.com/long-covid-19-and-other-chronic-respiratory-conditions-after-viral-infections-may-stem-from-an-overactive-immune-response-in-the-lungs-186970">overactive, inflammatory immune response</a>.</p>
<p>This means that the virus’s first contact with the immune system is probably through the surfaces of the nose, mouth and throat. This is supported by the presence of SIgA antibodies against SARS-CoV-2 <a href="http://dx.doi.org/10.3389/fimmu.2020.611337">in the secretions of infected people</a>, including their saliva, nasal fluid and tears. These locations, especially the tonsils, have specialized areas that specifically trigger mucosal immune responses.</p>
<p><a href="http://dx.doi.org/10.3390/pathogens11040397">Some research suggests</a> that if these SIgA antibody responses form as a result of vaccination or prior infection, or occur quickly enough in response to a new infection, they could prevent serious disease by confining the virus to the upper respiratory tract until it is eliminated.</p>
<h2>How do nasal vaccines work?</h2>
<p>Vaccines can be <a href="http://dx.doi.org/10.1016/B978-0-12-415847-4.00055-0">given through mucosal routes</a> via the mouth or nose. This induces an immune response through areas that stimulate the mucosal immune system, leading mucosal secretions to produce SIgA antibodies.</p>
<p>There are <a href="http://dx.doi.org/10.1016/B978-0-12-811924-2.00001-8">several existing mucosal vaccines</a>, most of them taken by mouth. Currently only one, the flu vaccine, is delivered nasally.</p>
<p>In the case of nasal vaccines, the viral antigens intended to stimulate the immune system would be taken up by immune cells within the lining of the nose or tonsils. While the exact mechanisms by which nasal vaccines work in people have not been thoroughly studied, researchers believe they <a href="http://dx.doi.org/10.1007/BF00915547">work analogously to oral mucosal vaccines</a>. Antigens in the vaccine induce B cells in mucosal sites to mature into plasma cells that secrete a form of IgA. That IgA is then transported into mucosal secretions throughout the body, where it becomes SIgA.</p>
<p>If the SIgA antibodies in the nose, mouth or throat target SARS-CoV-2, they could neutralize the virus before it can drop down into the lungs and establish an infection.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/jgApmHG5aMY?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Nasal vaccines could provide a more approachable alternative to injections for patients leery of needles.</span></figcaption>
</figure>
<h2>What advantage do mucosal vaccines have against COVID-19?</h2>
<p>I believe that arguably the best way to protect an individual against COVID-19 is to block the virus at its point of entry, or at least to confine it to the upper respiratory tract, where it might inflict relatively little damage.</p>
<p>Breaking chains of viral transmission is crucial to controlling epidemics. Researchers know that <a href="http://dx.doi.org/10.1093/cid/ciab691">COVID-19 spreads</a> during normal breathing and speech, and is exacerbated by sneezing, coughing, shouting, singing and other forms of exertion. Because these emissions mostly originate from saliva and nasal secretions, where the predominant form of antibody present is SIgA, it stands to reason that secretions with a sufficiently high level of SIgA antibodies against the virus could neutralize and thereby diminish its transmissibility.</p>
<p><a href="http://dx.doi.org/10.3389/fimmu.2022.957107">Existing vaccines</a>, however, do not induce SIgA antibody responses. Injected vaccines primarily induce circulating IgG antibodies, which are effective in preventing serious disease in the lungs. Nasal vaccines specifically induce SIgA antibodies in nasal and salivary secretions, where the virus is initially acquired, and can more effectively prevent transmission.</p>
<p>Nasal vaccines may be a useful supplement to injected vaccines in hot spots of infection. Since they don’t require needles, they might also help overcome vaccine hesitancy due to <a href="https://theconversation.com/over-half-of-adults-unvaccinated-for-covid-19-fear-needles-heres-whats-proven-to-help-161636">fear of injections</a>.</p>
<h2>How close are researchers to creating a nasal COVID-19 vaccine?</h2>
<p>There have been <a href="https://doi.org/10.1038/d41586-022-02824-3">over 100 oral or nasal COVID-19 vaccines in development</a> around the world.</p>
<p>Most of these have been or are currently being tested in animal models. <a href="http://dx.doi.org/10.1126/scitranslmed.abn6868">Many</a> <a href="http://dx.doi.org/10.1126/science.abo2523">have reported</a> successfully inducing protective antibodies in the blood and secretions, and have prevented infection in these animals. However, few have been successfully tested in people. Many <a href="https://www.pharmalive.com/altimmune-to-halt-trials-for-intranasal-covid-19-vaccine">have been abandoned</a> without fully reporting study details.</p>
<p>According to the <a href="https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines">World Health Organization</a>, 14 nasal COVID-19 vaccines are in clinical trials as of late 2022. Reports from <a href="https://doi.org/10.1038/d41586-022-02851-0">China and India</a> indicate that nasal or inhaled vaccines have been approved in these countries. But little information is publicly available about the results of the studies supporting approval of these vaccines.</p><img src="https://counter.theconversation.com/content/192567/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael W. Russell receives consultation fees from Therapyx, Inc., and has received previous research grants (now inactive) from the National Institutes of Health; he is also named on current grants to Therapyx, Inc. Therapyx has no interests in products for COVID-19.</span></em></p>An effective nasal vaccine could stop the virus that causes COVID-19 right at its point of entry. But devising one that works has been a challenge for researchers.Michael W. Russell, Professor Emeritus of Microbiology and Immunology, University at BuffaloLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1935032022-11-07T13:35:27Z2022-11-07T13:35:27ZWhat is inflammation? Two immunologists explain how the body responds to everything from stings to vaccination and why it sometimes goes wrong<figure><img src="https://images.theconversation.com/files/493585/original/file-20221104-18-efs0p0.jpg?ixlib=rb-1.1.0&rect=107%2C242%2C5883%2C3745&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Insect bites or stings, like the one on this person's hand, are a manifestation of inflammation.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/cropped-hand-with-mosquito-bite-against-white-royalty-free-image/1187314357?phrase=insect%20bite&adppopup=true">Suthep Wongkhad/EyeEm via Getty Images</a></span></figcaption></figure><p>When your body fights off an infection, you develop a fever. If you have arthritis, your joints will hurt. If a bee stings your hand, your hand will swell up and become stiff. These are all manifestations of <a href="https://doi.org/10.1007/s11515-011-1123-9">inflammation</a> occurring in the body.</p>
<p>We are two <a href="https://scholar.google.com/citations?user=jJVj3sUAAAAJ&hl=en&oi=ao">immunologists</a> <a href="https://scholar.google.com/citations?user=af7TahQAAAAJ&hl=en&oi=ao">who study</a> how the immune system reacts <a href="https://pubmed.ncbi.nlm.nih.gov/?term=nagarkatti+p&sort=date">during infections, vaccination and autoimmune diseases</a> where the body starts attacking itself.</p>
<p>While inflammation is commonly associated with the pain of an injury or the many diseases it can cause, it is an important part of the normal immune response. The problems arise when this normally helpful function overreacts or overstays its welcome.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/493374/original/file-20221103-26-eq1cei.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="An image showing many small white cells swarming a larger sphere." src="https://images.theconversation.com/files/493374/original/file-20221103-26-eq1cei.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/493374/original/file-20221103-26-eq1cei.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/493374/original/file-20221103-26-eq1cei.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/493374/original/file-20221103-26-eq1cei.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/493374/original/file-20221103-26-eq1cei.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=565&fit=crop&dpr=1 754w, https://images.theconversation.com/files/493374/original/file-20221103-26-eq1cei.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=565&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/493374/original/file-20221103-26-eq1cei.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=565&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Inflammation is a process in which antibody-producing cells – like the large beige cell on the left of this image – rush to the site of an infection to attack an invader, such as the flu virus in yellow.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/immune-response-to-a-virus-illustration-royalty-free-illustration/724237117?phrase=antibodies%20infection&adppopup=true">Juan Gaertner/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<h2>What is inflammation?</h2>
<p>Generally speaking, the term inflammation refers to all activities of the immune system that occur where the body is trying to fight off potential or real infections, clear toxic molecules or recover from physical injury. There are <a href="https://doi.org/10.1186%2F1476-9255-1-1">five classic physical signs</a> of acute inflammation: heat, pain, redness, swelling and loss of function. Low-grade inflammation might not even produce noticeable symptoms, but the underlying cellular process is the same.</p>
<p>Take a bee sting, for example. The immune system is like a military unit with a wide range of tools in its arsenal. After sensing the toxins, bacteria and physical damage from the sting, the immune system <a href="https://theconversation.com/coronavirus-b-cells-and-t-cells-explained-141888">deploys various types of immune cells</a> to the site of the sting. These include <a href="https://www.niaid.nih.gov/research/immune-cells">T cells, B cells, macrophages and neutrophils</a>, among other cells.</p>
<p>The <a href="https://www.ncbi.nlm.nih.gov/books/NBK26884/">B cells produce antibodies</a>. Those antibodies can kill any bacteria in the wound and neutralize toxins from the sting. <a href="https://doi.org/10.3389/fimmu.2012.00174">Macrophages and neutrophils engulf bacteria</a> and destroy them. <a href="https://doi.org/10.1038/d41586-021-00367-7">T cells don’t produce antibodies, but kill any virus-infected cell</a> to prevent viral spread. </p>
<p>Additionally, these immune cells produce <a href="https://doi.org/10.1177/1091581815584918">hundreds of types of molecules</a> called cytokines – otherwise known as mediators – that help fight threats and repair harm to the body. But just like in a military attack, inflammation comes with collateral damage.</p>
<p>The mediators that help kill bacteria also kill some healthy cells. Other similar mediating molecules cause blood vessels to leak, leading to accumulation of fluid and influx of more immune cells. </p>
<p>This collateral damage is the reason you develop swelling, redness and pain around a bee sting or after getting a flu shot. Once the immune system clears an infection or foreign invader – whether the toxin in a bee sting or a chemical from the environment – different parts of the inflammatory response take over and help repair the damaged tissue.</p>
<p>After a few days, your body will neutralize the poison from the sting, eliminate any bacteria that got inside and heal any tissue that was harmed. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/493375/original/file-20221103-15-myadsi.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A diagram of a man showing two airways, one open and the other more constricted." src="https://images.theconversation.com/files/493375/original/file-20221103-15-myadsi.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/493375/original/file-20221103-15-myadsi.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/493375/original/file-20221103-15-myadsi.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/493375/original/file-20221103-15-myadsi.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/493375/original/file-20221103-15-myadsi.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/493375/original/file-20221103-15-myadsi.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/493375/original/file-20221103-15-myadsi.png?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"></a>
<figcaption>
<span class="caption">Asthma is caused by inflammation that leads to swelling and a narrowing of airways in the lungs, as seen in the right cutaway in this image.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Asthma_(Lungs).png#/media/File:Asthma_(Lungs).png">BruceBlaus/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>Inflammation as a cause of disease</h2>
<p>Inflammation is a double-edged sword. It is critical for fighting infections and repairing damaged tissue, but when inflammation occurs for the wrong reasons or <a href="https://theconversation.com/long-covid-how-researchers-are-zeroing-in-on-the-self-targeted-immune-attacks-that-may-lurk-behind-it-169911">becomes chronic</a>, the damage it causes <a href="https://theconversation.com/despite-its-disastrous-effects-covid-19-offers-some-gifts-to-medicine-an-immunology-expert-explains-what-it-can-teach-us-about-autoimmune-disease-174952">can be harmful</a>. </p>
<p><a href="https://doi.org/10.1111/j.1600-065x.2011.01020.x">Allergies</a>, for example, develop when the immune system mistakenly recognizes innocuous substances – like peanuts or pollen – as dangerous. The harm can be minor, like itchy skin, or dangerous if someone’s throat closes up.</p>
<p>Chronic inflammation damages tissues over time and can lead to <a href="https://doi.org/10.1038/s41591-019-0675-0">many noninfectious clinical disorders</a>, including cardiovascular diseases, neurodegenerative disorders, obesity, diabetes and some types of cancers. </p>
<p>The immune system can sometimes mistake one’s own organs and tissues for invaders, leading to inflammation throughout the body or in specific areas. This self-targeted inflammation is what causes the symptoms of <a href="https://doi.org/10.1289/ehp.99107s5661">autoimmune diseases</a> such as lupus and arthritis. </p>
<p>Another cause of chronic inflammation that researchers like us are currently studying is defects in the <a href="https://doi.org/10.3389/fimmu.2016.00160">mechanisms that curtail inflammation</a> after the body clears an infection.</p>
<p>While inflammation mostly plays out at a cellular level in the body, it is far from a simple mechanism that happens in isolation. Stress, diet and nutrition, as well as genetic and environmental factors, have all been shown <a href="https://doi.org/10.3389%2Ffimmu.2020.570083">to regulate inflammation</a> in some way. </p>
<p>There is still a lot to be learned about what leads to harmful forms of inflammation, but a <a href="https://doi.org/10.3390%2Fnu11081933">healthy diet</a> and <a href="https://doi.org/10.1016%2Fj.copsyc.2015.03.007">avoiding stress</a> can go a long way toward helping maintain the delicate balance between a strong immune response and harmful chronic inflammation.</p><img src="https://counter.theconversation.com/content/193503/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Prakash Nagarkatti receives funding from the National Science Foundation and the National Institutes of Health. </span></em></p><p class="fine-print"><em><span>Mitzi Nagarkatti receives funding from the National Institutes of Health.</span></em></p>Inflammation is a complicated and important part of how the immune system responds to threats to the body. But when the inflammatory response goes awry, it can lead to serious problems.Prakash Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South CarolinaMitzi Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South CarolinaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1932672022-10-27T12:25:52Z2022-10-27T12:25:52ZNewly discovered species of bacteria in the microbiome may be a culprit behind rheumatoid arthritis<figure><img src="https://images.theconversation.com/files/491956/original/file-20221026-27-v3j4to.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1998%2C1494&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Rheumatoid arthritis leads to painful joint inflammation, often in the hands and wrists.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/ray-of-painful-hands-royalty-free-image/991972390">Peter Dazeley/The Image Bank via Getty Images</a></span></figcaption></figure><p>Rheumatoid arthritis affects <a href="https://rheumatoidarthritis.net/what-is-ra/ra-statistics">1 in 100 people worldwide</a>. It causes inflamed, painful and swollen joints, often in the hands and wrists, and can lead to loss of joint function as well as chronic pain and joint deformities and damage. What causes this condition has been unknown.</p>
<p>In our <a href="https://www.science.org/doi/10.1126/scitranslmed.abn5166">October 2022 study</a>, my colleagues and I found an important clue to a potential culprit behind this disease: the bacteria in your gut.</p>
<h2>What causes rheumatoid arthritis?</h2>
<p>Rheumatoid arthritis is an <a href="https://www.niehs.nih.gov/health/topics/conditions/autoimmune/index.cfm">autoimmune condition</a>, meaning it develops when the body’s immune system starts to attack itself. Proteins called antibodies, which usually help fight off viruses and bacteria, begin to attack the joints instead.</p>
<p>The origins of the antibodies that cause rheumatoid arthritis have been an area of study for many years. Some <a href="https://doi.org/10.1371/journal.pone.0035296">research has shown</a> that these antibodies can start forming at sites like the mouth, lung and intestines over 10 years before symptoms arise. But until now, it was unclear why researchers were finding these antibodies in these particular areas.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/NU3wCCTsmrY?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Rheumatoid arthritis can develop at any age.</span></figcaption>
</figure>
<p>We wanted to investigate what could trigger the formation of these antibodies. Specifically, we wondered if bacteria in the <a href="https://www.genome.gov/genetics-glossary/Microbiome">microbiome</a>, a community of microorganisms that live in the intestines, might be the ones activating the immune response that leads to rheumatoid arthritis. Since microbes commonly live at the same sites as the antibodies driving rheumatoid arthritis, we hypothesized that these bacteria could be triggering the production of these antibodies. We reasoned that though these antibodies were meant to attack the bacteria, rheumatoid arthritis develops when they spread beyond the intestines to attack the joints.</p>
<p>First, we sought to identify the intestinal bacteria targeted by these antibodies. To do this, we exposed the bacteria in the feces of a subset of people at risk for developing rheumatoid arthritis to these antibodies, allowing us to isolate just the bacterial species that reacted and bound to the antibodies.</p>
<p>We found that one previously unknown species of bacteria was present in the intestines of around 20% of people who were either diagnosed with rheumatoid arthritis or produce the antibodies that cause the disease. As a member of the Cherokee Nation of Oklahoma, I suggested we name this species <em>Subdoligranulum didolesgii</em> (“didolesgii” means arthritis or rheumatism in Cherokee) as a nod to the contributions that other Indigenous scholars have made to science as well as the fact that rheumatoid arthritis <a href="https://doi.org/10.1186/ar578">affects Indigenous people</a> at a higher rate than other populations. </p>
<p><em>Subdoligranulum didolesgii</em> has not been detected in the feces of healthy people before, and it is currently unknown how prevalent this bacteria is in the general population.</p>
<p>We also found that these bacteria can activate specialized immune cells called T cells in people with rheumatoid arthritis. T cells drive inflammatory responses in the body, and have been linked to the development of <a href="https://doi.org/10.1186/s13075-020-2104-7">different autoimmune diseases</a>. </p>
<p>These findings suggest that these gut bacteria may be activating the immune systems of people with rheumatoid arthritis. But instead of attacking the bacteria, their immune system attacks the joints. </p>
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<figcaption><span class="caption">Most of your immune system is located in your gut.</span></figcaption>
</figure>
<h2>Why this bacteria?</h2>
<p>It is still unknown why people with rheumatoid arthritis develop an immune response to <em>Subdoligranulum didolesgii</em>. But we think it may be the culprit when it comes to rheumatoid arthritis because this bacteria is found only in the intestines of people with rheumatoid arthritis, and not in the intestines of healthy people. </p>
<p>While many immune responses <a href="https://doi.org/10.1038/nri2515">happen in the intestines</a>, they are usually self-contained and do not spread to other areas of the body. However, we believe that a particularly strong intestinal immune response against <em>Subdoligranulum didolesgii</em> could allow antibodies to bypass the intestinal “firewall” and spread to the joints.</p>
<p>To confirm our hypothesis, we gave mice an oral dose of <em>Subdoligranulum didolesgii</em> and monitored their reaction. Within 14 days, the mice began to develop joint swelling and antibodies that attacked their joints.</p>
<h2>The future of rheumatoid arthritis treatment</h2>
<p>My colleagues and I hope this research can shed light on the origins of rheumatoid arthritis. Our next goal is to discover how common these bacteria are in the general population and test whether the presence of these bacteria in the gut may lead to the development of rheumatoid arthritis in people.</p>
<p>It’s important to note that <a href="https://doi.org/10.1016/j.bcp.2016.09.007">antibiotics</a> are unlikely to be helpful treatment for the microbiomes of patients with rheumatoid arthritis. Although <em>Subdoligranulum didolesgii</em> may be triggering an autoimmune response for some people with rheumatoid arthritis, antibiotics eliminate both helpful and harmful bacteria in the gut. Additionally, removing the bacteria won’t necessarily stop the immune system from attacking the joints once it has started.</p>
