tag:theconversation.com,2011:/fr/topics/immune-response-19104/articlesImmune response – The Conversation2024-03-21T20:24:31Ztag:theconversation.com,2011:article/2262052024-03-21T20:24:31Z2024-03-21T20:24:31ZMeasles is highly contagious, but vaccine-preventable: A primer on recent outbreaks, transmission, symptoms and complications, including ‘immune amnesia’<figure><img src="https://images.theconversation.com/files/583049/original/file-20240320-16-lkngkh.jpg?ixlib=rb-1.1.0&rect=0%2C135%2C3962%2C2913&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A measles virus particle. Measles is one of the most contagious pathogens known.</span> <span class="attribution"><span class="source">(CDC and NIAID)</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Canada is seeing a resurgence of measles, with cases in the first quarter of 2024 already far surpassing the total for all of 2023. There were <a href="https://www.canada.ca/en/public-health/services/publications/diseases-conditions/measles-rubella-surveillance/2023/week-52.html">12 cases last year</a>, and more than three times that number so far in 2024, with 38 reported as of March 19. </p>
<p>Most of these cases (28) <a href="https://www.quebec.ca/en/health/health-issues/a-z/measles/measles-outbreak">are in Québec</a>, and <a href="https://www.publichealthontario.ca/-/media/Documents/M/24/measles-ontario-epi-summary.pdf?rev=c082f5ae0c6c446f9624d47b7e3c8535&sc_lang=en">eight are in Ontario</a>, while <a href="https://www.saskhealthauthority.ca/news-events/news/measles-exposure-risk-saskatoon">Saskatchewan</a> and <a href="https://news.gov.bc.ca/releases/2024HLTH0026-000274">British Columbia</a> have each reported one case. </p>
<p>As an immunologist with a focus on host-microbe interactions and antiviral immunity, I have been following recent measles outbreaks. </p>
<h2>Symptoms and complications</h2>
<p>Measles (also known as rubeola) is a serious but vaccine-preventable disease caused by an RNA virus of the family <a href="https://www.britannica.com/science/paramyxovirus-virus-family">Paramyxoviridae</a>. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/583046/original/file-20240320-24-qx59sq.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A child seen from behind with a red rash all over his skin" src="https://images.theconversation.com/files/583046/original/file-20240320-24-qx59sq.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/583046/original/file-20240320-24-qx59sq.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=720&fit=crop&dpr=1 600w, https://images.theconversation.com/files/583046/original/file-20240320-24-qx59sq.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=720&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/583046/original/file-20240320-24-qx59sq.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=720&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/583046/original/file-20240320-24-qx59sq.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=905&fit=crop&dpr=1 754w, https://images.theconversation.com/files/583046/original/file-20240320-24-qx59sq.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=905&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/583046/original/file-20240320-24-qx59sq.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=905&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Measles rash appears on the face before spreading downward to other areas of the body.</span>
<span class="attribution"><span class="source">(U.S. Centers for Disease Control)</span></span>
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<p>Measles usually begins with fever, runny nose, conjunctivitis (red watery eyes), sore throat and coughing. These can be initially mistaken for common cold or flu.</p>
<p>However, these non-specific signs and symptoms are typically followed by clinical manifestations that are characteristic of measles. These include Koplik spots (tiny white specks with bluish-white centres in the inner lining of the cheeks), and subsequently a <a href="https://www.cdc.gov/measles/symptoms/signs-symptoms.html">measles rash</a> appearing on the face before spreading downward to other areas of the body.</p>
<p>In most cases, measles resolves on its own. However, <a href="https://www.mayoclinic.org/diseases-conditions/measles/symptoms-causes/syc-20374857">severe complications</a> may arise, especially in immunocompromised individuals. <a href="https://www.cdc.gov/globalhealth/measles/about/index.html">Complications</a> can include pneumonia, encephalitis (brain inflammation and swelling), blindness, deafness and permanent neurological consequences. When measles occurs during pregnancy, it can result in miscarriage, premature labour, stillbirth, birth defects or even fetal death. The most severe cases of measles can be fatal. </p>
<p>Also of note, infection with the measles virus can weaken the immune system for months or years, increasing the risk of infections with a wide range of microbes. While measles-associated immunosuppression has been documented for decades, we are only beginning to decipher its underlying mechanisms. For example, a phenomenon called “<a href="https://doi.org/10.1038/s41467-018-07515-0">immune amnesia</a>” is thought to contribute, at least partially, to unrelated infections in the aftermath of measles.</p>
<h2>What is immune amnesia?</h2>
<p>The naturally occurring (wild-type) strains of measles virus can target, infect and kill memory B and T lymphocytes, which are instrumental to antimicrobial defence. This is because one of the three measles virus receptors, called CD150, happens to be abundantly present on the surface of these lymphocytes.</p>
<p>Long-lived memory cells, which accumulate as a result of immunizations and infections over time, remain in a poised state to mount rapid and rigorous recall responses when we re-encounter microbes. B cells orchestrate the production of antibodies that neutralize extracellular microbes, and T cells work to destroy infected cells. Therefore, when people lose their precious memory cells to measles, the immune system is set back to a default mode, as if it has never seen any microbes or vaccines in the past.</p>
<p>To add insult to injury, <a href="https://doi.org/10.1093/infdis/jiaa407">measles virus may also eliminate “memory-like” innate T cells</a>, which also express CD150, thus removing yet another potent weapon from our antimicrobial arsenal. Therefore, collectively, the ability of measles virus to find and kill memory and memory-like lymphocytes can lead to adaptive and <a href="https://doi.org/10.1371/journal.ppat.1009071">innate immune amnesia</a>, rendering a measles patient or survivor prone to many opportunistic infections.</p>
<h2>How does measles spread and how contagious is it?</h2>
<figure class="align-right ">
<img alt="microscopic image of a virus" src="https://images.theconversation.com/files/583047/original/file-20240320-20-nv4olv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/583047/original/file-20240320-20-nv4olv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=459&fit=crop&dpr=1 600w, https://images.theconversation.com/files/583047/original/file-20240320-20-nv4olv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=459&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/583047/original/file-20240320-20-nv4olv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=459&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/583047/original/file-20240320-20-nv4olv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=577&fit=crop&dpr=1 754w, https://images.theconversation.com/files/583047/original/file-20240320-20-nv4olv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=577&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/583047/original/file-20240320-20-nv4olv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=577&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">Microscopic view of a measles virus particle (red).</span>
<span class="attribution"><span class="source">(CDC and NIAID)</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>Measles virus spreads easily through airborne droplets released by infected people when they breathe, talk, laugh, cough or sneeze. In addition, measles virus infectious particles can remain active in the air and on contaminated surfaces for up to two hours.</p>
<p>Measles virus is one of the most contagious respiratory pathogens known, with <a href="https://doi.org/10.1016/S1473-3099(17)30307-9">each person with measles passing on their infection to 12 to 18 other people</a> in a susceptible population. Measles virus is more transmissible than influenza viruses and SARS-CoV-2 variants.</p>
<h2>How effective are measles vaccines?</h2>
<p>Measles vaccines are safe, affordable and extremely effective. According to the World Health Organization (WHO), <a href="https://www.who.int/news-room/fact-sheets/detail/measles">measles claimed 2.6 million lives each year before 1963</a> when a measles vaccine became available. Since then, widespread immunization programs have saved millions of lives, including an estimated 56 million just between 2000 and 2021.</p>
<p>Measles vaccines contain a live measles virus strain that has been attenuated so that it does not inflict harm; yet, it is sufficient to generate protective immune responses. </p>
<p>The measles-mumps-rubella (MMR) vaccine or the measles-mumps-rubella-varicella (MMRV) vaccine is routinely administered to children in <a href="https://www.canada.ca/en/public-health/services/diseases/measles/health-professionals-measles.html">two doses</a>, with a first dose being given after the first birthday, typically between 12-15 months of age, followed by a booster dose recommended after 18 months of age and before attending school. This should afford lifelong protection against measles in most people. </p>
<p>According to the United States Centers for Disease Control and Prevention (CDC), one and two doses of the MMR vaccine are <a href="https://www.cdc.gov/vaccines/vpd/mmr/public/index.html">93 per cent and 97 per cent effective</a> in preventing measles, respectively. </p>
<p>Teens and adults should also <a href="https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-12-measles-vaccine.html#">remain up to date with regard to measles immunization</a> since measles can affect anyone. There are blood tests that can be ordered by health-care providers to determine immunity to measles. </p>
<p>The MMR vaccine can be <a href="https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-12-measles-vaccine.html#">given at any time</a> during one’s lifespan, but the MMRV vaccine is authorized in Canada only between one and 13 years of age.</p>
<h2>Why are measles cases returning?</h2>
<p>Recent years have witnessed a rise in measles outbreaks within and outside Canada. This is primarily due to an alarming decline in measles vaccination caused by <a href="https://theconversation.com/measles-global-increase-in-cases-likely-driven-by-covid-pandemic-182250">delayed childhood immunizations amid COVID-19</a> lockdowns, vaccine hesitancy <a href="https://theconversation.com/measles-outbreak-why-are-anti-vaxxers-risking-a-public-health-crisis-116334">creating vulnerable societal pockets</a>, anti-vaccine sentiments and <a href="https://time.com/6564694/measles-antivaccine-misinformation/">digital misinformation</a> spread through online social media, and the resumption of global travel post-COVID.</p>
<p>Measles outbreaks occur soon after <a href="https://doi.org/10.1001/jama.2020.20895">herd immunity</a> is compromised. Herd immunity is achieved when an adequately large proportion of a population becomes immune to a specific pathogen through prior infections or vaccination. As a result, the probability of an infectious case encountering a susceptible person drops dramatically. </p>
<p>For measles, the necessary <a href="https://www.who.int/news/item/23-11-2022-nearly-40-million-children-are-dangerously-susceptible-to-growing-measles-threat">threshold for herd immunity is 95 per cent</a>. This means when 95 per cent of people in a population are immune, the remaining five per cent (including newborns, unvaccinated or undervaccinated children and immunodeficient people who cannot receive a measles vaccine) are also indirectly protected since the risk of measles virus transmission is significantly minimized.</p>
<p>By receiving two doses of a measles vaccine, one protects not only themselves but also the vulnerable members of their community. The only way to avoid measles and its serious complications, including proneness to a broad spectrum of unrelated infections, is to vaccinate widely, to engage those who are hesitant to have their children immunized in a respectful dialogue, and to educate the public regarding the unparalleled benefits of measles vaccines.</p>
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Read more:
<a href="https://theconversation.com/how-better-conversations-can-help-reduce-vaccine-hesitancy-for-covid-19-and-other-shots-159321">How better conversations can help reduce vaccine hesitancy for COVID-19 and other shots</a>
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<p>It is also crucial to isolate infected individuals for four days after the appearance of a measles rash to prevent measles virus transmission to others.</p>
<p>In Canada, measles has been <a href="https://www.canada.ca/en/public-health/services/diseases/measles/surveillance-measles.html">a nationally notifiable disease</a> since 1924 (except between 1959 and 1968), and the Canadian Measles and Rubella Surveillance System (CMRSS) ensures the weekly collection of measles data from every province and territory, including zero report submissions.</p><img src="https://counter.theconversation.com/content/226205/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mansour Haeryfar 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>Canada is seeing a surge in measles cases. Find out what measles is, why it’s returning to Canada, and how people can protect themselves and others.Mansour Haeryfar, Professor of Immunology, Western UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2149192024-01-15T13:33:10Z2024-01-15T13:33:10ZWhat if every germ hit you at the exact same time? An immunologist explains<figure><img src="https://images.theconversation.com/files/565348/original/file-20231212-15-ba3kr2.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Your immune system encounters a legion of potential pathogens every day.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/woman-shielding-eyes-by-large-green-coronavirus-royalty-free-image/1250588799">Klaus Vedfelt/DigitalVision via Getty Images</a></span></figcaption></figure><figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=293&fit=crop&dpr=1 600w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=293&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=293&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=368&fit=crop&dpr=1 754w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=368&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/281719/original/file-20190628-76743-26slbc.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=368&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<p><em><a href="https://theconversation.com/us/topics/curious-kids-us-74795">Curious Kids</a> is a series for children of all ages. If you have a question you’d like an expert to answer, send it to <a href="mailto:curiouskidsus@theconversation.com">curiouskidsus@theconversation.com</a>.</em></p>
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<blockquote>
<p><strong>What would happen if all the diseases in the world hit us at the exact same time? – Gabriella, age 12, Irving, Texas</strong></p>
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<p>When I was younger, I would watch “Batman” on my black-and-white television after school. Usually, Batman would face either the Joker, the Penguin, the Puzzler, Catwoman or any one of his usual opponents. However, on some occasions, Batman would have to face them all at the same time.</p>
<p>What would happen if, like Batman, the immune system had to face all of its rivals at once?</p>
<p><a href="https://scholar.google.com/citations?user=6JOQvNwAAAAJ&hl=en">I am an immunologist</a> who teaches the fundamentals of immunology to college undergraduates. My research generally focuses on factors that regulate immune responses and prevent autoimmune diseases – conditions where the immune system attacks your own body. As a scientist studying how we build immunity against pathogens such as the virus that causes COVID-19, understanding how the immune system combats multiple threats at the same time is immensely important to me. </p>
<p>There’s no reason why you can’t come down with strep throat at the same time as when you have a cold. In fact, sometimes fighting off one enemy can leave a hole in your defenses that another opportunistic pathogen can take advantage of.</p>
<h2>BAM! Understanding the rivals</h2>
<p>The first point to consider is what your immune system protects you from. The potential bad guys <a href="https://theconversation.com/immune-cells-that-fight-cancer-become-exhausted-within-hours-of-first-encountering-tumors-new-research-210947">include cancer cells</a> and dangerous microorganisms – including bacteria, viruses, fungi and more – that cause infections. The immune system must also be careful <a href="https://theconversation.com/immune-health-is-all-about-balance-an-immunologist-explains-why-both-too-strong-and-too-weak-an-immune-response-can-lead-to-illness-215217">not to damage</a> healthy cells and beneficial microorganisms that live on and inside you. </p>
<p>You interact with <a href="https://kids.frontiersin.org/articles/10.3389/frym.2022.629355">thousands of microorganisms</a> with every breath of air you take. Is the immune system facing off against all of them? Sort of. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/565525/original/file-20231213-27-oegbgf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Microscope images of two T regulatory cells wrapped around an antigen-presenting cell" src="https://images.theconversation.com/files/565525/original/file-20231213-27-oegbgf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/565525/original/file-20231213-27-oegbgf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/565525/original/file-20231213-27-oegbgf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/565525/original/file-20231213-27-oegbgf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/565525/original/file-20231213-27-oegbgf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/565525/original/file-20231213-27-oegbgf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/565525/original/file-20231213-27-oegbgf.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>
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<span class="caption">T regulatory cells (red) determine whether an immune response should be mounted.</span>
<span class="attribution"><a class="source" href="https://flic.kr/p/SjQFf7">NIAID/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>It takes a <a href="https://theconversation.com/how-does-fever-help-fight-infections-theres-more-to-it-than-even-some-scientists-realize-210240">tremendous amount of energy</a> to fight a battle once a rival gains a foothold within your blood or tissues, so your immune system works to <a href="https://theconversation.com/how-do-viruses-get-into-cells-their-infection-tactics-determine-whether-they-can-jump-species-or-set-off-a-pandemic-216139">prevent it from getting in the body</a> in the first place. Your skin, <a href="https://theconversation.com/why-do-our-noses-get-snotty-when-we-are-sick-a-school-nurse-explains-the-powers-of-mucus-212949">snot</a>, saliva and <a href="https://theconversation.com/can-you-cry-underwater-205464">tears</a> form a critical <a href="https://www.ncbi.nlm.nih.gov/books/NBK279396/">first line of defense</a>. This is why <a href="https://doi.org/10.1089%2Fsur.2013.134">burn victims</a> who lose too much skin often die from overwhelming infection – their defensive barriers are too compromised and pathogens pour in.</p>
<p>The immune system greatly prefers <a href="https://theconversation.com/a-pediatric-nurse-explains-the-science-of-sneezing-160970">catching a microbe in snot</a> and blowing it out of your nose, or giving you time to wash it off the skin of your hands, over having to wage a cellular war. Gathering an army of <a href="https://theconversation.com/coronavirus-b-cells-and-t-cells-explained-141888">immune cells</a> to fight pathogens takes a lot of energy and makes you feel awful. </p>
<p>For example, the immune system <a href="https://theconversation.com/how-does-fever-help-fight-infections-theres-more-to-it-than-even-some-scientists-realize-210240">increases your body temperature</a> to make it an uncomfortable place for microorganisms to live and grow, but that fever can also make you want to lie down for days.</p>
<h2>BOOM! Where are their weaknesses?</h2>
<p>When Batman faced multiple opponents, he would find a weakness shared by all of the opponents and target it to foil their plans. The immune system uses the exact same strategy.</p>
<p>Certain microbes are considered pathogens largely because they are in the wrong place – such as inside your body instead of on your skin – and causing damage. Pathogens have specific parts on their surfaces called <a href="https://doi.org/10.1038/s41392-021-00687-0">pathogen associated molecular patterns, or PAMPs</a>.</p>
<p>Very importantly, your body doesn’t make PAMPS. This means if your immune system comes across a PAMP, it knows it isn’t supposed to be there and will mount an attack. Because the same PAMP is present on many different pathogens, a strategy to combat one PAMP can defeat many pathogens.</p>
<p>There are molecules in cells all over your body that can recognize PAMPS and destroy anything those PAMPS are on. It’s as though your immune system set up booby traps that can only attack your enemies.</p>
<p>Many of those booby traps are <a href="https://doi.org/10.1038/35100529">toll-like receptors</a>. This family of molecules is located on the surface and inside of many of your cells. Once microbes contact these booby traps, they trigger an alarm that warn other cells of potential danger. In technical terms, this alarm is <a href="https://theconversation.com/what-is-inflammation-two-immunologists-explain-how-the-body-responds-to-everything-from-stings-to-vaccination-and-why-it-sometimes-goes-wrong-193503">called inflammation</a>.</p>
<h2>SPLAT! Raising an army of defenders</h2>
<p>Whereas Batman would need to think of a new strategy to combat the Joker, the Penguin and Catwoman, your immune system devised a plan long ago. </p>
<p>When the virus that causes COVID-19 emerged in 2019, it was something people’s immune systems likely had never seen before. However, some people already had immune cells that could target components of the virus. How is that possible?</p>
<p>The immune system makes many immune cells that are specific to antigens, or unique and recognizable parts of cancers and microorganisms, it hasn’t encountered before. This occurs through a process where pieces of your DNA <a href="https://doi.org/10.1038/nri2941">randomly recombine to form</a> unique immune cell receptors. The DNA in each of these immune cells is different from the DNA in any other cell in your body. Researchers believe that each person can generate <a href="https://www.ncbi.nlm.nih.gov/books/NBK27140/">at least a trillion different combinations</a> of immune receptors, which is <a href="https://doi.org/10.1038/nrmicro2644">more than the number of pathogens</a> an average person would ever face in their lifetime overall.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/Na-Zc-xWCLE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Your immune system can churn out billions of unique antibodies.</span></figcaption>
</figure>
<p>Although the immune system makes a lot of immune cells, most of them aren’t used because you’re not exposed to the antigen they’re made to recognize. However, when an immune cell recognizes an antigen, it rapidly <a href="https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Boundless)/11%3A_Immunology/11.07%3A_Antibodies/11.7C%3A_Clonal_Selection_of_Antibody-Producing_Cells">makes many copies of itself</a>. Since pathogens can also multiply rapidly, clonal selection allows you to rapidly raise an army to fight them.</p>
<p>Usually this strategy works well with <a href="https://theconversation.com/when-covid-19-or-flu-viruses-kill-they-often-have-an-accomplice-bacterial-infections-187056">one or two coinfections</a>, such as if you have the common cold and an eye infection at the same time. But what if you were infected with a trillion pathogens at the same time? It would take a tremendous amount of energy and time to build an appropriate army against each microorganism all at once. Unfortunately, the immune system likely would be overwhelmed by this challenge, and you would probably die. </p>
<p>Fortunately, your immune system – like Batman – usually figures out the best way to shift a battle against rivals to its favor, pulling out a victory in the final minutes of the episode.</p>
<hr>
<p><em>Hello, curious kids! Do you have a question you’d like an expert to answer? Ask an adult to send your question to <a href="mailto:curiouskidsus@theconversation.com">CuriousKidsUS@theconversation.com</a>. Please tell us your name, age and the city where you live.</em></p>
<p><em>And since curiosity has no age limit – adults, let us know what you’re wondering, too. We won’t be able to answer every question, but we will do our best.</em></p><img src="https://counter.theconversation.com/content/214919/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Joseph Larkin III receives funding from the Grayson Jockey Research Foundation, The National Institutes of Health, and industry. </span></em></p>Your immune system is often able to fend off pathogens it’s never seen before. But defending your body against all of them all at once is a tough challenge.Joseph Larkin III, Associate Professor of Microbiology and Cell Science, University of FloridaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2110902023-09-25T15:03:20Z2023-09-25T15:03:20ZImplants like pacemakers and insulin pumps often fail because of immune attacks − stopping them could make medical devices safer and longer-lasting<figure><img src="https://images.theconversation.com/files/549651/original/file-20230921-21-b8f110.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Foreign body responses can cause insulin pumps to degrade.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/young-diabetic-patient-keeps-an-insulin-pump-in-the-royalty-free-image/1041117870">Click_and_Photo/iStock via Getty Images</a></span></figcaption></figure><p>Biomedical implants – such as pacemakers, breast implants and orthopedic hardware like screws and plates to replace broken bones – have improved patient outcomes across a wide range of diseases. However, <a href="https://doi.org/10.1002%2Fbtm2.10300">many implants fail</a> because the body rejects them, and they need to be removed because they no longer function and can cause pain or discomfort.</p>
<p>An immune reaction called the <a href="https://doi.org/10.1002/adfm.202007226">foreign body response</a> – where the body encapsulates the implant in sometimes painful scar tissue – is a key driver of implant rejection. Developing treatments that target the mechanisms driving foreign body responses could improve the design and safety of biomedical implants.</p>
<p>I am a <a href="https://scholar.google.com/citations?user=TG52tUAAAAAJ&hl=en">biomedical engineer</a> who studies why the body forms scar tissue around medical devices. Along with my colleagues <a href="https://scholar.google.com/citations?user=XMWljcMAAAAJ&hl=en">Dharshan Sivaraj</a>, <a href="https://scholar.google.com/citations?user=UcM7zG8AAAAJ&hl=en">Jagan Padmanabhan</a> and <a href="https://scholar.google.com/citations?user=zY_J9IQAAAAJ&hl=en">Geoffrey Gurtner</a>, we wanted to learn more about what causes foreign body responses. In our research, recently published in the journal Nature Biomedical Engineering, we <a href="https://www.nature.com/articles/s41551-023-01091-5">identified a gene</a> that appears to drive this reaction because of the increased stress implants put on the tissues surrounding them.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/4h9nfYbov38?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Many implants need to be replaced because the immune system damages them over time.</span></figcaption>
</figure>
<h2>Mechanics of implant rejection</h2>
<p>Researchers hypothesize that foreign body responses are triggered by the chemical and material composition of the implant. Just as a person can tell the difference between touching something soft like a pillow versus something hard like a table, cells can tell when there are changes to the softness or stiffness of the tissues surrounding them as a result of an implant.</p>
<p>The <a href="https://doi.org/10.1096/fj.202101354">increased mechanical stress</a> on those cells sends a signal to the immune system that there is a foreign body present. Immune cells activated by mechanical pressure respond by building a capsule made of scar tissue around the implant in an attempt to shield it off. The more severe the immune reaction, the thicker the capsule. This protects the body from getting an infection from injuries like a splinter in your finger.</p>
<p>All biomedical implants cause some level of foreign body response and are surrounded by at least a small capsule. Some people have very strong reactions that result in a large, thick capsule that constricts around the implant, impeding its function and causing pain. <a href="https://doi.org/10.1002%2Fbtm2.10300">Between 10% to 30% of implants</a> need to be removed because of this scar tissue. For example, a neurostimulator could trigger the formation of a dense capsule of scar tissue that <a href="https://doi.org/10.1073/pnas.2115857119">inhibits electrical stimulation</a> from properly reaching the nervous system.</p>
<p>To understand why the immune systems of some people build thick capsules around implants while others do not, we gathered capsule samples from 20 patients whose breast implants were removed – 10 who had severe reactions, and 10 who had mild reactions. By genetically analyzing the samples, we found that a <a href="https://www.nature.com/articles/s41551-023-01091-5">gene called RAC2</a> was highly expressed in samples taken from patients with severe reactions but not in those with mild reactions. This gene is found <a href="https://doi.org/10.1128/mcb.22.21.7645-7657.2002">only in immune cells</a>, and it codes for a <a href="https://doi.org/10.1074/jbc.M306491200">member of a family of proteins</a> involved in cell growth and structure.</p>
<p>Because this protein seemed to be linked to a lot of the downstream reactions that lead to foreign body responses, we decided to explore how RAC2 affects the formation of capsules. We found that immune cells activate RAC2 along with other proteins <a href="https://www.nature.com/articles/s41551-023-01091-5">in response to mechanical stress</a> from implants. These proteins summon additional immune cells to the area that <a href="https://doi.org/10.3390%2Fma8095269">combine into a massive clump</a> to attack a large invader. These combined cells spit out fibrous proteins like collagen that form scar tissue.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/549655/original/file-20230921-25-uccyoe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Clinician holding a silicone breast implant" src="https://images.theconversation.com/files/549655/original/file-20230921-25-uccyoe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/549655/original/file-20230921-25-uccyoe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/549655/original/file-20230921-25-uccyoe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/549655/original/file-20230921-25-uccyoe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/549655/original/file-20230921-25-uccyoe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/549655/original/file-20230921-25-uccyoe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/549655/original/file-20230921-25-uccyoe.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 mechanical stress that medical devices like breast implants place on surrounding tissues can trigger a foreign body response.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/plastic-surgeon-holding-breast-silicone-implant-royalty-free-image/1300316377">megaflopp/iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<p>To confirm RAC2’s role in foreign body responses, we artificially stimulated the mechanical signaling proteins surrounding silicone implants surgically placed in mice. This stimulation produced a severe and humanlike foreign body response in the mice. In contrast, blocking RAC2 resulted in an <a href="https://www.nature.com/articles/s41551-023-01091-5">up to threefold reduction</a> in foreign body responses.</p>
<p>These findings suggest that activating mechanical stress pathways triggers immune cells with RAC2 to generate severe foreign body responses. Blocking RAC2 in immune cells may significantly reduce this reaction.</p>
<h2>Developing new treatments</h2>
<p>Implant failure is conventionally treated by using <a href="https://doi.org/10.1186/s13036-019-0209-9">biocompatible materials</a> that the body can better tolerate, such as certain polymers. These don’t completely remove the risk of foreign body reactions, however.</p>
<p>My colleagues and I believe that treatments that target the pathways associated with RAC2 could potentially mitigate or prevent free body responses. Heading off this reaction would help improve the effectiveness and safety of medical implants.</p>
<p>Because <a href="https://doi.org/10.1128/mcb.22.21.7645-7657.2002">only immune cells express RAC2</a>, a drug designed to block only that gene would theoretically target only immune cells without affecting other cells in the body. Such a drug could also be administered via injection or even coated onto an implant to minimize side effects.</p>
<p>A complete understanding of the molecular mechanisms driving foreign body responses would be the final frontier in developing truly bio-integrative medical devices that could integrate with the body with no problems for the recipient’s entire life span.</p><img src="https://counter.theconversation.com/content/211090/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kellen Chen 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>From breast implants to prosthetic knees, implants can trigger a foreign body response that results in your body rejecting them. Suppressing an immune cell gene could reduce this risk.Kellen Chen, Assistant Professor of Surgery, University of ArizonaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2077242023-06-22T02:11:07Z2023-06-22T02:11:07ZDo I need a booster vaccine if I recently had COVID? What if I’m not sure what I had?<figure><img src="https://images.theconversation.com/files/533059/original/file-20230621-14332-ci9rr5.jpg?ixlib=rb-1.1.0&rect=38%2C7%2C5121%2C3435&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/officers-nurse-use-needles-suck-covid19-2090251705">Shutterstock</a></span></figcaption></figure><p>In early 2021, recommendations about COVID vaccines were pretty straightforward – get two doses, as soon as you are eligible. A year later, we knew getting a third dose <a href="https://www.nature.com/articles/s41591-022-01727-0">was important</a> for protection against the new Omicron variant. </p>
<p>Today, though, the situation is far more complex – new updated vaccines are available, the majority of Australians have <a href="https://kirby.unsw.edu.au/sites/default/files/COVID19-Blood-Donor-Report-Round3-Aug-Sep-2022.pdf">likely been infected</a> at least once with an Omicron strain, and waves of infection continue to occur. </p>
<p>So how should you manage and time your booster shots?</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/over-half-of-eligible-aged-care-residents-are-yet-to-receive-their-covid-booster-and-winter-is-coming-205403">Over half of eligible aged care residents are yet to receive their COVID booster. And winter is coming</a>
</strong>
</em>
</p>
<hr>
<h2>Why do vaccines need boosters?</h2>
<p>Vaccines work by training our body’s immune system to react harder, faster, stronger and better when we get infected by a pathogenic virus or bacteria. </p>
<p>Unfortunately, this protective benefit is not permanent and immunity tends to “wane” over time. The extent to which vaccine protection wanes is a function of two main factors. </p>
<p>First, your <a href="https://www.youtube.com/watch?v=la6nXuAw-Oo">immune system</a> (in the form of antibodies, memory B cells and T cells) is not infinite, and the levels of vaccine-induced immune responses will gradually decline over time. Second, pathogens circulating in the community can mutate, which enables “escape” from being recognised by the immune system. The more the virus escapes, the less protection the vaccine can give you.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-does-my-back-get-so-sore-when-im-sick-the-connection-between-immunity-and-pain-207222">Why does my back get so sore when I'm sick? The connection between immunity and pain</a>
</strong>
</em>
</p>
<hr>
<h2>Some vaccines need frequent boosting, others last forever</h2>
<p>Not all pathogens have the same ability to create or tolerate mutations. For viruses that change little (such as measles), your childhood vaccines remain highly protective and you might never need a booster. </p>
<p>In contrast, some viruses can rapidly and dramatically change (looking at you, influenza), quickly rendering our vaccines outdated and making updates necessary.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/i-need-a-flu-shot-and-a-covid-booster-can-i-get-them-at-the-same-time-204027">I need a flu shot and a COVID booster. Can I get them at the same time?</a>
</strong>
</em>
</p>
<hr>
<h2>So, where does COVID fit in?</h2>
<p>SARS-CoV-2, the virus that causes COVID, has demonstrated an ability to rapidly change since emerging in 2019. Although the early pandemic in Australia featured vaccine supply constraints, we now lucky to have many different vaccine options. </p>
<p>Recommendations currently favour updated mRNA “bivalent” boosters from Pfizer or Moderna, each containing equal parts of the original virus strain and an Omicron strain. </p>
<p>But the virus continues to change (currently XBB strains are <a href="https://www.health.nsw.gov.au/Infectious/covid-19/Documents/weekly-covid-overview-20230610.pdf#page=9">dominant</a>, and further updates to the composition of the vaccine are to be expected in the future (<a href="https://www.fda.gov/vaccines-blood-biologics/updated-covid-19-vaccines-use-united-states-beginning-fall-2023">most likely to target XBB.1.5</a>).</p>
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<h2>That’s great, but I recently had COVID, so …</h2>
<p>Are you sure? Queuing for a PCR test seems like a fever dream from the past. Now, many of the RATs stacked in our cupboards are rapidly expiring. Influenza and RSV are <a href="https://www.abc.net.au/news/2023-05-08/rsv-flu-outbreak-hits-queensland-hard-cases-5-times-higher/102272112">back with gusto</a> (and cause similar symptoms). </p>
<p>If you did have confirmed COVID, <a href="https://www.cell.com/immunity/fulltext/S1074-7613(22)00238-2">our research</a> shows the majority of people mount a <a href="https://www.cell.com/immunity/fulltext/S1074-7613(23)00091-2">strong immune response</a> following each infection. </p>
<p>This means that once you recover, your immunity has been “updated” to reflect the virus variant that caused your infection and you will have higher protective antibody levels in your blood.</p>
<h2>Well, I definitely had something. What does that mean for my COVID booster?</h2>
<p>There are a couple of things to consider here. </p>
<p>Firstly, there is no such thing as “too much” immunity. Beyond the regular <a href="https://www.health.gov.au/our-work/covid-19-vaccines/advice-for-providers/clinical-guidance/adverse-events">side-effects of a vaccine</a>, there are no known additional risks to being re-vaccinated soon after an infection. </p>
<p>On the other hand, getting vaccinated quickly after recovery will not do much to further boost your immunity. <a href="https://www.health.gov.au/our-work/covid-19-vaccines/getting-your-vaccination/booster-doses">Current recommendations</a> are to wait six months after infection or your last dose before seeking another booster. </p>
<p>This allows your immune system time to rest, so that it can be effectively re-activated by vaccination. If you’d prefer to minimise your risk of COVID, and you don’t know what caused a recent illness, “<a href="https://www.health.gov.au/top-up-covid-19-protection">topping up</a>” your immunity via a booster may be the way to go.</p>
<h2>How should we balance booster shots and infections in the community?</h2>
<p>The short answer is, we need more information and time to figure that out. </p>
<p>Our communities now have high immunity (from both vaccines and infections), so balancing the risks and rewards of COVID boosters is increasingly complex. </p>
<p>Ultimately, your personal health care provider is best placed to offer specific advice. Generally however, those who are vaccinated (with three or more doses), younger (64 and under), and otherwise healthy have the least to gain.</p>
<p>For those who are older (especially over 65s) or who have health complications, regular COVID boosters are likely to be an important tool for staying healthy, especially over the winter season. While we still need more data, <a href="https://jamanetwork.com/journals/jama/fullarticle/2794072">multiple studies</a> suggest booster vaccines can <a href="https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00354-6/fulltext">reduce the risk</a> of developing long COVID, providing another reason to keep up-to-date. </p>
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<h2>The bottom line</h2>
<p>Unfortunately, COVID is among us and likely here for good. But like old mate influenza, we now have effective tools to blunt the impacts of COVID, and even better options will come through the pipeline to unlock further health improvements (like the transformative <a href="https://www.nature.com/articles/d41586-023-01529-5">new vaccines for RSV</a>). </p>
<p>For now, stay tuned to the latest <a href="https://www.health.gov.au/news/atagi-2023-booster-advice">advice from the Australian Technical Advisory Group on Immunisation</a> (ATAGI) about additional vaccine boosters and rest assured scientists and public health officials are still working to better understand how best to maintain high levels of population immunity via regular immunisation.</p><img src="https://counter.theconversation.com/content/207724/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Adam Wheatley receives funding from NHMRC, MRFF and ARC. </span></em></p><p class="fine-print"><em><span>Jennifer Juno receives funding from the NHMRC, MRFF and NIH.</span></em></p>Firstly, there is no such thing as ‘too much’ immunity. Beyond the regular side-effects of a vaccine, there are no known additional risks to being re-vaccinated soon after an infection.Adam Wheatley, Laboratory Head, Department of Microbiology and Immunology, The University of MelbourneJennifer Juno, Laboratory Head, The Peter Doherty Institute for Infection and ImmunityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2069242023-06-05T15:01:08Z2023-06-05T15:01:08ZSeveral Down syndrome features may be linked to a hyperactive antiviral immune response – new research<figure><img src="https://images.theconversation.com/files/529898/original/file-20230603-15-so1fli.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3679%2C2647&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Addressing the increased risks of certain diseases among those with Down syndrome could help improve their quality of life.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/boy-with-down-syndrome-playing-outdoors-in-garden-royalty-free-image/1271658791">Halfpoint Images/Moment via Getty Images</a></span></figcaption></figure><p>People with <a href="https://www.globaldownsyndrome.org/about-down-syndrome/facts-about-down-syndrome/">Down syndrome</a>, or trisomy 21, a genetic condition caused by an extra copy of human chromosome 21, experienced a remarkable increase in life expectancy during the 20th century. In the early 1900s, less than 20% of newborns with Down syndrome <a href="https://doi.org/10.1038/gim.2016.127">survived past age 5</a>. In the U.S. today, more than 90% of babies with this condition <a href="https://doi.org/10.1038/gim.2016.127">live past age 10</a> and have a life expectancy of <a href="https://doi.org/10.1001/jamanetworkopen.2022.12910">nearly 60 years</a>. These increases were <a href="https://doi.org/10.1016%2FS0074-7750(10)39004-5">likely fueled</a> by greater inclusion in general society, the discontinuation of institutionalization in psychiatric facilities and better medical care.</p>
<p>Despite these advances, people with trisomy 21 experience an increased risk of many <a href="https://doi.org/10.1038/s41572-019-0143-7">co-occurring conditions</a>, such as congenital heart defects, autoimmune conditions, autism spectrum disorders and Alzheimer’s disease. On the other hand, people with Down syndrome tend to have <a href="https://doi.org/10.17294/2330-0698.1824">lower levels of hypertension</a> and <a href="https://doi.org/10.1038/gim.2016.23">certain types of cancers</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/529897/original/file-20230603-25-nrpa24.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Karyotype of Down syndrome, with a circle around three copies of chromosome 21" src="https://images.theconversation.com/files/529897/original/file-20230603-25-nrpa24.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/529897/original/file-20230603-25-nrpa24.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=480&fit=crop&dpr=1 600w, https://images.theconversation.com/files/529897/original/file-20230603-25-nrpa24.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=480&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/529897/original/file-20230603-25-nrpa24.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=480&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/529897/original/file-20230603-25-nrpa24.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=603&fit=crop&dpr=1 754w, https://images.theconversation.com/files/529897/original/file-20230603-25-nrpa24.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=603&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/529897/original/file-20230603-25-nrpa24.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=603&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Down syndrome is also called trisomy 21 because those with the condition have three copies of chromosome 21.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/downs-syndrome-karyotype-illustration-royalty-free-illustration/685025123">Kateryna Kon/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<p>Understanding how an extra chromosome 21 causes these risks and resiliencies could advance collective understanding of major medical conditions that also affect the general population. For example, the <a href="https://doi.org/10.1038/s41582-018-0132-6">increased risk of Alzheimer’s disease</a> among adults with Down syndrome can be explained in part by the presence of a gene on chromosome 21 that leads to excess production of the beta-amyloid proteins and plaques characteristic of Alzheimer’s.</p>
<p>In our newly published research, my research team <a href="https://scholar.google.com/citations?user=6gRbVeAAAAAJ&hl=en">and I</a> found that <a href="https://www.nature.com/articles/s41588-023-01399-7">genes involved in controlling the immune system</a> are critical to the development of multiple hallmarks of Down syndrome. Our findings contribute to a growing body of research on the immune system’s important role in the appearance and severity of some of the negative health effects of trisomy 21, supporting the idea that restoring immune balance could help improve the quality of life of people with the condition.</p>
<h2>When too much of a good thing is bad</h2>
<p>The genes we identified, which encode what are called <a href="https://doi.org/10.1038%2Ficb.2012.9">interferon receptors</a>, are an important part of the immune system’s antiviral defense. These genes enable our cells to recognize a set of proteins called interferons, which virus-infected cells produce to alert the yet uninfected cells around them about the presence of a virus during an infection.</p>
<p>While interferons do trigger a beneficial immune response against viral infections, chronic interferon hyperactivity could have detrimental effects. Too much interferon signaling is known to be harmful in medical conditions such as <a href="http://dx.doi.org/10.1136/lupus-2018-000270">systemic lupus erythematosus</a>, a group of genetic disorders known as <a href="https://doi.org/10.1038/s41577-021-00633-9">interferonopathies</a> and <a href="https://doi.org/10.1038/s41577-020-00429-3">severe COVID-19</a>.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/529899/original/file-20230603-17-pq5zrq.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="3D model of human interferon-beta structure" src="https://images.theconversation.com/files/529899/original/file-20230603-17-pq5zrq.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/529899/original/file-20230603-17-pq5zrq.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=418&fit=crop&dpr=1 600w, https://images.theconversation.com/files/529899/original/file-20230603-17-pq5zrq.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=418&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/529899/original/file-20230603-17-pq5zrq.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=418&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/529899/original/file-20230603-17-pq5zrq.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=526&fit=crop&dpr=1 754w, https://images.theconversation.com/files/529899/original/file-20230603-17-pq5zrq.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=526&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/529899/original/file-20230603-17-pq5zrq.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=526&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Interferons are involved in antiviral immune responses.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:1AU1_Human_Interferon-Beta05.png">Nevit Dilmen/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>Notably, four of the six human interferon receptor genes are <a href="https://doi.org/10.1038%2Ficb.2012.9">located on chromosome 21</a>. Most people have only two copies of each chromosome and so would have only two copies of these genes. Because people with Down syndrome have three copies of chromosome 21, they also have three copies of the interferon receptor genes on it. This contributes to the <a href="https://doi.org/10.7554/eLife.16220">overproduction of interferon receptors</a> seen in those with Down syndrome.</p>
<p>Our team wanted to know whether this <a href="https://www.nature.com/articles/s41588-023-01399-7">extra copy of interferon receptor genes</a>, compared with the roughly 200 other genes located on chromosome 21, contribute to features of Down syndrome. To do this, we used a mouse model of Down syndrome. In this mouse model, a large region of its genome that is equivalent to a large portion of human chromosome 21 is triplicated to reproduce many features of Down syndrome.</p>
<p>Using <a href="https://theconversation.com/human-genome-editing-offers-tantalizing-possibilities-but-without-clear-guidelines-many-ethical-questions-still-remain-200983">CRISPR gene editing</a> technology, we reduced the number of interferon receptor genes from three to the typical two, leaving all other triplicated genes intact. We found that <a href="https://www.nature.com/articles/s41588-023-01399-7">correcting the number of interferon receptor genes</a> significantly reduced abnormal gene expression patterns across multiple tissue types, both during embryonic development and in adult mice. These mice also had more regulated immune responses, normal heart development, reduced developmental delays, improved performance on memory and learning tasks and even a more typical skull and facial morphology.</p>
<p>Overall, our findings suggest that the tripling of interferon receptor genes may cause a number of key traits of Down syndrome.</p>
<h2>Therapeutic implications and future directions</h2>
<p>Our research indicates that many, though not all, aspects of Down syndrome may be associated with hyperactivity of the immune system’s interferon response. It also supports the possibility of using drugs that attenuate this response to treat some of the negative health effects of trisomy 21.</p>
<p>Our team is currently leading two clinical trials to test the safety and efficacy of one such drug, <a href="https://www.uptodate.com/contents/tofacitinib-drug-information">tofacitinib (Xeljanz)</a>. This drug belongs to a class of drugs known as JAK inhibitors used to treat autoinflammatory conditions. One trial <a href="https://clinicaltrials.gov/ct2/show/NCT04246372">focuses on autoimmune skin conditions</a> more common in Down syndrome. The second trial <a href="https://clinicaltrials.gov/ct2/show/NCT05662228">focuses on Down syndrome regression disorder</a>, or DSRD, a rare but devastating <a href="https://doi.org/10.3389%2Ffneur.2022.940175">neurological condition</a> that can result in loss of speech, sleep disruptions, difficulty moving and hallucinations. There is evidence that suggests that a subset of DSRD cases may be caused by <a href="https://doi.org/10.1186/s11689-022-09446-w">immune dysregulation affecting the brain</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/529900/original/file-20230603-27-v9th5q.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Person with Down syndrome holding a potted plant in a nursery" src="https://images.theconversation.com/files/529900/original/file-20230603-27-v9th5q.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/529900/original/file-20230603-27-v9th5q.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/529900/original/file-20230603-27-v9th5q.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/529900/original/file-20230603-27-v9th5q.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/529900/original/file-20230603-27-v9th5q.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/529900/original/file-20230603-27-v9th5q.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/529900/original/file-20230603-27-v9th5q.png?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">Treating the common health risks that occur with Down syndrome could help improve quality of life.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/portrait-of-happy-confident-florist-in-flower-shop-royalty-free-image/1327764759">Flashpop/DigitalVision via Getty Images</a></span>
</figcaption>
</figure>
<p>Our study findings also support further investigation into the effects of interferon hyperactivity on fetal development more generally. Two of the key traits of Down syndrome that we found were affected by the tripling of interferon receptors – congenital heart disease and skull and facial shape – develop in utero.</p>
<p>Though our research shows promise on the potential of JAK inhibitors and other drugs that modulate the immune system to improve health outcomes in Down syndrome, more research in people is needed to determine their safety and efficacy.</p><img src="https://counter.theconversation.com/content/206924/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Joaquin Espinosa receives funding from the National Institutes of Health, the Global Down Syndrome Foundation, and the Anna and John J. Sie Foundation. Dr. Espinosa has provided consulting services to Elli Lily and Co. and Gilead Sciences Inc. and currently serves in the advisory board of Perha Pharmaceuticals.</span></em></p>People with Down syndrome have an extra chromosome 21. Understanding the effects of those triplicated genes could help improve the health of those with Down syndrome and other medical conditions.Joaquin Espinosa, Professor of Pharmacology, University of Colorado Anschutz Medical CampusLicensed 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/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/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>
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<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/1665402021-09-20T12:30:54Z2021-09-20T12:30:54ZNew treatments for COVID-19 may stave off the worst effects of the virus<figure><img src="https://images.theconversation.com/files/421219/original/file-20210914-27-1b25ilp.jpg?ixlib=rb-1.1.0&rect=18%2C0%2C6154%2C4078&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Emergency medical technicians aid a COVID-19 patient at his home in Louisville, Kentucky. Like much of the U.S., Louisville is experiencing an uptick in COVID-19 patients requiring emergency transport to medical facilities. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/members-of-louisville-metro-emergency-medical-services-tend-news-photo/1235239202?adppopup=true">John Cherry/Getty Images</a></span></figcaption></figure><p>Even with <a href="https://doi.org/10.1056/NEJMoa2110362">three highly effective vaccines</a> available in abundance throughout the country, the delta variant of SARS-CoV-2 continues to cause a large number of new infections, <a href="https://www.mayoclinic.org/coronavirus-covid-19/vaccine-tracker">particularly in states where vaccination rates remain low</a>. What’s more, as schools and businesses reopen and the holiday season approaches, another rise in infections <a href="https://time.com/6096892/fourth-covid-19-wave-us/">may be on the way</a>.</p>
<p>There is, however, some good news. Numerous medications, including fledgling and repurposed drugs, are accessible. For hospitalized COVID-19 patients, these new treatments, along with supportive care advances – such as <a href="https://doi.org/10.1016/j.tacc.2020.09.008">placing some patients on their stomachs</a> in a “prone position” – <a href="https://doi.org/10.1016/S2213-2600(20)30579-8">were helping</a> bring down mortality rates before the Delta variant hit and are continuing to improve patient outcomes today.</p>