<p>Nevertheless, we believe that these bacteria can be used as tools to develop treatments for rheumatoid arthritis and hopefully ways to prevent disease from happening in the first place.</p><img src="https://counter.theconversation.com/content/193267/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Meagan Chriswell 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>A new species of bacteria that doesn’t normally live in the gut may trigger an immune response so strong that it spreads to the joints.Meagan Chriswell, MD/PhD Candidate in Immunology, University of Colorado Anschutz Medical CampusLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1898672022-09-23T12:34:56Z2022-09-23T12:34:56ZHIV therapies currently need to be taken regularly for life – longer-lasting antibody treatments could one day offer an equally effective one-shot alternative<figure><img src="https://images.theconversation.com/files/485987/original/file-20220921-15282-mal6o3.jpg?ixlib=rb-1.1.0&rect=3%2C0%2C2236%2C1333&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Broadly neutralizing antibodies are able to recognize multiple strains of HIV at once.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/monoclonal-antibody-is-an-antibody-made-by-cloning-royalty-free-image/1302640944">Naeblys/iStock via Getty Images Plus</a></span></figcaption></figure><p><a href="https://www.verywellhealth.com/antiretroviral-therapy-5216107">Antiretroviral therapy</a> has had an enormous impact on treating HIV infections around the world. The <a href="https://www.unaids.org/en/resources/fact-sheet">millions of people</a> currently taking these treatments under medical supervision can reasonably expect to reduce their viral loads to <a href="https://www.niaid.nih.gov/diseases-conditions/treatment-prevention">undetectable levels</a>, eliminate the risk of transmission and live a normal life span. However, antiretroviral therapy is not without shortcomings. People need to take these medications regularly for life, and <a href="https://doi.org/10.1038%2Fs41598-018-21081-x">low compliance</a> can lead to drug resistance.</p>
<p>There is a promising new option on the horizon. I am a <a href="https://scholar.google.com/citations?user=LyV-cJVvSncC&hl=en">researcher who studies AIDS treatments</a>, and I believe that <a href="https://my.clevelandclinic.org/health/treatments/22246-monoclonal-antibodies">monoclonal antibodies</a> could become game-changers for the treatment of HIV infections.</p>
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<figcaption><span class="caption">HIV poses a challenge to the immune system.</span></figcaption>
</figure>
<h2>HIV presents challenges to antibodies</h2>
<p><a href="https://my.clevelandclinic.org/health/body/22971-antibodies">Antibodies</a> are proteins that serve as major players in the immune system’s response to pathogens, which cause disease, and allergens, which cause allergic reactions. Antibodies recognize specific markers, or antigens, on a potentially harmful substance and help the body eliminate it.</p>
<p>Over the past few decades, researchers have been able to isolate individual antibodies specific to the individual pathogen or allergen they are meant to attack. With this advance, <a href="https://my.clevelandclinic.org/health/treatments/22246-monoclonal-antibodies">monoclonal antibodies</a> made in the lab have become a <a href="https://www.pharmavoice.com/news/2018-09-biologics/612566/">major segment of the pharmaceutical industry</a>. You can see numerous ads on TV or in magazines promoting monoclonal antibodies to treat osteoporosis, autoimmune disorders and various types of cancers.</p>
<p>Antibodies can also be used to treat viral infections, including <a href="https://combatcovid.hhs.gov/what-are-monoclonal-antibodies">COVID-19</a>. But using antibodies gets more complicated with HIV, the virus that causes AIDS in people.</p>
<p>One reason is that HIV has an <a href="https://doi.org/10.1093/bmb/58.1.19">enormous number of variants</a> circulating across the world and even within a single infected individual. In fact, the genetic variation of HIV within a single patient exceeds the genetic variation of all circulating influenza strains worldwide during an entire flu season.</p>
<p>The immune system of an individual infected with HIV creates antibodies to neutralize the virus. However, because these antibodies can usually recognize only one particular strain, they are unable to neutralize other HIV strains circulating in the population. Furthermore, HIV can <a href="https://doi.org/10.1073%2Fpnas.0630530100">mutate within an infected individual</a> and escape antibodies specific to the variant causing the original infection.</p>
<p>This ability to mutate and escape ongoing immune responses is a critical factor in the virus’s ability to continuously replicate, a hallmark of AIDS. It also makes it difficult to design an antibody treatment that can account for HIV’s enormous genetic variability.</p>
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<figcaption><span class="caption">Monoclonal antibodies are used to treat many types of cancer.</span></figcaption>
</figure>
<h2>Broadly neutralizing antibodies show promise</h2>
<p>The discovery of rare individuals who make anti-HIV antibodies that can be effective against <a href="https://doi.org/10.1186/s12977-018-0453-y">up to 80% of circulating strains</a>, however, has boosted prospects for antibody treatments for HIV.</p>
<p>These <a href="https://doi.org/10.1080%2F22221751.2020.1713707">broadly neutralizing antibodies</a>, or bnAbs, have seen impressive results. <a href="https://doi.org/10.1038/s41591-018-0001-2">Monkey</a> <a href="https://doi.org/10.1073%2Fpnas.1214785109">studies</a> have found that a single administration of bnAbs can prevent infection from SHIV, the nonhuman primate version of HIV. One study found that <a href="https://doi.org/10.1038/nature12744">two broadly neutralizing antibodies</a> were able to reduce viral loads to undetectable levels in infected monkeys.</p>
<p>In people, one study administering <a href="https://doi.org/10.1038/s41586-018-0531-2">two bnAbs</a> also saw suppression of HIV replication and nearly undetectable viral loads. One <a href="https://doi.org/10.1056/NEJMoa2031738">early-phase clinical trial</a> in 2021 showed that one bnAb could potentially offer protection against HIV infection.</p>
<h2>Long-term production of antibodies</h2>
<p>All the monkey and human studies mentioned above required re-administering the broadly neutralizing antibodies every three weeks or so to maintain effective concentrations. This runs into the same problem antiretroviral therapies face in terms of requiring the individual to retake the drug frequently for life. But researchers have found a potential solution.</p>
<p>Using a small virus that doesn’t cause disease, called an <a href="https://doi.org/10.1038/s41591-022-01762-x">adeno-associated virus</a>, to deliver broadly neutralizing antibodies into the body can stimulate muscle cells to continually produce these antibodies. Because muscle cells have a <a href="https://education.seattlepi.com/average-life-span-skeletal-muscle-cells-6414.html">prolonged life span</a> and can last on average 10 to 16 years, they can be turned into factories that produce the antibodies essentially for life. </p>
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<figcaption><span class="caption">Broadly neutralizing antibodies can target many HIV strains circulating around the world.</span></figcaption>
</figure>
<p>One study my colleagues and I conducted using adeno-associated virus found that one monkey was able to produce these antibodies for <a href="https://doi.org/10.3389%2Ffimmu.2020.00449">over six years</a> after a single injection. </p>
<p>Another monkey that researchers dubbed the “<a href="https://doi.org/10.1016/j.immuni.2019.02.010">The Miami Monkey</a>” is considered functionally cured, meaning its viral loads have been at undetectable levels for prolonged periods even without continuous antiviral drug therapy. <a href="https://doi.org/10.1016/j.immuni.2019.02.005">Two other monkeys</a> have also been cured of their AIDS virus infections with this approach.</p>
<p>Adeno-associated virus vectors for HIV antibody therapies still face one more hurdle: <a href="https://doi.org/10.1016/S2352-3018(19)30003-7">anti-drug antibodies</a>, or antibodies the body produces in response to the antibodies in the treatment. Anti-drug antibodies can result when the body registers an antibody treatment as foreign and mounts an immune response against it, negating the treatment. They have also have caused problems for antibody treatments in <a href="https://doi.org/10.1634%2Ftheoncologist.2016-0061">cancer</a> and <a href="https://www.uptodate.com/contents/tumor-necrosis-factor-alpha-inhibitors-induction-of-antibodies-autoantibodies-and-autoimmune-diseases">autoimmune disorders</a>. That may especially be the case for broadly neutralizing antibodies, which have unusual structures that deviate from what the body normally expects an antibody to look like.</p>
<p>Researchers are working hard to develop simple and accessible approaches to help patients build tolerance to broadly neutralizing antibodies. Some of these approaches include delivering treatments to other areas that have greater immune tolerance than the muscle, such as <a href="https://doi.org/10.1016%2Fj.omtm.2019.11.010">to the liver</a> and <a href="https://doi.org/10.1007%2Fs12016-018-8680-5">through the mouth</a>.</p>
<p>Stay tuned.</p><img src="https://counter.theconversation.com/content/189867/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ronald C. Desrosiers receives funding from the National Instituyes of Health. He receives no corporate/commercial/company support.</span></em></p>Antiretroviral therapies for HIV, while extremely effective, need to be taken daily for life. Designing antibody treatments that need to be taken only once could improve compliance and reduce drug resistance.Ronald C. Desrosiers, Professor of Pathology, Vice-chair for Research, University of MiamiLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1908262022-09-22T12:40:17Z2022-09-22T12:40:17ZWhen should you get the new COVID-19 booster and the flu shot? Now is the right time for both<figure><img src="https://images.theconversation.com/files/485731/original/file-20220920-16871-cf9dvv.jpg?ixlib=rb-1.1.0&rect=140%2C60%2C6569%2C4386&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">It is safe to get the newly formulated COVID-19 booster shot and the flu shot at the same time.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/close-up-photo-female-nurse-giving-vaccine-to-woman-royalty-free-image/1361778753?adppopup=true">SDI Productions/ E+ via Getty Images</a></span></figcaption></figure><p>At this point in the COVID-19 pandemic, nearly everyone has experienced the panic and uncertainty that come with having mild COVID-like symptoms – such as a cough and sore throat – only to test negative day after day. With cold and flu season just around the corner, that state of frustrating uncertainty is likely to strike most of us again. </p>
<p>Both COVID-19 and the flu are contagious respiratory illnesses that have <a href="https://www.cdc.gov/flu/symptoms/flu-vs-covid19.htm">similar symptoms</a>, making it difficult to distinguish between the two viral infections without a lab test. Testing is the only way to know which virus is causing your symptoms. In fact, labs are working to create one test that can detect <a href="https://doi.org/10.1001/jama.2022.11031">both COVID-19 and the flu</a>. </p>
<p>As a <a href="https://hhs.purdue.edu/directory/elizabeth-libby-richards/">nursing professor</a> with <a href="https://scholar.google.com/citations?user=Pdh4gSgAAAAJ&hl=en&oi=ao">experience in public health promotion</a>, I am often asked about the differences between the flu and COVID-19. This year I am fielding many questions about the timing of getting the new COVID-19 booster and the flu shot and whether they can be given together.</p>
<h2>Parsing the symptoms</h2>
<p>Symptoms of both COVID-19 and the flu can range from mild – or no noticeable symptoms at all – to severe. While flu infection does not typically affect one’s ability to taste or smell, <a href="https://my.clevelandclinic.org/health/symptoms/16708-loss-of-taste-and-smell">loss of taste or smell</a> has been a common symptom associated with COVID-19 infection. Both infections can cause fevers, chills, body aches and fatigue. More severe symptoms of either infection include difficulty breathing and subsequent infections like pneumonia. </p>
<p>During the 2021-2022 flu season, <a href="https://www.washingtonpost.com/health/2022/01/05/flurona-coronavirus-flu-symptoms/">the term “flurona”</a> made its way into the COVID-19 vernacular. Flurona refers to a simultaneous infection with both the flu and COVID-19. While only a few cases of co-infections <a href="https://doi.org/10.3389/fmed.2021.681469">have been reported</a>, it would not be surprising to see more of them this coming flu season. Vaccination for both the flu and COVID-19 is your best protection against both.</p>
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<figcaption><span class="caption">What flurona is – and isn’t.</span></figcaption>
</figure>
<h2>Timing the shots</h2>
<p>With the <a href="https://theconversation.com/will-omicron-specific-booster-shots-be-more-effective-at-combating-covid-19-5-questions-answered-189610">newly formulated COVID-19 booster shot</a> now available and flu season just around the corner, a natural question is whether there is an optimal timing for the two shots.</p>
<p>The answer to that question is to get both as soon as possible. It is important to consider that it takes approximately two weeks after vaccination for the body to develop antibodies from both the <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/how-they-work.html">COVID-19 vaccines</a> and the <a href="https://www.cdc.gov/flu/prevent/keyfacts.htm">flu vaccine</a>. </p>
<p>As long as you have completed your primary COVID-19 vaccine series and it has been at least eight weeks since your last COVID-19 booster, now is the time to <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/stay-up-to-date.html?">get the updated COVID-19 vaccine</a> that targets both the original strain of SARS-CoV-2 – the virus that causes COVID-19 – and the most recent omicron subvariants. The original COVID-19 vaccines and booster series have dramatically reduced the <a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm7023e2.htm">number of COVID-19 infection and death rates</a>, as well as <a href="https://www.cdc.gov/mmwr/volumes/71/wr/mm7112e1.htm">cases of severe COVID-19</a> that lead to hospitalization. </p>
<p>While everyone 6 months of age and older are recommended to receive both the COVID-19 and flu vaccines, certain populations have a higher risk for severe infection, such as <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/pregnancy.html">pregnant women</a>, and should be extra vigilant about getting vaccinated. </p>
<p>Further, among those vaccinated against COVID-19, symptoms during an infection <a href="https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/breakthrough-infections-coronavirus-after-vaccination#">tend to be milder</a>. However, due in part to the quickly evolving nature of the virus, it’s become clear that immune protection from COVID-19 vaccination or infection does not last forever. While studies show that the primary COVID-19 series maintains efficacy against severe disease and death six months after vaccination, protection against infection decreases by between <a href="https://doi.org/10.1016/S0140-6736(22)00152-0">20% to 30% by six months</a> after vaccination. </p>
<p>This decline in immune protection is exactly <a href="https://www.yalemedicine.org/news/covid-19-booster">why booster shots are so critical</a>. Without a large uptake of <a href="https://theconversation.com/low-vaccine-booster-rates-are-now-a-key-factor-in-covid-19-deaths-and-racial-disparities-in-booster-rates-persist-187272">booster shots in the population</a>, COVID-19 infection rates could surge again.</p>
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<figcaption><span class="caption">The updated COVID-19 booster shots are now available.</span></figcaption>
</figure>
<p>Timing is also important with the flu vaccine. Flu cases typically begin to rise in October and peak between December and February, <a href="https://www.cdc.gov/flu/about/season/flu-season.htm">but can last through May</a>. Ideally, people should get vaccinated before flu begins to spread, making <a href="https://www.cdc.gov/flu/season/faq-flu-season-2022-2023.htm">September or early October</a> the ideal flu vaccination time. </p>
<h2>A difficult flu season ahead</h2>
<p>Due to lockdowns, reduced travel, school closures and mask mandates in the first and second years of the pandemic, both the <a href="https://www.cdc.gov/flu/about/burden/past-seasons.html">2020-2021 and 2021-2022 flu seasons</a> were estimated to have fewer hospitalizations and deaths from the flu compared to many of the pre-pandemic years. </p>
<p>In the fall of 2021, experts became concerned about the potential for a <a href="https://theconversation.com/flu-season-paired-with-covid-19-presents-the-threat-of-a-twindemic-making-the-need-for-vaccination-all-the-more-urgent-169011">COVID-19 and flu “twindemic,”</a> especially as COVID-19 restrictions were lifting and masks were coming off. Fortunately, the worst didn’t bear out – flu numbers in the 2021-2022 season did not return to pre-pandemic levels. However, the possibility of a “twindemic” is not out of the picture for the coming flu season.</p>
<p>Flu seasons are <a href="https://www.cdc.gov/flu/about/burden/faq.htm">inherently difficult to predict</a>. With most people traveling again, schools open, mask mandates lifted and workers headed back to the office, people are undoubtedly going to be exposed to germs that they have been more protected from for the last two and a half years. </p>
<p>To further compound this, flu vaccine rates <a href="https://www.cdc.gov/flu/fluvaxview/dashboard/vaccination-dashboard.html#">have been lower during the pandemic</a>, suggesting that Americans may be out of the habit of getting their annual flu shot. </p>
<h2>Pairing the shots</h2>
<p>Many are also wondering whether they can or should get both the updated COVID-19 booster and the flu shot at the same time. The good news is, <a href="https://www.cdc.gov/flu/season/faq-flu-season-2022-2023.htm">yes, it is safe</a> for both adults and children 12 years of age and up who are eligible for the updated COVID-19 booster to get these vaccines simultaneously. </p>
<p>A recent study found that common vaccine side effects such as pain at the injection site <a href="https://doi.org/10.1001/jamanetworkopen.2022.22241">occurred at slightly higher rates</a> when someone received the flu vaccine and a COVID-19 vaccine at the same time, as opposed to receiving only a COVID-19 booster. However, those reactions, including fatigue and headache, were mild and resolved within a day or two.</p>
<p>You don’t need to make two separate vaccine visits as long as you are due for your next COVID-19 shot. However, I don’t recommend waiting to get your flu shot if you are not yet due for a COVID-19 booster. The Centers for Disease Control and Prevention suggests everyone receive their flu vaccine by <a href="https://www.cdc.gov/flu/season/faq-flu-season-2022-2023.htm">the end of October</a>. But if you miss that deadline, it is absolutely better to get vaccinated later in the season than not at all.</p>
<h2>Community matters too</h2>
<p>Getting the flu and COVID-19 vaccines isn’t just about your own health, it’s about family and community health too. Communities with higher vaccination rates have <a href="https://theconversation.com/what-is-herd-immunity-a-public-health-expert-and-a-medical-laboratory-scientist-explain-170520">fewer opportunities to spread the virus</a>. </p>
<p>Keep in mind <a href="https://www.cdc.gov/flu/prevent/whoshouldvax.htm">that many people cannot be vaccinated</a> because they have weakened immune systems or are undergoing treatments. They depend on those around them for protection. While one person may experience mild symptoms if they contract the flu or COVID-19, they could spread the virus to others who could become severely ill. Because it’s impossible to predict how people will react if they get sick, getting the flu and COVID-19 vaccines is the best prevention strategy.</p><img src="https://counter.theconversation.com/content/190826/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Libby Richards has received funding from the National Institutes of Health. She is is affiliated with the American Public Health Association. </span></em></p>When COVID-19 and the flu co-infect, it’s ‘flurona.’ But such cases are rare, and there are effective ways to protect yourself from both viruses.Libby Richards, Associate Professor of Nursing, Purdue UniversityLicensed 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>
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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>
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<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/1699112022-08-31T16:19:23Z2022-08-31T16:19:23ZLong COVID: How researchers are zeroing in on the self-targeted immune attacks that may lurk behind it<figure><img src="https://images.theconversation.com/files/458432/original/file-20220418-117906-3mgme6.jpg?ixlib=rb-1.1.0&rect=0%2C18%2C6048%2C3992&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Approximately 30% of people who get COVID-19 develop long-term symptoms, or long COVID-19.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/portrait-of-sickness-woman-sitting-alone-on-the-bed-royalty-free-image/1222224164?adppopup=true">Boy Anupong/Moment via Getty Images</a></span></figcaption></figure><p>For almost three years, scientists have raced to understand the immune responses in patients who develop severe COVID-19, with an enormous effort aimed at defining where <a href="https://doi.org/10.1016/S2666-5247(21)00025-2">healthy immunity</a> ends and destructive immunity begins.</p>
<p>In the early days of the COVID-19 pandemic, much attention focused on reports of <a href="https://doi.org/10.3389/fimmu.2020.01446">harmful inflammation</a> and so-called <a href="https://doi.org/10.1056/NEJMra2026131">cytokine storms</a> – dangerous immune overreactions that can lead to tissue damage and death – in patients with severe COVID-19. It wasn’t long before researchers began to <a href="https://theconversation.com/covid-19-causes-some-patients-immune-systems-to-attack-their-own-bodies-which-may-contribute-to-severe-illness-148509">identify antibodies that target the patient’s own body</a> rather than attacking SARS-CoV-2, the virus the causes COVID-19. </p>
<p>Those <a href="https://theconversation.com/an-autoimmune-like-antibody-response-is-linked-with-severe-covid-19-146255">studies revealed that patients with severe COVID-19</a> share some of the key traits of chronic autoimmune diseases – diseases in which the patient’s immune systems chronically attack their own tissues. Scientists <a href="https://dx.doi.org/10.1111%2Fimr.12091">have long suspected</a> and <a href="https://doi.org/10.1016/j.it.2009.05.005">sometimes even documented</a> links between viral infection and chronic autoimmune diseases, but the research remains murky. However, the COVID-19 pandemic has offered an opportunity to better understand <a href="https://theconversation.com/despite-its-disastrous-effects-covid-19-offers-some-gifts-to-medicine-an-immunology-expert-explains-what-it-can-teach-us-about-autoimmune-disease-174952">potential connections between these conditions</a>. </p>