<p>As an <a href="https://scholar.google.com/citations?user=NAnp8WsAAAAJ&hl=en">infectious diseases physician and scientist</a>, I <a href="https://uvahealth.com/findadoctor/profile/patrick-e-jackson">have been working</a> to find new treatments for patients since the pandemic’s beginning. Here’s a look at some of them, with one caveat: While these medications might help many patients, none substitute for the vaccine, which is still <a href="https://www.cnbc.com/2021/09/01/are-covid-vaccines-becoming-less-effective-.html">the best defense against the virus</a>. </p>
<figure class="align-center ">
<img alt="A man in a blue uniform who is wearing a mask speaks to a woman sitting in a recliner in a living room." src="https://images.theconversation.com/files/421217/original/file-20210914-21-ht0c0f.jpg?ixlib=rb-1.1.0&rect=11%2C34%2C7726%2C5232&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/421217/original/file-20210914-21-ht0c0f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=410&fit=crop&dpr=1 600w, https://images.theconversation.com/files/421217/original/file-20210914-21-ht0c0f.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=410&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/421217/original/file-20210914-21-ht0c0f.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=410&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/421217/original/file-20210914-21-ht0c0f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=515&fit=crop&dpr=1 754w, https://images.theconversation.com/files/421217/original/file-20210914-21-ht0c0f.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=515&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/421217/original/file-20210914-21-ht0c0f.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=515&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">In Houston, Texas, a fire department medic tells a woman with COVID-19 that her husband, who is also infected with COVID-19, should be taken to the hospital. Houston continues to see a surge in hospitalizations due to the delta variant.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/houston-fire-department-medic-tries-to-convince-a-woman-news-photo/1340254111?adppopup=true">John Moore via Getty Images</a></span>
</figcaption>
</figure>
<h2>The right drug at the right time</h2>
<p>COVID-19 has <a href="https://doi.org/10.1016/j.healun.2020.03.012">two main phases</a>. </p>
<p>In the early stage of the disease, the SARS-CoV-2 virus replicates in the body; the virus itself causes illness. Within the first 10 days or so, the immune system eliminates the virus, but this process can cause collateral damage. </p>
<p>A second phase of the disease may kick in, which occurs when the patient has a disordered inflammatory response. </p>
<p>That’s why it’s critical to use the right treatment drug at the right time. For instance, an <a href="https://ascpt.onlinelibrary.wiley.com/doi/pdf/10.1002/psp4.12543">antiviral drug may help a patient</a> with early and mild symptoms. But it’s not useful for someone on a ventilator after weeks in the hospital. </p>
<p>Conversely, patients in the ICU might benefit from an inflammation-reducing drug, which can prevent damage to organs such as the kidney and lungs; this damage <a href="https://doi.org/10.3389/fimmu.2021.602848">is called sepsis</a>. But the same drug used during the viral phase of disease might hamper a patient’s ability to fight off COVID-19.</p>
<h2>Antiviral drugs</h2>
<p>Three antiviral <a href="https://doi.org/10.1038/s41423-020-0426-7">monoclonal antibody drugs</a> authorized for use in the U.S. may keep the virus from <a href="https://doi.org/10.1038/s41423-020-0426-7">infecting new cells</a> by targeting the <a href="https://doi.org/10.1038/s41401-020-0485-4">SARS-CoV2 spike protein</a>. For outpatients with early COVID-19, these drugs <a href="https://doi.org/10.1016/j.eclinm.2021.101102">reduce the risk</a> of hospitalization and death. <a href="https://www.fda.gov/drugs/drug-safety-and-availability/fda-authorizes-regen-cov-monoclonal-antibody-therapy-post-exposure-prophylaxis-prevention-covid-19">One of them</a> – REGEN-COV – may prevent high-risk patients from getting sick. </p>
<p>These antiviral drugs might also help hospitalized patients whose bodies are unable to make antibodies on their own, either because of immune-compromising drugs or an impaired immune system from another condition. </p>
<p><a href="https://doi.org/10.1101/2021.06.15.21258542">One study that has not yet been peer reviewed shows</a> that hospitalized patients with no natural antiviral antibodies had a reduced risk of dying after receiving one of these drugs. But that treatment is typically unavailable except through a compassionate-use program. To get the medication for a patient, a physician must ask both the drug manufacturer and the FDA for approval.</p>
<p>Another problem: Administering these antiviral drugs on a large scale is a challenge. Health care workers must give them shortly after the start of symptoms. The infusion or injection must be in a monitored setting. Patients may find it difficult to quickly access the treatment.</p>
<h2>Mixed signals on remdesivir</h2>
<p>One of these antiviral drugs, remdesivir, <a href="https://doi.org/10.1021/acscentsci.0c00489">shows activity in the lab</a> against a broad range of viruses, including coronaviruses like SARS-CoV-2. It works by blocking the virus from making more copies of its genetic material.</p>
<p><a href="https://doi.org/10.1056/NEJMoa2007764">Two clinical trials</a> performed early in the pandemic <a href="https://doi.org/10.1016/j.cegh.2020.07.011">show that remdesivir</a> shortens recovery time for hospitalized COVID-19 patients. A more recent trial suggested it <a href="https://doi.org/10.1093/jac/dkab321">reduced the risk of death</a>. But two additional trials, <a href="https://doi.org/10.1056/NEJMoa2023184">one conducted primarily in low- and middle-income countries</a> by the World Health Organization and <a href="https://doi.org/10.1016/S1473-3099(21)00485-0">another in Western Europe</a>, did not show a clear benefit of remdesivir in hospitalized patients.</p>
<p>The medical community has interpreted the conflicting data in different ways. Remdesivir received FDA approval to treat COVID-19; both the <a href="https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/">Infectious Diseases Society of America</a> and the <a href="https://www.covid19treatmentguidelines.nih.gov/management/clinical-management/clinical-management-summary/">National Institutes of Health</a> recommend the drug for hospitalized patients. But the World Health Organization <a href="https://app.magicapp.org/#/guideline/nBkO1E">does not</a>, at least outside of a clinical trial.</p>
<figure class="align-center ">
<img alt="A young woman sitting on a bed with a small child who is hiding her face." src="https://images.theconversation.com/files/421222/original/file-20210914-19-oyr13e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/421222/original/file-20210914-19-oyr13e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=402&fit=crop&dpr=1 600w, https://images.theconversation.com/files/421222/original/file-20210914-19-oyr13e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=402&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/421222/original/file-20210914-19-oyr13e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=402&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/421222/original/file-20210914-19-oyr13e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=505&fit=crop&dpr=1 754w, https://images.theconversation.com/files/421222/original/file-20210914-19-oyr13e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=505&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/421222/original/file-20210914-19-oyr13e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=505&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A 25-year-old Houston, Texas, woman grieves with her daughter after her mother died at home of COVID-19. The woman said they had not yet been vaccinated, citing fears of the shot.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/covid-positive-woman-grieves-with-her-daughter-after-her-news-photo/1340293876?adppopup=true">John Moore via Getty Images</a></span>
</figcaption>
</figure>
<h2>Anti-inflammatory drugs</h2>
<p>Steroids like dexamethasone can broadly suppress the immune system and, in turn, reduce inflammation. For hospitalized patients, a regimen of dexamethasone <a href="https://doi.org/10.1056/NEJMoa2021436">decreased the risk of death</a>, according to a February 2021 study published in the New England Journal of Medicine. The benefit was greatest for patients requiring the most respiratory support. But in the same study, for patients with no need for oxygen therapy, dexamethasone had no benefit, and in fact could be harmful. </p>
<h2>IL-6 inhibitors</h2>
<p>Steroids are a blunt instrument for immune suppression; other anti-inflammatory drugs affect the immune system more precisely. Critically ill COVID-19 patients with inflammation may have elevated levels of the IL-6 cytokine, a molecule the immune system uses to coordinate a response. For these patients, both tocilizumab and sarilumab – two drugs that block cells from responding to IL-6 – <a href="https://doi.org/10.1056/NEJMoa2100433">may reduce inflammation and decrease mortality when combined with dexamethasone</a>.</p>
<h2>JAK inhibitors</h2>
<p>A class of drugs called JAK inhibitors – JAK being shorthand for a family of enzymes called Janus kinases – may also modify the body’s inflammatory response. They are used for some autoimmune conditions, including rheumatoid arthritis, and they block inflammation caused by IL-6.</p>
<p>Adding baricitinib, a JAK inhibitor, to remdesivir <a href="https://doi.org/10.1056/NEJMoa2031994">helped hospitalized patients recover faster</a> than using remdesivir alone. <a href="https://doi.org/10.1016/S2213-2600(21)00331-3">Baricitinib also reduced mortality</a> in hospitalized patients treated with dexamethasone. And, with the sickest COVID-19 patients, it helped reduce inflammation. </p>
<p>Of the drugs discussed, at the moment only the antiviral monoclonal antibodies are available for doctors to prescribe for patients who are not in the hospital. There is still a clear need for other drugs to help patients with early symptoms who are not hospitalized. Older medications that may be repurposed to treat these patients include <a href="https://doi.org/10.1016/S0140-6736(21)01744-X">inhaled corticosteroids</a> and fluvoxamine, an antidepressant. </p>
<h2>A dangerous trend</h2>
<p>As for the now-controversial drug ivermectin: Preliminary results from one randomized, placebo-controlled trial <a href="https://www.latimes.com/business/story/2021-08-11/ivermectin-no-effect-covid">did not show any benefit</a> for COVID-19 treatment. Two more trials, also randomized and placebo-controlled, are underway. </p>
<p>For now, based on current evidence, ivermectin should not be used to treat COVID-19 patients. When used incorrectly, <a href="https://www.fda.gov/consumers/consumer-updates/why-you-should-not-use-ivermectin-treat-or-prevent-covid-19">this drug could cause serious harm</a>. Ivermectin has been approved for treatment of parasitic worms and head lice; but using it off-label to treat COVID-19 <a href="https://emergency.cdc.gov/han/2021/han00449.asp">has resulted in overdoses and hospitalizations</a>. Ivermectin toxicity can cause nausea, vomiting, diarrhea, low blood pressure, confusion, seizures and death.</p>
<p>The urgent search for COVID-19 treatments has highlighted the need for high-quality science. Early on, limited studies led some to believe that <a href="https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or">hydroxychloroquine</a> would be useful for COVID-19. But over time, more rigorous research <a href="https://www.cochrane.org/news/chloroquine-or-hydroxychloroquine-useful-treating-people-covid-19-or-preventing-infection">showed the drug to have no value</a> for COVID-19 treatment. </p>
<p><a href="https://www.nia.nih.gov/health/placebos-clinical-trials#:%7E:text=The%20%E2%80%9Cgold%20standard%E2%80%9D%20for%20testing,a%20placebo%20or%20standard%20care">Randomized, placebo-controlled trials</a> – in which patients are randomly assigned to receive either the test drug or a placebo – represent medicine’s gold standard. They help doctors avoid the many sources of bias that can lead us to conclude a drug is helpful when it really isn’t. Going forward, it is this kind of research – and evidence – that is essential to finding new and effective COVID-19 treatments. </p>
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<p class="fine-print"><em><span>Patrick Jackson receives funding from the National Institutes of Health and the Ivy Foundation. He is a member of a grassroots political organization, Indivisible Charlottesville.</span></em></p>Medications to treat COVID-19 are in no way a substitute for the vaccine. But under the right circumstances, some show great promise for helping patients.Patrick Jackson, Assistant Professor of Infectious Diseases, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1682242021-09-17T21:30:30Z2021-09-17T21:30:30ZFDA panel recommends limiting Pfizer booster shots to Americans 65 and older, and those at high risk of severe COVID-19<figure><img src="https://images.theconversation.com/files/421927/original/file-20210917-25-1arptol.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3303%2C2190&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">No third dose for now.</span> <span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/VirusOutbreakBooster/2591977a51e545daad893fd64a8d699f/photo?Query=vaccine%20AND%20panel&mediaType=photo&sortBy=arrivaldatetime:desc&dateRange=Anytime&totalCount=76&currentItemNo=0">AP Photo/Robert F. Bukaty</a></span></figcaption></figure><p>The key scientific advisory council of the Food and Drug Administration has <a href="https://www.nytimes.com/live/2021/09/17/world/covid-delta-variant-vaccine">voted to deny</a> use of a “booster” shot of Pfizer’s mRNA vaccine to the general public – a move that will likely disappoint some <a href="https://www.cnn.com/2021/09/16/health/covid-19-boosters-agencies-khn-partner/index.html">public health experts pushing for a third dose</a> to help slow the spread of COVID-19.</p>
<p>In a 16-2 vote on Sept. 17, 2021, an independent committee of physicians, scientists and public health experts recommended against full use of the third dose of the vaccine, which now goes by the brand name “Comirnaty.” However, the panel did recommend the shot for Americans age 65 and older or those at high risk for severe COVID-19. In recommending against the shot for the general public, the committee cited reasons such as lack of sufficient safety data in younger age groups as well as indications that the initial doses still seem to be providing robust protection against severe illness leading to hospitalization and death. The panel also agreed in a poll – but not a formal vote – that boosters would be beneficial for certain populations, such as health care workers and others at high risk for occupational exposure.</p>
<p>Although the vote is not binding, it is likely that it will form the basis of a formal FDA recommendation.</p>
<p>As <a href="https://scholar.google.com/citations?user=-oDHlFYAAAAJ&hl=en">an immunologist</a> who <a href="https://doi.org/10.1038/s41590-020-00814-z">studies COVID-19</a> and <a href="https://doi.org/10.1016/j.celrep.2018.09.029">immune responses to vaccination</a>, I saw the push for a booster as predictable, although the outcome of the vote was always far from certain. Over the past year, <a href="https://doi.org/10.1056/nejmc2032195">significant research</a> and <a href="https://www.nytimes.com/2021/06/28/health/coronavirus-vaccines-immunity.html">public reporting</a> have focused on the durability of the immune response following the first and second doses of the COVID-19 mRNA vaccines. This work has been critical to scientists’ understanding of how long the immune responses from vaccination can provide protection, and whether that protection extends to new and emerging variants of the SARS-CoV-2 virus.</p>
<h2>Waning antibodies</h2>
<p>The good news is that the mRNA vaccines do appear to provide <a href="https://doi.org/10.1056/nejmoa2108891">continued efficacy</a> against serious illness or death caused by new strains of the coronavirus, including the highly infectious <a href="https://www.cdc.gov/coronavirus/2019-ncov/variants/delta-variant.html">delta variant</a>.</p>
<p>But data on the longevity of this protection has been more mixed and is still limited in scope. Although there are indications that immune “memory” <a href="https://doi.org/10.1038/s41586-021-03738-2">is being established</a> in vaccine recipients – almost certainly providing partial protection in the long term – the antibodies responsible for stopping the virus in its tracks before infection occurs appear to <a href="https://doi.org/10.1016/j.lanepe.2021.100208">wane over the course of months</a> following the second dose.</p>
<p>This is not surprising to immunologists and does not mean the vaccine isn’t working. Antibodies wane as a normal course of an immune response to any vaccine. This is why you need a tetanus booster every decade or so, and why the measles, mumps and rubella vaccine is administered in three doses – not just two.</p>
<p>The question is simply how fast antibodies decline, and at what point they no longer provide adequate protection. At that point, an additional dose of the vaccine is recommended to “boost” the antibody numbers back up to protective levels. In this case, widespread reporting of <a href="https://www.cdc.gov/vaccines/covid-19/health-departments/breakthrough-cases.html">breakthrough infections</a> – infections in individuals who have been fully vaccinated – and research citing the <a href="http://dx.doi.org/10.15585/mmwr.mm7034e4">possibility of declining immunity</a> in populations vaccinated early in the pandemic brought discussions of the need for boosters quickly to the forefront.</p>
<p>Against this backdrop of mixed data, the FDA panel had to weigh the risks and benefits surrounding booster shots. While the third dose of vaccine would have been identical to those already <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-first-covid-19-vaccine">fully approved</a> – and as such <a href="https://doi.org/10.1056/nejmoa2110475">deemed safe</a> – they would not be without <a href="https://theconversation.com/vaccines-against-sars-cov-2-will-have-side-effects-thats-a-good-thing-151090">side effects</a> similar to those seen in the first and second doses.</p>
<p>In addition, serious conditions <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/myocarditis.html">such as myocarditis</a> – an inflammation of the heart – that have been recorded in rare and isolated cases after the initial vaccine shots will likely occur following the booster as well. This, in addition to a debate around the absolute benefit of a third shot to maintain current protection levels in otherwise healthy vaccinated individuals, has led many public health officials to <a href="https://doi.org/10.1016/S0140-6736(21)02046-8">express concern</a> that the review is premature and risks further confusing and alienating an <a href="https://www.kff.org/policy-watch/the-red-blue-divide-in-covid-19-vaccination-rates/">already divided American public</a>.</p>
<h2>Separating politics from data</h2>
<p>With the Biden administration having <a href="https://www.businessinsider.com/fda-cdc-heads-push-back-on-bidens-covid-19-booster-shot-plan-2021-9">already publicly backed a third dose</a> for all vaccinated Americans in August, the committee was tasked with separating the politics from the data to weigh in on whether the benefits of a booster shot outweighed the risks to an already-hesitant American public.</p>
<p>In rejecting the proposal, the FDA panel has signaled its confidence in the original vaccination course among healthy individuals, and will wait for additional data before identifying waning antibody levels as a significant threat to public safety. However, its support for boosting those at high risk for exposure to COVID-19 suggests a recognition that additional shots may yet be necessary to fully protect the public at large.</p>
<p>[<em>Get the best of The Conversation, every weekend.</em> <a href="https://theconversation.com/us/newsletters/weekly-highlights-61?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=weeklybest">Sign up for our weekly newsletter</a>.]</p><img src="https://counter.theconversation.com/content/168224/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Matthew Woodruff's research is supported by the National Institute of Health, and is a co-founder of Jefferson's Electorate. </span></em></p>An FDA panel has voted against recommending approval of a booster COVID-19 shot for the general population – disappointing some public health officials.Matthew Woodruff, Instructor of Human Immunology, Emory UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1667772021-09-12T08:19:31Z2021-09-12T08:19:31ZWorms can affect vaccine efficacy: lessons for COVID-19?<figure><img src="https://images.theconversation.com/files/419749/original/file-20210907-25-197nrh4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Schistosoma under the microscope.. </span> <span class="attribution"><span class="source">Getty Images</span></span></figcaption></figure><p>Over a year since the first case of the SARS-CoV-2 pandemic, fast advances in vaccine development have given the world a fighting chance against the coronavirus. <a href="https://www.nejm.org/doi/full/10.1056/nejmoa2035389">SARS-CoV-2</a> vaccines have become leading instruments against severe health effects associated with COVID-19 disease. </p>
<p>SARS-CoV-2 vaccines reduce severe disease and improve survival of infected patients. Their impact has been seen in <a href="https://doi.org/10.1016/S0140-6736(21)00677-2">developed countries</a> where mass vaccination has been most efficient. In developing regions, such as many African countries, SARS-CoV-2 vaccination campaigns have been relatively <a href="https://theconversation.com/interested-in-vaccine-rollouts-across-africa-heres-a-map-to-guide-you-156802">slow</a>. </p>
<p>The impact of COVID-19 has differed among <a href="https://dx.doi.org/10.1016%2FS0140-6736(20)32580-0">developing African countries</a>. In some, SARS-CoV-2 infections have been relatively low. Others have reported high numbers. Vaccine coverage of the continent is still <a href="https://www.afro.who.int/news/eight-10-african-countries-miss-crucial-covid-19-vaccination-goal">low</a> as countries await adequate supplies.</p>
<p>But there is an added worry: the effectiveness of vaccines in developing countries, particularly those with very high levels of <a href="https://www.sciencedirect.com/sdfe/pdf/download/eid/3-s2.0-B9780702040641000646/first-page-pdf">chronic parasitic infections</a>. These are a major cause of morbidity and mortality and are prominent among the so-called <a href="https://www.sciencedirect.com/sdfe/pdf/download/eid/3-s2.0-B9780702040641000646/first-page-pdf">neglected tropical diseases</a>. </p>
<p>One of these is schistosomiasis, also known as bilharzia. Symptoms of it present as a sudden onset of fever, dry cough, diarrhoea and abdominal pain. About <a href="https://www.sciencedirect.com/science/article/pii/S1413867015000264#:%7E:text=Schistosomiasis%20is%20the%20second%20most,207%20million%20cases%20of%20schistosomiasis.">90%</a> of the people requiring treatment for this debilitating parasite are sub-Saharan Africans. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172021/">Research</a> – on both animal models and human studies – suggests that chronic schistosomiasis infection can result in decreased vaccine efficacy. </p>
<p>In a recent paper, we <a href="https://www.sciencedirect.com/science/article/pii/S1471492221001744?casa_token=SrJAN4GljBgAAAAA:5pniuFDMhIrOAeI2nRz4RSK4PV_8VcQlnDiSLTXWa0bDzGmKWxPUBVq3JiZKHq8TthNNd5YVuwaq">reviewed</a> evidence on the influence of infection with the parasitic worms causing schistosomiasis on host immune responses to vaccines. The vaccines we focused on were to prevent measles, hepatitis B, tetanus and tuberculosis.</p>
<p>We found that measles and hepatitis B vaccines were less effective in people who have schistosomiasis. </p>
<p>We also evaluated the potential of using medication designed to treat parasitic worm infections in restoring vaccine responses affected by schistosomiasis. We found that it can improve vaccination effectiveness. </p>
<p>We concluded that treatment for schistosomiasis should be considered an important part of SARS-CoV-2 vaccination campaigns where the parasite is commonly found.</p>
<h2>Impact of schistosomiasis on vaccination</h2>
<p><a href="https://www.who.int/news-room/fact-sheets/detail/schistosomiasis">Schistosomiasis</a> is a neglected tropical disease which affects more than 236 million people. Most live in Africa. </p>
<p>No direct evidence is available yet on whether SARS-CoV-2 vaccines can be affected by schistosomiasis. But <a href="https://doi.org/10.1016/j.pt.2021.07.009">evidence</a> shows that for viruses such as hepatitis B and measles, the parasite reduces the level of protection given by their specific vaccines. For example, if a person is infected by the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189399/">schistosome parasite</a> some time after being vaccinated, they might rapidly lose the immunity provided by the vaccination.</p>
<p>In addition, schistosomiasis commonly causes enlarged liver and spleen, known as <a href="https://doi.org/10.1016/j.pt.2021.07.009">hepatosplenomegaly</a>. This condition is associated with weakened immune responses to vaccines in endemic areas. </p>
<p>The efficacy of SARS-CoV-2 virus vaccines might be affected too. If they were, the regions mostly likely to bear the impact would be in sub-Saharan Africa where schistosomiasis is endemic. </p>
<h2>Strategic efforts</h2>
<p>Our findings call for prompt evaluation of the potential impact of parasitic infections, such as schistosomiasis, on the efficacy of SARS-CoV-2 vaccines.</p>
<p>The World Health Organisation has endorsed only one drug, <a href="http://apps.who.int/iris/bitstream/handle/10665/152781/9789241564861_eng.pdf;jsessionid=BA0FA02F103B66A1C97491E0A7DEB1F9?sequence=1">praziquantel</a>, to treat and control schistosomiasis disease. In African regions where the disease is endemic, praziquantel is often given annually to vulnerable populations.</p>
<p><a href="https://doi.org/10.1016/j.pt.2021.07.009">Studies</a> have shown that praziquantel either has no effect on viral vaccine immunity or improves immunity by clearing worms from people with schistosomiasis. </p>
<p>Praziquantel treatment is safe and generally accessible. </p>
<p>Based on our findings we believe there’s a case to be made for offering the treatment along with mass SARS-CoV-2 vaccination campaigns where schistosomiasis is endemic. </p>
<p>The other intervention that’s needed is that <a href="https://doi.org/10.1093/trstmh/traa202">current disruptions</a> of mass praziquantel administration should be addressed.</p>
<p>Disruptions were understandable in the early stages of the pandemic. But it’s now critical to maintain past successes against the parasite. And it could be vital to the success of vaccination against the SARS-CoV-2 virus.</p><img src="https://counter.theconversation.com/content/166777/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Justin Komguep Nono receives funding from the EDCTP2 programme supported by the European Union and the Poliomyelitis research Foundation of South Africa. He is co-chair of the research working group of the Global Schistosomiasis Alliance (GSA) and a founding member of JRJ Health, a health-promoting association based in Cameroon. None of these entities had any role in the conceptualisation, design, analysis of data, decision to publish, and preparation of the present article. </span></em></p><p class="fine-print"><em><span>Fungai Musaigwa receives funding from National Research Foundation (South Africa), Polio Research Foundation (South Africa) and University of Cape Town. </span></em></p>Although there is no evidence yet that it affects COVID-19 vaccines, schistosomiasis, a neglected tropical disease, has been associated with lower vaccine immunity for several vaccines.Justin Komguep Nono, Research Officer, Institute of Medical Research and Medicinal Plant Studies (Cameroon) and Research fellow, University of Cape TownFungai Musaigwa, PhD candidate, University of Cape TownLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1665352021-08-25T12:28:09Z2021-08-25T12:28:09ZPregnant or worried about infertility? Get vaccinated against COVID-19<figure><img src="https://images.theconversation.com/files/417466/original/file-20210823-27-1vwqfzl.jpg?ixlib=rb-1.1.0&rect=3634%2C0%2C7799%2C3805&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Despite rampant misinformation, studies show that COVID-19 vaccines are safe for both the mom and baby.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/pregnant-vaccination-pregnant-woman-in-face-mask-royalty-free-image/1306737732?adppopup=true"> Marina Demidiuk/iStock via Getty Images Plus</a></span></figcaption></figure><p>As the <a href="https://www.nytimes.com/2021/08/16/us/covid-delta-variant-us.html">delta variant of SARS-CoV-2 surges</a> across the U.S., <a href="https://news.gallup.com/poll/353081/one-five-americans-remain-vaccine-resistant.aspx">almost 1 in 5 Americans</a> continue to <a href="https://www.forbes.com/sites/alisondurkee/2021/06/11/here-are-the-biggest-groups-that-are-still-refusing-the-covid-19-vaccine-poll-finds/?sh=2cf3b28a42cc">resist getting shots</a> that are <a href="https://www.statnews.com/2021/07/20/states-are-sitting-on-millions-of-surplus-covid-19-vaccine-doses-as-expiration-dates-approach/">widely available</a>, <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/safety-of-vaccines.html">safe</a> and <a href="https://www.washingtonpost.com/health/2021/08/18/covid-vaccine-effectiveness/">effective</a> – particularly for preventing the most severe outcomes of the virus. </p>
<p>While people have many different justifications for not getting the shot, one particularly insidious bit of <a href="https://medical.mit.edu/covid-19-updates/2021/02/want-to-get-pregnant-should-i-avoid-vaccine">pseudoscience</a> has surfaced. It is routinely invoked in the <a href="https://heavy.com/news/dr-sean-brooks-phd-oxford-ohio-video/">contentious debate over vaccine policy</a> in the U.S. and continues to stir <a href="https://www.dw.com/en/why-many-africans-are-wary-of-covid-19-vaccines/a-56774599">confusion and skepticism</a> toward vaccines in young women <a href="https://www.hindustantimes.com/india-news/no-covid-19-vaccine-affects-fertility-clarifies-health-ministry-101625050744190.html">across the globe</a>.</p>
<p>This misinformed argument reasons that the coronavirus vaccines could <a href="https://doi.org/10.1515/jom-2021-0059">affect fertility in women</a> by mistakenly triggering the creation of antibodies that react with an important placental protein called syncytin-1. This protein contains minor similarities to the <a href="https://doi.org/10.1038/s41541-021-00369-6">coronavirus spike protein</a> used in all current COVID-19 vaccines. Thus, the false narrative goes, the immune system will not be able to differentiate between the two and will create antibodies that interfere with proper development of the placenta. </p>
<p>This argument lacks understanding of how the immune system does its job. </p>
<p>As <a href="https://scholar.google.com/citations?user=-oDHlFYAAAAJ&hl=en">an immunologist</a> who studies <a href="https://www.nature.com/articles/s41590-020-00814-z">COVID-19 infection</a> and the ways it can cause the immune system 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">turn against itself</a>, this misunderstanding comes up frequently in my conversations with friends, family members and even medical workers who are legitimately concerned about their health and their future ability to have children. </p>
<p>It is completely understandable to have questions about how a new vaccine might affect reproductive health. But the <a href="https://www.medrxiv.org/content/10.1101/2021.05.23.21257686v1">science is clear</a> that getting vaccinated does not put women at risk for infertility. It protects women, their unborn children and their families from a serious disease that, ironically, could in fact <a href="https://theconversation.com/covid-19-could-cause-male-infertility-and-sexual-dysfunction-but-vaccines-do-not-164139">affect fertility in men</a>.</p>
<h2>Antibodies rarely make mistakes</h2>
<p>The immune system is an immensely complicated network of cells, tissues and proteins that interact with one another – and the outside world. It works to maintain a balanced, healthy environment so the rest of the cells in the body can do their jobs. Among other things, the immune system helps direct <a href="https://doi.org/10.3389/fimmu.2019.02729">fetal development</a>, oversees and <a href="https://doi.org/10.1038/s41422-020-0332-7">manages the microbes</a> that aid in digestion and, of course, fights off infection.</p>
<p>One of the immune system’s most critical jobs is to differentiate between the body’s own cells and those of outside invaders to prevent accidental <a href="https://www.healthline.com/health/autoimmune-disorders">attacks on itself</a>. In immunology, this careful selection of responses is called “immune tolerance.” People whose immune systems fail to maintain this tolerance and instead attack their own cells and tissues are diagnosed with <a href="https://www.healthline.com/health/autoimmune-disorders">autoimmune disorders</a>. These can range in symptoms and severity depending on the tissue being attacked. An example is <a href="https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648">rheumatoid arthritis</a> – a misdirected antibody attack on soft tissue in the joints.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/417467/original/file-20210823-20-1vbx9kp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Conceptual illustration of antibodies attacking neurons" src="https://images.theconversation.com/files/417467/original/file-20210823-20-1vbx9kp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/417467/original/file-20210823-20-1vbx9kp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/417467/original/file-20210823-20-1vbx9kp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/417467/original/file-20210823-20-1vbx9kp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/417467/original/file-20210823-20-1vbx9kp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/417467/original/file-20210823-20-1vbx9kp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/417467/original/file-20210823-20-1vbx9kp.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"></a>
<figcaption>
<span class="caption">This depiction of antibodies attacking neurons illustrates what happens in some individuals with autoimmune disorders.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/antibodies-attacking-neurons-conceptual-royalty-free-illustration/1265278544?adppopup=true">Kateryna Kon/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<p>The immune system has a series of checks and balances that are intended to prevent such autoimmune attacks. When B-cells – the cells in the immune system that produce antibodies – are first “born,” <a href="https://www.nature.com/articles/nri.2017.19">they carefully screen themselves</a> to make sure that they won’t target the body’s own organs. That <a href="https://doi.org/10.1038/nri.2017.19">self-screening continues</a> as B-cells patrol the body looking for an infection to fight; if they find something potentially threatening, <a href="https://theconversation.com/vaccines-against-sars-cov-2-will-have-side-effects-thats-a-good-thing-151090">like a vaccine</a>, they engage in a <a href="https://doi.org/10.1146/annurev-immunol-051116-052510">highly orchestrated dance</a> with other immune cells. Through that weeks-long process, only B-cells that produce antibodies against the outside invader survive. B-cells with self-destructive potential are killed. </p>
<p>Importantly, in parts of the body where it is absolutely critical that the immune system not mistakenly turn on its own cells – such as a developing placenta or in the brain – the entire region is immunosuppressive. This means that the threshold for activating the body’s immune response in those areas is set at an even higher bar.</p>
<p>This is not emerging science. These are well-established concepts among immunology experts. and have been <a href="https://doi.org/10.1111/j.1600-065X.1975.tb00162.x">for almost a half-century</a>. As a result, it was not particularly noteworthy that a new preliminary study of women with fully developed immune responses against coronavirus showed <a href="https://doi.org/10.1101/2021.05.23.21257686">no activity</a> against the placental protein syncytin-1. Another study unsurprisingly demonstrated that the vaccine <a href="https://doi.org/10.1097/AOG.0000000000004457">does not damage the placenta</a>.</p>
<h2>COVID-19 is the real threat to the immune system</h2>
<p>It is important to remember that the COVID-19 vaccines authorized – and in the case of <a href="https://theconversation.com/what-does-full-fda-approval-of-a-vaccine-do-if-its-already-authorized-for-emergency-use-165654">Pfizer-BioNTech, fully approved</a> – in the U.S. <a href="https://getvaccineanswers.org/question/vaccine-protection?gclid=Cj0KCQjwsZKJBhC0ARIsAJ96n3XY7rtZpPJ_zn0o3B2anb87qVjKu0t82izbmZP0oHT2wYtz_PpUyvwaApJFEALw_wcB">carry the instructions</a> to make the same spike protein that the virus uses to force its way into cells. Regardless of whether a person is infected with COVID-19 or receives a vaccine that emulates part of the virus, the immune system will respond aggressively to the spike protein that the body sees as foreign. <a href="https://doi.org/10.1126/sciimmunol.abe5511">Study</a> after <a href="https://doi.org/10.4049/immunohorizons.2100011">study</a> confirm that in people who contract the virus, the majority of the immune response is directed at the spike protein.</p>
<p>However, there is one critical difference between vaccination and infection.</p>
<p>When you get vaccinated, your immune system has the time to respond under relatively low-risk circumstances. In other words, the immune system senses a threat and begins to build up its arsenal without rushing. But when it is confronted with a severe infection, the immune system recruits every weapon it has, as quickly as possible, to fend off severe infection or death. </p>
<p>[<em>Understand new developments in science, health and technology each week.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-understand">Subscribe to The Conversation’s science newsletter</a>.]</p>
<p>This is important because we now know that under the severe stress of fighting COVID-19, the immune system fires up <a href="https://theconversation.com/an-autoimmune-like-antibody-response-is-linked-with-severe-covid-19-146255">an emergency response pathway</a> and begins producing antibodies that are not well selected. Many of these antibodies will target the virus, but <a href="https://doi.org/10.1101/2020.10.21.20216192">our work now under review</a> and <a href="https://doi.org/10.1038/s41586-021-03631-y">others’ published findings</a> confirm that in more than half of severe patients, a large number of antibodies also target their own cells.</p>
<p>Simply put: The danger of this kind of “auto-reactivity” in COVID-19 doesn’t come from responding against the spike protein in a vaccine – it occurs when the body has to fight a real COVID-19 infection.</p>
<h2>Getting vaccinated protects unborn children</h2>
<p>Getting vaccinated costs people a couple of days of <a href="https://theconversation.com/vaccines-against-sars-cov-2-will-have-side-effects-thats-a-good-thing-151090">not feeling 100%</a>. In return, it provides protection from contracting a serious disease with the potential to cause serious illness or death. Being vaccinated also gives <a href="https://www.news-medical.net/news/20210411/mRNA-based-COVID-19-vaccination-during-pregnancy-provides-passive-SARS-CoV-2-immunity-to-neonates-16-days-after-first-dose.aspx">crossover protection</a> to an unborn child.</p>
<p>COVID-19 infection, on the other hand, puts pregnant women at risk of <a href="https://doi.org/10.1001/jamapediatrics.2021.1050">severe disease, pregnancy complications and death</a>. It may also affect a couple’s ability to have children by decreasing a man’s <a href="https://theconversation.com/covid-19-could-cause-male-infertility-and-sexual-dysfunction-but-vaccines-do-not-164139">sperm counts and causing erectile dysfunction</a>.</p>
<p>The science is clear, but for me this is also deeply personal. My wife was vaccinated in March, and we are expecting a baby in December. We are both deeply grateful for a vaccine that has given us the confidence to support a healthy pregnancy in the midst of a pandemic.</p><img src="https://counter.theconversation.com/content/166535/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Matthew Woodruff's research is supported by the National Institute of Health. </span></em></p>A COVID-19 vaccine does not cause infertility – but it can protect you from the dangerous complications of contracting the virus.Matthew Woodruff, Instructor of Human Immunology, Emory UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1642032021-07-13T12:29:51Z2021-07-13T12:29:51ZDelta variant makes it even more important to get a COVID-19 vaccine, even if you’ve already had the coronavirus<figure><img src="https://images.theconversation.com/files/410467/original/file-20210708-17-6rnsvs.jpg?ixlib=rb-1.1.0&rect=0%2C160%2C1959%2C1240&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Infection from the coronavirus can produce weaker immunity than vaccination.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/covid-19-royalty-free-illustration/1214152807"> Wenmei Zhou/ DigitalVision Vectors via Getty Images</a></span></figcaption></figure><p>As someone who studies <a href="https://scholar.google.com/citations?user=MEMHuGoAAAAJ&hl=en&oi=ao">immune responses to respiratory infections</a>, I’ve watched news of the emerging coronavirus variants with concern. I wondered whether vaccination or previous infection would provide protection against SARS-CoV-2 strains, especially the new, <a href="https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html?CDC_AA_refVal">highly transmissible delta variant</a>, which has <a href="https://covid.cdc.gov/covid-data-tracker/#global-variant-report-map">rapidly spread to at least 70 countries</a>.</p>
<p>A person can develop immunity – the ability to resist infection – in two ways: either after being infected with a virus or by getting vaccinated. However, immune protection isn’t always equal. Vaccine immunity and natural immunity for SARS–CoV–2 can differ in terms of the <a href="https://doi.org/10.1038/s41564-020-00813-8">strength of the immune response</a> or the <a href="https://doi.org/10.1056/NEJMoa2026116">length of time that the protection lasts</a>. Additionally, not everyone will get the <a href="https://doi.org/10.1038/s41586-020-2456-9">same level of immunity from infection</a>, while immune responses to the vaccines are <a href="https://www.nejm.org/doi/full/10.1056/NEJMc2103916">very consistent</a>. </p>
<p>The difference in immune response between vaccination and infection seems to be even <a href="https://doi.org/10.1038/s41586-021-03777-9">greater when dealing with new variants</a>. In early July, two new studies were published that show COVID-19 vaccines, though slightly less effective than they are against the older strains of the virus, <a href="https://www.nejm.org/doi/10.1056/NEJMc2107799">still seem to provide excellent immune response</a> against the new variants. Researchers looked at how antibodies bind to new variants of the coronavirus and found that people who were previously infected with coronavirus <a href="https://doi.org/10.1038/s41586-021-03777-9">might be susceptible to the new strains</a>, while people who were vaccinated were more likely to be protected. </p>
<p>COVID-19 vaccines offer a safe and reliable path to immunity against both the older strains of coronavirus <a href="https://doi.org/10.1038/s41586-021-03777-9">and against emerging strains, especially the new delta variant</a>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/410473/original/file-20210708-21-1b3alqe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A coronavirus particle with antibodies binding to the spike proteins." src="https://images.theconversation.com/files/410473/original/file-20210708-21-1b3alqe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/410473/original/file-20210708-21-1b3alqe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=524&fit=crop&dpr=1 600w, https://images.theconversation.com/files/410473/original/file-20210708-21-1b3alqe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=524&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/410473/original/file-20210708-21-1b3alqe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=524&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/410473/original/file-20210708-21-1b3alqe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=658&fit=crop&dpr=1 754w, https://images.theconversation.com/files/410473/original/file-20210708-21-1b3alqe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=658&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/410473/original/file-20210708-21-1b3alqe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=658&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 immune system will usually produce a good immune response – including antibodies and T cells – following infection, but not always.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/cell-binding-antigen-illustration-royalty-free-illustration/1148113635">Keith Chambers/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<h2>Immunity after infection is unpredictable</h2>
<p>Immunity comes from the immune system’s ability to remember an infection. Using this immune memory, the body will know how to fight off an infection if it encounters the pathogen again. Antibodies are proteins that can bind to a virus and prevent infection. T cells direct the removal of infected cells and viruses already bound by antibodies. These two are some of the main players that contribute to immunity.</p>
<p>After a SARS-CoV-2 infection, a person’s <a href="https://doi.org/10.1016/S0140-6736(21)00675-9">antibody</a> and T cell responses can provide <a href="https://doi.org/10.1126/science.abf4063">protection against reinfection</a>. Roughly 84% to 91% of people who developed antibodies against the original strains of coronavirus were unlikely to be infected again <a href="https://doi.org/10.1056/NEJMoa2034545">for six months</a>, even after <a href="https://doi.org/10.1016/j.cell.2020.11.029">a mild infection</a>. People who had no symptoms during the infection are also likely to develop immunity, though they tend to make <a href="https://doi.org/10.1038/s41564-020-00813-8">fewer antibodies</a> than those who felt ill. So for some people, natural immunity may be strong and long-lasting.</p>
<p>One big problem is that not everyone will develop immunity after a SARS-CoV-2 infection. As many as 9% of infected people do not have <a href="https://doi.org/10.1056/NEJMoa2026116">detectable antibodies</a>, and up to 7% <a href="https://doi.org/10.1126/science.abf4063">don’t have T cells that recognize the virus</a> 30 days after infection. </p>
<p>For people who do develop immunity, the <a href="https://doi.org/10.1038/s41586-020-2456-9">strength and duration</a> of the protection can vary a lot. Up to 5% of people may <a href="https://doi.org/10.1126/science.abf4063">lose their immune protection</a> within a few months. Without a strong immune defense, these people are susceptible to reinfection by the coronavirus. Some have had second bouts of COVID-19 as soon as <a href="https://doi.org/10.1002/jmv.26637">one month after their first infection</a>; and, though it occurs rarely, some people have been <a href="https://doi.org/10.1001/jamainternmed.2021.2959">hospitalized</a> or have even <a href="https://doi.org/10.1016/j.jinf.2021.01.020">died</a> after reinfection.</p>
<p>A growing problem is that people who were previously infected by strains present earlier in the pandemic may be more susceptible to reinfection from the delta variant. One recent study found <a href="https://doi.org/10.1038/s41586-021-03777-9">that 12 months after infection</a>, 88% of people still had antibodies that could block infection of cultured cells with by the original coronavirus variant – but <a href="https://doi.org/10.1038/s41586-021-03777-9">fewer than 50%</a> had antibodies that could block the delta variant.</p>
<p>To top this all off, a person who is infected may also be able to transmit the coronavirus, even <a href="https://doi.org/10.1001/jamanetworkopen.2020.35057">without feeling sick</a>. The new variants are especially problematic in this case, as <a href="https://doi.org/10.1126/science.abg3055">they are more easily transmitted</a> than the original strains.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/410474/original/file-20210708-25-10k1eid.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A medical worker drawing a vaccine dose into a syringe." src="https://images.theconversation.com/files/410474/original/file-20210708-25-10k1eid.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/410474/original/file-20210708-25-10k1eid.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/410474/original/file-20210708-25-10k1eid.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/410474/original/file-20210708-25-10k1eid.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/410474/original/file-20210708-25-10k1eid.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/410474/original/file-20210708-25-10k1eid.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/410474/original/file-20210708-25-10k1eid.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">Vaccines produce a strong and consistent immune response that works even against the new delta variant.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/VirusOutbreakFloridaVaccine/e30be483e6ad41ca97efe3b1c6ba0301/photo">AP Photo/Lynne Sladky</a></span>
</figcaption>
</figure>
<h2>Vaccination leads to reliable protection</h2>
<p>COVID-19 vaccines generate both <a href="https://doi.org/10.1056/NEJMoa2022483">antibody and T cell responses</a> – and these responses are much stronger and more consistent than immunity after natural infection. One study found that six months after receiving their first dose of the Moderna vaccine, <a href="https://doi.org/10.1056/NEJMc2103916">100% of people tested had antibodies against SARS-CoV-2</a>. This is the longest period that has been reported in published studies so far. In a study looking at the Pfizer and Moderna vaccines, antibody levels were also much higher in vaccinated people than in those who had <a href="https://doi.org/10.1056/NEJMoa2028436">recovered from infection</a>.</p>
<p>[<em><a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-corona-important">The Conversation’s most important coronavirus headlines, weekly in a science newsletter</a></em>]</p>
<p>Even better, a <a href="https://doi.org/10.1056/NEJMoa2101765">study in Israel</a> showed that the Pfizer vaccine blocked 90% of infections after both doses – even with new variants present in the population. And a <a href="https://doi.org/10.1093/cid/ciab229">decrease in infections</a> means people are less likely to transmit the virus to the people around them. </p>
<p>For those who have already been infected with the coronavirus, there is still a big benefit to getting vaccinated. A study with the original COVID-19 virus showed that vaccination after infection produces roughly <a href="https://doi.org/10.1056/NEJMc2101667">100 times more antibodies</a> than infection alone, and 100% of people who were vaccinated after infection had <a href="https://doi.org/10.1038/s41586-021-03777-9">protective antibodies against the delta variant</a>.</p>
<p>The COVID-19 vaccines aren’t perfect, but they produce strong antibody and T cell responses that offer a safer and more reliable means of protection than natural immunity – especially with new variants on the loose. </p>
<p><em>This is an updated version of an <a href="https://theconversation.com/why-you-should-get-a-covid-19-vaccine-even-if-youve-already-had-the-coronavirus-155712">article originally published</a> on March 25, 2021.</em></p><img src="https://counter.theconversation.com/content/164203/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jennifer T. Grier 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>COVID-19 vaccination produces a more consistent immune response than a past infection. With the delta variant, the difference in protection may be even greater.Jennifer T. Grier, Clinical Assistant Professor of Immunology, University of South CarolinaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1619742021-06-17T12:30:45Z2021-06-17T12:30:45ZA mix-and-match approach to COVID-19 vaccines could provide logistical and immunological benefits<figure><img src="https://images.theconversation.com/files/406821/original/file-20210616-22-aqq0jd.jpg?ixlib=rb-1.1.0&rect=21%2C5%2C3595%2C2281&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">One of this and one of that might be a good strategy to coronavirus vaccination.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/in-this-photo-illustration-silhouette-of-hands-in-medical-news-photo/1232570041">SOPA Images/LightRocket via Getty Images</a></span></figcaption></figure><p>While it’s now pretty easy to get a COVID-19 shot in most places in the U.S., the vaccine rollout in other parts of the world has been slow or inconsistent due to <a href="https://www.nytimes.com/2021/05/03/world/global-coronavirus-vaccine-shortage.html">shortages, uneven access</a> and <a href="https://www.nytimes.com/live/2021/04/13/world/johnson-vaccine-blood-clots">concerns about safety</a>.</p>
<p>Researchers hope that a mix-and-match approach to COVID-19 vaccines will help alleviate these issues and create more flexibility in the immunization regimens available to people.</p>
<p>Around the world, different pharmaceutical companies have taken different approaches to developing vaccines. Pfizer-BioNTech and Moderna created <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html">mRNA vaccines</a>. Oxford-AstraZeneca and Johnson & Johnson went with what are called <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/viralvector.html">viral vectors</a>. The Novavax COVID-19 vaccine is <a href="https://www.nytimes.com/interactive/2020/health/novavax-covid-19-vaccine.html">protein-based</a>.</p>
<p>So mixing vaccines could mean more than just switching manufacturers – like from Pfizer for dose one to Moderna for dose two. You might be tapping into a <a href="https://www.nature.com/articles/s41577-020-00434-6">different way to stimulate your immune response</a> if you opt for a first dose of AstraZeneca and a second dose of Moderna.</p>
<p>The most obvious benefits of treating various brands and kinds of COVID-19 vaccine as interchangeable are <a href="https://health-desk.org/articles/what-do-we-know-about-the-risks-of-combining-more-than-one-of-the-approved-vaccines">logistical</a> – people can get whatever shot is available without worry. By speeding up the global vaccination rollout, <a href="https://www.cbc.ca/news/health/covid-19-vaccine-mix-match-1.5964162">mixing and matching vaccines could help end this pandemic</a>. Researchers also hope combining different vaccines will trigger a <a href="https://www.npr.org/sections/health-shots/2021/05/05/993882203/giving-2-doses-of-different-covid-19-vaccine-could-boost-immune-response">more robust, longer-lasting immune response</a> compared to receiving both doses of a single vaccine. This approach may <a href="https://www.advisory.com/en/daily-briefing/2021/05/19/mixing-vaccines">better protect people</a> from emerging variants.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/406824/original/file-20210616-3785-1kbo76i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="artist's rendition of a coronavirus particle and antibodies" src="https://images.theconversation.com/files/406824/original/file-20210616-3785-1kbo76i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/406824/original/file-20210616-3785-1kbo76i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=300&fit=crop&dpr=1 600w, https://images.theconversation.com/files/406824/original/file-20210616-3785-1kbo76i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=300&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/406824/original/file-20210616-3785-1kbo76i.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=300&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/406824/original/file-20210616-3785-1kbo76i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=377&fit=crop&dpr=1 754w, https://images.theconversation.com/files/406824/original/file-20210616-3785-1kbo76i.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=377&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/406824/original/file-20210616-3785-1kbo76i.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">After vaccination, your body makes antibodies (blue in this illustration) that will hunt for coronavirus proteins (pink).</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/antibodies-attacking-coronavirus-particle-royalty-free-image/1307403039">Christoph Burgstedt/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<h2>Biological effects of a mix-and-match approach</h2>
<p>Scientists suspect there are a few ways that receiving two different COVID-19 vaccines <a href="https://www.nature.com/articles/s41577-021-00526-x">may result in a stronger immune response</a>.</p>
<p>Each company used slightly <a href="https://viralvector.design.blog/">different regions of the SARS-CoV-2 spike protein</a> in their formulations. It’s the virus’s spike protein that your immune system responds to, so exposure to different portions of the spike protein should mean your body will make an array of corresponding antibodies that can fend off future infection. The range of antibodies should then provide better protection and increase the likelihood that you’ll be protected from variants with changes in the spike protein.</p>