<p>As <a href="https://scholar.google.com/citations?user=-oDHlFYAAAAJ&hl=en">an immunologist</a> and member of an interdisciplinary team of physicians and scientists investigating the intersection between COVID-19 and autoimmunity, I have been working to understand the origins of these untamed antibody responses and their long-term effects. Led by <a href="https://med.emory.edu/departments/medicine/profile/?u=ISANZ">Ignacio Sanz</a>, a specialist in investigating the immune dysfunctions that underlie autoimmune diseases like lupus, our group has <a href="https://www.nytimes.com/2020/10/27/health/covid-antibodies-autoimmunity.html">long suspected</a> that these misdirected immune responses may follow patients well after recovery and could even contribute to the debilitating set of symptoms <a href="https://theconversation.com/deciphering-the-symptoms-of-long-covid-19-is-slow-and-painstaking-for-both-sufferers-and-their-physicians-164754">commonly referred to as “long COVID-19</a>.” </p>
<p>Our new study, published in the journal Nature, <a href="https://doi.org/10.1038/s41586-022-05273-0">helps shed light on these questions</a>. We now know that in patients with severe COVID-19, many of the developing antibodies responsible for neutralizing the viral threat are simultaneously targeting their own organs and tissues. We also show that self-directed antibodies can persist for months or even years in those suffering from long COVID-19. </p>
<p>As researchers like us continue to study COVID-19, our understanding of the link between antiviral immunity and chronic autoimmune disease is rapidly evolving.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/2ECsro9t_c0?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">More than three years into the pandemic, there is not one unifying explanation for why people experience the symptoms known as long COVID-19.</span></figcaption>
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<h2>The immune system makes mistakes when under duress</h2>
<p>It’s easy to assume that your immune system is laser-focused on identifying and destroying foreign invaders, but that isn’t the case – at least under some circumstances. Your immune system, even in its healthy state, contains a contingent of cells that are fully capable of targeting and destroying your own cells and tissues. </p>
<p>To prevent self-destruction, the immune system relies on an intricate series of fail-safes that are collectively termed <a href="https://www.youtube.com/watch?v=vDwNpDT-8L0">self-tolerance</a> to identify and eliminate potentially traitorous immune cells. One of the most important steps in this process occurs as the immune system builds up its arsenal against a potential threat. </p>
<p>When your immune system first encounters a pathogen or even a perceived threat – such as a vaccine that resembles a virus – it rapidly recruits “B” cells that have the potential to become antibody-producers. Then, any of these “naive” B cell recruits – naive being a technical term used in immunology – that demonstrate an ability to competently attack the invader are put into <a href="https://doi.org/10.3389/fimmu.2018.02469">a boot camp of sorts</a>. </p>
<p>Here, the cells are trained to better recognize and combat the threat. The training period is intense and mistakes are not tolerated; B cells with any discernible potential for misdirected attacks against their host are killed. However, like any training process, this buildup and mobilization takes time – <a href="https://doi.org/10.1016/j.immuni.2007.07.009">typically a week or two</a>. </p>
<p>So, what happens when the threat is more immediate – when someone is quite literally fighting for their life in an intensive care unit?</p>
<p>Researchers now know that under the stress of severe viral infection with SARS-CoV-2, <a href="https://dx.doi.org/10.2139%2Fssrn.3652322">that training process collapses</a>. Instead, it is replaced by an <a href="https://doi.org/10.1038/s41590-020-00814-z">emergency response</a> in which new recruits with little training are rushed into battle.</p>
<p>Friendly fire is the unfortunate result. </p>
<h2>High-risk immune responses are mostly transient</h2>
<p>Our team’s new work reveals that in the heat of battle with severe COVID-19, the same antibodies responsible for fighting the virus are uncomfortably prone to targeting a patient’s own tissue. Importantly, this effect seems mostly restricted to severe disease. We identified the cells that produce these rogue antibodies much less frequently in patients with mild forms of the illness whose immune responses were more measured.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/481949/original/file-20220831-20-kthrj2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Three-dimensional illustration of a nerve cell being attacked by antibodies." src="https://images.theconversation.com/files/481949/original/file-20220831-20-kthrj2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/481949/original/file-20220831-20-kthrj2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=372&fit=crop&dpr=1 600w, https://images.theconversation.com/files/481949/original/file-20220831-20-kthrj2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=372&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/481949/original/file-20220831-20-kthrj2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=372&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/481949/original/file-20220831-20-kthrj2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=467&fit=crop&dpr=1 754w, https://images.theconversation.com/files/481949/original/file-20220831-20-kthrj2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=467&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/481949/original/file-20220831-20-kthrj2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=467&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Researchers have discovered that the antibodies produced to fight the virus in severe COVID-19 can sometimes turn against the bodies own cells and tissues.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/nerve-cell-attacked-by-antibodies-royalty-free-image/1364982274?adppopup=true">peterschreiber.media/iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<p>So, does that mean that everyone who gets severe COVID-19 develops an autoimmune disorder?</p>
<p>Fortunately, no. By following patients after their infection has resolved, we have found that months later, most of the concerning indications of autoimmunity have subsided. And this makes sense. Though we are identifying this phenomenon in human COVID-19, researchers studying these emergency immune responses for more than a decade in mice have determined that they are <a href="https://doi.org/10.1016/j.immuni.2020.11.006">mostly short-lived</a>.</p>
<p>“Mostly” being the operative word. </p>
<h2>Implications for recovery from long COVID-19</h2>
<p>Although most people fully recover from their run-in with the virus, <a href="https://doi.org/10.1371/journal.pmed.1003773">up to 30% have not returned to normal even three months after recovery</a>. This has created a group of patients who are experiencing what is known as <a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm7037a2.htm">post-acute sequelae of COVID-19, or PASC</a> – the technical terminology for long COVID-19.</p>
<p>With <a href="https://theconversation.com/long-covid-leaves-newly-disabled-people-facing-old-barriers-a-sociologist-explains-175424">debilitating symptoms</a> that can include the long-term loss of taste, smell or both, general fatigue, brain fog and a variety of other conditions, these patients have continued to suffer and are <a href="https://theconversation.com/deciphering-the-symptoms-of-long-covid-19-is-slow-and-painstaking-for-both-sufferers-and-their-physicians-164754">rightfully looking for answers</a>. </p>
<p>An obvious question for researchers who are studying these patients is whether the same self-targeted antibodies that are emerging in severe COVID-19 are lingering in those who suffer from long COVID-19. They are. Our new study makes clear that newly developed self-antibodies <a href="https://doi.org/10.1038/s41586-022-05273-0">can persist for months</a>. What’s more, in work currently under development and not yet peer-reviewed, we find that these responses are <a href="https://doi.org/10.1101/2021.09.21.21263845">not restricted to those recovering from severe illness</a>, and are readily identifiable in a large subset of long COVID-19 patients who had recovered from more mild illness as well. </p>
<p>Just as it was in the race to better understand the causes of acute disease earlier in the pandemic, we researchers are now working to get a more complete understanding of the cells and antibodies directing this self-attack for months and years following the resolution of infection.</p>
<p>Are they directly contributing to the symptoms long COVID-19 sufferers are experiencing? If so, are there therapeutic interventions that could blunt or eliminate the threats they pose? Are long COVID-19 patients at increased risk for the development of true, chronic autoimmune diseases in the future? Or, is all of this just a red herring – a temporary quirk of the immune system that will resolve on its own?</p>
<p>Only time and continued work in this critical area will tell.</p><img src="https://counter.theconversation.com/content/169911/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Matthew Woodruff's research is supported by the NIH. He is a co-founder of Jefferson's Electorate.</span></em></p>A new study finds that misdirected immune responses can persist for months in those who are suffering from long COVID-19.Matthew Woodruff, Instructor of Human Immunology, Emory UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1879052022-08-19T12:42:26Z2022-08-19T12:42:26ZWhat is listeria? A microbiologist explains the bacterium behind recent deadly food poisoning outbreaks<figure><img src="https://images.theconversation.com/files/479719/original/file-20220817-21-a18luh.jpg?ixlib=rb-1.1.0&rect=132%2C0%2C3875%2C2951&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Investigators in Florida traced a listeria outbreak to ice cream.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/ice-cream-jar-with-4-flavors-strawberry-vanilla-royalty-free-image/1279372828?adppopup=true">Graiki/Moment via Getty Images</a></span></figcaption></figure><p>Bacteria do, and will, end up in food. Everyone eats – intentionally or unintentionally – <a href="https://doi.org/10.7717/peerj.659">millions to billions</a> of live microbes every day. </p>
<p>Most are completely harmless, but some can cause serious illnesses in humans. Because of these potential pathogens, there is a long <a href="https://www.mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/in-depth/pregnancy-nutrition/art-20043844">list of foods to avoid</a>, including uncooked eggs, raw fish and unwashed fruits and vegetables, particularly for pregnant women. The foods themselves are not bad, but the same cannot be said for certain bacterial passengers, such as <em>Listeria monocytogenes</em>, or listeria for short. </p>
<p>This particular pathogen has found ways to indiscriminately get into our foods. While deli and dairy foods like cold cuts, cheese, milk and eggs are frequently culprits for causing listeriosis – the general name for listeria-caused infections – fresh vegetables and fruits have also been implicated.</p>
<p>The variety of foods responsible for <a href="https://www.cdc.gov/listeria/outbreaks/index.html">U.S. listeria outbreaks in the past decade</a> shows just how easily these bacteria get around. Listeria has turned up in <a href="https://www.cdc.gov/listeria/outbreaks/eggs-12-19/index.html">hard-boiled eggs</a>, <a href="https://www.cdc.gov/listeria/outbreaks/enoki-mushrooms-03-20/index.html">enoki mushrooms</a>, <a href="https://www.cdc.gov/listeria/outbreaks/precooked-chicken-07-21/index.html">cooked chicken</a> and, <a href="https://www.cdc.gov/listeria/outbreaks/packaged-salad-12-21-b/index.html">in 2021, packaged salad</a> – <a href="https://www.cdc.gov/listeria/outbreaks/packaged-salad-mix-12-21/index.html">twice</a>.</p>
<p>Even the frozen aisle is not spared from listeria contamination. Contaminated ice cream in Florida was behind this year’s listeria outbreak, with 25 reported cases spanning 11 states since January 2021, according to <a href="https://www.cdc.gov/listeria/outbreaks/monocytogenes-06-22/details.html">an early August 2022 report</a> from the Centers for Disease Control and Prevention. Those who fell ill ranged in age from less than 1 to 92 years old, and 24 of the cases have involved hospitalizations.</p>
<p>How can such a tiny organism bypass extensive disinfection efforts and wreak such havoc? <a href="https://scholar.google.com/citations?user=G_tH2rUAAAAJ&hl=en">As a microbiologist</a> who has been working with listeria and trying to solve these mysteries, I’d like to share some insider secrets about this unique little pathogen and its strategies of survival inside and outside our bodies.</p>
<h2>Farm to table</h2>
<p>To prevent consumer exposure to listeria, the food industries follow <a href="https://www.fda.gov/files/food/published/Draft-Guidance-for-Industry--Control-of-Listeria-monocytogenes-in-Ready-To-Eat-Foods-%28PDF%29.pdf">stringent disinfection and surveillance guidelines</a> from the Food and Drug Administration and the U.S. Department of Agriculture. Any detection of listeria triggers a recall of potentially contaminated food products. </p>
<p>Since 2017, there have been <a href="https://www.fsis.usda.gov/recalls">over 270 listeria-related food recalls</a>. These are incredibly costly and can sometimes lead to fears in consumers <a href="https://www.npr.org/sections/thetwo-way/2018/01/29/581531318/panera-bread-recalls-cream-cheese-across-u-s-over-listeria-fears">as well as nationwide disruptions in food services</a>. However, the recalls represent one of the few tools that the food industry has to protect consumers from foodborne infections. </p>
<p>Not all listeria strains are created equal. <a href="https://doi.org/10.1016/j.ijmm.2010.05.002">Genetic variations</a> in listeria make a big difference in whether the pathogen ends up being involved in multistate outbreaks or simply hitching a ride harmlessly through our digestive tract. Essentially, based on the <a href="https://doi.org/10.1093/jaoac/85.2.524">different methods used</a>, listeria can be subtyped into different lineages, with some associated with outbreaks more frequently than others.</p>
<p>Researchers are investigating ways to tell these listeria strains apart, distinguishing the less harmful ones from those that are particularly dangerous, or hypervirulent. Being able to accurately identify them can help policymakers assess risks and make economically feasible decisions to improve food safety.</p>
<figure class="align-center ">
<img alt="Illustration of red-orange rod-shaped Listeria bacteria." src="https://images.theconversation.com/files/477025/original/file-20220801-70681-jygdr6.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C6000%2C3979&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/477025/original/file-20220801-70681-jygdr6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/477025/original/file-20220801-70681-jygdr6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/477025/original/file-20220801-70681-jygdr6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/477025/original/file-20220801-70681-jygdr6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/477025/original/file-20220801-70681-jygdr6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/477025/original/file-20220801-70681-jygdr6.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">Listeria is an intracellular pathogen. Inside the body, it can grow inside a cell and spread to neighboring cells.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/listeria-monocytogenes-illustration-royalty-free-illustration/685023881">Kateryna Kon/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<h2>Listeria is tough</h2>
<p>Listeria can live in any place where food is grown, packaged, stored, transported, prepared or served. Our research team has even found listeria in <a href="https://doi.org/10.3390/pathogens7030060">organic lettuce harvested from a backyard garden</a>. </p>
<p>Listeria can survive and grow in temperatures as cold as <a href="https://ask.usda.gov/s/article/Can-Listeria-grow-at-refrigerator-temperatures">24 degrees Fahrenheit</a> (-4.4 Celsius) because it has <a href="https://doi.org/10.1080/10408390701856272">adapted to cold temperatures</a> and developed <a href="https://doi.org/10.4315/0362-028X-69.6.1473">tricks for overcoming cold stress</a>. Considering the average refrigerator maintains a temperature range of 35 F to 38 F (1.7 C to 3.3 C), even when the food is stored properly at refrigeration temperatures, a harmless few listeria can grow to dangerous levels of contamination over time.</p>
<p>Listeria is also extremely versatile in adapting to and surviving all kinds of disinfection processes. When it grows on surfaces, listeria protects itself with <a href="https://doi.org/10.3390%2Fpathogens6030041">a biofilm structure</a>, a kind of coating that forms a physical and chemical barrier and prevents disinfectants from reaching the bacteria within.</p>
<p>Surviving the harsh conditions outside our body is only the first part of the story. Before even beginning to cause infections, listeria needs to get to the intestines without getting caught and destroyed by the body’s defenses.</p>
<p>Traveling and surviving passage through a <a href="https://doi.org/10.3389%2Ffcimb.2014.00009">human digestive tract is not easy</a> for bacteria. Saliva enzymes can degrade bacterial cell walls. So can stomach acids and bile salts. Antibodies in our digestive tract can recognize and target bacteria for degradation. Moreover, <a href="https://doi.org/10.1084%2Fjem.20170495">resident gut microbes</a> are strong competitors for the limited amount of space and nutrients in our intestines.</p>
<p>After digestion, the body’s intestinal movement sends traffic one way – out of the body. In order to stick around and cause infections, bacteria have to attach themselves and hang on against the bowel movement while competing for nutrients. Successful pathogens can establish these survival and attachment tasks while undermining our immune defenses. </p>
<p>Listeria that manage to stick around in our intestines can trigger an immune response. In healthy people, that might manifest as <a href="https://www.cdc.gov/listeria/symptoms.html">minor diarrhea or vomiting that goes away without medical attention</a>. </p>
<p>However, those with compromised immune systems or immune systems temporarily weakened as a result of medication or <a href="https://doi.org/10.3389/fimmu.2020.575197">pregnancy</a> can be more susceptible to severe infections. In the absence of an effective immune system, listeria can invade other tissues and organs by creating an efficient niche for growth.</p>
<h2>Listeria in stealth mode</h2>
<p>Listeria is what we microbiologists call an intracellular pathogen. In an infected individual, listeria can grow inside a cell and <a href="https://doi.org/10.1083%2Fjcb.146.6.1333">spread to neighboring cells</a>. Hiding inside our cells this way, listeria avoids detection by antibodies or other immune defenses that are designed to detect and destroy threats that exist outside of our cells.</p>
<p>Once in stealth mode, listeria can move into and infect different organs. Wherever it goes, inflammation follows as the body’s immune system tries to go after the bacteria. The inflammation eventually results in collateral damage in nearby tissues. </p>
<p>In fact, deaths from listeria infections are often associated with the more invasive forms of the disease in which the microbes have breached the intestinal barriers and moved to other body parts. <a href="https://www.cdc.gov/listeria/symptoms.html">Life-threatening illnesses</a> that can result from listeria include meningitis – inflammation around the brain and spinal cord that can occur when these microbes infect the brain – or <a href="https://doi.org/10.1016/j.ijantimicag.2017.12.032">endocarditis</a>, infection of the heart’s inner lining. And in pregnant individuals, if the pathogen reaches the placenta, it can spread to the fetus and cause stillbirth or miscarriage.</p>
<p>As such, invasive listeria cases often have an alarmingly high <a href="https://www.fda.gov/animal-veterinary/animal-health-literacy/get-facts-about-listeria#">hospitalization rate of more than 90% and a fatality rate that can reach 30%</a>. </p>
<p>The scary statistics argue for a proactive and effective infection control to protect vulnerable populations, such as elderly or pregnant individuals, from listeria exposure. </p>
<h2>Think, cook and eat</h2>
<p>If you have risk factors and want to take extra precautions, maybe turn that unpasteurized cider into a hot, mulled cider to kill the bacteria with boiling and simmering. Eat soft cheeses on foods that get cooked, such as pizzas or grilled sandwiches, instead of eating them cold, straight from the refrigerator. Essentially, use heat to bring out the delicious flavors and eliminate potential listeria contamination in your food. </p>
<p>Ultimately, it’s nearly impossible to live in a completely sterile environment, eating food devoid of all living microorganisms. So enjoy your favorites, but <a href="https://www.fsis.usda.gov/food-safety">stay up to date with ongoing recalls</a> and follow the expiration guidelines, especially for ready-to-eat food.</p><img src="https://counter.theconversation.com/content/187905/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Yvonne Sun 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>Listeria causes serious illness and food recalls nearly every year.Yvonne Sun, Assistant Professor of Microbiology, University of DaytonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1809262022-06-09T14:13:05Z2022-06-09T14:13:05ZAdapting to life with COVID-19: Lessons our own immune system can teach us about public health information<figure><img src="https://images.theconversation.com/files/467858/original/file-20220608-21-d97uhv.jpg?ixlib=rb-1.1.0&rect=16%2C150%2C3562%2C2317&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">With mask mandates and vaccine requirements lifting, public health information remains crucial so people can weigh their own COVID-19 risks.</span> <span class="attribution"><span class="source">THE CANADIAN PRESS/Nathan Denette</span></span></figcaption></figure><p>The last of Ontario’s COVID-19 mask mandates — which have still been in effect in settings like hospitals and public transit — are scheduled to expire on June 11. While border protocols, such as random testing, have been extended at least until the end of June, long lineups at Toronto’s Pearson International Airport are <a href="https://www.thestar.com/politics/federal/2022/06/07/needless-covid-19-screening-is-causing-canadas-airport-delays-critics-charge-while-ottawa-says-its-following-the-science.html">fuelling calls to lift them</a>.</p>
<p>COVID-19 is still with us, but just as the virus has changed since 2020, so have our personal and public reactions toward it. As personal risk assessment becomes more important with fewer and fewer public health mandates, there are good lessons to be learned from how our immune system works.</p>