<p>And different vaccine technologies activate unique aspects of the immune system thanks to how they present their portion of the spike protein.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/406816/original/file-20210616-19-33zx55.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="diagram of vaccine platform options" src="https://images.theconversation.com/files/406816/original/file-20210616-19-33zx55.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/406816/original/file-20210616-19-33zx55.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=320&fit=crop&dpr=1 600w, https://images.theconversation.com/files/406816/original/file-20210616-19-33zx55.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=320&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/406816/original/file-20210616-19-33zx55.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=320&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/406816/original/file-20210616-19-33zx55.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=402&fit=crop&dpr=1 754w, https://images.theconversation.com/files/406816/original/file-20210616-19-33zx55.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=402&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/406816/original/file-20210616-19-33zx55.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=402&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 build vaccines based on a number of what they call platforms – different technological ways to safely introduce your immune system to the targeted virus.</span>
<span class="attribution"><a class="source" href="https://www.mdpi.com/2076-393X/9/2/97/xml">Blakney AK, Ip S, Geall AJ. An Update on Self-Amplifying mRNA Vaccine Development. Vaccines. 2021; 9(2):97.</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>The <a href="https://www.pfizer.com/science/coronavirus">Pfizer</a> and <a href="https://www.modernatx.com/covid19vaccine-eua/recipients/moderna-vaccine">Moderna</a> vaccines are composed of a small snippet of mRNA, genetic material that contains the recipe to make a region of the SARS-CoV-2 spike protein. Wrapped up in a fat coat, the mRNA slips into a vaccinated person’s cells where it directs production of the viral protein. The person’s immune system then recognizes the foreign spike protein and produces antibodies against it.</p>
<p>Several other COVID-19 vaccines rely on a <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/viralvector.html">viral vector</a>. In these cases, researchers <a href="https://theconversation.com/how-does-the-johnson-and-johnson-vaccine-compare-to-other-coronavirus-vaccines-4-questions-answered-155944">modified an adenovirus that usually causes the common cold</a> to deliver the DNA instructions for producing a portion of the SARS-CoV-2 spike protein. The modified virus is safe because it can’t replicate in people. Along with <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/janssen.html">J&J</a> and <a href="https://theconversation.com/how-good-is-the-astrazeneca-vaccine-and-is-it-really-safe-5-questions-answered-157562">AstraZeneca’s</a>, examples of COVID-19 viral vector vaccines in use globally include <a href="https://sputnikvaccine.com/">Russia’s Sputnik V</a>and the <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31605-6/fulltext">CanSino Biologics vaccine</a>.</p>
<p>Your immune system can develop an <a href="https://www.reuters.com/article/us-health-coronavirus-vector-immunity-fo/astrazeneca-sputnik-vaccines-face-hurdles-if-covid-shots-become-annual-affair-idUSKBN2AQ0VX">immune response to the viral vector vaccine itself</a>, which could reduce the vaccine’s effectiveness against the coronavirus. Experts hope that combining vaccine platforms, for example using an mRNA-based vaccine or one that includes a different viral vector <a href="https://sputnikvaccine.com/about-vaccine/">for the second dose</a>, <a href="https://www.gavi.org/vaccineswork/it-safe-mix-and-match-covid-19-vaccines">could reduce that risk</a>.</p>
<h2>Investigating combos’ safety and effectiveness</h2>
<p>Around the world, studies are underway <a href="https://www.advisory.com/en/daily-briefing/2021/05/19/mixing-vaccines">in animals</a> <a href="https://www.reuters.com/world/middle-east/countries-weigh-mix-match-covid-19-vaccines-2021-05-24/">and people</a> <a href="https://udaipurtimes.com/news/dose-mixing-of-covid-vaccines-study-being-planned-in-india/cid3107291.htm">to investigate</a> the safety, types of immune response generated and how long immunity lasts when one person receives two different COVID-19 vaccines.</p>
<p><a href="https://www.nature.com/articles/d41586-021-01359-3">Results from a Spanish trial</a> of more than 600 people indicated that vaccination with both the viral-vector AstraZeneca and mRNA-based Pfizer-BioNTech COVID-19 vaccines triggers a robust immune response against the SARS-CoV-2 virus.</p>
<p>Preliminary results from a <a href="https://www.news-medical.net/news/20210609/Mix-and-match-COVID-19-vaccines-safe-and-effective-German-study.aspx">German study</a> that has not yet been peer-reviewed found that getting the AstraZeneca vaccine first followed by the Pfizer vaccine resulted in production of more protective antibodies and provided better protection against variants of concern compared to two AstraZeneca doses.</p>
<p><a href="https://comcovstudy.org.uk/home">The Com-COV study</a> in the U.K. is also investigating the safety and effectiveness of giving patients a combination of the AstraZeneca and Pfizer-BioNTech shots. <a href="https://doi.org/10.1016/S0140-6736(21)01115-6">Preliminary findings</a> indicate that people who got one shot of each type were more likely to report mild to moderate side effects than those who received two doses of the same vaccine. Final results of this study, including the effectiveness of this approach, are expected in June 2021. The <a href="https://comcovstudy.org.uk/about-com-cov2">expanded Com-CoV2 study</a> is testing other combinations of COVID-19 vaccines, namely from Moderna’s mRNA platform and Novavax’s protein platform.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/406825/original/file-20210616-21-151t241.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="vials of three vaccines with syringe" src="https://images.theconversation.com/files/406825/original/file-20210616-21-151t241.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/406825/original/file-20210616-21-151t241.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=380&fit=crop&dpr=1 600w, https://images.theconversation.com/files/406825/original/file-20210616-21-151t241.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=380&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/406825/original/file-20210616-21-151t241.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=380&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/406825/original/file-20210616-21-151t241.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=477&fit=crop&dpr=1 754w, https://images.theconversation.com/files/406825/original/file-20210616-21-151t241.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=477&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/406825/original/file-20210616-21-151t241.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=477&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Mixing might be important as the coronavirus continues to evolve.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/three-vials-with-different-vaccines-against-covid-19-by-news-photo/1231116175">Thomas Kienzle/AFP via Getty Images</a></span>
</figcaption>
</figure>
<h2>Combos could be a good anti-variant strategy</h2>
<p>Emerging coronavirus variants are one of the <a href="https://www.nih.gov/news-events/news-releases/nih-clinical-trial-evaluating-mixed-covid-19-vaccine-schedules-begins">most intriguing reasons</a> to consider mixing vaccines. Administering vaccines that target different variants would provide broad collective immunity and limit emergence of new possibly more dangerous strains.</p>
<p>It’s possible that people who are currently fully vaccinated will need a third shot to address genetic differences in new variants. Changing platforms for this booster shot – for instance, if your first round was viral-vector based, switching to mRNA or one that is protein-based – could help bolster your immune response.</p>
<p>Flu vaccines routinely protect against <a href="https://www.cdc.gov/flu/prevent/quadrivalent.htm">multiple strains of the influenza virus</a> – but these are usually manufactured by the same company. In the future, this approach could lead to vaccines that contain multiple regions of SARS-CoV-2 to protect against several variants, or regions of both the coronavirus and influenza proteins, protecting against both viruses in a single shot.</p>
<h2>What’s allowed so far</h2>
<p>For now, though, the Centers for Disease Control and Prevention in the U.S. allows the mixing of the mRNA-based Pfizer and Moderna shots only in “<a href="https://www.cnbc.com/2021/01/22/cdc-changes-covid-vaccine-guidance-to-ok-mixing-pfizer-and-moderna-shots-in-exceptional-si.html">exceptional situations</a>,” such as limited vaccine supply or if a patient doesn’t know which vaccine they originally received.</p>
<p>Canada’s public health agency recently approved the <a href="https://www.npr.org/sections/coronavirus-live-updates/2021/06/04/1002975563/want-to-mix-2-different-covid-19-vaccines-canada-is-fine-with-that">mixing of different COVID-19 vaccines</a> if limited supply prevents someone from getting their second dose of the same vaccine, or <a href="https://www.ctvnews.ca/health/coronavirus/national-vaccine-panel-allows-for-mixing-and-matching-covid-19-vaccines-1.5451067">if someone is apprehensive about a second dose of AstraZeneca</a> due to publicized side effects.</p>
<p>EU countries are so far <a href="https://www.reuters.com/article/us-health-coronavirus-astrazeneca/european-countries-may-have-to-mix-covid-19-shots-amid-astrazeneca-crisis-idUSKBN2BU1LV">awaiting further study results</a> before allowing mixing vaccine doses.</p>
<p>[<em>You’re smart and curious about the world. So are The Conversation’s authors and editors.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=youresmart">You can read us daily by subscribing to our newsletter</a>.]</p><img src="https://counter.theconversation.com/content/161974/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Maureen Ferran receives funding from The National Cancer Institute, NIH.</span></em></p>Various companies use different ingredients and different delivery systems in their COVID-19 vaccines. Researchers are investigating whether it’s better for individuals to mix what’s available.Maureen Ferran, Associate Professor of Biology, Rochester Institute of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1612592021-05-21T12:26:11Z2021-05-21T12:26:11ZWhy do we get shots in the arm? It’s all about the muscle<figure><img src="https://images.theconversation.com/files/401985/original/file-20210520-15-1sxwoph.jpg?ixlib=rb-1.1.0&rect=503%2C0%2C3704%2C2552&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A man receives the COVID-19 vaccine in Lima, Peru.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/elderly-man-being-inoculated-with-the-covid-19-vaccine-in-a-news-photo/1232367320?adppopup=true">Carlos Garcia Granthon/Fotoholica Press/LightRocket via Getty Images</a></span></figcaption></figure><p>Millions have rolled up their sleeves for the COVID-19 vaccine, but why haven’t they rolled up their pants legs instead? Why do we get most shots in our arms? </p>
<p>As an <a href="https://www.purdue.edu/hhs/nur/directory/faculty/richards_libby.html">associate professor of nursing</a> with a background in public health, and as a mother of two curious kids, I field this question fairly often. So here’s the science behind why we get most vaccines in our arm. </p>
<p>It’s worth noting that <a href="https://www.cdc.gov/vaccines/hcp/admin/administer-vaccines.html">most, but not all, vaccines</a> are given in the muscle – this is known as an <a href="https://www.healthline.com/health/intramuscular-injection#purpose">intramuscular injection</a>. Some vaccines, like the rotavirus vaccine, are given orally. Others are given just beneath the skin, or subcutaneously – think of the <a href="https://www.cdc.gov/vaccines/vpd/mmr/public/index.html">measles, mumps and rubella vaccine</a>. However, many others are given in the muscle. </p>
<p>But why is the muscle so important, and does location matter? And why the arm muscle – called the <a href="https://www.physio-pedia.com/Deltoid">deltoid </a>– in the top of the shoulder?</p>
<h2>Muscles have immune cells</h2>
<p>Muscles make an excellent vaccine administration site because muscle tissue contains important immune cells. These immune cells recognize the <a href="https://www.news-medical.net/life-sciences/What-is-an-Antigen.aspx">antigen</a>, a tiny piece of a virus or bacteria introduced by the vaccine that stimulates an immune response. In the case of the <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html">COVID-19 vaccine,</a> it is not introducing an antigen but rather administering the blueprint for producing antigens. The immune cells in the muscle tissue pick up these antigens and present them to the <a href="https://www.verywellhealth.com/understanding-the-purpose-of-lymph-nodes-2249122">lymph nodes</a>. Injecting the vaccine into muscle tissue keeps the vaccine localized, allowing immune cells to sound the alarm to other immune cells and get to work.</p>
<p>Once a vaccine is recognized by the immune cells in the muscle, these cells carry the antigen to lymph vessels, which transport the antigen-carrying immune cells into the lymph nodes. Lymph nodes, key components of our immune system, contain more immune cells that recognize the antigens in vaccines and start the <a href="https://www.technologynetworks.com/immunology/articles/antigen-vs-antibody-what-are-the-differences-293550">immune process of creating antibodies</a>. </p>
<p>Clusters of lymph nodes are located in areas close to vaccine administration sites. For instance, many vaccines are injected in the deltoid because it is close to lymph nodes located just under the armpit. When vaccines are given in the thigh, the lymph vessels don’t have far to travel to reach the cluster of lymph nodes in the groin. </p>
<figure class="align-center ">
<img alt="A man gives a shot to another man at a vaccination center." src="https://images.theconversation.com/files/401986/original/file-20210520-15-8bwrro.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/401986/original/file-20210520-15-8bwrro.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/401986/original/file-20210520-15-8bwrro.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/401986/original/file-20210520-15-8bwrro.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/401986/original/file-20210520-15-8bwrro.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/401986/original/file-20210520-15-8bwrro.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/401986/original/file-20210520-15-8bwrro.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">It’s much easier to roll up one’s shirt sleeve than to drop one’s drawers – and it is faster, too.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/people-receive-a-covid-19-vaccination-shot-at-the-broadway-news-photo/1317682308?adppopup=true">Spencer Platt/Getty Images</a></span>
</figcaption>
</figure>
<h2>Muscles keep the action localized</h2>
<p>Muscle tissue also tends to keep vaccine reactions localized. Injecting a vaccine into the deltoid muscle may result in <a href="https://doi.org/10.1136/bmj.321.7271.1237">local inflammation</a> or soreness at the injection site. If certain vaccines are injected into fat tissue, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1118997/">the chance of irritation and inflammation reaction increases</a> because fat tissue has poor blood supply, leading to poor absorption of some vaccine components. </p>
<p>Vaccines that include the use of <a href="https://www.cdc.gov/vaccinesafety/concerns/adjuvants.html">adjuvants</a> – or components that enhance the immune response to the antigen – must be given in a muscle to avoid widespread irritation and inflammation. <a href="https://www.chop.edu/centers-programs/vaccine-education-center/vaccine-ingredients/aluminum">Adjuvants </a> act in a variety of ways to stimulate a stronger immune response. </p>
<p>Yet another deciding factor in <a href="https://www.healthline.com/health/intramuscular-injection#injection-sites">vaccine administration location</a> is the size of the muscle. Adults and children ages three and older tend to receive vaccines in their upper arm in the deltoid. Younger children receive their vaccines mid-thigh because their arm muscles are smaller and less developed. </p>
<p></p>
<p>Another consideration during vaccine administration is convenience and patient acceptability. Can you imagine taking down your pants at a mass vaccination clinic? Rolling up your sleeve is way easier and more preferred. Infectious disease outbreaks, as in flu season or amid epidemics like COVID-19, require our public health system to vaccinate as many people as possible in a short time. For these reasons, a shot in the arm is preferred simply because the upper arm is easily accessible. </p>
<p>All things considered, when it comes to the flu shot and the COVID-19 vaccine, for most adults and kids, the arm is the preferred vaccination route. </p>
<p>[<em>Understand new developments in science, health and technology, each week.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-understand">Subscribe to The Conversation’s science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/161259/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Libby Richards receives funding from the National Institutes of Health and the American Nurses Foundation. </span></em></p>Most shots work best when inserted into muscle. The shoulder muscle known as the deltoid works best.Libby Richards, Associate Professor of Nursing, Purdue UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1600982021-05-09T19:45:40Z2021-05-09T19:45:40ZTaking one for the team: 6 ways our cells can die and help fight infectious disease<figure><img src="https://images.theconversation.com/files/399422/original/file-20210507-15-1umzp1t.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C389%2C243&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">White blood cells dying</span> </figcaption></figure><p>We have all heard of COVID-19, the flu and bacterial infections. But what is actually happening to our cells when we contract these diseases? Many of our body’s cells don’t live to tell the tale. But cell death isn’t necessarily a bad thing — in fact, the death of infected cells can provide a sacrificial mechanism to stop pathogens in their tracks before they can spread through our body. </p>
<p>Over the years, researchers have realised there are many ways for our cells to die. Our genetics contain a comprehensive “licence to die”, with the route to cell death dictated by both the type of the cell and the pathogen. Let’s check some out:</p>
<h2>The dancing death</h2>
<p>In the time it takes you to read this sentence, ten million cells in your body will have died, through a type of death called <em>apoptosis</em>. This term, coined in 1972 by <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2008650/">Australian pathologist John Kerr</a>, comes from the Greek phrase for “leaves falling from a tree”.</p>
<p>Apoptosis is the most common form of cell death, and has also been nicknamed the “dance of death”, because of the extraordinary shape changes exhibited by the cells under a microscope as they sacrifice themselves. </p>
<p>For example, apoptotic cells dying from radiation or <a href="https://www.nature.com/articles/s42003-020-0955-8">infection with influenza A virus</a> (aka, the flu) generate large, bubble-like structures on their surface called blebs, before shooting out long beaded necklace-like protrusions and finally shattering into pieces. </p>
<p>The death of flu-infected cells is suggested to both <a href="https://www.nature.com/articles/s41419-018-1035-6">aid and limit viral spread</a>. Nevertheless, it’s a spectacular event to witness (and an excellent reminder to get your flu shot this winter).</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/Y-EuAmKK5pM?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">White blood cell blebbing and dying.</span></figcaption>
</figure>
<h2>Out with a bang</h2>
<p>Vaccinia virus is used worldwide to vaccinate against <a href="https://www.who.int/news-room/feature-stories/detail/smallpox-vaccines">smallpox</a>. In fact, it was the very first vaccine, developed in 1796 by Edward Jenner.</p>
<p>We now also know that vaccinia virus can make our cells more sensitive to a particular type of cell death, caused by a molecule called <a href="https://www.cell.com/fulltext/S0092-8674(09)00642-4">TNF</a>. This can help prevent the disease spreading by killing off infected cells before the virus has a chance to replicate.</p>
<p>Many of our cells have a roughly spherical or balloon-like shape, encapsulated by a protective layer called the cell membrane. Just like bursting a balloon with a pin, puncture to the cell membrane marks the point of no return.</p>
<p>This process occurs during <a href="https://www.nature.com/articles/s41467-020-16887-1"><em>necroptosis</em></a> — an explosive type of cell death in which proteins inside the cell punch holes in the membrane. The cell pops and dies, shutting down the machinery needed for viral replication.</p>
<h2>The spider web of death</h2>
<p>When they aren’t busy haunting our nightmares, spiders can be found weaving silken masterpieces of extraordinary detail and strength. The web of a <a href="https://australian.museum/learn/animals/spiders/golden-orb-weaving-spiders/">golden orb weaving spider</a>, for example, is strong enough to entangle small birds. </p>
<p>On a smaller but equally impressive scale, our immune system contains specialised cells called neutrophils that can weave a deadly web of their own and entrap bacteria. Neutrophils gallantly sacrifice themselves in the process of casting their web, in a type of cell death perhaps fittingly called <em>NETosis</em>. </p>
<p>When infected with bacteria such as <em><a href="https://link.springer.com/article/10.1007/s00281-013-0384-6">Streptococcus pneumoniae</a></em>, which causes pneumonia and meningitis, neutrophils eject a specialised web made from their own DNA. These webs can entangle nearby bacteria to prevent their escape until other immune cell reinforcements arrive to clear the infection. Sometimes, proteins found in these webs can also kill the bacteria - quite an impressive defence mechanism!</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/398843/original/file-20210505-17-z3zgx4.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Cartoon illustrating different forms of cell death" src="https://images.theconversation.com/files/398843/original/file-20210505-17-z3zgx4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/398843/original/file-20210505-17-z3zgx4.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=662&fit=crop&dpr=1 600w, https://images.theconversation.com/files/398843/original/file-20210505-17-z3zgx4.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=662&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/398843/original/file-20210505-17-z3zgx4.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=662&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/398843/original/file-20210505-17-z3zgx4.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=832&fit=crop&dpr=1 754w, https://images.theconversation.com/files/398843/original/file-20210505-17-z3zgx4.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=832&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/398843/original/file-20210505-17-z3zgx4.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=832&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">There are a surprising number of ways cells can lay down their lives for the greater good.</span>
<span class="attribution"><span class="license">Author provided</span></span>
</figcaption>
</figure>
<h2>The last meal</h2>
<p>Just as our bodies are compartmentalised into organs such as the stomach, liver or heart, our individual cells also have specialised compartments. One of the cell’s “stomachs” (a structure called the “autophagosome”) engulfs and digests cellular contents such as damaged molecules through the process of <em>autophagy</em>.</p>
<p>However, in some circumstances, the machinery that drives this Pac-Man-style action can also facilitate the cell’s demise. Coincidentally, the bacteria <em>Helicobacter pylori</em> can infect cells of the human stomach lining, called epithelial cells, which can cause ulcers and gastritis. The cells can respond with a process called <a href="https://www.nature.com/articles/s41419-017-0011-x">autophagic cell death</a>, in which the induction of autophagy causes the cell to die. </p>
<h2>A fiery death</h2>
<p>Pyromania, derived from the Greek word <em>pyr</em>, meaning fire, is an obsessive desire to set things ablaze. Some of our immune cells also have the ability to self-immolate and cause inflammation as part of our response to infection.</p>
<p>Since its relatively recent discovery in <a href="https://pubmed.ncbi.nlm.nih.gov/11303500/">2001</a>, this type of cell death, called <em>pyroptosis</em>, has become a hot topic (sorry) among cell biologists, and is often facilitated by a molecular complex called the <a href="https://www.sciencedirect.com/science/article/pii/S0092867410000759">inflammasome</a>.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/what-is-autoinflammatory-disease-the-rare-immune-condition-with-waves-of-fever-128696">What is autoinflammatory disease, the rare immune condition with waves of fever?</a>
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<p>In 2021, understanding pyroptosis is more important than ever, as it has been linked to <a href="https://www.jimmunol.org/content/205/2/307">infection with SARS-CoV-2 infection</a>, the virus that causes COVID-19.</p>
<p>Activation of the factors that cause pyroptosis may help explain the excessive inflammation seen in patients with severe COVID-19. And this could potentially offer a new way to combat the disease.</p>
<h2>Overdosing on iron and fat</h2>
<p>There’s no doubt the key to a long and healthy life is a balanced diet and exercise. However, sometimes we can’t resist the urge to devour a burger and fries with ice cream for dessert. With enough hard work, we can burn it off again. But for individual cells, overindulging can be fatal. </p>
<p>Too much iron and/or harmful types of fat molecules can cause cells to die by <em>ferroptosis</em>. Cells infected with <em><a href="https://rupress.org/jem/article/216/3/556/120345/A-major-role-for-ferroptosis-in-Mycobacterium">Mycobacterium tuberculosis</a></em>, the bacterium that causes TB, can increase their iron content and cause ferrototic cell death! Pass the salad, thanks.</p>
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Read more:
<a href="https://theconversation.com/tick-tock-how-stress-speeds-up-your-chromosomes-ageing-clock-127728">Tick, tock... how stress speeds up your chromosomes' ageing clock</a>
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<p>The survival of the human body is a fine balancing act between cell growth and cell death. Understanding our cells’ complex “licence to die” could give us new ways to combat disease.</p><img src="https://counter.theconversation.com/content/160098/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Georgia Atkin-Smith receives funding from the CASS Foundation (Medicine/Science Grant) and is a postdoctoral researcher at both La Trobe University and the Walter and Eliza Hall Institute of Medical Research.</span></em></p><p class="fine-print"><em><span>Ivan Poon receives funding from the National Health and Medical Research Council and the Australian Research Council. Ivan is an Associate Professor at the La Trobe Institute for Molecular Science. </span></em></p>The survival of the human body is a fine balancing act between cell growth and cell death. Understanding our cells’ complex “licence to die” could give us new ways to combat disease.Georgia Atkin-Smith, Research scientist, La Trobe UniversityIvan Poon, Associate Professor, Biochemistry, La Trobe UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1557122021-03-25T12:26:42Z2021-03-25T12:26:42ZWhy you should get a COVID-19 vaccine – even if you’ve already had the coronavirus<figure><img src="https://images.theconversation.com/files/391257/original/file-20210323-2308-kn86fb.jpg?ixlib=rb-1.1.0&rect=314%2C233%2C4778%2C3862&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Vaccination produces a much stronger and more consistent immune response than infection.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/covid-19-vaccine-circular-pattern-royalty-free-image/1287876073?adppopup=true"> Andriy Onufriyenko/Moment via Getty Images</a></span></figcaption></figure><p>A few weeks ago, a message popped up in the corner of my screen. “What do you think about people who have recently had COVID–19 getting the vaccine?” A friend of mine was eligible for a COVID–19 vaccine, but she had recently gotten over an infection with SARS–CoV–2. More people are becoming eligible for vaccines each week – including millions of people who have already <a href="https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html">recovered from a coronavirus infection</a>. Many are wondering whether they need the vaccine, especially people who have already been infected.</p>