<h2>Clear communication</h2>
<p>In immunology, the way a threat — such as a virus — is presented to the immune system matters as much as the threat itself. The same can be said of public health messaging: its effectiveness rests on how it’s presented.</p>
<p>The <a href="https://www.youtube.com/watch?v=LmpuerlbJu0">immune system</a> is a diverse collection of tissues, cells, and molecules that — at its core — specialize in highly co-ordinated communication. Antibodies and T-cells are key in assessing how the immune system responds to a novel virus, like SARS-CoV-2. To recognize and respond to the threat, those cells need specific messages clearly presented in specific ways. This leads to tailored protective actions, including those carried out by antibodies.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/LmpuerlbJu0?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">An animated look at how the body’s immune system fights infections.</span></figcaption>
</figure>
<p>Antibodies act as specialized flags that not only identify viral particles so the immune system can find them, but also block those particles from infecting healthy cells. </p>
<p>Parts of the immune system remain fairly constant, but other parts are adaptive and can be tweaked in response to threats. T-cells and B-cells are highly sensitive to this, and shape adaptive immunity.</p>
<p>To make antibodies, B-cells must be able to recognize a fragment of the virus. A special class of T-cells called helpers must <a href="https://doi.org/10.1038/nri3084">present the virus fragment to the B-cell in a very specific way</a>. This leads to antibody-mediated protection.</p>
<p>Likewise, for a different class of T-cells — called killers — a small piece of the virus needs to be shown in a slightly different way. This specific presentation of the viral fragment is crucial to generating adaptive immunity, which then mobilizes the process of destroying the virus. </p>
<p>This is precisely what vaccines are designed to enable, but in a safe context avoiding actual virus exposure. Successful immune response gives us an army of trained killers that only recognize that one unique virus fragment.</p>
<p>Clearly, <a href="https://www.theatlantic.com/health/archive/2020/08/covid-19-immunity-is-the-pandemics-central-mystery/614956/">details matter</a> to the immune system. Change what that virus fragment looks like (mutate it), and that same trained immune system may let the virus slip by and need more guidance to <a href="https://doi.org/10.1038/s41586-021-04085-y">re-adapt</a>. And it does adapt. Continuously. </p>
<h2>Adapting messages</h2>
<p>The same concept applies in public health messaging and <a href="https://doi.org/10.1057/s41599-020-00645-1">science communication</a>. When the context changes, so should the strategy and the messaging to the public.</p>
<p>Over the course of the pandemic, its context has changed as the virus has changed. The more is learned about the virus, the better the public health messaging can be tailored. If that is done well, it can help minimize the impact of the virus on communities, at least in theory.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/467854/original/file-20220608-24-9xkmys.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A man in a suit wearing a face mask and four people with cameras pointed at him, shot from above with light fixture in the foreground" src="https://images.theconversation.com/files/467854/original/file-20220608-24-9xkmys.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/467854/original/file-20220608-24-9xkmys.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/467854/original/file-20220608-24-9xkmys.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/467854/original/file-20220608-24-9xkmys.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/467854/original/file-20220608-24-9xkmys.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/467854/original/file-20220608-24-9xkmys.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/467854/original/file-20220608-24-9xkmys.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">Dr. Kieran Moore, Ontario’s chief medical officer of health, wears a mask as he arrives at Queen’s Park in Toronto in April. He is greeted by media, also wearing masks.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Nathan Denette</span></span>
</figcaption>
</figure>
<p>In early 2020, local viral spread was low and our understanding of transmission was nascent. <a href="https://www.nytimes.com/2021/04/27/science/face-mask-guidelines-timeline.html">Public health advice</a> reflected this. Today, community viral spread is high and we understand its transmission routes. Public messaging should have adapted to this knowledge. Instead, masks and other <a href="https://www.cbc.ca/news/canada/toronto/covid19-ontario-march-9-mask-mandates-1.6378148">protections have been dropped</a>.</p>
<p>Paramount from a public health strategy perspective, we have learned that this virus is <a href="https://doi.org/10.1016/S0140-6736(21)00869-2">mostly spread</a> via <a href="https://doi.org/10.1126/science.abd9149">airborne routes</a>, in the same way that cigarette smoke moves and lingers. Picture it just like that!</p>
<p>But what <a href="https://doi.org/10.1038/d41586-022-00925-7">hasn’t been done well</a> is shaping public understanding of this to inform a strong mental model that can be applied to assess personal and public risk. We know mask <a href="https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/types-of-masks.html">quality matters</a>, with K/N95 as the <a href="https://thetyee.ca/Analysis/2022/01/06/N95-Mask-We-Should-Be-Wearing/">best choice</a>. We know indoor air <a href="https://doi.org/10.1063/5.0057100">ventilation and filtration</a> matters. And we know that vaccines work to train your immune system, <a href="https://doi.org/10.1056/NEJMc2119912">with three</a> or <a href="https://doi.org/10.1056/NEJMc2202542">four doses</a> being ideal in this particular context.</p>
<h2>Adapting to COVID-19</h2>
<p>As the sixth wave waned in Canada, the message was that it was time to try “<a href="https://www.cbc.ca/news/politics/canada-more-sustainable-covid-response-1.6339609">living with COVID-19</a>.”</p>
<p>This shift in messaging has consequences. It accepts that recurrent waves of the virus will circulate, with the accompanying impact on our personal and community health. This includes the unknown impact of emerging subvariants and future novel variants. To minimize those risks, there is a need to not just surrender to living with the virus and hope for a return to normal, but to <a href="https://www.stcatharinesstandard.ca/news/niagara-region/2022/02/11/no-more-hopium-learning-to-live-with-covid-19.html">adapt to living with COVID-19</a>.</p>
<p><a href="https://covid19-sciencetable.ca/ontario-dashboard/">Without accurate testing data</a>, it’s hard to tell the number of cases in the community right now. However, we do know that subvariants of Omicron <a href="https://news.un.org/en/story/2022/04/1116182">BA.4 and BA.5</a> have <a href="https://www.publichealthontario.ca/-/media/Documents/nCoV/voc/covid-19-omicron-risk-assessment.pdf?sc_lang=en">been detected in Canada</a>. </p>
<p>Despite the effectiveness of current vaccines, vaccination will not solve this on its own. More tools are on the way in the form of <a href="https://doi.org/10.1101/2022.02.14.480449">variant-tailored</a>, <a href="https://doi.org/10.1038/d41573-022-00074-6">pan-coronavirus</a> and <a href="https://doi.org/10.1101/2022.01.24.477597">mucosal</a> vaccines (<a href="https://doi.org/10.1016/j.cell.2022.02.005">nasal sprays</a>) and <a href="https://www.canada.ca/en/health-canada/news/2022/01/health-canada-authorizes-paxlovidtm-for-patients-with-mild-to-moderate-covid-19-at-high-risk-of-developing-serious-disease.html">antivirals</a>. </p>
<p>Right now, the virus <a href="https://health-infobase.canada.ca/covid-19/wastewater/">continues to circulate in the community</a>, with too little understanding of where the risk is. COVID-19 and public health protections require a <a href="https://www.forbes.com/sites/carminegallo/2020/12/10/the-virologist-who-created-a-swiss-cheese-metaphor-to-explain-the-pandemic-has-a-message-for-educators/?sh=50c33b376335">layered approach</a>.</p>
<h2>The path back to ‘normal’</h2>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/467856/original/file-20220608-12-uvt0vb.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A long line of people with luggage" src="https://images.theconversation.com/files/467856/original/file-20220608-12-uvt0vb.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/467856/original/file-20220608-12-uvt0vb.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=411&fit=crop&dpr=1 600w, https://images.theconversation.com/files/467856/original/file-20220608-12-uvt0vb.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=411&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/467856/original/file-20220608-12-uvt0vb.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=411&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/467856/original/file-20220608-12-uvt0vb.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=516&fit=crop&dpr=1 754w, https://images.theconversation.com/files/467856/original/file-20220608-12-uvt0vb.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=516&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/467856/original/file-20220608-12-uvt0vb.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=516&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">People wait in line to check in at Pearson International Airport in Toronto on May 12. Major delays have affected passengers at security and clearance points.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Nathan Denette</span></span>
</figcaption>
</figure>
<p>The path back to a sense of normal doesn’t involve ignoring the threat, and letting it pass, hoping the damage will be manageable. Rather, much like the immune system depends on clear communication to adapt, the path back to normal may depend on public education about vaccination, risk mitigation — such as knowing when it’s <a href="https://www.canada.ca/en/public-health/services/diseases/2019-novel-coronavirus-infection/prevention-risks/about-non-medical-masks-face-coverings.html">best to mask</a> and which mask to choose — and policy development to improve <a href="https://www.whitehouse.gov/ostp/news-updates/2022/03/23/lets-clear-the-air-on-covid/">indoor air quality</a>. </p>
<p>Our immune system adapts to a changing virus by showing our T- and B-cells what has mutated in the latest variant. It learns from the most recent and best available evidence, and creates the best-prepared army of precision antibodies and killer cells. We must enable this at the public response level too.</p>
<p>As individuals, we are the B- and T-cells of our community immunity right now. We need clearly presented strategic information to recognize and precisely assess the threat. As the pandemic continues — and yes, it does continue — public and personal behaviour needs to evolve with the changing pandemic context, with <a href="https://www.scienceupfirst.com/share/">clear public health messaging</a> and infrastructure action. </p>
<p>Like the pieces of immune system, we are all in this together, not individually.</p><img src="https://counter.theconversation.com/content/180926/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Adam J. MacNeil receives funding from the Natural Sciences and Engineering Research Council of Canada (NSERC), New Frontiers in Research Fund (NFRF), Canadian Institutes of Health Research (CIHR), Mitacs, Ontario & the Canada Foundation for Innovation (CFI). </span></em></p>To help people make informed decisions about ongoing COVID-19 risks, public health messaging needs to adapt as the pandemic evolves, just as immune systems adapt to new viruses and variants.Adam J. MacNeil, Associate Professor of Immunology, Brock UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1821122022-05-06T12:33:22Z2022-05-06T12:33:22ZCOVID-19 official counts can miss mild cases – here’s how serosurveys that analyze blood for signs of past infection can help<figure><img src="https://images.theconversation.com/files/461644/original/file-20220505-17-7g5jqg.jpg?ixlib=rb-1.1.0&rect=50%2C62%2C2413%2C1584&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Researchers can test blood samples taken for other reasons to see if patients have previously had COVID-19.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/leila-kohbodi-and-melvin-narciso-prepare-viles-of-blood-news-photo/563577159">Don Bartletti/Los Angeles Times via Getty Images</a></span></figcaption></figure><p><em>It’s an eye-catching statistic: <a href="http://dx.doi.org/10.15585/mmwr.mm7117e3">58% of the whole population and 75% of kids</a> in the U.S. <a href="https://covid.cdc.gov/covid-data-tracker/#national-lab">had been infected by the coronavirus</a> by the end of February 2022. That’s a pretty big jump from the official case count that hovered <a href="https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/past-reports/03042022.html">around a quarter of Americans</a> having been diagnosed with COVID-19. A report from the U.S. Centers for Disease Control and Prevention based these higher proportions on what’s called a <a href="https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/about-serology-surveillance.html">serosurvey: a study that looks at people’s blood</a> to see if they’ve had a particular illness.</em></p>
<p><em><a href="https://scholar.google.com/citations?user=eNuipnQAAAAJ&hl=en&oi=ao">Isobel Routledge</a> is an infectious disease epidemiologist <a href="https://doi.org/10.1038/s41467-021-23651-6">who uses serosurveys</a> <a href="https://doi.org/10.1038/s41467-022-30051-x">in her own research</a>. Here she explains the science behind the approach and what a serosurvey can – and can’t – tell you.</em></p>
<h2>What does a serosurvey look for?</h2>
<p>When you’re infected by or vaccinated against a pathogen, like the SARS-CoV-2 virus that causes COVID-19, your body produces antibodies to fight it. Some types of antibodies remain in your blood long after you’ve recovered. During a serosurvey, researchers look in blood samples for these long-lasting antibodies. They act as markers of past exposure to the pathogen.</p>
<p>The power of this type of study is that it can reveal whether someone was previously infected with a particular pathogen, even if they didn’t have symptoms or take a test. Having specific antibodies in your blood can also mean you’re immune to a certain disease – scientists are still investigating what the <a href="https://doi.org/10.1038/s41591-021-01432-4">markers of protection against COVID-19</a> might be, though.</p>
<p>If they test enough blood samples – ideally through a random sample of the population – researchers can use a serosurvey to estimate the proportion of a population that has been previously infected or vaccinated, and in some cases <a href="https://doi.org/10.1128/CVI.00131-10">estimate the proportion of the population that is immune</a> to a particular disease.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/461646/original/file-20220505-23-zgjut1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="person holds up a vaccination sticker next to arm with bandaid" src="https://images.theconversation.com/files/461646/original/file-20220505-23-zgjut1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/461646/original/file-20220505-23-zgjut1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/461646/original/file-20220505-23-zgjut1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/461646/original/file-20220505-23-zgjut1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/461646/original/file-20220505-23-zgjut1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/461646/original/file-20220505-23-zgjut1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/461646/original/file-20220505-23-zgjut1.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">Researchers can focus on specific antibodies that your body makes after catching COVID-19 that are different from the ones triggered by vaccination.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/year-old-newly-vaccinateda-against-covid-19-holds-up-a-news-photo/1233291434">Scott Heins/Getty Images</a></span>
</figcaption>
</figure>
<h2>Can serosurveys tell the difference between an infection and vaccination?</h2>
<p>Yes. In a recent study, my colleagues and I wanted to separate out those who had been previously infected with SARS-CoV-2 and those who had been vaccinated. So we looked for <a href="https://doi.org/10.1038/s41467-022-30051-x">two different bio-markers</a> in the blood samples.</p>
<p>Vaccines administered in the U.S. <a href="https://theconversation.com/what-happens-when-the-covid-19-vaccines-enter-the-body-a-road-map-for-kids-and-grown-ups-164624">trigger your body to produce antibodies</a> to a particular part of the SARS-CoV-2 virus called the spike protein. If we identified antibodies to the spike protein, that means a person could have been vaccinated, been previously infected with SARS-CoV-2, or both.</p>
<p>When people are naturally infected with SARS-CoV-2, they produce antibodies to another part of the coronavirus called the nucleocapsid protein. If we identified antibodies to the nucleocapsid protein, then we knew the patient had previously contracted COVID-19. Vaccination doesn’t trigger these particular antibodies. The CDC study used this type of test to separate out only those who were previously infected. </p>
<h2>How far back in time can this method ‘see’?</h2>
<p>Antibodies take a few weeks to build up to their maximum level. Then their concentration wanes in the weeks and months after exposure to an infectious disease.</p>
<p>Colleagues of mine at the University of California, San Francisco are currently studying the dynamics of this process for COVID-19 in the <a href="https://doi.org/10.1126/sciadv.abh3409">Long-term Impact of Infection With Novel Coronavirus (LIINC)</a> study. Since March 2020, they’ve been following volunteers who’ve recovered from COVID-19, collecting blood and saliva samples at regular intervals to monitor changes in antibody levels.</p>
<p>Based on over a year of observations, the team estimated that someone who had previously had COVID-19 could test negative on an antibody test on average anywhere between 96 and 925 days after their infection. It seems to depend a lot on disease severity and the specific test used.</p>
<p>Several tests, including the <a href="http://dx.doi.org/10.15585/mmwr.mm7117e3">one used in the recent CDC study</a>, showed no evidence of any decrease in detecting antibodies over six months of observation. Additional studies using a different test found that the majority of patients had detectable levels of nucleocapsid antibodies in the blood at <a href="https://doi.org/10.1016/S0140-6736(21)00238-5">a year</a> and at <a href="https://doi.org/10.3389/fimmu.2022.829665">16 months</a> after infection.</p>
<p>The CDC study looked at blood samples collected between September 2021 and February 2022, which was at most two years after anyone would have contracted COVID-19. Based on current evidence, I’d not too concerned about a lot of false negatives based on how long ago people were infected. However, if there were some missed infections in this study, that would mean that the true proportion of the population that was previously infected is slightly more than the estimated 58%. </p>
<h2>Why are serosurveys important to do?</h2>
<p>Traditional disease surveillance measures, such as counts of reported cases or positive tests, are super important for monitoring the spread and burden of infectious diseases. But for a disease like COVID-19 that can cause lots of asymptomatic and mild infections, the numbers of reported cases may represent only the tip of the iceberg.</p>
<p>Case counts often miss asymptomatic infections, as well as infections in those who do not have access to health care or testing. It can also be tricky to compare data from disease surveillance systems over time and in different places.</p>
<p>Serosurveys are a way of capturing asymptomatic and unreported infections, and a well-designed serosurvey can often provide a “truer” picture of infection history in a population than case counts. But serosurveys have their own, separate biases.</p>
<h2>What factors make a serosurvey tricky to do well?</h2>
<p>You need to consider who is in the group you’ve taken your samples from and whether they’re representative of the wider U.S. in terms of demographics, including location, age, biological sex, race/ethnicity, socioeconomic status, occupation and so on. Otherwise your finding might not be generalizable to the population as a whole.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/461647/original/file-20220505-22-k709u8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="people donating blood at a blood drive" src="https://images.theconversation.com/files/461647/original/file-20220505-22-k709u8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/461647/original/file-20220505-22-k709u8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/461647/original/file-20220505-22-k709u8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/461647/original/file-20220505-22-k709u8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/461647/original/file-20220505-22-k709u8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/461647/original/file-20220505-22-k709u8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/461647/original/file-20220505-22-k709u8.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">The people who donate blood may be different from the population as a whole, so a survey based largely on their samples may not be representative of the larger population.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/phlebotomist-herbert-collins-draws-blood-from-victoria-news-photo/1224220324">Scott Olson/Getty Images</a></span>
</figcaption>
</figure>
<p>Many studies, including the CDC report and my own work, rely on what’s called convenience sampling. We piggyback on blood samples that were initially collected for clinical testing or blood donation and then reuse them for the serosurvey. This means we’re only including people who are getting blood tests for health conditions or checkups, or those donating blood. We’re missing out on parts of the U.S. population who don’t access health care or donate blood. </p>
<p><a href="https://doi.org/10.1038/d41586-022-00336-8">Randomly selecting a representative sample</a> of the entire population can get around those biases. However, this kind of study is extremely expensive and time-consuming to carry out. Just a small number have been <a href="https://doi.org/10.1371/journal.pone.0267322">conducted at the state level</a>.</p>
<p>A further challenge is defining the threshold for considering an antibody test as positive or negative. These tests measure the concentration of a particular antibody in the sample. Antibody responses can vary depending on the <a href="https://doi.org/10.1093/infdis/jiaa523">severity of illness and time since infection</a>. If researchers set the cutoff for a positive result too high, it can lead to more false negatives.</p>
<p>The recent CDC serosurvey acknowledged some limitations in how generalizable it really is. No data on race/ethnicity was available to weight the study results, and the study was likely to have over-represented people who could seek health care. If the antibody test was less accurate with mild or older infections, the true proportion of the population that was previously exposed could have been even higher than the 58% estimate. Despite these limitations, this study does provide hugely valuable data for tracking changes in SARS-CoV-2 transmission over time.</p><img src="https://counter.theconversation.com/content/182112/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Isobel Routledge receives funding from the National Institutes of Health. </span></em></p>Your blood can hold a record of past illnesses. That information can reveal how many people have had a certain infection – like 58% of Americans having had COVID-19 by the end of February 2022.Isobel Routledge, Postdoctoral Scholar in Medicine, University of California, San FranciscoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1810272022-04-15T12:16:17Z2022-04-15T12:16:17ZWhy we can’t ‘boost’ our way out of the COVID-19 pandemic for the long term<figure><img src="https://images.theconversation.com/files/458005/original/file-20220413-9289-3x1gnw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Although the COVID-19 vaccines have saved millions of lives, they have been insufficient at preventing breakthrough infections.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/covid-19-vaccine-filling-syringe-royalty-free-image/1297565599?adppopup=true">Andriy Onufriyenko/Moment via Getty Images</a></span></figcaption></figure><p>With <a href="https://theconversation.com/do-you-need-a-second-booster-shot-an-epidemiologist-scoured-the-latest-research-and-has-some-answers-180488">yet another COVID-19 booster</a> available for vulnerable populations in the U.S., many people find themselves <a href="https://www.npr.org/sections/health-shots/2022/04/04/1090912213/another-booster-a-vaccine-for-omicron-heres-what-could-be-next-for-covid-vaccine">wondering what the end game will be</a>.</p>
<p>The <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html#">mRNA vaccines</a> currently used in the U.S. against COVID-19 have been highly successful at preventing hospitalization and death. <a href="https://www.commonwealthfund.org/blog/2022/impact-us-covid-19-vaccination-efforts-march-update">The Commonwealth Fund recently reported</a> that in the U.S. alone, the vaccines have prevented over 2 million people from dying and over 17 million from hospitalization.</p>
<p>However, the vaccines have <a href="https://doi.org/10.1038/d41586-022-00775-3">failed to provide long-term protective immunity</a> to prevent <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/effectiveness/why-measure-effectiveness/breakthrough-cases.html?">breakthrough infections</a> – cases of COVID-19 infection that occur in people who are fully vaccinated. </p>
<p>Because of this, the Centers for Disease Control and Prevention recently endorsed a second booster shot for individuals 50 years of age and older and people who are immunocompromised. Other countries including <a href="https://www.reuters.com/world/middle-east/top-israeli-health-official-approves-second-covid-19-vaccine-booster-2021-12-30/">Israel</a>, the <a href="https://www.bbc.com/news/health-55045639">U.K.</a> and <a href="https://www.reuters.com/world/asia-pacific/skorea-give-second-covid-booster-shot-people-over-60-yonhap-2022-04-12/">South Korea</a> have also approved a second booster. </p>
<p>However, it has become <a href="https://www.nytimes.com/live/2022/04/05/world/covid-19-mandates-cases-vaccine">increasingly clear</a> that the second booster does not provide long-lasting protection against breakthrough infections. As a result, it will be necessary to retool the existing vaccines to increase the duration of protection in order to help bring the pandemic to an end. </p>
<p><a href="https://scholar.google.com/citations?user=jJVj3sUAAAAJ&hl=en">As immunologists</a> <a href="https://scholar.google.com/citations?user=af7TahQAAAAJ&hl=en">studying</a> <a href="https://pubmed.ncbi.nlm.nih.gov/?term=nagarkatti+p&sort=date&size=200">immune response to infections and other threats</a>, we are trying to better understand the vaccine booster-induced immunity against COVID-19. </p>
<h2>Activating longer-term immunity</h2>
<p>It’s a bit of a medical mystery: Why are mRNA vaccines so successful in preventing the serious form of COVID-19 but not so great at protecting against <a href="https://theconversation.com/what-is-a-breakthrough-infection-6-questions-answered-about-catching-covid-19-after-vaccination-164909">breakthrough infections</a>? Understanding this concept is critical for stopping new infections and controlling the pandemic. </p>
<p>COVID-19 infection is unique in that the majority of people who get it recover with mild to moderate symptoms, while a <a href="https://doi.org/10.1097/PRA.0000000000000475">small percentage get the severe disease</a> that can lead to hospitalization and death. </p>
<p>Understanding how our immune system works during the mild versus severe forms of COVID-19 is also important to the process of developing more targeted vaccines. </p>
<p>When people are first exposed to SARS-CoV-2 – the virus that causes COVID-19 – or to a vaccine against COVID-19, the immune system activates two key types of immune cells, called <a href="https://www.ncbi.nlm.nih.gov/books/NBK459471/#">B and T cells</a>. The B cells produce Y-shaped protein molecules called antibodies. The antibodies bind to the protruding spike protein on the surface of the virus. This blocks the virus from entering a cell and ultimately prevents it from causing an infection.</p>
<p>However, if not enough antibodies are produced, the virus can escape and infect the host cells. When this happens, the immune system activates what are known as <a href="https://doi.org/10.1038/d41586-022-00063-0">killer T cells</a>. These cells can recognize virus-infected cells immediately after infection and destroy them, thereby preventing the virus from replicating and causing widespread infection.</p>
<p>Thus, there is <a href="https://doi.org/10.1016/j.xcrm.2022.100562">increasing evidence</a> that antibodies may help prevent breakthrough infections while the killer T cells provide protection against the severe form of the disease. </p>
<h2>Why booster shots?</h2>
<p>The B cells and T cells are unique in that after they mount an initial immune response, they get <a href="https://doi.org/DOI:%2010.1126/science.abm0829">converted into memory cells</a>. Unlike antibodies, memory cells can stay in a person’s body <a href="https://doi.org/10.1038/nm917">for several decades</a> and can mount a rapid response when they encounter the same infectious agent. It is because of such memory cells that some vaccines against diseases such as smallpox <a href="https://doi.org/10.1016/j.amjmed.2008.08.019">provide protection for decades</a>.</p>
<p>But with certain vaccines, such as hepatitis, it is necessary to give <a href="https://www.cdc.gov/vaccines/hcp/conversations/understanding-vacc-work.html">multiple doses of a vaccine</a> to boost the immune response. This is because the first or second dose is not sufficient to induce robust antibodies or to sustain the memory B and T cell response. </p>
<p>This boosting, or amplifying of the immune response, <a href="https://doi.org/10.1038/s41421-022-00373-7">helps to increase</a> the number of B cells and T cells that can respond to the infectious agent. Boosting also <a href="https://doi.org/10.3389/fimmu.2021.612747">triggers the memory response</a>, thereby providing prolonged immunity against reinfection. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/6eMh0Vpyoik?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">T-cell activation explained.</span></figcaption>
</figure>
<h2>COVID vaccine boosters</h2>
<p>While the third dose – or first booster – of COVID-19 vaccines was <a href="https://www.cdc.gov/mmwr/volumes/71/wr/mm7104e3.htm">highly effective</a> in preventing the severe form of COVID-19, the protection afforded against infection <a href="https://www.npr.org/sections/goatsandsoda/2022/01/19/1071809356/covid-booster-omicron-efficacy">lasted for less than four to six months</a>. </p>
<p>That diminished protection even after the third dose is what led <a href="https://www.cdc.gov/media/releases/2022/s0328-covid-19-boosters.html#">the CDC to endorse the fourth shot</a> of COVID-19 vaccine – called the second booster – for people who are immunocompromised and those aged 50 and older. </p>
<p>However, a recent <a href="https://doi.org/10.1101/2022.02.15.22270948">preliminary study from Israel</a> that has not yet been peer-reviewed showed that the second booster did not further boost the immune response but merely restored the waning immune response seen during the third dose. Also, the second booster provided little extra protection against COVID-19 when compared to the initial three doses.</p>
<p>So while the second booster certainly provides a small benefit to the most vulnerable people by extending immune protection by a few months, there has been <a href="https://www.npr.org/sections/goatsandsoda/2022/02/22/1029057935/who-might-benefit-from-a-4th-shot-and-who-might-not">considerable confusion</a> over what the availability of the fourth shot means for the general population. </p>
<h2>Frequent boosting and immune exhaustion</h2>
<p>In addition to the inability of the current COVID-19 vaccines to provide long-term immunity, some researchers believe that frequent or constant exposure to foreign molecules found in an infectious agent may cause immune “exhaustion.” </p>
<p><a href="https://doi.org/10.1038/cddis.2015.162">Such a phenomenon</a> has been widely reported with HIV infection and cancer. In those cases, because the T cells “see” the foreign molecules all the time, they can get worn down and fail to rid the body of the cancer or HIV.</p>
<p>Evidence also suggests that in severe cases of COVID-19, the <a href="https://doi.org/10.1038/s41423-021-00750-4">killer T cells may be exhibiting</a> immune exhaustion and therefore be unable to mount a strong immune response. Whether repeated COVID-19 vaccine boosters can cause similar T cell exhaustion is a possibility that needs further study. </p>
<h2>Role of adjuvants to boost vaccine-induced immunity</h2>
<p>Another reason why the mRNA vaccines have failed to induce sustained antibody and memory response may be related to <a href="https://www.cdc.gov/vaccinesafety/concerns/adjuvants.html">ingredients called adjuvants</a>. Traditional vaccines such as those for diphtheria and tetanus <a href="https://theconversation.com/adjuvants-the-unsung-heroes-of-vaccines-156548">use adjuvants</a> to boost the immune response. These are compounds that activate <a href="https://doi.org/10.1038/s41590-021-01091-0">the innate immunity</a> that consists of cells known as macrophages. These are specialized cells that help the T cells and B cells, ultimately inducing a stronger antibody response.</p>
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<p>Because mRNA-based vaccines are a relatively new class of vaccines, they do not include the traditional adjuvants. The current mRNA vaccines used in the U.S. rely on small balls of fat called lipid nanoparticles to deliver the mRNA. These lipid molecules <a href="https://doi.org/10.1038/s41590-022-01168-4">can act as adjuvants</a>, but how precisely these molecules affect the long-term immune response remains to be seen. And whether the current COVID-19 vaccines’ failure to trigger strong long-lived antibody response is related to the adjuvants in the existing formulations remains to be explored. </p>
<p>While the current vaccines are highly effective in preventing severe disease, the next phase of vaccine development will need to focus on how to trigger a long-lived antibody response that would last for at least a year, making it likely that COVID-19 vaccines will become an annual shot.</p><img src="https://counter.theconversation.com/content/181027/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Prakash Nagarkatti receives funding from the National Institutes of Health and the National Science Foundation</span></em></p><p class="fine-print"><em><span>Mitzi Nagarkatti receives funding from National Institutes of Health</span></em></p>Research suggests that too-frequent immunizations may lead to a phenomenon called “immune exhaustion.”Prakash Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South CarolinaMitzi Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South CarolinaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1795272022-03-29T18:55:45Z2022-03-29T18:55:45ZHow does the COVID-19 prevention drug Evusheld work and who should receive it? An infectious disease specialist explains<figure><img src="https://images.theconversation.com/files/454810/original/file-20220328-17-p5v6as.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1024%2C683&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">While many immunocompromised and high-risk patients may benefit from AstraZeneca's Evusheld, drug distribution and access have been uneven.</span> <span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/VirusOutbreakCovidAntibodyDrug/2716fff2b7694fb69cb8ca8d2953813a">AP Photo/Ted S. Warren</a></span></figcaption></figure><p><em>The U.S. Food and Drug Administration granted <a href="https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-new-long-acting-monoclonal-antibodies-pre-exposure">emergency use authorization</a> to AstraZeneca’s COVID-19 antibody drug Evusheld on Dec. 8, 2021. Infectious disease physician Patrick Jackson of the University of Virginia explains how it works, who’s eligible and why some patients are having difficulties accessing it.</em></p>
<h2>1. What is Evusheld, and how does it work?</h2>
<p>Evusheld is the <a href="https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-new-long-acting-monoclonal-antibodies-pre-exposure">first FDA-authorized drug</a> to prevent COVID-19 in high-risk people who aren’t adequately protected by vaccination alone. <a href="https://www.fda.gov/media/154701/download">Data from a preliminary study</a> that has not yet been peer reviewed showed Evusheld reduced the risk of symptomatic COVID-19 by 77% in unvaccinated high-risk adults.</p>
<p>When the immune system is exposed to a foreign protein – for example, by infection or vaccination – it produces antibodies in response to the potential threat. Evusheld is a combination of two antibodies, tixagevimab and cilgavimab, that bind to the spike protein of the virus that causes COVID-19 and prevent it from entering and infecting cells. Evusheld is a <a href="https://doi.org/10.1038/s41586-020-2548-6">monoclonal antibody drug</a>, meaning that it is made of mass-produced identical antibodies that originally came from a <a href="https://courses.lumenlearning.com/microbiology/chapter/polyclonal-and-monoclonal-antibody-production/">single type</a> of white blood cell. Evusheld <a href="https://bloodcancer.org.uk/news/antivirals-and-monoclonal-antibodies-whats-the-difference/">functions differently</a> from antiviral drugs like molnupiravir, which work by stopping the virus from replicating within cells.</p>
<p>Tixagevimab and cilgavimab are versions of natural human antibodies that have been modified to <a href="https://doi.org/10.1126/scitranslmed.abl8124">last much longer</a> in the body than they normally would. This allows Evusheld to provide COVID-19 protection for several months following a single dose. It is expected that Evusheld will need to be given <a href="https://www.astrazeneca.com/media-centre/statements/2022/fda-evusheld-dosage-update-us.html">about every six months</a> to keep antibody levels high enough to be effective against the virus. Patients may need to keep getting Evusheld doses as long as there is a significant risk of COVID-19.</p>
<p>Evusheld is not intended to treat COVID-19, but to help prevent vulnerable patients from getting sick in the first place.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/M3zllm8QbCM?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Monoclonal antibodies have a wide range of medical uses, including pregnancy tests and cancer treatment.</span></figcaption>
</figure>
<h2>2. Who should be receiving Evusheld?</h2>
<p>Evusheld can be used by people ages 12 and up who fall into <a href="https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-new-long-acting-monoclonal-antibodies-pre-exposure">two specific groups</a> unable to receive the full benefit of COVID-19 vaccination.</p>
<p>The first group is people who are moderately to severely immunocompromised because of a medical condition or treatment. While most in this group get some protection from the COVID-19 vaccines, the immune systems of some <a href="https://doi.org/10.1093/cid/ciac103">may not be able to make enough</a> protective antibodies on their own. This includes people receiving treatment for certain cancers, solid organ or stem cell transplant recipients and people with certain immune system disorders. People who take immunosuppressive medications, such as high-dose steroids and common autoimmune disease treatments, may also be eligible.</p>
<p>Evusheld is also authorized for the small number of people who had a severe reaction to the COVID-19 vaccines and can’t receive the full recommended dose regimen. It is important to note that this does not apply to <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/expect/after.html">common mild reactions</a>, such as pain at the injection site or mild fever. Most people who have rare allergic reactions to the COVID-19 vaccines can still <a href="https://doi.org/10.1001/jamainternmed.2021.8515">safely receive additional doses</a>, and should discuss their options with their doctor.</p>
<h2>3. When are you supposed to take Evusheld?</h2>
<p>Evusheld is used to prevent COVID-19 before a person has been exposed to the virus. Currently it isn’t approved to treat someone who is already sick with COVID-19 or to prevent an infection after recent exposure. </p>
<p>There are <a href="https://www.covid19treatmentguidelines.nih.gov/management/clinical-management/nonhospitalized-adults--therapeutic-management/">several COVID-19 treatments</a> available for high-risk people who do become infected. Unpublished data that have not yet been peer reviewed suggest that Evusheld may have a role in <a href="https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/azd7442-phiii-trial-positive-in-covid-outpatients.html">COVID-19 treatment</a> in addition to prevention, but using the drug in this way has not yet been authorized by the FDA.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/454796/original/file-20220328-23-121o4r1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Health care provider preparing to give a patient a shot." src="https://images.theconversation.com/files/454796/original/file-20220328-23-121o4r1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/454796/original/file-20220328-23-121o4r1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/454796/original/file-20220328-23-121o4r1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/454796/original/file-20220328-23-121o4r1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/454796/original/file-20220328-23-121o4r1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/454796/original/file-20220328-23-121o4r1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/454796/original/file-20220328-23-121o4r1.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">Immunocompromised patients can bolster their protection against COVID-19 with both vaccination and monoclonal antibody drugs like Evusheld.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/doctor-preparing-to-inject-male-patient-with-royalty-free-image/1297299344">Andrej Filipovic/iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<p>Evusheld is given <a href="https://www.fda.gov/media/154703/download">at least two weeks after</a> a patient’s last vaccine dose. This is to ensure the vaccine has had enough time to establish its full protective effects. This recommendation may change as researchers learn more about how vaccines and monoclonal antibodies like Evusheld work together. </p>
<p>Generally, immunocompromised people who can get vaccinated and boosted for COVID-19 should do so in addition to taking Evusheld. While they may not be as strongly protected as others, vaccination is still likely to provide some benefit. </p>
<h2>4. How effective is Evusheld against variants?</h2>
<p>One significant shortcoming of monoclonal antibody drugs like Evusheld is that they are <a href="https://www.covid19treatmentguidelines.nih.gov/therapies/anti-sars-cov-2-antibody-products/anti-sars-cov-2-monoclonal-antibodies/">not all equally effective</a> against different variants of the virus that causes COVID-19.</p>
<p>Evusheld entered clinical trials before the omicron variant <a href="https://covariants.org/per-country?region=World">dominated infections</a> around the world. Lab studies have given <a href="https://covdb.stanford.edu/page/susceptibility-data/">conflicting results</a> on how effective Evusheld might be against the omicron subvariants currently circulating in the U.S. It also isn’t clear how well those lab studies predict real-world protection against COVID-19.</p>
<p>In response to this concern, the FDA <a href="https://www.fda.gov/drugs/drug-safety-and-availability/fda-authorizes-revisions-evusheld-dosing">recently doubled</a> the authorized dose of Evusheld. The idea is that if the Evusheld antibodies are less effective against one of the omicron subvariants, more antibodies might still offer protection. Future variants may make Evusheld more or less effective.</p>
<h2>5. Are there any other preventive treatments?</h2>
<p>Other than the vaccines, Evusheld is currently the only drug approved or authorized in the U.S. for the prevention of COVID-19.</p>
<p>Until recently, two other monoclonal antibody drugs, casirivimab-imdevimab and bamlanivimab-etesevimab, were used to prevent disease in people who were recently exposed to COVID-19. Unfortunately, these drugs are <a href="https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-limits-use-certain-monoclonal-antibodies-treat-covid-19-due-omicron">not effective</a> against the omicron variant that is now the source of almost all U.S. COVID-19 cases.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/454809/original/file-20220328-15-1h2yobe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Closeup of Evusheld vials on a tray" src="https://images.theconversation.com/files/454809/original/file-20220328-15-1h2yobe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/454809/original/file-20220328-15-1h2yobe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/454809/original/file-20220328-15-1h2yobe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/454809/original/file-20220328-15-1h2yobe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/454809/original/file-20220328-15-1h2yobe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/454809/original/file-20220328-15-1h2yobe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/454809/original/file-20220328-15-1h2yobe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Evusheld is currently authorized for use as a COVID-19 prophylactic in only certain groups of people.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/vials-of-a-test-production-are-pictured-at-the-assembly-news-photo/1238317963">Jonathan Nackstrand/AFP via Getty Images</a></span>