<p><a href="https://scholar.google.com/citations?user=MEMHuGoAAAAJ&hl=en&oi=ao">I study immune responses to respiratory infections</a>, so I get a lot of these types of questions. A person can develop immunity – the ability to resist infection – from being infected with a virus or from getting a vaccine. However, immune protection isn’t always equal. The strength of the immune response, the length of time that the protection lasts and the variation of the immune response across people is very different between vaccine immunity and natural immunity for SARS–CoV–2. COVID–19 vaccines offer safer and more reliable immunity than natural infection. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/391258/original/file-20210323-13-vbg1w4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Electron microscope image of four SARS–CoV–2 particles" src="https://images.theconversation.com/files/391258/original/file-20210323-13-vbg1w4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/391258/original/file-20210323-13-vbg1w4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=469&fit=crop&dpr=1 600w, https://images.theconversation.com/files/391258/original/file-20210323-13-vbg1w4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=469&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/391258/original/file-20210323-13-vbg1w4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=469&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/391258/original/file-20210323-13-vbg1w4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=589&fit=crop&dpr=1 754w, https://images.theconversation.com/files/391258/original/file-20210323-13-vbg1w4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=589&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/391258/original/file-20210323-13-vbg1w4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=589&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 immune system will usually generate an immune response to a SARS-CoV-2 infection, but not always.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Novel_Coronavirus_SARS-CoV-2.jpg#/media/File:Novel_Coronavirus_SARS-CoV-2.jpg">National Institutes of Allergy and Infectious Diseases</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<h2>Immunity after infection is unpredictable</h2>
<p>Immunity comes from the immune system’s ability to remember an infection. Using this immune memory, the body will know to fight if it encounters the disease again. Antibodies are proteins that can bind to a virus and prevent infection. T cells are cells that direct the removal of infected cells and viruses already bound by antibodies. These two are some of the main players that contribute to immunity.</p>
<p>After a SARS-CoV-2 infection, a person’s antibody and T cell responses may be strong enough to provide <a href="https://doi.org/10.1126/science.abf4063">protection against reinfection</a>. Research shows that 91% of people who develop antibodies against the coronavirus are unlikely to be infected again <a href="https://doi.org/10.1056/NEJMoa2034545">for six months</a>, even after <a href="https://doi.org/10.1016/j.cell.2020.11.029">a mild infection</a>. People who had no symptoms during the infection are also likely to develop immunity, though they tend to make <a href="https://doi.org/10.1038/s41564-020-00813-8">fewer antibodies</a> than those who felt ill. So for some people, natural immunity may be strong and long-lasting. </p>
<p>The problem is that not everyone will develop immunity after a SARS-CoV-2 infection. As many as 9% of infected people do not have <a href="https://doi.org/10.1056/NEJMoa2026116">detectable antibodies</a>, and up to 7% of people <a href="https://doi.org/10.1126/science.abf4063">don’t have T cells that recognize the virus</a> 30 days after infection. </p>
<p>For people who do develop immunity, the <a href="https://doi.org/10.1038/s41586-020-2456-9">strength and duration</a> of the protection can vary a lot. Up to 5% of people may <a href="https://doi.org/10.1126/science.abf4063">lose their immune protection</a> within a few months. Without a strong immune defense, these people are susceptible to reinfection by the coronavirus. Some have had second bouts of COVID–19 as soon as <a href="https://doi.org/10.1002/jmv.26637">one month after their first infection</a>; and, though rare, some people have been <a href="https://doi.org/10.1016/j.jinf.2021.01.020">hospitalized or even died</a>. </p>
<p>A person who is reinfected may also be able to transmit the coronavirus even <a href="https://doi.org/10.1001/jamanetworkopen.2020.35057">without feeling sick</a>. This could put the person’s loved ones at risk. </p>
<p>And what about the variants? So far, there isn’t any hard data about the new coronavirus variants and natural immunity or reinfection, but it is certainly possible that immunity from one infection won’t be as strong against infection with a different variant.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/391251/original/file-20210323-21-w4qpa2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A healthy human T cell, a large blue rumpled sphere" src="https://images.theconversation.com/files/391251/original/file-20210323-21-w4qpa2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/391251/original/file-20210323-21-w4qpa2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/391251/original/file-20210323-21-w4qpa2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/391251/original/file-20210323-21-w4qpa2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/391251/original/file-20210323-21-w4qpa2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/391251/original/file-20210323-21-w4qpa2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/391251/original/file-20210323-21-w4qpa2.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">COVID–19 vaccines produce a strong immune response in terms of both antibodies and T cells, like the T cell in this photo.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Healthy_Human_T_Cell.jpg#/media/File:Healthy_Human_T_Cell.jpg">National Institutes of Allergy and Infectious Diseases/National Institutes of Health</a></span>
</figcaption>
</figure>
<h2>Vaccination leads to reliable protection</h2>
<p>COVID–19 vaccines generate both <a href="https://doi.org/10.1056/NEJMoa2022483">antibody and T cell responses</a> – but this is much stronger and more consistent than immunity from natural infection. One study found that four months after receiving their first dose of the Moderna vaccine, <a href="https://doi.org/10.1056/NEJMc2032195">100% of people tested had antibodies against SARS-CoV-2</a>. This is the longest period that has been studied so far. In a study looking at the Pfizer and Moderna vaccines, antibody levels were also much higher in vaccinated people than in those who had <a href="https://doi.org/10.1056/NEJMoa2028436">recovered from infection</a>.</p>
<p>Even better, a <a href="https://doi.org/10.1056/NEJMoa2101765">study in Israel</a> showed that the Pfizer vaccine blocked 90% of infections after both doses – even with a variant present in the population. And a <a href="https://doi.org/10.1093/cid/ciab229">decrease in infections</a> means people are less likely to transmit the virus to the people around them.</p>
<p>The COVID–19 vaccines aren’t perfect, but they produce strong antibody and T cell responses that offer a safer and more reliable means of protection than natural immunity.</p>
<h2>Infection and vaccination together</h2>
<p>To my friend’s message, I instantly replied that she should absolutely get the vaccine. After getting vaccinated, my friend could be comfortable knowing that she has long-lasting, effective immunity and less of a chance of spreading the coronavirus to her friends and family. </p>
<p>But more good news has emerged since I sent that message. A new study showed that vaccination after infection produces <a href="https://doi.org/10.1056/NEJMc2101667">six times more antibodies</a> than a vaccine by itself. This isn’t to say that anyone should try to get infected before they get vaccinated – vaccine immunity alone is more than strong enough to provide protection and the dangers of a fight with COVID-19 far outweigh the benefits. But when my friend and the many others who were already infected get their vaccines, they’ll be well protected.</p>
<p>Natural immunity from infection is simply far too unreliable in the face of such a devastating virus. Current COVID-19 vaccines offer incredibly strong, consistent protection to the great majority of people. So, for anyone eligible, even those who have already had a SARS-CoV-2 infection, COVID-19 vaccines offer immense benefits.</p>
<p>[<em>Get facts about coronavirus and the latest research.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=coronavirus-facts">Sign up for The Conversation’s newsletter.</a>]</p><img src="https://counter.theconversation.com/content/155712/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jennifer T. Grier 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>If you’ve already had the coronavirus and recovered, you might be tempted to give the vaccine a pass. A scientist explains why the shot offers the best protection against future infection.Jennifer T. Grier, Clinical Assistant Professor of Immunology, University of South CarolinaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1575992021-03-24T18:51:58Z2021-03-24T18:51:58ZDo I still need to get a COVID vaccine if I’ve had coronavirus?<p>The COVID vaccine rollout is underway, with Australians lining up to get their jabs. But what if you have already had COVID-19? Is it still a good idea to get vaccinated?</p>
<p>Although natural exposure to the virus stimulates immunity, we don’t yet know how long this immunity will last. And people will vary in their ability to mount a protective immune response.</p>
<p>Even if you’ve had COVID-19, you should still get vaccinated. A COVID vaccine may offer more reliable and sustained immunity than a previous infection. At the very least, it will add an extra layer of targeted protection.</p>
<p>Here’s how our immune response works after a natural infection versus a vaccine.</p>
<h2>From B cells to neutralising antibodies</h2>
<p>Soon after becoming infected with SARS-CoV-2 (the virus that causes COVID-19), our immune cells (T cells and B cells) activate. Activated B cells produce so-called <a href="https://www.news-medical.net/health/What-are-Neutralizing-Antibodies.aspx">neutralising antibodies</a>. These antibody-secreting cells defend our bodies against the infection by making antibodies that bind to spikes on the virus surface, and block the virus from entering our cells. </p>
<p>Neutralising antibodies spill over into the bloodstream and travel around the body looking to mop up virus. After the infection has resolved, these activated B cells calm down and transition to a resting state. They move from our blood to our lymph nodes and bones. These so-called <a href="https://pubmed.ncbi.nlm.nih.gov/32978311/">memory B cells</a> survive for decades, along with help from memory T cells. </p>
<p>But they need a nudge once in a while to ensure they’re ready to kick into gear if we’re exposed to an infection.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/391088/original/file-20210323-12-gvuope.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/391088/original/file-20210323-12-gvuope.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/391088/original/file-20210323-12-gvuope.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/391088/original/file-20210323-12-gvuope.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/391088/original/file-20210323-12-gvuope.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/391088/original/file-20210323-12-gvuope.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/391088/original/file-20210323-12-gvuope.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">
<figcaption>
<span class="caption">SARS-CoV-2 viral particles have surface spikes (in green), to which antibodies attach.</span>
<span class="attribution"><span class="source">NIAID/flickr</span></span>
</figcaption>
</figure>
<h2>Our immune cells rely on memory</h2>
<p>When we’re re-exposed to a virus, or receive a vaccine booster, these memory cells awaken, become activated and produce large amounts of antibodies much faster. This immune memory reduces the risk we’ll become infected with SARS-CoV-2. But if we do, it allows for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608032/">quicker healing from COVID-19</a>.</p>
<p>Sustained <a href="https://www.nature.com/articles/s41467-020-20247-4">neutralising antibody levels</a> indicate a good degree of protection against SARS-CoV-2. How long we hang onto natural immunity after COVID-19 is variable and depends on <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899649/">viral, human and environmental factors</a>. For example, the viral variant can make a difference, along with our genes, underlying health conditions, and age.</p>
<p>These factors can affect our neutralising antibody levels, which can wane over time to dip below protective levels. </p>
<p>As COVID-19 hasn’t been around for a particularly long time, it’s difficult to know how long natural immunity generally lasts. However, antibodies and immune memory appear to last for <a href="https://pubmed.ncbi.nlm.nih.gov/32964627/">at least two months</a>.</p>
<p>For patients who have recovered from SARS, a related coronavirus, research has shown they maintained <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851497/">antibodies for up to two to three years</a> following infection. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-second-phase-of-australias-covid-vaccine-rollout-is-underway-despite-a-rocky-start-heres-what-you-need-to-know-157426">The second phase of Australia's COVID vaccine rollout is underway, despite a rocky start. Here's what you need to know</a>
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<h2>Immune responses to a vaccine</h2>
<p>Again, because of the short time frame, we have limited data on sustained antibody responses following vaccination. But immunity appears to be strong <a href="https://pubmed.ncbi.nlm.nih.gov/33617777/">three months after</a> the Oxford/AstraZeneca vaccine. </p>
<p>With COVID-19 vaccines, certain variable factors have been targeted, in a way they can’t with natural infections. For example, considerations like the dose size and the time between doses are all established to confer optimal immunity.</p>
<p>As we continue to monitor people who have received the COVID vaccines, we’ll develop a better understanding of protective immunity and its longevity. </p>
<h2>Staying on top of variants</h2>
<p>Natural immunity from infection may protect against other variants to some degree, but vaccines will play a crucial role as the virus continues to mutate.</p>
<p>It may be necessary to get regular <a href="https://theconversation.com/why-do-we-need-booster-shots-and-could-we-mix-and-match-different-covid-vaccines-155951">boosters</a> of the COVID vaccine until the pandemic is under control. This will provide protection against variants our pre-existing antibodies may not be able to neutralise. </p>
<p>Boosters enhance our broad immunity to parts of the spike proteins shared between different virus variants. Antibodies produced to these common regions can neutralise the virus and stop infection. </p>
<p>We saw this to a limited extent in people who had common cold infections with <a href="https://pubmed.ncbi.nlm.nih.gov/32978311/">other coronaviruses</a> before COVID-19. </p>
<h2>Only one jab? Vaccines as a cure for long COVID?</h2>
<p>There’s been some research suggesting people who have had COVID may only need <a href="https://jamanetwork.com/journals/jama/fullarticle/2777171">one dose of the vaccine</a> to be protected. </p>
<p>For people who have had COVID, one dose may serve to top up their antibodies to protective levels. This is because they’re starting on a stronger footing in terms of their antibody levels and immune memory, compared to people who haven’t had the virus.</p>
<p>But experts in Australia still recommended <a href="https://www.abc.net.au/news/health/2021-03-23/covid-19-people-who-have-had-it-may-need-one-dose-vaccine/13252338">two doses</a>, regardless of whether you’ve had COVID.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/why-well-get-covid-booster-vaccines-quickly-and-how-we-know-theyre-safe-156120">Why we'll get COVID booster vaccines quickly and how we know they're safe</a>
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<p>Meanwhile, reports have indicated people experiencing <a href="https://www.abc.net.au/news/health/2021-03-24/coronavirus-long-covid-could-the-vaccine-cure-it/100023114">long COVID</a> may also benefit from vaccination. We’re not sure how this happens, but symptoms may improve with clearance of any hidden virus reservoirs from the body. Research into this phenomenon is ongoing.</p>
<p>At the end of the day, when the vaccine is available to you, you should get vaccinated, even if you’ve had COVID-19. While the vaccine is likely to protect you, it’s also important to protect others, as we look towards a goal of herd immunity.</p><img src="https://counter.theconversation.com/content/157599/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Cassandra Berry 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>People who have had COVID will still benefit from having a COVID vaccine. Here’s why.Cassandra Berry, Professor of Immunology, Murdoch UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1566152021-03-19T11:29:36Z2021-03-19T11:29:36ZHow effective is the first shot of the Pfizer or Moderna vaccine?<figure><img src="https://images.theconversation.com/files/411570/original/file-20210715-52849-4vv9ib.jpg?ixlib=rb-1.1.0&rect=152%2C73%2C3234%2C2360&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Make that second appointment and get your final dose for full protection.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/detail-photo-of-the-back-of-a-covid-19-vaccination-record-news-photo/1316475438">MediaNews Group/Reading Eagle via Getty Images</a></span></figcaption></figure><p>Maybe you’ve postponed your second COVID-19 vaccine appointment, whether because of scheduling hassles or general reluctance. But how safe are you after just a single dose?</p>
<p><a href="https://scholar.google.com/citations?user=6yMIM1MAAAAJ&hl=en">As an immunologist</a>, I hear this question frequently – and the answer has changed as new genetic strains of the coronavirus become more common. <a href="https://covid.cdc.gov/covid-data-tracker/?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fcases-updates%2Fvariant-proportions.html#variant-proportions">By the beginning of July 2021</a>, the <a href="https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html">delta variant</a> had become the most dominant strain of SARS-CoV-2 circulating in the U.S.</p>
<p>The Moderna and Pfizer mRNA vaccines weren’t designed specifically to ward off the delta variant. While overall they still <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/effectiveness.html">provide excellent protection</a> after the full two doses, new research suggests <a href="https://doi.org/10.1038/s41586-021-03777-9">a single dose provides less immunity</a> against the coronavirus strains that are out there now than it did against the original strain.</p>
<p>Bottom line: Two shots are way better than one.</p>
<figure class="align-center ">
<img alt="Nurses prepare to give medical workers vaccines." src="https://images.theconversation.com/files/390402/original/file-20210318-21-1xg2fuo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/390402/original/file-20210318-21-1xg2fuo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/390402/original/file-20210318-21-1xg2fuo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/390402/original/file-20210318-21-1xg2fuo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/390402/original/file-20210318-21-1xg2fuo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/390402/original/file-20210318-21-1xg2fuo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/390402/original/file-20210318-21-1xg2fuo.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">Medical workers receive vaccination against COVID-19 on Dec. 20, 2020, in Tel Aviv.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/medical-workers-vaccinate-medical-stuff-members-against-news-photo/1230224367?adppopup=true">Amir Levy/Getty Images</a></span>
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</figure>
<h2>How well had the vaccines been working?</h2>
<p>Soon after the Pfizer COVID-19 vaccine was authorized in December 2020, researchers in Israel found that a <a href="https://doi.org/10.1016/S0140-6736(21)00448-7">single dose was highly effective</a> in one medical center’s thousands of vaccinated health care workers. A single dose reduced the rate of infection by up to 85% after four weeks post-shot compared to those who were not vaccinated.</p>
<p>This real-world finding was consistent with an analysis <a href="https://doi.org/10.1056/NEJMoa2034577">of Pfizer’s clinical trial data</a> reported in 2020 in the New England Journal of Medicine. In that study, the 52% protection from the first dose included infections that occurred in the first 12 days after vaccination, when one would not expect the vaccine to have had time to generate protective antibodies.</p>
<p>Another real-world study of adults ages 70 and older conducted by Public Health England in early 2021 determined that <a href="https://doi.org/10.1136/bmj.n1088">a single dose of the Pfizer vaccine was 61% effective</a> at preventing symptomatic disease 28 days after vaccination. Two doses increased effectiveness to 85%-90%.</p>
<h2>So, what’s changed?</h2>
<p>Essentially, it comes down to new variants. Scientists are particularly concerned about the delta variant because it <a href="https://www.nytimes.com/2021/07/15/briefing/delta-variant-spread-contagious.html">appears to be especially contagious</a>.</p>
<p>All of the vaccines for COVID-19 <a href="https://doi.org/10.1038/s41586-021-03738-2">generate antibodies against the spike glycoprotein</a> on the surface of the coronavirus. If you encounter the coronavirus after you’ve been vaccinated, these antibodies protect you by binding to the spike on its surface, preventing the virus from entering your cells to cause an infection.</p>
<p>The problem is that the delta variant can evade some – but not all – of the antibodies generated by the current vaccines.</p>
<h2>How well do vaccines protect against delta so far?</h2>
<p>It looks like the delta variant is relatively resistant to the anti-spike antibodies vaccination generates. This change is what makes it all the more important to get the second dose of an mRNA vaccine.</p>
<p>The first shot <a href="https://doi.org/10.1038/s41577-020-00479-7">introduces your body</a> to the virus’s spike protein so your immune system can start to produce targeted antibodies and immune cells. <a href="https://theconversation.com/why-it-takes-2-shots-to-make-mrna-vaccines-do-their-antibody-creating-best-and-what-the-data-shows-on-delaying-the-booster-dose-153956">The second shot</a> gives your body another chance to practice mounting that immune response against COVID-19. The second dose triggers the creation of more anti-spike antibodies, and these are more effective at protecting you because they bind more tightly to the viral spike if they encounter it.</p>
<p>In a study published in the journal Nature in July, researchers tested serum from the blood of 16 recent Pfizer vaccine recipients in France. After the first dose of the mRNA vaccine, serum from <a href="https://doi.org/10.1038/s41586-021-03777-9">only two of the 16 vaccinated people neutralized the delta variant</a> of the virus. The good news, though, is that after the second vaccine dose, serum from 15 out of 16 people neutralized the delta variant.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/411572/original/file-20210715-25-1hqj2pl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="masked people walk past a public Christmas tree" src="https://images.theconversation.com/files/411572/original/file-20210715-25-1hqj2pl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/411572/original/file-20210715-25-1hqj2pl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/411572/original/file-20210715-25-1hqj2pl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/411572/original/file-20210715-25-1hqj2pl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/411572/original/file-20210715-25-1hqj2pl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/411572/original/file-20210715-25-1hqj2pl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/411572/original/file-20210715-25-1hqj2pl.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 delta variant started gaining a foothold in the U.K. at the end of 2020.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/pedestrians-wearing-a-protective-face-covering-to-combat-news-photo/1229735590">Tolga Akmen/AFP via Getty Images</a></span>
</figcaption>
</figure>
<p>Out of the lab and in the real world, Public Health England has collected data on all symptomatic cases of COVID-19 in the country in which the coronavirus was genetically sequenced. Of the 1,054 cases of delta infection through the middle of May 2021, a preliminary analysis that has not yet been peer-reviewed found that <a href="https://doi.org/10.1101/2021.05.22.21257658">one dose of the Pfizer vaccine was 33% effective</a> at preventing symptomatic infection. Protection rose to 88% after two doses. Those protection levels for delta are lower than what they found for the older alpha variant: 51% effectiveness after dose one and 93% after dose two.</p>
<p>A smaller preliminary study from Canada that also has not yet been peer-reviewed identified a <a href="https://doi.org/10.1101/2021.06.28.21259420">similar level of protection</a>. In 165 people with delta infection, researchers found 56% protection from symptomatic infection with one dose of Pfizer and 87% with two. Importantly, researchers calculated that protection from hospitalization or death from delta after even a single dose was 78% for Pfizer and 96% for Moderna.</p>
<h2>Am I protected?</h2>
<p>You are well protected if you have completed your vaccination: two doses of the Pfizer or Moderna or the single-dose Johnson & Johnson vaccine. If you have had only one of the two required doses of the mRNA vaccines, then you should finish vaccination by getting the second shot. That will raise your COVID-19 protection from what <a href="https://doi.org/10.1101/2021.05.22.21257658">might be as low as 33%</a> better than an unvaccinated person <a href="https://www.cdc.gov/vaccines/covid-19/effectiveness-research/protocols.html">up to 90%</a>.</p>
<p>[<em>Get our best science, health and technology stories.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-best">Sign up for The Conversation’s science newsletter</a>.]</p>
<p>The picture is more complicated if you are immunocompromised. Studies have found that <a href="https://doi.org/10.1126/sciimmunol.abj1031">some immunocompromised patients</a> <a href="https://doi.org/10.7326/M21-1451">don’t produce antibodies</a> after vaccination. In these cases, some studies suggest that <a href="https://doi.org/10.7326/L21-0282">booster shots may offer hope</a>, with a third dose of an mRNA vaccine triggering a protective antibody response.</p>
<p>For mRNA vaccines against COVID-19, the <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/faq.html">CDC recommendation remains the same</a>: For Pfizer, get two doses 21 days apart, and for Moderna, get two doses 28 days apart. Sticking to the schedule and getting both doses means you will have very high levels of protection once your body has time to build immunity.</p>
<hr>
<p><em>Editor’s note: Since this article was initially published on March 19, 2021, the coronavirus has continued to mutate. This updated version reflects research as of July 2021 suggesting that a single dose of the Moderna or Pfizer COVID-19 vaccine is not enough to reliably ward off infection. The recommendation remains to receive the full course of two shots.</em></p><img src="https://counter.theconversation.com/content/156615/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>William Petri receives funding from National Institutes of Health, the Gates Foundation and Regeneron.</span></em></p>An immunologist explains that you get some protection from the first dose of the mRNA vaccines but you need two to build up strong immunity, particularly to newer coronavirus variants.William Petri, Professor of Medicine, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1564642021-03-09T13:35:58Z2021-03-09T13:35:58Z3 medical innovations fueled by COVID-19 that will outlast the pandemic<figure><img src="https://images.theconversation.com/files/388126/original/file-20210305-19-1xbafnd.jpg?ixlib=rb-1.1.0&rect=1233%2C95%2C5784%2C5892&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Gene-based vaccines had never been approved for humans before the coronavirus pandemic.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/covid-19-rna-vaccine-illustration-royalty-free-illustration/1296294288?adppopup=true">Juan Gaertner/Science Photo Library via Getty Images</a></span></figcaption></figure><p><em>A number of technologies and tools got a chance to prove themselves for the first time in the context of COVID-19. Three researchers working in gene-based vaccines, wearable diagnostics and drug discovery explain how their work rose to the challenge of the pandemic, and their hopes that each technology is now poised to continue making big changes in medicine.</em></p>