</figcaption>
</figure>
<p>Researchers are looking into whether another monoclonal antibody, <a href="https://clinicaltrials.gov/ct2/show/NCT05210101">sotrovimab</a>, which is currently being used as a treatment for COVID-19 in <a href="https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-sotrovimab-emergency-use-authorization">certain U.S. regions</a> that have not yet been overtaken by the <a href="https://theconversation.com/what-is-the-new-covid-19-variant-ba-2-and-will-it-cause-another-wave-of-infections-in-the-us-179619">BA.2 omicron subvariant</a>, could also be used to bolster immunity in immunocompromised people.</p>
<p>There is no evidence that drugs like <a href="https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/#toc-6">hydroxychloroquine</a> or <a href="https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/#toc-17">ivermectin</a> are useful for preventing COVID-19.</p>
<h2>6. Why is it so difficult to access Evusheld?</h2>
<p>The U.S. government has <a href="https://www.reuters.com/world/us/astrazeneca-says-us-buy-additional-500000-evusheld-doses-2022-01-12/">purchased hundreds of thousands of doses</a> of Evusheld and is distributing these through state and territorial health departments. But that’s far fewer doses than the <a href="https://www.theatlantic.com/health/archive/2022/02/covid-pandemic-immunocompromised-risk-vaccines/622094/">7 million or more immunocompromised people</a>, or <a href="https://doi.org/10.1001/jama.2016.16477">roughly 2.7% of American adults</a>, who might benefit from this drug. While AstraZeneca has said there are <a href="https://khn.org/news/article/evusheld-covid-prevention-monoclonal-antibody-therapy-availability-hhs/">more doses</a>, it is unclear whether the U.S. plans to purchase more. </p>
<p>While some hospitals have had overwhelming demand, others have <a href="https://www.nytimes.com/2022/03/06/us/politics/evusheld-covid-treatment.html">unused doses</a>. Some hospitals have had to <a href="https://khn.org/news/article/evusheld-covid-prevention-monoclonal-antibody-therapy-availability-hhs/">implement allocation systems</a> to ensure that patients at highest risk are prioritized, and those policies are <a href="https://www.npr.org/sections/health-shots/2022/01/25/1075432400/hospitals-use-a-lottery-to-allocate-scarce-covid-drugs-for-the-immunocompromised">not standardized</a>. The recent FDA decision to <a href="https://www.fda.gov/drugs/drug-safety-and-availability/fda-authorizes-revisions-evusheld-dosing">increase the standard Evusheld dose</a> also means that supply won’t be able to stretch as far. </p>
<p>Unfortunately, because Congress has failed to fund ongoing COVID-19 programs, this might further <a href="https://www.whitehouse.gov/briefing-room/statements-releases/2022/03/15/fact-sheet-consequences-of-lack-of-funding-for-efforts-to-combat-covid-19-if-congress-does-not-act/">decrease the supply</a> of Evusheld available to patients.</p>
<h2>7. How do I know if I need Evusheld, and how can I get it?</h2>
<p>If you think you might benefit from Evusheld, talk to your doctor about whether you qualify. The doctor can write you a prescription. </p>
<p>Evusheld is administered as two injections during one session, and patients are observed for one hour to monitor for rare allergic reactions. Because of limited supply and these special monitoring requirements, Evusheld is given only at certain locations. Many state health departments have websites that let you look up nearby medical centers that have Evusheld. The federal government also has a <a href="https://covid-19-therapeutics-locator-dhhs.hub.arcgis.com/">treatment locator</a> for Evusheld and other COVID-19 drugs, though this may not be completely up to date.</p>
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<p class="fine-print"><em><span>Patrick Jackson receives funding from the National Institutes of Health. He is affiliated with Indivisible Charlottesville.</span></em></p>Evusheld is an antibody drug from AstraZeneca intended to help prevent COVID-19 infection for immunocompromised and other vulnerable patients.Patrick Jackson, Assistant Professor of Infectious Diseases, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1773092022-02-25T13:45:50Z2022-02-25T13:45:50ZHow long does protective immunity against COVID-19 last after infection or vaccination? Two immunologists explain<figure><img src="https://images.theconversation.com/files/448252/original/file-20220224-21-6fh8pi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Researchers are working to develop vaccines that provide long-term immune protection from COVID-19. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/senior-woman-getting-vaccinated-royalty-free-image/1303314299?adppopup=true">Marko Geber/Digital Vision via Getty Images</a></span></figcaption></figure><p>As the <a href="https://theconversation.com/is-the-omicron-variant-mother-natures-way-of-vaccinating-the-masses-and-curbing-the-pandemic-175496">omicron variant of SARS-CoV-2</a> took hold across the globe in late 2021, it became readily apparent that the pandemic had entered a new phase. Having experienced a previous COVID-19 infection or being vaccinated still left many people wondering how vulnerable they were to the virus.</p>
<p>Some <a href="https://www.nytimes.com/interactive/2021/world/covid-vaccinations-tracker.html">4.9 billion people</a> – or 63.9% of the world’s population – have received at least one dose of the COVID-19 vaccine as of late February 2022. And more than 430 million cases of COVID-19 have been confirmed since the start of the pandemic. </p>
<p>So with the majority of the world population being either immunized against COVID-19 or having recovered from infection, people have rightly begun to ask: How long will the immunity triggered by either vaccination, an active infection or a combination of both provide immune protection?</p>
<p>This is a challenging question because the virus is relatively new and novel variants have continuously emerged. However, researchers are beginning to better understand how existing immunity protects against reinfection and the prevention of severe COVID-19 that can lead to hospitalization and death.</p>
<p>As <a href="https://pubmed.ncbi.nlm.nih.gov/?term=nagarkatti+p&sort=date&size=200&show_snippets=off">immunologists</a> studying inflammatory and <a href="https://sc.edu/study/colleges_schools/medicine/about_the_school/faculty-staff/nagarkatti_mitzi.php">infectious diseases</a>, including COVID-19, we are interested in understanding the nature of such protective immunity.</p>
<h2>The role of antibodies and ‘killer’ T cells</h2>
<p><a href="https://theconversation.com/what-happens-when-the-covid-19-vaccines-enter-the-body-a-road-map-for-kids-and-grown-ups-164624">Upon vaccination</a> or infection with COVID-19, your body produces two types of protective immune responses. The first type involves B cells, which produce antibodies. </p>
<p>Antibodies are Y-shaped proteins that form the first line of defense against an infection or perceived invader, such as a vaccine. Much like a lock and key, antibodies can directly bind to a virus – or <a href="https://theconversation.com/the-bodys-fight-against-covid-19-explained-using-3d-printed-models-153766">to the spike protein of COVID-19</a>, in the case of the mRNA vaccines – and prevent it from gaining entry into cells. However, once a virus successfully enters the cells, antibodies are no longer effective. The virus begins replicating in the infected cells and spreading to other cells.</p>
<p>This is when the immune system calls into action another type of immune cell known as <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/killer-t-cell">killer T cells</a>, which act as the second line of defense. </p>
<p>Unlike antibodies, killer T cells cannot directly “see” the virus and thus cannot prevent a virus from entering cells. However, the killer T cells can recognize a virus-infected cell and immediately destroy the cell before the virus gets a chance to replicate. In this way, killer T cells can help prevent a virus from multiplying and spreading.</p>
<p>Throughout the COVID-19 pandemic, the public has widely and mistakenly believed that antibodies provide the bulk of protective immunity, <a href="https://doi.org/10.1038/d41586-022-00238-9">while not recognizing the important role of killer T cells</a>. This is in part because antibodies are easy to detect, whereas killer T-cell detection is complex and involves advanced technology. When antibodies fail, it is the killer T cells that are responsible for <a href="https://doi.org/10.1038/d41586-022-00063-0">preventing the more severe outcomes of COVID-19</a>, such as hospitalization and death. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/448440/original/file-20220224-17-1l426i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="3-D rendering of four light blue killer T cells attacking a tumor or virus-infected cell." src="https://images.theconversation.com/files/448440/original/file-20220224-17-1l426i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/448440/original/file-20220224-17-1l426i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/448440/original/file-20220224-17-1l426i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/448440/original/file-20220224-17-1l426i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/448440/original/file-20220224-17-1l426i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/448440/original/file-20220224-17-1l426i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/448440/original/file-20220224-17-1l426i.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">Killer T cells are shown attacking a virus-infected cell or tumor.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/white-blood-cells-or-t-lymphocytes-or-natural-royalty-free-image/1298190135?adppopup=true">Libre de droit/iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<h2>Memory is key to long-term protective immunity</h2>
<p>Then come the real veterans of the immune system, which can provide long-lived and strong immunity against an infection based on their past experience.</p>
<p>After performing their tasks of clearing the infection or the spike protein of the virus, the antibody-producing B cells and killer T cells get converted into what are called <a href="https://doi.org/10.1038/s41577-020-00436-4">memory cells</a>. When these cells encounter the same protein from the virus, they recognize the threat immediately and mount a robust response that helps prevent an infection. </p>
<p>This explains why multiple doses of COVID-19 vaccines that increase the number of <a href="https://doi.org/10.1038/d41586-022-00214-3">memory B cells</a> prevent reinfection – or <a href="https://theconversation.com/what-is-a-breakthrough-infection-6-questions-answered-about-catching-covid-19-after-vaccination-164909">breakthrough infections</a> – better when compared with a single dose. And a similar increase in <a href="https://www.nih.gov/news-events/nih-research-matters/moderna-covid-19-vaccine-generates-long-lasting-immune-memory">memory killer T cells</a> prevents severe disease and hospitalization. </p>
<p>Memory cells can remain in the immune system for long periods – sometimes even <a href="https://doi.org/10.1038/nm917">up to 75 years</a>. This explains why people develop lifelong protective immunity in certain cases, such as <a href="https://www.cdc.gov/vaccines/vpd/mmr/public/index.html#">after measles vaccination</a> or <a href="https://doi.org/10.1016/j.amjmed.2008.08.019">smallpox infection</a>. </p>
<p>The trick, however, is that memory cells are highly specific. If new strains or variants of a virus emerge, <a href="https://theconversation.com/will-omicron-the-new-coronavirus-variant-of-concern-be-more-contagious-than-delta-a-virus-evolution-expert-explains-what-researchers-know-and-what-they-dont-169020">as has been the case numerous times</a> during the COVID-19 pandemic, memory cells may not be as effective.</p>
<p>This raises the question: When do these different key players of the immune system emerge after infection, and how long do they last?</p>
<h2>Duration and longevity of immunity against COVID-19</h2>
<p>Antibodies begin mobilizing within the <a href="https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/antibody-serology-testing-covid-19-information-patients-and-consumers#">first few days</a> following an infection with COVID-19 or after receiving the vaccine. They steadily increase in concentration <a href="https://doi.org/10.1038/s41467-021-24979-9">for weeks and months thereafter</a>. So by three months following infection, people have a robust antibody response. This is why the Centers for Disease Control and Prevention has long held that <a href="https://www.cdc.gov/coronavirus/2019-ncov/your-health/quarantine-isolation.html?">people who have had a confirmed COVID-19 infection</a> in the past 90 days do not need to quarantine when they come into contact with someone with COVID-19.</p>
<p>But by about six months, antibodies start declining. This is what led to the so-called “<a href="https://doi.org/10.1038/d41586-021-02532-4">waning immunity</a>” that researchers observed in the fall of 2021, months after many people had been fully vaccinated. </p>
<p>However, immunity is far more complex and nuanced, and antibodies only tell part of the story. Some B cells are long-lived, and they continue to produce antibodies against a virus. For this reason, antibodies against SARS-CoV-2 have been detected <a href="https://doi.org/10.3389/fmed.2021.684864">even a year after</a> an infection. Similarly, memory B cells can be detected for <a href="https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/vaccine-induced-immunity.html">at least eight months</a>, and memory killer T cells have been observed for close to two years following COVID-19 infection. </p>
<p>In general, vaccines have also been shown to trigger an immune memory <a href="https://www.nih.gov/news-events/nih-research-matters/moderna-covid-19-vaccine-generates-long-lasting-immune-memory">similar to that of natural infection</a>. However, long-term studies of the comparison do not yet exist. Nonetheless, a recent study that is not yet peer-reviewed showed that <a href="https://doi.org/10.1101/2022.02.14.480394">a third dose of vaccine</a> increases memory B cell diversity, which leads to better protection even against variants like omicron.</p>
<p>But the mere detection of an immune response does not translate to full protection against COVID-19.</p>
<p>Based on the limited amount of time and research that researchers like us have been able to study COVID-19, it is difficult to precisely correlate the levels of antibodies and killer T cells with the degree of protection they offer. </p>
<p>So while it is becoming clear that some form of immune response against the virus can be detected for more than a year after COVID-19 infection, their levels may not be enough to provide full protection against reinfection. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/1KdlU1sQcyc?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The immune system is one of the most complex parts of the human body.</span></figcaption>
</figure>
<h2>Immunity from vaccination versus infection</h2>
<p>One recent study from the U.K. Health Security Agency showed that protection against infection from two doses of vaccine <a href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1050236/technical-briefing-34-14-january-2022.pdf">may last for up to six months</a>. Similarly, another study showed that the mRNA vaccines were <a href="https://doi.org/10.1056/NEJMoa2117128">highly protective at two months</a>, but that their effectiveness decreased by seven months – in part due to the <a href="https://theconversation.com/delta-variant-makes-it-even-more-important-to-get-a-covid-19-vaccine-even-if-youve-already-had-the-coronavirus-164203">emergence of the delta variant</a>. In both studies, the vaccines were found to be better at preventing hospitalization and death than in preventing infection over time.</p>
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<p>There are <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/prior-covid-infection-more-protective-than-vaccination-during-delta-surge-us-2022-01-19/">contradictory reports</a> on whether the protective immunity triggered following an active infection is better than that induced by the current vaccines. This may have resulted from the emergence of different variants of the virus during the study. </p>
<p>However, the broad consensus is that COVID-19 infection can <a href="https://doi.org/10.1101/2021.09.12.21263461">give rise to protection comparable to that from the vaccines</a>, as shown in a recent study that has not yet been peer-reviewed.</p>
<h2>Hybrid immunity</h2>
<p>Researchers have also found that the protective immunity acquired from the combination of a COVID-19 infection followed by vaccination – called hybrid immunity – is very potent and <a href="https://doi.org/10.1056/NEJMoa2118691">remains effective for more than a year</a> after infection with COVID-19.</p>
<p>Interestingly, hybrid immunity triggers a <a href="https://doi.org/10.1126/sciimmunol.abn8014">very strong antibody response</a> <a href="https://www.hopkinsmedicine.org/news/newsroom/news-releases/in-covid-19-vaccinated-people-those-with-prior-infection-likely-to-have-more-antibodies">over an extended period</a>.</p>
<p>Such studies show how important it is for even people who have been previously infected with COVID-19 to get vaccinated to ensure the most robust protection against COVID-19.</p>
<p>With the growing knowledge that both vaccines and active infections can trigger a strong and sustained killer T cell response that protects against hospitalization and death, immunologists are now researching how to develop vaccines that can trigger a similar sustained long-term antibody response to prevent reinfections. Hybrid immunity from those who are vaccinated and have experienced COVID-19 infection may offer some useful clues.</p><img src="https://counter.theconversation.com/content/177309/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Prakash Nagarkatti receives funding from the National Institutes of Health and the National Science Foundation</span></em></p><p class="fine-print"><em><span>Mitzi Nagarkatti receives funding from the National Institutes of Health. </span></em></p>Because COVID-19 is a relatively new virus, researchers still aren’t sure exactly how long vaccines and prior infections provide protection.Prakash Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South CarolinaMitzi Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South CarolinaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1760302022-02-16T16:31:02Z2022-02-16T16:31:02ZHow new COVID-19 variants emerge: Natural selection and the evolution of SARS-CoV-2<figure><img src="https://images.theconversation.com/files/445852/original/file-20220211-19-bmg99i.jpg?ixlib=rb-1.1.0&rect=17%2C0%2C3785%2C2844&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">New variants of SARS-CoV-2, the virus that causes COVID-19, arise through mutations when the virus replicates in an infected host's cells. </span> <span class="attribution"><span class="source">(NIAID, cropped from original)</span></span></figcaption></figure><iframe style="width: 100%; height: 175px; border: none; position: relative; z-index: 1;" allowtransparency="" src="https://narrations.ad-auris.com/widget/the-conversation-canada/how-new-covid-19-variants-emerge--natural-selection-and-the-evolution-of-sars-cov-2" width="100%" height="400"></iframe>
<p>Nature is analogue. It is not a binary system. In the living world there are no explicit switches that discreetly turn systems on or off. Rather, nature adjusts systems through analogue dials, like an old radio — gradually changing variables to achieve balance and equilibrium to ensure that life is sustainable and carries on.</p>
<p>Evolution proceeds in this way, with new life forms appearing and some disappearing over millennia — or, in the case of microbial pathogens (viruses, bacteria and parasites) over days or weeks.</p>
<p><a href="https://doi.org/10.1016/j.tim.2017.03.003">Evolutionary change results from two opposing forces</a>: Positive selection reproduces beneficial genetic variations that enable the virus to survive, while negative selection pressure hinders the virus’s survival and ability to reproduce.</p>
<p>Evolution can be studied at the molecular level. For <a href="https://doi.org/10.1016/0166-6851(96)02687-4">many years</a>, <a href="https://doi.org/10.1016/0166-6851(84)90085-9">my research</a> was <a href="https://doi.org/10.1016/0161-5890(87)90052-6">focused on</a> the <a href="https://doi.org/10.1021/bi00401a061">African trypanosome</a>, the <a href="https://doi.org/10.1016/0035-9203(80)90184-4">parasite responsible for African sleeping sickness</a>.</p>
<h2>Antigenic variation</h2>
<p>Trypanosomes live in the bloodstream of its mammalian hosts (including humans) and early observations of their numbers showed a consistent wave-like pattern of increases followed by declining numbers and then, after a week or so, rising numbers again.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/445210/original/file-20220208-21-17yh7nz.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Graph showing the growth curve of a parasite" src="https://images.theconversation.com/files/445210/original/file-20220208-21-17yh7nz.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/445210/original/file-20220208-21-17yh7nz.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=348&fit=crop&dpr=1 600w, https://images.theconversation.com/files/445210/original/file-20220208-21-17yh7nz.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=348&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/445210/original/file-20220208-21-17yh7nz.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=348&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/445210/original/file-20220208-21-17yh7nz.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=438&fit=crop&dpr=1 754w, https://images.theconversation.com/files/445210/original/file-20220208-21-17yh7nz.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=438&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/445210/original/file-20220208-21-17yh7nz.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=438&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Growth Curve of African trypanosomiasis in an Infected Human.</span>
<span class="attribution"><a class="source" href="https://doi.org/10.1136/bmj.1.2">Ross, R., & Thomson, D. (1910). A Case of Sleeping Sickness showing Regular Periodical Increase of the Parasites Disclosed. Br Med J, 1(2582), 1544-1545. https://doi.org/10.1136/bmj.1.2</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span>
</figcaption>
</figure>
<p>Trypanosomes are vulnerable to the antibodies produced by their host’s immune system, which bind to the parasite and eliminate it. This immune response causes the trypanosome numbers to drop, as illustrated by the low points of the wave pattern. But before the trypanosomes disappear entirely, their numbers rise again and the wave repeats.</p>
<p>This intriguing growth pattern generated much interest and research in my laboratory and, ultimately, we learned that the parasite can alter its molecular identity to evade the host’s antibodies before it is completely eliminated. This means that the population of trypanosomes responsible for each of the wave peaks is a variant distinct from all the others. <a href="https://doi.org/10.1146/annurev.iy.08.040190.000503">Antibodies directed against one variant have no effect on subsequent variants</a>, so the wave pattern continues. </p>
<p>The trypanosome’s very successful strategy <a href="https://doi.org/10.1139/o88-141">evolved to help it survive in the face of constant negative selection pressure from antibodies</a>. This mechanism that helps a parasite or pathogen evade the host’s immune system is called antigenic variation.</p>
<h2>COVID-19’s waves are similar to sleeping sickness</h2>
<p>I am reminded of the growth curve of trypanosomes when looking at the pattern of Canadian case counts from the ongoing COVID-19 pandemic. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/445211/original/file-20220208-27-bkcw59.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Graph showing COVID-19 cases in Canada since Jan. 25, 2020" src="https://images.theconversation.com/files/445211/original/file-20220208-27-bkcw59.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/445211/original/file-20220208-27-bkcw59.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=628&fit=crop&dpr=1 600w, https://images.theconversation.com/files/445211/original/file-20220208-27-bkcw59.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=628&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/445211/original/file-20220208-27-bkcw59.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=628&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/445211/original/file-20220208-27-bkcw59.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=789&fit=crop&dpr=1 754w, https://images.theconversation.com/files/445211/original/file-20220208-27-bkcw59.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=789&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/445211/original/file-20220208-27-bkcw59.png?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"></a>
<figcaption>
<span class="caption">Case counts of COVID-19 in Canada since Jan. 25, 2020.</span>
<span class="attribution"><a class="source" href="https://covid19tracker.ca/">(N. Little. COVID-19 Tracker Canada (2020))</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>The peaks in cases reflect the arrival of new variants, <a href="https://doi.org/10.1056/NEJMp2119682">the most recent of which is omicron, the variant now circulating most widely globally</a>.</p>
<p>The strategy used by SARS-CoV-2, the virus that causes COVID-19, is similar to the trypanosome’s, although the mechanism for generating novel variants is quite different. For the virus, new variants arise by mutation in genes that <a href="https://doi.org/10.3390/v13061002">encode the so-called “spike protein</a>,” the part of the virus that enables it to enter cells and infect people. </p>
<p>Mutations arise due to “errors” that occur when the virus is replicating itself in the cells of the host’s respiratory system. Because the virus has a mechanism that can <a href="https://doi.org/10.3390/v13091882">attempt to repair the “errors</a>,” SARS-CoV-2 evolves more slowly than the trypanosome. It evolves more slowly because the virus has a mechanism that can <a href="https://doi.org/10.3390/v13091882">try to repair the “errors.</a>” However, this repair process is not perfect, and some mutations get retained.</p>
<p>If mutations result in a spike protein distinct from any other variant preceding it, <a href="https://doi.org/10.1016/j.chom.2021.02.020">we will see a new variant appearing</a>. The omicron variant is particularly interesting (and somewhat ominous) because of its high <a href="https://doi.org/10.26355/eurrev_202112_27653">number of mutations, not only in the spike protein but in other viral genes</a> as well.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/445860/original/file-20220211-15-1hllema.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A yellow coronavirus with red spikes against a black background" src="https://images.theconversation.com/files/445860/original/file-20220211-15-1hllema.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/445860/original/file-20220211-15-1hllema.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/445860/original/file-20220211-15-1hllema.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/445860/original/file-20220211-15-1hllema.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/445860/original/file-20220211-15-1hllema.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/445860/original/file-20220211-15-1hllema.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/445860/original/file-20220211-15-1hllema.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">The red projections seen on the outside of the SARS-CoV-2 virus are spike proteins, which enable the virus to attach to and infect host cells, and then replicate.</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>By employing this strategy of antigenic variation, the survival of the SARS-CoV-2 virus is assured. So, the appearance of new variants is due to mutations that represent the positive selection force: genetic variations that help the organism get reproduced. </p>
<p>The decline of case numbers during a pandemic is due to negative selection forces. These include <a href="https://doi.org/10.1186/s12992-021-00795-0">effective public health interventions</a> that limit the spread from one person to the next (such as masks), as well as the hosts’ immune response (antibodies) resulting from either infection, vaccination or both. </p>
<p>An infected person will, over time, generate antibodies against the virus and begin to eliminate that variant, like in the trypanosome case. But because SARS-CoV-2 mutations occur slowly, the virus needs to find a new, non-immune person to carry on. In order to find new non-immune hosts, the virus induces symptoms that help it to spread: the coughing and sneezing that enable it to jump from one person to the next via droplets.</p>
<h2>Antibodies and illness</h2>
<p>Given the capacity of SARS-CoV-2 to mutate, there are certainly new variants arising continuously. However, if medical and public health interventions are successful in reducing transmission between infected and uninfected/unvaccinated people, it is quite possible that the virus will evolve to generate a <a href="https://doi.org/10.1038/s41586-021-03792-w">less virulent variant that could establish itself as an endemic infection producing mild symptoms</a>.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/445861/original/file-20220211-124-1ei9iw0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Cluster of blue coronaviruses against a lavender background" src="https://images.theconversation.com/files/445861/original/file-20220211-124-1ei9iw0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/445861/original/file-20220211-124-1ei9iw0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=616&fit=crop&dpr=1 600w, https://images.theconversation.com/files/445861/original/file-20220211-124-1ei9iw0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=616&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/445861/original/file-20220211-124-1ei9iw0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=616&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/445861/original/file-20220211-124-1ei9iw0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=774&fit=crop&dpr=1 754w, https://images.theconversation.com/files/445861/original/file-20220211-124-1ei9iw0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=774&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/445861/original/file-20220211-124-1ei9iw0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=774&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Transmission electron micrograph of alpha variant SARS-CoV-2 virus particles.</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>When people infected with a pathogenic microbe experience symptoms of illness, those symptoms often serve a purpose: they can contribute to either the microbe’s survival or the survival of the infected host. A classic case is <a href="https://pubmed.ncbi.nlm.nih.gov/1465231">diarrhea resulting from infection with cholera</a> or from <a href="https://pubmed.ncbi.nlm.nih.gov/10549428">amoebic dysentery</a>. Both infections produce life-threatening diarrhea, but the symptom serves different purposes in each disease. </p>
<p>In the case of cholera, this symptom serves the microbe because it enables the bacteria to exit the host’s body and, in places with poor sanitation, contaminate the water supply and transmit to new hosts. In the case of amoebic dysentery, the symptom is a result of the host’s body attempting to rid itself of the infection.</p>
<p>Clinicians must be able to distinguish between these two scenarios in the management of infectious diseases in order to avoid contributing to the problem rather than solving it. In the case of COVID-19, clinical symptoms like sneezing and coughing that enable the virus to spread through the air are positively selecting variants that help the virus spread to new, susceptible individuals (such as unvaccinated people). </p>
<p>That means measures like masking, social distancing and vaccination can impede spread by helping to prevent aerosol transmission. </p>
<p>Continued efforts to achieve a fully vaccinated population are crucial. The unvaccinated and the uninfected are ideal hosts for SARS-CoV-2, and ideal for generating new variants due to the absence of negative selection by antibodies, which makes it easier for the virus to replicate and produce new mutations. </p>
<p>Although nature may move slowly in an analogue manner, humans can flip binary switches and <a href="https://doi.org/10.3389/ijph.2022.1604729">we can act now to ensure global vaccine equity</a>. Ensuring global vaccine coverage is not only imperative from an evolutionary perspective but is clearly <a href="https://doi.org/10.1371/journal.pmed.1003797">the ethical option as well</a>.</p><img src="https://counter.theconversation.com/content/176030/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael Clarke 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>COVID-19 variants are the products of the evolution of the SARS-CoV-2 virus. They arise via mutations, but other forces also have roles to play in the generation and transmission of variants.Michael Clarke, Adjunct Professor, Interfacluty Program in Public Health, Schulich School of Medicine and Dentistry, Western University, Western UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1749522022-02-16T13:16:37Z2022-02-16T13:16:37ZDespite its disastrous effects, COVID-19 offers some gifts to medicine – an immunology expert explains what it can teach us about autoimmune disease<figure><img src="https://images.theconversation.com/files/445510/original/file-20220209-13-1osyf8u.jpeg?ixlib=rb-1.1.0&rect=0%2C0%2C5491%2C3145&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Immunologists are studying how the SARS-CoV-2 virus interacts with antibodies in the immune system. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/antibody-proteins-attacking-coronavirus-royalty-free-illustration/1227513270">Christoph Burgstedt/Science Photo Library via Getty Images</a></span></figcaption></figure><p>For all the misery that the pandemic has wrought, it has also opened up a vast storehouse of knowledge about medical issues beyond COVID-19. While it’s still too early to draw conclusions, <a href="https://doi.org/10.1172/JCI154886">evidence is emerging</a> of links between autoimmune disorders and the virus that causes COVID-19. </p>
<p>As a <a href="https://www.unomaha.edu/college-of-information-science-and-technology/about/faculty-staff/dario-ghersi.php">bioinformatics researcher</a> with medical training and expertise in <a href="https://scholar.google.com/citations?user=WZ6huJ0AAAAJ&hl=en">immune system modeling</a>, I find this development especially exciting.</p>
<p>The immune system is the most powerful weapon against infection. But on rare occasions, something devastating happens: The immune system turns against its own body – a condition that researchers call autoimmunity. This can result in any of a wide range of autoimmune disorders. They include <a href="https://www.cdc.gov/arthritis/basics/rheumatoid-arthritis.html">rheumatoid arthritis</a>, <a href="https://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/multiple_sclerosis/conditions/">multiple sclerosis</a> and
<a href="https://www.mayoclinic.org/diseases-conditions/lupus/symptoms-causes/syc-20365789">lupus</a>, an inflammatory disease in which the immune system attacks multiple tissues.</p>
<p>Researchers are still trying to solve the mystery of what causes these diseases, in hopes of developing therapies to treat them. COVID-19 may accelerate that process by giving researchers new insight into old findings about the immune system. </p>
<h2>From autoimmunity to COVID-19</h2>
<p>Molecules called interferons are a significant component of the body’s defense against viruses. These proteins are especially important in the early stages of an infection, frequently getting ahead of it before symptoms appear. Immune cells produce interferons, which then do what their name implies – literally run interference when a virus begins to multiply. At least that’s what they’re supposed to do.</p>
<p>But reports from early in the pandemic showed that in some patients with severe COVID-19, one interferon, known as Type I, <a href="https://doi.org/10.1126/science.369.6511.1550">showed a weak response</a> to the virus. Some patients actually developed antibodies <a href="https://doi.org/10.1126/sciimmunol.abl4340">specifically targeting</a> Type I interferons – essentially knocking out one of the body’s first lines of defense against the disease.</p>
<p>Researchers had discovered similar occurrences decades before. After introducing interferons to treat a patient with cancer in 1980, doctors found that some of the patient’s antibodies were <a href="https://doi.org/10.1038/289496a0">effectively neutralizing</a> those interferons. And in 1982, researchers reported that antibodies had <a href="https://pubmed.ncbi.nlm.nih.gov/6177744/">disarmed the interferons</a> in a patient with lupus. <a href="https://doi.org/10.1126/sciimmunol.abd1554">Interferon-fighting antibodies</a> could explain some severe COVID-19 cases. </p>
<p>Another explanation is that, instead of becoming weaker in the face of COVID-19, interferons mount a stronger-than-usual defense, <a href="https://doi.org/10.1126/sciimmunol.abd1554">inducing organ damage</a> while fighting the virus. Researchers are investigating the possibility that – for patients with the worst cases – Type I interferon is COVID-19’s all-or-nothing double-edged sword: either rendered inactive before it can fight the infection, or somehow becoming hyperactive and potentially detrimental to the body in later stages. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/444582/original/file-20220204-21-fu5clx.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A pair of fair-skinned hands with extremely swollen knuckles, the end of the left pinky sharply angled at the top knuckle and light blue sleeve cuffs at the wrists." src="https://images.theconversation.com/files/444582/original/file-20220204-21-fu5clx.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/444582/original/file-20220204-21-fu5clx.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=409&fit=crop&dpr=1 600w, https://images.theconversation.com/files/444582/original/file-20220204-21-fu5clx.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=409&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/444582/original/file-20220204-21-fu5clx.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=409&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/444582/original/file-20220204-21-fu5clx.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=514&fit=crop&dpr=1 754w, https://images.theconversation.com/files/444582/original/file-20220204-21-fu5clx.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=514&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/444582/original/file-20220204-21-fu5clx.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=514&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">COVID-19 is helping to advance understanding of autoimmune illnesses like rheumatoid arthritis.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/photo-by-tim-leedy-4-12-12gloria-heere-had-an-operation-for-news-photo/1315557713">MediaNews Group/Reading Eagle via Getty Images</a></span>
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<h2>A window into autoimmunity</h2>
<p>Throughout the pandemic, doctors have also noticed that patients with severe COVID-19 infections have symptoms that are <a href="https://doi.org/10.1016/S0140-6736(20)31103-X">similar to autoimmune disorder symptoms</a>, such as blood vessel inflammation, rashes and organ damage. Following COVID-19 infection, some patients have even developed full-blown autoimmune disorders, such as Type 1 diabetes, lupus and <a href="http://dx.doi.org/10.1136/annrheumdis-2020-218520">psoriatic arthritis</a>, a disease marked by skin rashes along with stiff, swollen and painful joints. </p>
<p>Some immunologists suspect that the SARS-CoV-2 virus may be triggering the body to attack itself <a href="https://theconversation.com/severe-covid-may-be-caused-by-autoantibodies-here-is-what-that-means-152053">with autoantibodies</a> – or antibodies that target the body’s own tissues. This could explain why some people who had COVID-19 later developed autoimmune disorders.</p>
<p>It’s not the first time researchers have suggested a possible connection between viruses and autoimmune disorders. For example, a 2019 study of patients with <a href="https://doi.org/10.3390/v11080762">Type 1 diabetes</a> found that those patients also carried several gastrointestinal viruses.</p>
<p>Immunologists are now looking more closely at other viruses and their possible involvement in autoimmune disorders. One example is the <a href="https://www.cdc.gov/epstein-barr/index.html">Epstein-Barr virus</a>, or EBV, which is responsible for infectious mononucleosis. This virus causes swollen lymph nodes, fever, sore throat and persistent tiredness. Studies in the past two years suggest that the Epstein-Barr virus might also play a role in <a href="https://doi.org/10.1126/science.abj8222">causing multiple sclerosis</a> and <a href="https://doi.org/10.3390/v13020277">lupus</a>. </p>
<p>So how could COVID-19 cause autoimmunity? One theory is that the virus makes immune cells hyperactive. For example, a computational analysis identified a section of the virus that looks like part of a dangerous <a href="https://doi.org/10.1073/pnas.2010722117">type of strep bacteria</a>. This could cause an extreme reaction as the immune system gears up to fight a particularly powerful enemy.</p>
<p>Pieces of the SARS-CoV-2 virus can also <a href="https://doi.org/10.1016/j.csbj.2021.06.041">mimic parts of human proteins</a>, such as coagulation factors, which regulate bleeding. In some people, the immune system responds by going after those lookalikes. The resulting autoimmune reactions could be causing symptoms like the blood clots and multiorgan damage occurring in patients with COVID-19.</p>
<h2>The long view</h2>
<p>The condition commonly known as “<a href="https://theconversation.com/deciphering-the-symptoms-of-long-covid-19-is-slow-and-painstaking-for-both-sufferers-and-their-physicians-164754">long COVID-19</a>” is characterized by persistent tiredness, difficulty in concentrating, shortness of breath and a <a href="https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html">plethora of other symptoms</a>. Interestingly, the symptoms of long COVID bear a <a href="https://doi.org/10.1073/pnas.2024358118">strong resemblance to myalgic encephalomyelitis</a>, or ME. More commonly known as <a href="https://doi.org/10.1128/CDLI.9.4.747-752.2002">chronic fatigue syndrome</a>, ME is a condition characterized by extreme tiredness, pain, sleep problems and a lack of concentration. Long COVID includes some of the same symptoms. </p>
<p>A 2021 study suggested that in both illnesses, the symptoms may be the work of autoantibodies, or <a href="https://doi.org/10.1073/pnas.2024358118">antibodies that attack the immune system</a>. Another study found autoantibodies in patients with long COVID who were <a href="https://doi.org/10.1093/cid/ciab611">experiencing cognitive symptoms</a>, like having trouble concentrating. </p>
<p>[<em>Over 140,000 readers rely on The Conversation’s newsletters to understand the world.</em> <a href="https://memberservices.theconversation.com/newsletters/?source=inline-140ksignup">Sign up today</a>.]</p>
<p>There is now more work under way to further decipher the relationship between autoimmune disorders and viral infections like COVID-19. And doctors are now looking at new therapies for <a href="https://doi.org/10.1016/S2665-9913(20)30120-X">controlling an overreactive immune system</a>.</p>
<p>In the past two years, the pandemic has given medical science an extraordinary amount of knowledge, with more to come.</p><img src="https://counter.theconversation.com/content/174952/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dario Ghersi receives funding from the National Institutes of Health. </span></em></p>COVID-19 has taken away so much. An immunology researcher describes the good it may leave behind.Dario Ghersi, Associate Professor of Biomedical Informatics, University of Nebraska OmahaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1756532022-01-30T19:08:50Z2022-01-30T19:08:50ZWhat we know now about COVID immunity after infection – including Omicron and Delta variants<figure><img src="https://images.theconversation.com/files/443100/original/file-20220128-15-1419tzc.jpg?ixlib=rb-1.1.0&rect=8%2C16%2C5599%2C3715&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://photos-cdn.aap.com.au/Image/20211215001606766150?path=/aap_dev12/device/imagearc/2021/12-15/d4/18/2b/aapimage-7iueq5j875g1mxnmv9ks_layout.jpg">AAP Image/Bianca De Marchi</a></span></figcaption></figure><p>COVID is rampant in Australia and many parts of the world right now. Some people battling or recovering from infection may wonder if catching COVID will give them longer term immunity for when the next wave comes.</p>
<p>Since the early days of the pandemic we’ve known COVID induces a wide range of <a href="https://www.nature.com/articles/s41591-020-0995-0">immune responses</a> and one infection provides <a href="https://www.nature.com/articles/s41577-021-00550-x">partial protection from future infections</a>. </p>