<p></p><hr><p></p>
<h2>Genetic vaccines</h2>
<p><strong>Deborah Fuller, Professor of Microbiology, University of Washington</strong></p>
<p>Thirty years ago, researchers for the first time injected mice with genes from a foreign pathogen to <a href="https://doi.org/10.1038/356152a0">produce an immune response</a>. Like many new discoveries, these first gene-based vaccines had their ups and downs. Early mRNA vaccines were hard to store and <a href="https://doi.org/10.1038/nrd.2017.243">didn’t produce the right type of immunity</a>. DNA vaccines were more stable but weren’t efficient at getting into the cell’s nucleus, so they <a href="https://dx.doi.org/10.1038%2Fnrg2432">failed to produce sufficient immunity</a>.</p>
<p>Researchers slowly overcame the problems of <a href="https://doi.org/10.1038/mt.2008.200">stability</a>, getting the genetic instructions <a href="https://doi.org/10.1073/pnas.1209367109">where they needed to be</a> and making them induce <a href="https://doi.org/10.1038/nrd.2017.243">more effective immune responses</a>. By 2019, academic labs and biotechnology companies all over the world had dozens of promising mRNA and DNA vaccines for infectious diseases, as well as for cancer in development or in <a href="https://dx.doi.org/10.3390%2Fvaccines7020037">phase 1 and phase 2 human clinical trials</a>.</p>
<p>When COVID-19 struck, mRNA vaccines in particular were ready to be put to a real-world test. The <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">94% efficacy of the mRNA vaccines</a> surpassed health officials’ highest expectations.</p>
<p>DNA and mRNA vaccines offer huge advantages over traditional types of vaccines, since they use only genetic code from a pathogen – rather than the entire virus or bacteria. Traditional vaccines take months, if not years, to develop. In contrast, once scientists get the genetic sequence of a new pathogen, they can <a href="https://doi.org/10.3389/fimmu.2020.583077">design a DNA or mRNA vaccine in days</a>, identify a lead candidate for clinical trials within weeks and have <a href="https://doi.org/10.1038/s41541-020-0159-8">millions of doses manufactured within months</a>. This is basically what happened with the coronavirus.</p>
<p>Gene-based vaccines also produce precise and effective immune responses. They stimulate not only antibodies that block an infection, but also a strong T cell response that can <a href="https://www.gavi.org/vaccineswork/what-are-nucleic-acid-vaccines-and-how-could-they-be-used-against-covid-19#:%7E:text=Nucleic%20acid%20vaccines%20use%20genetic,immune%20response%20against%20it">clear an infection if one occurs</a>. This makes these vaccines better able to respond to mutations, and it also means they could be capable of <a href="https://www.genengnews.com/insights/immunotherapy-targets-emerging-infectious-diseases/">eliminating chronic infections</a> or <a href="https://doi.org/10.1038/d41586-019-03072-8">cancerous cells</a>.</p>
<p>The hopes that gene-based vaccines could one day provide a vaccine for malaria or HIV, cure cancer, replace less effective traditional vaccines or be ready to stop the next pandemic before it gets started are no longer far-fetched. Indeed, many <a href="https://doi.org/10.1016/j.coi.2020.01.006">DNA</a> and <a href="https://doi.org/10.1038/nrd.2017.243">mRNA</a> vaccines against a wide range of infectious diseases, for treatment of chronic infections and for cancer are already in advanced stages and clinical trials. As someone who has been working on these vaccines for decades, I believe their proven effectiveness against COVID-19 will usher in a new era of vaccinology with <a href="https://doi.org/10.1016/j.ymthe.2020.06.017">genetic vaccines at the forefront</a>.</p>
<p></p><hr><p></p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/388127/original/file-20210305-23-1yr4ab5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A person wearing a smart watch." src="https://images.theconversation.com/files/388127/original/file-20210305-23-1yr4ab5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/388127/original/file-20210305-23-1yr4ab5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/388127/original/file-20210305-23-1yr4ab5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/388127/original/file-20210305-23-1yr4ab5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/388127/original/file-20210305-23-1yr4ab5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/388127/original/file-20210305-23-1yr4ab5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/388127/original/file-20210305-23-1yr4ab5.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">Smartwatches and other wearable technologies allow users to capture more continuous health data than ever before.</span>
<span class="attribution"><a class="source" href="https://pixabay.com/photos/smartwatch-gadget-technology-smart-828786/">Pixabay</a></span>
</figcaption>
</figure>
<h2>Wearable tech and early illness detection</h2>
<p><strong>Albert H. Titus, Professor of Biomedical Engineering, University at Buffalo</strong></p>
<p>During the pandemic, researchers have taken full advantage of the proliferation of smartwatches, smart rings and other wearable health and wellness technology. These devices can measure a person’s <a href="https://doi.org/10.1038/s41598-020-78355-6">temperature</a>, <a href="https://dx.doi.org/10.2196%2F10828">heart rate</a>, <a href="https://dx.doi.org/10.2196%2Fjmir.9157">level of activity</a> and other <a href="https://dx.doi.org/10.2196%2F16811">biometrics</a>. With this information, researchers have been able to track and <a href="https://doi.org/10.2196/26107">detect COVID-19 infections</a> even before people notice they have any symptoms.</p>
<p>As wearable usage and adoption <a href="https://www.gartner.com/en/newsroom/press-releases/2021-01-11-gartner-forecasts-global-spending-on-wearable-devices-to-total-81-5-billion-in-2021">grew in recent years</a>, researchers began studying the ability of these devices to <a href="https://dx.doi.org/10.3390%2Fnano9060813">monitor disease</a>. However, although real-time data collection was possible, previous work had focused primarily on chronic diseases.</p>
<p>But the pandemic both served as a lens to focus many researchers in the field of health wearables and offered them an unprecedented opportunity to study real-time <a href="https://doi.org/10.1038/s41928-020-00533-1">infectious disease detection</a>. The number of people potentially affected by a single disease – COVID-19 – at one time gave researchers a large population to draw from and to test hypotheses on. Combined with the fact that <a href="https://www.gartner.com/en/newsroom/press-releases/2021-01-11-gartner-forecasts-global-spending-on-wearable-devices-to-total-81-5-billion-in-2021">more people than ever</a> are using wearables with health monitoring functions and that these devices collect lots of useful data, researchers were able to try to diagnose a disease solely using data from wearables – an experiment they could only dream of before.</p>
<p>Wearables can detect symptoms of COVID-19 or other illnesses <a href="https://doi.org/10.1038/s41551-020-00640-6">before symptoms are noticeable</a>. While they have proved to be capable of detecting sickness early, the symptoms wearables detect are <a href="https://doi.org/10.1038/s41928-020-00533-1">not unique to COVID-19</a>. These symptoms can be predictive of a number of potential illnesses or other health changes, and it is much harder to say what illness a person has versus simply saying they are <a href="https://doi.org/10.1016/j.jiph.2011.05.002">sick with something</a>. </p>
<p>Moving into the post-pandemic world, it’s likely that more people will <a href="https://www.gartner.com/en/newsroom/press-releases/2021-01-11-gartner-forecasts-global-spending-on-wearable-devices-to-total-81-5-billion-in-2021">incorporate wearables</a> into their lives and that the devices will only improve. I expect the knowledge researchers have gained during the pandemic on how to use wearables to monitor health will form a starting point for how to handle future outbreaks – not just of viral pandemics, but potentially of other events such as food poisoning outbreaks and seasonal flu episodes. But since wearable tech is concentrated within pockets of affluent and <a href="https://dx.doi.org/10.1016%2Fj.ijinfomgt.2020.102209">younger populations</a>, the research community and society as a whole must simultaneously address the disparities that exist.</p>
<p></p><hr><p></p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/388128/original/file-20210305-23-cskouk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A map showing proteins connections." src="https://images.theconversation.com/files/388128/original/file-20210305-23-cskouk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/388128/original/file-20210305-23-cskouk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=590&fit=crop&dpr=1 600w, https://images.theconversation.com/files/388128/original/file-20210305-23-cskouk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=590&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/388128/original/file-20210305-23-cskouk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=590&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/388128/original/file-20210305-23-cskouk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=742&fit=crop&dpr=1 754w, https://images.theconversation.com/files/388128/original/file-20210305-23-cskouk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=742&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/388128/original/file-20210305-23-cskouk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=742&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Every place that a coronavirus protein interacts with a human protein is a potential druggable site.</span>
<span class="attribution"><a class="source" href="http://qbi.ucsf.edu/COVID-19">QBI Coronavirus Research Group</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<h2>A new way to discover drugs</h2>
<p><strong>Nevan Krogan, Professor of Cellular Molecular Pharmacology and Director of the Quantitative Biosciences Institute, University of California, San Francisco</strong></p>
<p>Proteins are the molecular machines that make your cells function. When proteins malfunction or are hijacked by a pathogen, you often get disease. Most drugs work by disrupting the action of one or several of these <a href="https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet">malfunctioning or hijacked proteins</a>. So a logical way to look for new drugs to treat a specific disease is to study individual genes and proteins that are directly affected by that disease. For example, researchers know that the BRCA gene – a gene that protects your DNA from being damaged – is closely related to the development of breast and ovarian cancer. So a lot of work has focused on finding drugs that affect the <a href="https://doi.org/10.1038/s41571-018-0055-6">function of the BRCA protein</a>.</p>
<p>However, single proteins working in isolation are usually not solely responsible for disease. Genes and the proteins they encode are part of complicated networks – the BRCA protein <a href="https://doi.org/10.1073/pnas.0805242105">interacts with tens to hundreds</a> of other proteins that help it perform its cellular functions. My colleagues and I are part of a <a href="https://doi.org/10.1016/j.molcel.2018.07.010">small but growing</a> field of <a href="https://doi.org/10.1016/j.cell.2018.08.044">researchers</a> who study these <a href="https://doi.org/10.1038/nature04670">connections and interactions among proteins</a> – what we call protein networks. </p>
<p>For a few years now, my colleagues and I have been exploring the potential of these networks to find more ways drugs could ameliorate disease. When the coronavirus pandemic hit, we knew we had to try this approach and see if it could be used to rapidly find a treatment for this emerging threat. We immediately started <a href="https://theconversation.com/covid-19-treatment-might-already-exist-in-old-drugs-were-using-pieces-of-the-coronavirus-itself-to-find-them-133701">mapping the extensive network of human proteins</a> that SARS-CoV-2 hijacks so it can replicate.</p>
<p>Once we built this map, we pinpointed human proteins in the network that <a href="https://theconversation.com/covid-19-treatment-might-already-exist-in-old-drugs-were-using-pieces-of-the-coronavirus-itself-to-find-them-133701">drugs could easily target</a>. We found <a href="https://doi.org/10.1038/s41586-020-2286-9">69 compounds</a> that influence the proteins in the coronavirus network. 29 of them are already FDA-approved treatments for other illnesses. On Jan. 25 we published a paper showing that one of the drugs, Aplidin (Plitidepsin), currently being used to treat cancer, is <a href="https://doi.org/10.1126/science.abf4058">27.5 times more potent than remdesivir</a> in treating COVID-19, <a href="https://doi.org/10.1101/2021.01.24.427991">including one of the new variants</a> The drug has been approved for phase 3 clinical trials in 12 countries as a <a href="https://clinicaltrials.gov/ct2/show/NCT04784559">treatment for the new coronavirus</a>.</p>
<p>But this idea of mapping the protein interactions of diseases to look for novel drug targets doesn’t apply just to the coronavirus. We have now used this approach on <a href="http://hpmi.ucsf.edu">other pathogens</a> as well as other diseases including <a href="http://ccmi.org">cancer</a>, neurodegenerative and <a href="http://pcmi.ucsf.edu">psychiatric disorders</a>.</p>
<p>These maps are allowing us to connect the dots among many seemingly disparate aspects of single diseases and discover new ways drugs could treat them. We hope this approach will allow us and researchers in other areas of medicine to discover new therapeutic strategies and also see whether any old drugs might be repurposed to treat other conditions.</p>
<p>[<em>Understand new developments in science, health and technology, each week.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-understand">Subscribe to The Conversation’s science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/156464/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Deborah Fuller is a co-founder of Orlance, Inc that is developing a needle-free technology for delivery of DNA and RNA vaccines. She has grant funding from the National Institutes of Health, the Department of Defense and the Washington Research Foundation.</span></em></p><p class="fine-print"><em><span>Albert H. Titus has received research funding from the National Science Foundation, the National Institutes of Health, and the Department of Defense. He has also received funding for research in this area from Garwood Medical Devices. He is a Fellow of the National Academy of Inventors, a Senior Member of the IEEE, a member of BMES, ASEE, and is a member of the BME Council of Chairs. </span></em></p><p class="fine-print"><em><span>Nevan Krogan receives funding from NIH, DARPA and Roche Pharmaceuticals.</span></em></p>The coronavirus pandemic has driven a lot of scientific progress in the past year. But just as some of the social changes are likely here to stay, so are some medical innovations.Deborah Fuller, Professor of Microbiology, School of Medicine, University of WashingtonAlbert H. Titus, Professor of Biomedical Engineering, University at BuffaloNevan Krogan, Professor and Director of Quantitative Biosciences Institute & Senior Investigator at the Gladstone Institutes, University of California, San FranciscoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1552132021-03-08T13:35:53Z2021-03-08T13:35:53ZA year into the pandemic, the coronavirus is messing with our minds as well as our bodies<figure><img src="https://images.theconversation.com/files/387617/original/file-20210303-14-1pt7xvk.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C4193%2C2797&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">It's not a stretch to say asymptomatic spreaders unwittingly engage in zombielike behaviors. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/hordes-of-angry-walking-dead-zombies-royalty-free-image/908122164?adppopup=true">gremlin via Getty Images</a></span></figcaption></figure><p>COVID-19 has hijacked people’s lives, families and work. And, it has hijacked their bodies and minds in ways that they may not even be aware of. </p>
<p>As we see it, SARS-CoV-2, the virus that causes COVID-19, is a sort of zombie virus, turning people not into the undead but rather into the unsick. By interfering with our bodies’ normal immune response and blocking pain, the virus keeps the infected on their feet, spreading the virus. </p>
<p>People typically think of zombies as the stuff of science fiction. But in the biological world, <a href="https://doi.org/10.1016/S0031-9384(03)00163-X">zombies are all over the place</a>, from the <a href="https://doi.org/10.1186/s12862-014-0166-3">Ophiocordyceps</a> fungus that perpetuates itself by zombifying ants; to <a href="https://doi.org/10.1371/journal.pone.0023277">Toxoplasma gondii</a>, a single-celled parasite that completes its life cycle by leading rodents into the jaws of predators. <a href="https://doi.org/10.1016/S0031-9384(03)00163-X">Zombie viruses are also a real thing, influencing</a> their host’s behavior in ways that enhance the viruses’ <a href="https://doi.org/10.1016/j.beproc.2004.06.010">evolutionary fitness</a>.</p>
<p>One of us is a <a href="http://www.athenaaktipis.org/">professor of psychology</a>. The other is <a href="https://evolutionmedicine.com/about-joe-alcock-author-of-this-blog/">an emergency physician</a>. Both of us are evolutionary medicine researchers. And we suggest to you that SARS-CoV-2, the virus that causes COVID-19, is yet another zombie virus, a master manipulator operating under the radar. This pandemic may have unleashed a horde of the unsick: infected and unwitting victims of a manipulative virus. </p>
<figure class="align-center ">
<img alt="An image of the coronavirus." src="https://images.theconversation.com/files/387651/original/file-20210304-14-q616d7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/387651/original/file-20210304-14-q616d7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=365&fit=crop&dpr=1 600w, https://images.theconversation.com/files/387651/original/file-20210304-14-q616d7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=365&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/387651/original/file-20210304-14-q616d7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=365&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/387651/original/file-20210304-14-q616d7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=459&fit=crop&dpr=1 754w, https://images.theconversation.com/files/387651/original/file-20210304-14-q616d7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=459&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/387651/original/file-20210304-14-q616d7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=459&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The novel coronavirus, which first appeared in China in late 2019.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/corona-virus-close-up-royalty-free-image/1212213050?adppopup=true">Radoslav Zilinsky via Getty Images</a></span>
</figcaption>
</figure>
<h2>How the virus turns us into the unsick</h2>
<p>It is the unsick who spread the virus most readily. About 40% of those with SARS-CoV-2 are asymptomatic spreaders, never showing symptoms at all. And those who do show symptoms are <a href="https://doi.org/10.1038/s41591-020-0869-5">most contagious in the two days before symptoms appear</a>. Why people don’t feel sick earlier – or sick at all – might be part of the <a href="https://doi.org/10.1073/pnas.2009787117">evolutionary strategy of SARS-CoV-2</a>. </p>
<p>A look under the hood of the virus reveals more about that manipulative machinery. SARS-CoV-2 interferes with a person’s <a href="https://doi.org/10.1101/2020.08.18.256776">immune response</a>; this is why people don’t necessarily feel sick and withdrawn as they would in a typical viral infection. Instead, SARS-CoV-2 silences the body’s alarm signals that otherwise would orchestrate <a href="https://doi.org/10.1101/2020.08.18.256776">anti-viral defenses</a>. It blocks interferons, a set of molecules that help fight viruses. Interferon activity makes people feel more <a href="https://doi.org/10.1038/s41423-020-0402-2">depressed and socially withdrawn</a> – so when the novel coronanvirus impedes interferon activity, mood is lifted, sociality is increased and you feel less sick. </p>
<p>The virus also <a href="https://doi.org/10.1101/2020.07.17.209288">decreases pain perception</a>. Normally, pain <a href="https://doi.org/10.1146/annurev.psych.51.1.29">motivates us to hunker down</a> when we need to heal. But SARS-CoV-2 blocks this response by preventing <a href="https://doi.org/10.1101/2020.07.17.209288">the transmission of pain signals</a>. This is why people feel fine even when they are teeming with virus before the onset of symptoms. </p>
<p>At the same time, SARS-CoV-2 dampens the body’s response to infection. It <a href="https://doi.org/10.1101/2020.05.24.111823">hinders pro-inflammatory cytokines</a>, molecules that help spur the immune response. This too makes hosts feel better than they should. Typically, feeling sick helps our bodies prioritize healing by making us reduce our energy expenditure. With SARS-CoV-2, unsick hosts have the energy to do as much as they used to, maybe more. </p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/PSnSo9kYlH4?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">3D Animation: SARS-CoV-2 virus transmission leading to COVID-19.</span></figcaption>
</figure>
<h2>An evolutionary leg up</h2>
<p>How SARS-CoV-2 evolved to manipulate humans is still speculation. The virus could have first evolved in other mammals, like pangolins. There, it may have acquired its immune-evading, manipulative machinery before jumping to humans. </p>
<p>No intent or thought is involved; SARS-CoV-2 is not scheming to take over your body. This is simply evolution at work, nothing personal. The virus evolves because of variation and selection. And in a pandemic involving hundreds of millions of infections and trillions of viral replications, plenty of <a href="https://doi.org/10.1016/j.plrev.2005.11.002">genetic variants could give it an evolutionary leg up</a>. </p>
<p>More research is needed to determine whether new variants make people feel unsick for longer. That, of course, would make it even easier for the virus spread during the asymptomatic phase. For example, a paper in the Journal of Transnational Medicine reported that the <a href="https://doi.org/10.1186/s12967-020-02535-1">GZ69 variant</a> is associated with high shedding rates in asymptomatic patients, meaning that people are highly contagious even when they are feeling fine. </p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p>
<p>It’s possible that SARS-CoV-2 might make people feel even better than they would without infection from the virus. One study found people did not reduce their time out in public even when they had COVID-19 symptoms. If anything, they <a href="https://doi.org/10.1101/2020.04.19.20065219">went out more</a>. Any variant that does this clearly has an evolutionary advantage when it comes to transmission. Using surveys and social media data, <a href="https://www.cooperationintheapocalypse.org/">our research team</a> is now testing whether people are more social during their most infectious days. </p>
<h2>Things to consider</h2>
<p>We must take seriously the possibility that the virus is zombifying us – altering our behavior in ways that help perpetuate it. By keeping people feeling good when they are capable of spreading the virus, SARS-CoV-2 spreads under the radar, <a href="https://theconversation.com/how-the-coronavirus-escapes-an-evolutionary-trade-off-that-helps-keep-other-pathogens-in-check-140706">more like a sexually transmitted disease</a> than a respiratory virus. </p>
<p>Many of us have unwittingly acted as vehicles for its propagation, with stunning implications. Our behavior might not be in our own evolutionary interests. Instead, the unsick may be serving the virus.</p>
<p>Researchers often ignore the impact that viruses might have on our moods and behaviors. But like ants and rodents, humans are not exempt from the neural and behavioral hijacking that’s widespread in the natural world. </p>
<p>We believe that it is critical to consider the possible “anti-symptoms” of this virus: temporary reduction in pain, feeling more energetic than normal and perhaps even wanting to be around people more than usual. With all this in mind, here’s some advice, likely the most ironic you’ve heard in the last year: If you’ve been feeling surprisingly good the last few days, you might want to get a COVID-19 test.</p><img src="https://counter.theconversation.com/content/155213/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>SARS-CoV-2 is much like a zombie virus. It interferes with normal sickness behavior and blocks pain, turning its victims into unsick spreaders of the virus.Athena Aktipis, Associate Professor of Psychology, Center for Evolution and Medicine, Arizona State UniversityJoe Alcock, Professor of Emergency Medicine, University of New MexicoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1456682021-01-22T13:32:56Z2021-01-22T13:32:56ZA healthy microbiome builds a strong immune system that could help defeat COVID-19<figure><img src="https://images.theconversation.com/files/377088/original/file-20210104-23-1x5t54j.jpg?ixlib=rb-1.1.0&rect=97%2C64%2C7092%2C3977&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The microbes living in the gut are key to good health.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/intestinal-microbiome-medical-concept-royalty-free-image/1196631894?adppopup=true">Dr_Microbe/iStock/Getty Images Plus</a></span></figcaption></figure><p>You may not know it, but you have an army of microbes living inside of you that are essential for fighting off threats, including the virus that causes COVID-19.</p>
<p>In the past two decades scientists have learned our bodies are home to more bacterial cells than human ones. This community of bacteria that lives in and on us – called the microbiome – resembles a company, with each microbe species performing specialized jobs but all working to keep us healthy. In the gut, the bacteria balance the immune response against pathogens. These bacteria ensure the immune response is effective but not so violent that it causes collateral damage to the host. </p>
<p>Bacteria in our guts can elicit an effective immune response against viruses that not only infect the gut, such as <a href="http://doi.org/10.3390/v10020096">norovirus</a> <a href="http://doi.org/10.1126/science.1258025">and rotavirus</a>, but also those infecting the lungs, such as <a href="https://doi.org/10.1073/pnas.1019378108">the flu virus</a>. The beneficial gut microbes do this by ordering specialized immune cells to produce potent antiviral proteins that ultimately eliminate <a href="https://doi.org/10.1016/j.cell.2020.04.022">viral infections</a>. And the body of a person lacking these beneficial gut bacteria won’t have as strong an immune response to invading viruses. As a result, infections might go unchecked, taking a toll on health.</p>
<p><a href="https://scholar.google.com/citations?user=4y55zc0AAAAJ&hl=en">I am a microbiologist</a> fascinated by the ways bacteria shape human health. <a href="https://www.umassmed.edu/nutrition/melody-trial-info/">An important focus of my research</a> is figuring out how the beneficial bacteria populating our guts combat disease and infection. <a href="https://doi.org/10.1101/2021.01.05.20249061">My most recent work focuses on the link</a> between a particular microbe and the severity of COVID-19 in patients. My ultimate goal is to figure out how to enhance the gut microbiome with diet to evoke a strong immune response – for not just SARS-CoV-2 but all pathogens. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/377078/original/file-20210104-21-gqunkx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/377078/original/file-20210104-21-gqunkx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/377078/original/file-20210104-21-gqunkx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=429&fit=crop&dpr=1 600w, https://images.theconversation.com/files/377078/original/file-20210104-21-gqunkx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=429&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/377078/original/file-20210104-21-gqunkx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=429&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/377078/original/file-20210104-21-gqunkx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=539&fit=crop&dpr=1 754w, https://images.theconversation.com/files/377078/original/file-20210104-21-gqunkx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=539&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/377078/original/file-20210104-21-gqunkx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=539&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Good bacteria help the immune system ward off harmful microbes.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/good-bacteria-and-bad-bacteria-royalty-free-illustration/611994628?adppopup=true&uiloc=thumbnail_same_series_adp">chombosan/iStock/Getty Images Plus</a></span>