<p>Unfortunately, immunity wanes over time – <a href="https://www.sciencedirect.com/science/article/pii/S2666524721002676">people lose half their immunity every 3 months</a>. Further, new variants continue to emerge that are partially resistant to key immune responses – antibodies that neutralise earlier strains – <a href="https://www.nature.com/articles/s41586-022-04399-5">this is especially true of Omicron</a>.</p>
<p>We’re starting to get a more detailed understanding of COVID immunity across variants. Here’s what we know so far …</p>
<h2>Breakthrough infection happens but vaccines are still a must</h2>
<p>Since around <a href="https://www.health.gov.au/initiatives-and-programs/covid-19-vaccines/numbers-statistics">95% of Australians over 16</a> have had at least two COVID vaccines, most people catching COVID now have previously been vaccinated – this is called “breakthrough infection”. </p>
<p>The vaccines are effective at substantially reducing severe COVID illness. They are less effective, particularly over time, <a href="https://www.sciencedirect.com/science/article/pii/S2666524721002676">at preventing infections, including with new variants</a>. A third vaccine dose <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02249-2/fulltext">helps maintain immunity</a>, and everyone eligible should get a booster as soon as possible. </p>
<p>Because the Astra-Zeneca vaccine is <a href="https://www.nature.com/articles/s41591-021-01377-8">less effective</a> than the Pfizer or Moderna vaccines, it’s critically important for vulnerable older Australians immunised with two Astra-Zeneca vaccinations to be boosted with a third vaccine dose as quickly as possible. </p>
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<figcaption><span class="caption">Professor Peter Doherty explains vaccination and immunity in everyday terms.</span></figcaption>
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Read more:
<a href="https://theconversation.com/should-i-get-my-covid-vaccine-booster-yes-it-increases-protection-against-covid-including-omicron-172965">Should I get my COVID vaccine booster? Yes, it increases protection against COVID, including Omicron</a>
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<p>The good news is people first vaccinated with Astra-Zeneca and subsequently boosted with Pfizer or Moderna <a href="https://www.thelancet.com/action/showPdf?pii=S0140-6736%2821%2902717-3">develop</a> high levels of protective immune responses. </p>
<p>Recent work shows <a href="https://www.medrxiv.org/content/10.1101/2021.12.23.21268285v1">a nice boost in antibody immunity</a> after breakthrough infection. This boost in antibody immunity <a href="https://www.medrxiv.org/content/10.1101/2021.12.23.21268285v1">may not be as fast or strong as getting a vaccine</a>, but it has a big advantage in that the immunity is <a href="https://www.medrxiv.org/content/10.1101/2021.12.01.21266982v2">more specific to the infecting strain</a> such as Delta. </p>
<p>The current vaccines are still based on the original strain isolated in Wuhan, China in early 2020. Several vaccine manufacturer’s are racing to update their vaccines for the Omicron variant (much as we do with the yearly flu vaccines), but these <a href="https://www.nytimes.com/live/2022/01/25/world/omicron-covid-vaccine-tests?campaign_id=7&emc=edit_mbae_20220127&instance_id=51387&nl=morning-briefing%3A-asia-pacific-edition&regi_id=80788140&segment_id=80840&te=1&user_id=dc49badc67c435380a30db1d060cc51b#pfizer-and-biontech-begin-a-study-of-an-omicron-vaccine-with-initial-results-expected-in-the-first-half-of-the-year">variant-specific vaccines</a> are still some months away.</p>
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<strong>
Read more:
<a href="https://theconversation.com/will-an-omicron-specific-vaccine-help-control-covid-theres-one-key-problem-175137">Will an Omicron-specific vaccine help control COVID? There's one key problem</a>
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<h2>Infection immunity builds where COVID strikes first</h2>
<p>Another potential advantage for immunity derived by infection (acquired in the respiratory tract) compared to vaccination (given into the muscle) is that immunity is better focused to the surfaces of the nose, throat and eyes. This is where COVID is first encountered. </p>
<p>Surface antibodies (termed <a href="https://www.immunology.org/public-information/bitesized-immunology/receptors-and-molecules/immunoglobulin-iga">immunoglobulin A</a>) and specialised tissue “resident” immune cells (B and T-cells) are induced by infection but <a href="https://onlinelibrary.wiley.com/doi/10.1002/cti2.1354">not intramuscular vaccination</a>. </p>
<p>The level of protection offered by these “local” or “mucosal” responses is not yet clear in people, but <a href="https://www.jimmunol.org/content/early/2021/01/12/jimmunol.2001400">some studies in animal models</a> suggest they are helpful.</p>
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<a href="https://images.theconversation.com/files/443098/original/file-20220128-13-lfhj4o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="lab technician at CDC" src="https://images.theconversation.com/files/443098/original/file-20220128-13-lfhj4o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/443098/original/file-20220128-13-lfhj4o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=397&fit=crop&dpr=1 600w, https://images.theconversation.com/files/443098/original/file-20220128-13-lfhj4o.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=397&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/443098/original/file-20220128-13-lfhj4o.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=397&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/443098/original/file-20220128-13-lfhj4o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=499&fit=crop&dpr=1 754w, https://images.theconversation.com/files/443098/original/file-20220128-13-lfhj4o.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=499&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/443098/original/file-20220128-13-lfhj4o.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=499&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">Research and understanding of immune responses to COVID is developing.</span>
<span class="attribution"><a class="source" href="https://image.shutterstock.com/image-photo/scientist-working-laboratory-600w-1203801196.jpg">Shutterstock</a></span>
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<h2>Delta infection offers a little protection against Omicron</h2>
<p>The Omicron variant is slowly replacing the Delta variant around the world. It is more transmissible and avoids antibodies more effectively. </p>
<p>Do people who have been infected with the Delta variant have an advantage in terms of protection from the Omicron variant? The two strains share some sequence changes, but Omicron has many more mutations than Delta. </p>
<p>Only a minority of neutralising antibodies that fight <a href="https://doi.org/10.1101/2021.12.13.21267748">Delta can also neutralise the Omicron variant.</a> That said, neutralising antibodies against Delta are better at fighting Omicron than previous strains. This is particularly true for people who have <a href="https://www.medrxiv.org/content/10.1101/2021.12.01.21266982v2">caught Delta and been previously vaccinated</a>. </p>
<p>The reverse is also true – people who have caught Omicron have <a href="https://www.nature.com/articles/s41586-022-04399-5">some improved antibody protection against Delta</a>. This may not be much use as Delta is disappearing from prevalence, but the knowledge could be useful for future variants.</p>
<h2>T-cells might be key to cross-variant protection</h2>
<p>There is considerable interest in a type of immunity called <a href="https://www.news-medical.net/health/What-are-T-Cells.aspx">T-cells</a> and their potential ability to fight COVID infection.</p>
<p>Theoretically, T-cells could assist in protecting against severe infection with new strains because <a href="https://www.nature.com/articles/s41591-022-01700-x">T-cells usually cross react to all variants of SARS-CoV-2</a>, the virus that causes COVID.</p>
<p>However, the evidence to date points to the <a href="https://www.nature.com/articles/s41591-021-01377-8">central role of neutralising antibodies</a> obtained from infection or vaccination in protection from both getting an infection and preventing severe disease. A recent unpublished study suggests neutralising antibodies are <a href="https://www.medrxiv.org/content/10.1101/2021.12.23.21268285v1">boosted by breakthrough infections but not T-cells</a>. We know T-cells are very important in protecting from other infectious diseases and many cancers, but perhaps have a lesser role in COVID.</p>
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Read more:
<a href="https://theconversation.com/welcome-to-our-world-families-of-children-with-cancer-say-the-pandemic-has-helped-them-feel-seen-while-putting-them-in-peril-175143">'Welcome to our world': families of children with cancer say the pandemic has helped them feel seen, while putting them in peril</a>
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<h2>Gaining immunity isn’t the end of the story</h2>
<p>Overall, infections with Delta and Omicron provide a boost in immunity against these strains. Infection will probably help protect individuals from reinfection with the same variant. Infection may offer a small amount of protection from different variants and potentially from future variants. </p>
<p>However, immunity will not be enduring and it is still possible to get severe infections and ongoing symptoms (termed “Long COVID”) from breakthrough infections. They are best avoided! Current booster vaccines along with social measures are our best way to stay healthy while we wait for Omicron-specific vaccines.</p><img src="https://counter.theconversation.com/content/175653/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Stephen Kent receives funding from the Australian and Victorian governments for COVID-19 research. </span></em></p>Infection seems to add a boost to immunity – but vaccination is still vital and breakthrough infections should be avoided as much as possible.Stephen Kent, Professor and Laboratory Head, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1754962022-01-27T13:28:42Z2022-01-27T13:28:42ZIs the omicron variant Mother Nature’s way of vaccinating the masses and curbing the pandemic?<figure><img src="https://images.theconversation.com/files/442657/original/file-20220126-17-75f6ee.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C7592%2C3940&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Preliminary research suggests that the omicron variant may potentially induce a robust immune response.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/coronavirus-royalty-free-image/1357650209?adppopup=true">Olga Siletskaya/Moment via Getty Images</a></span></figcaption></figure><p>In the short time since the omicron variant was <a href="https://www.cnn.com/2021/12/02/world/south-africa-omicron-origins-covid-cmd-intl/index.html">identified in South Africa</a> in November 2021, <a href="https://doi.org/10.12998/wjcc.v10.i1.1">researchers have quickly learned</a> that it has three unique characteristics: It spreads efficiently and quickly, it generally causes milder disease than previous variants and it may confer strong protection against other variants such as delta. </p>
<p>This has many people wondering whether omicron could act as a vaccine of sorts, inoculating enough people to effectively bring about <a href="https://theconversation.com/what-is-herd-immunity-a-public-health-expert-and-a-medical-laboratory-scientist-explain-170520">herd immunity</a> – the threshold at which enough of the population is immune to the virus to stop its spread – and end the COVID-19 pandemic.</p>
<p>As <a href="https://sc.edu/study/colleges_schools/medicine/about_the_school/faculty-staff/nagarkatti_mitzi.php">immunology researchers</a> at the University of South Carolina who are <a href="https://pubmed.ncbi.nlm.nih.gov/?term=nagarkatti+p&sort=date&size=200&show_snippets=off">working on inflammatory and infectious diseases</a>, including COVID-19, we find the characteristics of omicron in the pandemic setting particularly intriguing. And it is these characteristics that can help answer that question. </p>
<p>Some 4.73 billion people across the globe – about 61.6% of the world’s population – have received at least <a href="https://www.nytimes.com/interactive/2021/world/covid-vaccinations-tracker.html">one dose of a COVID-19 vaccine</a>. In the United States, 63.4% of the population <a href="https://covid.cdc.gov/covid-data-tracker/#vaccinations_vacc-total-admin-rate-total">is fully vaccinated with two doses</a> as of late January 2022, while only 39.9% of Americans have received the booster dose. Such low levels of vaccination resulting from <a href="https://data.cdc.gov/stories/s/Vaccine-Hesitancy-for-COVID-19/cnd2-a6zw/">vaccine hesitancy</a> and the complexities of the <a href="https://dx.doi.org/10.1016%2Fj.ijpe.2021.108193">global vaccine supply chain</a> cast doubt on reaching <a href="https://theconversation.com/what-is-herd-immunity-a-public-health-expert-and-a-medical-laboratory-scientist-explain-170520">herd immunity</a> through vaccination anytime soon. </p>
<h2>How does omicron mimic a vaccine?</h2>
<p><a href="https://www.hhs.gov/immunization/basics/types/index.html">All vaccines</a> work on the principle of training the immune system to fight against an infectious agent. Each vaccine, regardless of how it is made, exposes the human or animal host to the critical molecules used by the infectious agent – in this case, the SARS-CoV-2 virus – to gain entry into the host’s cells.</p>
<p>Some vaccines expose the host only to select portions of the virus. For example, the Pfizer-BioNTech and Moderna vaccines use a <a href="https://theconversation.com/how-mrna-vaccines-from-pfizer-and-moderna-work-why-theyre-a-breakthrough-and-why-they-need-to-be-kept-so-cold-150238">molecule called messenger RNA</a>, or mRNA, to encode and produce a fragment of the “spike protein” – the knobby protrusion that is expressed on the outside of SARS-CoV-2 viruses – inside a person’s body. These spike proteins are the key way that <a href="https://theconversation.com/what-happens-when-the-covid-19-vaccines-enter-the-body-a-road-map-for-kids-and-grown-ups-164624">the coronavirus invades cells</a>, so the mRNA vaccines are designed to mimic that protein and trigger an immune response against it. </p>
<p>In contrast, some vaccines against other infections, <a href="https://theconversation.com/the-chickenpox-virus-has-a-fascinating-evolutionary-history-that-continues-to-affect-peoples-health-today-168636">such as chickenpox</a> and <a href="https://www.cdc.gov/vaccines/hcp/vis/vis-statements/mmr.html">measles, mumps and rubella (MMR)</a>, expose the host to a “live attenuated” form of the virus. These vaccines use small amounts of a weakened form of the live virus. They mimic a natural infection, trigger a strong immune response and afford lasting resistance to infection. </p>
<p>In some respects, omicron mimics these live attenuated vaccines because it causes milder infection and trains the body to trigger a strong immune response against the delta variant, as shown in a recent <a href="https://doi.org/10.1101/2021.12.27.21268439">study that is not yet peer-reviewed</a> from South Africa. </p>
<h2>Deliberate infection with omicron is not the answer</h2>
<p>While omicron may share certain characteristics with a vaccine, it should not be considered a viable alternative to the existing vaccines. For one, COVID-19 infection can result in <a href="https://www.nytimes.com/live/2022/01/10/world/omicron-covid-testing-vaccines">severe illness, hospitalization or death</a>, especially in <a href="https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html">vulnerable individuals with underlying conditions</a>. It can also cause long-term health effects in some people, called <a href="https://theconversation.com/deciphering-the-symptoms-of-long-covid-19-is-slow-and-painstaking-for-both-sufferers-and-their-physicians-164754">long COVID</a>. In contrast, vaccines currently available against COVID-19 have been tested for safety and efficacy. </p>
<p>The high transmission of omicron combined with ongoing vaccination efforts could help attain herd immunity soon and end the most acute phase of the pandemic. However, there is little chance of it eradicating COVID-19, since all signs point to the likelihood that the virus <a href="https://theconversation.com/is-covid-19-here-to-stay-a-team-of-biologists-explains-what-it-means-for-a-virus-to-become-endemic-168462">will become endemic</a> – meaning SARS-CoV-2 will be in circulation but will likely not be as disruptive to society.</p>
<p>Thus far, smallpox is the only infectious disease that <a href="https://www.cdc.gov/smallpox/index.html#">has been eradicated globally</a>, which shows how difficult it is to fully eliminate a disease. However, it is easier to control an infection effectively. One example is <a href="https://www.cdc.gov/polio/what-is-polio/polio-us.html">polio</a>, which has been reduced or eliminated in most countries through vaccination. </p>
<h2>What happens when the body meets a virus or vaccine</h2>
<p>Both viral infections or the mimicking of a virus through vaccination activate a critical component of the immune system, called B cells, in the body. These cells produce antibodies that bind to the virus, preventing it from infecting cells. These antibodies act much like anti-ballistic missiles that shoot down an incoming virus missile. However, once a virus manages to get inside the body’s cells, antibodies are less effective. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/442658/original/file-20220126-13-ngm9rq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A 3-D illustration of antibody proteins attacking a coronavirus pathogen cell." src="https://images.theconversation.com/files/442658/original/file-20220126-13-ngm9rq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/442658/original/file-20220126-13-ngm9rq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=300&fit=crop&dpr=1 600w, https://images.theconversation.com/files/442658/original/file-20220126-13-ngm9rq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=300&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/442658/original/file-20220126-13-ngm9rq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=300&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/442658/original/file-20220126-13-ngm9rq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=377&fit=crop&dpr=1 754w, https://images.theconversation.com/files/442658/original/file-20220126-13-ngm9rq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=377&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/442658/original/file-20220126-13-ngm9rq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=377&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Antibodies behave similarly to anti-ballistic missiles, shooting down their target – in this case, the SARS-CoV-2 virus.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/immunoglobulin-or-antibody-proteins-attack-a-corona-royalty-free-image/1299604801?adppopup=true">Christoph Burgstedt/iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<p>That’s where another key player in the immune system, called killer T cells, come in. These cells can recognize and destroy a cell as soon as it is infected, thereby preventing the virus from multiplying and spreading further. Think of this as an anti-ballistic missile that detects and destroys the factory where missiles are manufactured. </p>
<p>Immunologists believe that antibodies against COVID-19 prevent an individual from catching the infection, while the <a href="https://www.nature.com/articles/d41586-021-00367-7">killer T cells are crucial</a> in preventing severe disease. Despite its numerous mutations, omicron can trigger a <a href="https://www.nature.com/articles/d41586-022-00063-0#">strong killer T cell response</a>. This may explain why the COVID-19 vaccines – by triggering the T cells – have provided strong enough immunity against omicron to, in most cases, <a href="https://doi.org/10.1001/jamanetworkopen.2021.42725">prevent hospitalization and death</a>.</p>
<p>But, critically, the first wave of antibodies and killer T cells produced during infection or vaccination last for only a few months. This is why recurrent infections of COVID-19 have occurred even in the vaccinated population, and it’s also <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/booster-shot.html">why booster shots are needed</a>. In contrast, some vaccines – like the one against smallpox – have been shown to trigger immunity that lasts for several years. </p>
<h2>Memory immune response</h2>
<p>So what exactly triggers strong and lasting immunity? The lifelong immunity seen in certain infections such as smallpox can be explained by a phenomenon called “<a href="https://www.ncbi.nlm.nih.gov/books/NBK27158/">immunological memory</a>.”</p>
<p>After the B cells and killer T cells first encounter the virus, some of them get converted into what are called memory cells, which are known to <a href="https://doi.org/10.1038/nm917">live for several decades</a>. As their name suggests, when memory cells “see” a virus again after initial exposure, they recognize it, divide rapidly and mount a robust antibody and killer T cell response, thereby preventing reinfection.</p>
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<p>For this reason, memory cells are critical for establishing strong, long-lasting immunity. This is evidenced from studies with smallpox in which people that were infected or vaccinated were found to have the antibody response <a href="https://dx.doi.org/10.1016%2Fj.amjmed.2008.08.019">even after 88 years</a>! Why some infections or vaccines trigger long-lasting memory and others do not is under active investigation. Because COVID-19 is only two years old, we researchers don’t know yet how long the memory B and T cells last. Based on recurrent infections, it looks like longer-term immunity does not last very long, but that could also in part be due to the evolution of new variants. </p>
<p>All of these considerations leave room for hope that when new variants of SARS-CoV-2 inevitably arise, omicron will have left the population better equipped to fight them. So the COVID-19 vaccines combined with the omicron variant could feasibly move the world to a new stage in the pandemic – one where the virus doesn’t dominate our lives and where hospitalization and death are far less common.</p><img src="https://counter.theconversation.com/content/175496/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Prakash Nagarkatti receives funding from the National Institutes of Health and the National Science Foundation.</span></em></p><p class="fine-print"><em><span>Mitzi Nagarkatti receives funding from the National Institutes of Health.</span></em></p>Some of the omicron variant’s unique properties – such as its ability to spread rapidly while causing milder COVID-19 infections – could usher in a new phase of the pandemic.Prakash Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South CarolinaMitzi Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South CarolinaLicensed as Creative Commons – attribution, no derivatives.