</figcaption>
</figure>
<h2>How do resident bacteria keep you healthy?</h2>
<p>Our immune defense is part of a complex biological response against harmful pathogens, such as viruses or bacteria. However, because our bodies are inhabited by trillions of mostly beneficial bacteria, virus and fungi, activation of our immune response is tightly regulated to distinguish between harmful and helpful microbes.</p>
<p>Our bacteria are spectacular companions diligently helping prime our immune system defenses to combat infections. A seminal study found that mice treated with antibiotics that eliminate bacteria in the gut exhibited an impaired immune response. These animals had low counts of virus-fighting white blood cells, weak antibody responses and poor production of a protein that is vital for <a href="https://doi.org/10.1073/pnas.1019378108">combating viral infection and modulating the immune response</a>. </p>
<p><a href="https://doi.org/10.1371/journal.pone.0184976">In another study</a>, mice were fed <em>Lactobacillus</em> bacteria, commonly used as probiotic in fermented food. These microbes reduced the severity of influenza infection. The <em>Lactobacillus</em>-treated mice did not lose weight and had only mild lung damage compared with untreated mice. Similarly, others have found that treatment of mice with <em>Lactobacillus</em> protects against different <a href="https://doi.org/10.1038/srep04638">subtypes of</a> <a href="https://doi.org/10.1038/s41598-017-17487-8">influenza</a> <a href="https://doi.org/10.1371/journal.ppat.1008072">virus</a> and human respiratory syncytial virus – the <a href="https://doi.org/10.1038/s41598-019-39602-7">major cause of viral bronchiolitis and pneumonia in children</a>.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/377079/original/file-20210104-15-4sj7z4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/377079/original/file-20210104-15-4sj7z4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/377079/original/file-20210104-15-4sj7z4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/377079/original/file-20210104-15-4sj7z4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/377079/original/file-20210104-15-4sj7z4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/377079/original/file-20210104-15-4sj7z4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/377079/original/file-20210104-15-4sj7z4.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">Fermented foods like kimchi, red beets, apple cider vinegar, coconut milk yogurt, cucumber pickles and sauerkraut can help provide beneficial bacteria.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/fermented-food-sampler-royalty-free-image/899304124?adppopup=true">marekuliasz/iStock/Getty Images Plus</a></span>
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<h2>Chronic disease and microbes</h2>
<p>Patients with chronic illnesses including Type 2 diabetes, obesity and cardiovascular disease exhibit a hyperactive immune system that fails to recognize a harmless stimulus and is linked to an altered gut microbiome.</p>
<p>In these chronic diseases, the gut microbiome lacks bacteria that activate <a href="https://doi.org/10.1126/science.1198469">immune cells</a> that block the response against harmless bacteria in our guts. Such alteration of the gut microbiome is also observed in <a href="https://doi.org/10.1073/pnas.1002601107">babies delivered by cesarean section</a>, individuals consuming a poor <a href="https://doi.org/10.1038/nature12820">diet</a> and the <a href="https://doi.org/10.1038/nature11053">elderly</a>. </p>
<p>In the U.S., 117 million individuals – about half the adult population – <a href="https://health.gov/our-work/food-nutrition/2015-2020-dietary-guidelines/guidelines/">suffer from Type 2 diabetes, obesity, cardiovascular disease or a combination of them</a>. That suggests that half of American adults carry a faulty microbiome army.</p>
<p>Research in my laboratory focuses on identifying gut bacteria that are critical for creating a balanced immune system, which fights life-threatening bacterial and viral infections, while tolerating the beneficial bacteria in and on us.</p>
<p>Given that diet affects the diversity of bacteria in the gut, <a href="https://www.umassmed.edu/nutrition/melody-trial-info/">my lab studies show how diet can be used</a> as a therapy for chronic diseases. Using different foods, people can shift their gut microbiome to one that boosts a healthy immune response. </p>
<p>A fraction of patients infected with SARS-CoV-2, the virus that causes COVID-19 disease, develop severe complications that require hospitalization in intensive care units. What do many of those patients have in common? <a href="https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm">Old age</a> and chronic diet-related diseases like obesity, Type 2 diabetes and cardiovascular disease. </p>
<p><a href="http://doi.org/10.1016/j.jada.2008.12.019">Black and Latinx people are disproportionately affected by obesity, Type 2 diabetes and cardiovascular disease</a>, all of which are linked to poor nutrition. Thus, it is not a coincidence that <a href="https://www.cdc.gov/mmwr/volumes/69/wr/mm6933e1.htm">these groups have suffered more deaths from COVID-19</a> compared with whites. This is the case not only in the U.S. but also <a href="https://www.washingtonpost.com/world/europe/blacks-in-britain-are-four-times-as-likely-to-die-of-coronavirus-as-whites-data-show/2020/05/07/2dc76710-9067-11ea-9322-a29e75effc93_story.html">in Britain</a>. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/377080/original/file-20210104-19-193c73w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/377080/original/file-20210104-19-193c73w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/377080/original/file-20210104-19-193c73w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/377080/original/file-20210104-19-193c73w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/377080/original/file-20210104-19-193c73w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/377080/original/file-20210104-19-193c73w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/377080/original/file-20210104-19-193c73w.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">
<figcaption>
<span class="caption">Minority communities continue to bear the brunt of the pandemic.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/alice-gaskins-holds-sign-that-says-this-virus-is-killing-news-photo/1215626113?adppopup=true">Blake Nissen for The Boston Globe via Getty Images</a></span>
</figcaption>
</figure>
<h2>Discovering microbes that predict COVID-19 severity</h2>
<p>The COVID-19 pandemic has inspired me to shift my research and explore the role of the gut microbiome in the overly aggressive immune response against SARS-CoV-2 infection. </p>
<p>My colleagues and I have hypothesized that critically ill SARS-CoV-2 patients with conditions like obesity, Type 2 diabetes and cardiovascular disease exhibit an altered gut microbiome that aggravates <a href="https://theconversation.com/exercise-may-help-reduce-risk-of-deadly-covid-19-complication-ards-136922">acute respiratory distress syndrome</a>. </p>
<p>Acute respiratory distress syndrome, a life-threatening lung injury, in SARS-CoV-2 patients is thought to develop from a <a href="http://doi.org/10.1016/j.cytogfr.2020.05.003">fatal overreaction of the immune response</a> called a <a href="https://theconversation.com/blocking-the-deadly-cytokine-storm-is-a-vital-weapon-for-treating-covid-19-137690">cytokine storm</a> <a href="http://doi.org/10.1016/S2213-2600(20)30216-2">that causes an uncontrolled flood</a> <a href="http://doi.org/10.1016/S2213-2600(20)30216-2">of immune cells into the lungs</a>. In these patients, their own uncontrolled inflammatory immune response, rather than the virus itself, causes the <a href="http://doi.org/10.1007/s00134-020-05991-x">severe lung injury and multiorgan failures</a> that lead to death. </p>
<p>Several studies <a href="https://doi.org/10.1016/j.trsl.2020.08.004">described in one recent review</a> have identified an altered gut microbiome in patients with COVID-19. And some companies including Seres Therapeutics, 4d Pharma PLC, Evelo Biosciences, VEDANTA bioscience, and Finch Therapeutics have recently attracted investor attention for their work on therapies for diseases including cancer, depression and inflammatory bowel diseases.</p>
<p>Identification of specific bacteria within the microbiome that could predict COVID-19 severity is lacking. </p>
<p>To address this question, my colleagues and I recruited COVID-19 hospitalized patients with severe and moderate symptoms. We collected stool and saliva samples to determine whether bacteria within the gut and oral microbiome could predict COVID-19 severity. The identification of microbiome markers that can predict the clinical outcomes of COVID-19 disease is key to help prioritize patients needing urgent treatment. </p>
<p><a href="https://doi.org/10.1101/2021.01.05.20249061">We demonstrated</a>, in a paper which has not yet been peer reviewed, that the composition of the gut microbiome is the strongest predictor of COVID-19 severity compared to patient’s clinical characteristics commonly used to do so. Specifically, we identified that the presence of a bacterium in the stool – called <em>Enterococcus faecalis</em>– was a robust predictor of COVID-19 severity. Not surprisingly, <em>Enterococcus faecalis</em> has been associated with <a href="https://doi.org/10.1053/j.gastro.2011.05.035">chronic</a> <a href="https://doi.org/10.1016/S0002-9440(10)61172-8">inflammation</a>. </p>
<p><em>Enterococcus faecalis</em> collected from feces can be grown outside of the body in clinical laboratories. Thus, an <em>E. faecalis</em> test might be a cost-effective, rapid and relatively easy way to identify patients who are likely to require more supportive care and therapeutic interventions to improve their chances of survival.</p>
<p>But it is not yet clear from our research what is the contribution of the altered microbiome in the immune response to SARS-CoV-2 infection. A recent study has shown that <a href="https://doi.org/10.1101/2020.12.11.416180">SARS-CoV-2 infection triggers an imbalance in immune cells</a> called <a href="https://doi.org/10.1111/imr.12170">T regulatory cells that are critical to immune balance</a>.</p>
<p>[<em>Get our best science, health and technology stories.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-best">Sign up for The Conversation’s science newsletter</a>.]</p>
<p>Bacteria from the gut microbiome are responsible for the <a href="https://doi.org/10.7554/eLife.30916.001">proper activation</a> <a href="https://doi.org/10.1126/science.1198469">of those T-regulatory</a> <a href="https://doi.org/10.1038/nri.2016.36">cells</a>. Thus, researchers like me need to take repeated patient stool, saliva and blood samples over a longer time frame to learn how the altered microbiome observed in COVID-19 patients can modulate COVID-19 disease severity, perhaps by altering the development of the T-regulatory cells. </p>
<p>As a Latina scientist investigating interactions between diet, microbiome and immunity, I must stress the importance of better policies to improve access to healthy foods, which lead to a healthier microbiome. It is also important to design culturally sensitive dietary interventions for Black and Latinx communities. While a good-quality diet might not prevent SARS-CoV-2 infection, it can treat the underlying conditions related to its severity.</p><img src="https://counter.theconversation.com/content/145668/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ana Maldonado-Contreras receives funding from The Helmsley Charitable Trust and her work has been supported by the American Gastroenterological Association. She received The Charles A. King Trust Postdoctoral Research Fellowship. She is also member of the Diversity Committee of the American Gastroenterological Association.</span></em></p>The microbes in your gut influence how your immune system reacts to bacteria and viruses. A severe immune reaction is deadly; a small one lets the virus win. The right balance may depend on your diet.Ana Maldonado-Contreras, Assistant Professor of Microbiology and Physiological Systems, UMass Chan Medical SchoolLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1461822020-11-24T13:08:38Z2020-11-24T13:08:38ZWhy do older people heal more slowly?<figure><img src="https://images.theconversation.com/files/370451/original/file-20201119-17-1fna52z.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5664%2C3780&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The older you get, the more slowly you heal, and there are a number of reasons why.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/graze-at-knees-of-a-girl-royalty-free-image/476877169?adppopup=true">Westend61 via Getty Images</a></span></figcaption></figure><p>I recently visited an 83-year-old patient in the hospital after EMTs rushed her to the ER with an infected leg wound. Her ordeal started inconspicuously when she bumped into the sharp edge of a table and developed a small cut. The patient’s wound didn’t close, but she ignored it until she woke up in pain one morning two weeks after first injuring her leg. Her daughter called 911 after noticing angry, red skin discoloration and pus – both signs of an infection. Our medical team treated her with IV antibiotics and cleared up the infection, but the wound did not fully close until at least a month later, well after she was discharged from the hospital. </p>
<p>How different the story is when children get a cut. They may scream initially, but within days, the scab falls off, revealing new skin. Why was healing so delayed in my 83-year-old patient compared to a healthy child? </p>
<p>The answer is age. Decades of life slow down healing for most tissues, and wounds in skin can offer a window into why this slowdown occurs.</p>
<h2>Three stages of wound healing</h2>
<p>I am physician who <a href="https://www.steinhauserlab.com/">studies how aging predisposes patients to diseases</a> like diabetes and whether behavioral changes such as intermittent fasting may slow down aging. In order to understand why the skin wound in my older patient healed so slowly, it is important to first understand how wounds heal under the ideal conditions of youth.</p>
<p>The wound healing process is classically <a href="https://doi.org/10.1038/nature07039">categorized into three stages</a>.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/370454/original/file-20201119-16-188en5m.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A fresh scrape on a palm right after it occured." src="https://images.theconversation.com/files/370454/original/file-20201119-16-188en5m.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/370454/original/file-20201119-16-188en5m.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/370454/original/file-20201119-16-188en5m.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/370454/original/file-20201119-16-188en5m.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/370454/original/file-20201119-16-188en5m.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/370454/original/file-20201119-16-188en5m.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/370454/original/file-20201119-16-188en5m.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Right after a wound occurs, the inflammatory response begins.</span>
<span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/Wound_healing">Jpbarrass via Wikimedia Commons</a></span>
</figcaption>
</figure>
<p>The first stage is inflammation, essentially the body’s attempt to clean the wound. During the inflammatory phase, <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/phagocytes">immune cells called phagocytes</a> move into the wound, kill any contaminating bacteria, and ingest and dispose of dead cells and debris.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/370456/original/file-20201119-19-uyv7ld.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="An image of a hand with a partially healed scrape." src="https://images.theconversation.com/files/370456/original/file-20201119-19-uyv7ld.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/370456/original/file-20201119-19-uyv7ld.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/370456/original/file-20201119-19-uyv7ld.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/370456/original/file-20201119-19-uyv7ld.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/370456/original/file-20201119-19-uyv7ld.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/370456/original/file-20201119-19-uyv7ld.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/370456/original/file-20201119-19-uyv7ld.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">After a few days, the regenerative phase will be well at work closing the wound.</span>
<span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/Wound_healing">Jpbarrass via Wikimedia Commons</a></span>
</figcaption>
</figure>
<p>Inflammation sets the stage for the regenerative phase, where several processes work in concert to regrow damaged skin. Replacement skin cells are born when cells at the edge of the wound divide, while <a href="https://www.sciencedirect.com/topics/neuroscience/fibroblast">fibroblast cells</a> lay down a supportive scaffolding called <a href="https://www.sciencedirect.com/topics/neuroscience/extracellular-matrix">the extracellular matrix</a>. This holds the new cells together. Any damaged supporting structures of the skin, such as the blood vessels that supply critical oxygen and nutrients, also need to regrow. The second stage effectively closes the wound and restores a protective barrier against bacteria.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/370457/original/file-20201119-14-1sjnond.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A cut on someones hand mostly healed over and scarring." src="https://images.theconversation.com/files/370457/original/file-20201119-14-1sjnond.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/370457/original/file-20201119-14-1sjnond.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/370457/original/file-20201119-14-1sjnond.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/370457/original/file-20201119-14-1sjnond.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/370457/original/file-20201119-14-1sjnond.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/370457/original/file-20201119-14-1sjnond.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/370457/original/file-20201119-14-1sjnond.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Once the wound is fully closed, the remodeling phase will rebuild the tissue in a stronger way.</span>
<span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/Wound_healing">Jpbarrass via Wikimedia Commons</a></span>
</figcaption>
</figure>
<p>The regenerative phase is a relatively quick, but tenuous fix – new skin is fragile. The final remodeling phase plays out over a couple of years as the new skin is progressively strengthened by several parallel processes. The extracellular matrix, which was initially laid down in a haphazard fashion, is broken down and replaced in a more durable way. Any residual cells from prior phases that are no longer needed – such as immune cells or fibroblasts – become inactive or die. In addition to strengthening the new skin, these collective actions also account for the tendency of scars to visibly fade with time. </p>
<h2>Diseases disrupt the healing process</h2>
<p>One major way aging can derail the orderly and efficient progression through the stages of healing is through the health problems that stem from diseases of old age.</p>
<p>Diabetes is one example of a disease that is <a href="https://doi.org/10.1159/000501745">strongly associated with older age</a>. One of the many ways that diabetes negatively affects healing is by causing blood vessels to narrow. As a consequence of inadequate circulation, crucial nutrients and oxygen do not reach the wound in sufficient quantities <a href="https://doi.org/10.1016/j.suc.2020.05.002">to fuel the second regenerative phase</a>.</p>
<p>Diabetes is just one of many age-related diseases that disrupts normal processes in the body such as wound healing.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/370459/original/file-20201119-21-8r8bym.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A graphic showing a cell dividing." src="https://images.theconversation.com/files/370459/original/file-20201119-21-8r8bym.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/370459/original/file-20201119-21-8r8bym.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/370459/original/file-20201119-21-8r8bym.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/370459/original/file-20201119-21-8r8bym.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/370459/original/file-20201119-21-8r8bym.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/370459/original/file-20201119-21-8r8bym.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/370459/original/file-20201119-21-8r8bym.jpg?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">Cell division is a critical part of healing, and when cells lose that ability, healing suffers.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/cell-division-illustration-royalty-free-illustration/562878301?adppopup=true">Andrezj Wojcicki/Science Photo Library</a></span>
</figcaption>
</figure>
<h2>Cells age too</h2>
<p>Aside from the negative impacts of age-associated diseases, cells themselves age. In an extreme sign of aging called cellular senescence, cells <a href="https://doi.org/10.1016/0014-4827(61)90192-6">permanently lose the ability to divide</a>. Senescent cells <a href="https://doi.org/10.1073/pnas.92.20.9363">accumulate in skin</a> and <a href="https://doi.org/10.1126/science.1122446">many other organs</a> as people age and cause a host of problems. </p>
<p>When cells divide more slowly – or when they stop dividing altogether due to senescence – skin becomes thinner. The replacement of fat cells, which form a cushioning layer under the skin, also <a href="https://doi.org/10.1172/jci.insight.90349">declines with age</a>. The skin of older patients is therefore more prone to injury in the first place. </p>
<p>Once an older person’s skin is injured, the skin has a harder time healing properly as well. Aging and senescent immune cells <a href="https://doi.org/10.1038/s41590-017-0006-x">cannot defend against bacteria</a>, and the risk of serious skin infection rises. Then in the regenerative stage, slow rates of cell division translate into slow skin regrowth. My patient exhibited all of these negative effects of age – her thin, almost translucent skin ruptured from a minor bump, became infected and took nearly two months to fully regrow. </p>
<p>But senescent cells are more than just dysfunctional bystanders. For reasons that are not yet fully understood, senescent cells <a href="https://doi.org/10.1038/ncb1909">release toxic byproducts</a> that damage surrounding tissue and drive inflammation – even when there’s no bacterial threat present. Some of these byproducts can even <a href="https://doi.org/10.1038/ncb2784">accelerate senescence in neighboring cells</a>. This suggests that intrinsic aging of cells is in essence contagious and senescent cells actively fuel an uncontrolled cycle of inflammation and tissue damage that further impedes successful regeneration and healing.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/370606/original/file-20201120-23-16jbtxy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A black woman doctor speaking with an older white man." src="https://images.theconversation.com/files/370606/original/file-20201120-23-16jbtxy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/370606/original/file-20201120-23-16jbtxy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=434&fit=crop&dpr=1 600w, https://images.theconversation.com/files/370606/original/file-20201120-23-16jbtxy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=434&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/370606/original/file-20201120-23-16jbtxy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=434&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/370606/original/file-20201120-23-16jbtxy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=546&fit=crop&dpr=1 754w, https://images.theconversation.com/files/370606/original/file-20201120-23-16jbtxy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=546&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/370606/original/file-20201120-23-16jbtxy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=546&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">It’s not just skin that ages; tissues throughout the body lose their healing abilities as people get older.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/black-woman-doctor-talking-to-patient-in-hospital-royalty-free-image/104117233?adppopup=true">David Sacks/TheImageBank via Getty Images</a></span>
</figcaption>
</figure>
<h2>A whole body problem</h2>
<p>As the most outwardly visible tissue of the body, the skin provides a window into why people heal more slowly with age, but all tissues can be injured and are susceptible to the effects of aging. Injuries may be small, repetitive and build up over time – like the effect of smoking on the lungs. Or they may be discrete and dramatic – such as the death of heart cells with a heart attack. Different tissues may heal in different ways. Yet all tissues share a sensitivity to the repercussions of an aging immune system and a decline in the ability to regrow dead or damaged cells. </p>
<p>[<em>Get our best science, health and technology stories.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-best">Sign up for The Conversation’s science newsletter</a>.]</p>
<p>Understanding why healing slows down with age is important, but my patient asked a very practical question that physicians often face in one form or another: “Doctor, what can you do for me?” </p>
<p>Unfortunately, current treatment of wounds is fairly old-fashioned and often ineffective. Some of the options available include wound dressing changes, antibiotics when the wound is infected or treatment in a high oxygen chamber when circulation is bad due to diabetes. </p>
<p>There is hope, though, that medicine can do better and that progress in understanding the aging process will lead to new therapies. Neutralizing senescent cells in mice, for example, <a href="https://doi.org/10.1038/nature16932">improves a variety</a> of <a href="https://doi.org/10.1038/s41586-020-2403-9">age-associated diseases</a>. While it is way too early to say that researchers have discovered the fountain of youth, I am optimistic for a future when physicians will bend the aging curve and make skin and other organs heal faster and better.</p><img src="https://counter.theconversation.com/content/146182/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Matthew Steinhauser receives funding from the National Institutes of Health. He is a member of the American Diabetes Association, the Endocrine Society, and the American Heart Association. In the past five years, he has served as a consultant for Regeneron and Amgen. </span></em></p>Healing is a complicated process. As people age, higher rates of disease and the fact that old cells lose the ability to divide slow this process down.Matthew Steinhauser, Associate Professor of Medicine, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1469842020-11-13T13:41:19Z2020-11-13T13:41:19ZIngredients in flu vaccine won’t hurt you – two pharmacists explain why<figure><img src="https://images.theconversation.com/files/368705/original/file-20201110-15-bwb7pz.jpg?ixlib=rb-1.1.0&rect=0%2C22%2C3000%2C1598&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A man in San Pablo, California, gets a flu shot at a drive-through flu shot clinic Nov. 6, 2014.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/touro-medical-school-student-caitlin-harris-administers-a-news-photo/458535180?adppopup=true">Justin Sullivan/Getty Images</a></span></figcaption></figure><p>Misunderstandings about flu vaccines <a href="https://www.cdc.gov/flu/prevent/misconceptions.htm">have existed</a> for decades, leading to vaccine mistrust and lower-than-ideal vaccination rates. Now that a coronavirus vaccine appears to be close, experts are concerned that the lack of trust and understanding about flu vaccines could translate into lower-than-optimal coronavirus vaccination rates.</p>
<p>In fact, recent surveys suggest that many Americans would not get vaccinated for COVID-19; <a href="https://www.pewresearch.org/science/2020/09/17/u-s-public-now-divided-over-whether-to-get-covid-19-vaccine/">a Pew Research Center study</a> released in September reported that nearly half definitely or probably would not. The persistence of anti-vaccine sentiment, partly based on mistrust of vaccine ingredients, is likely contributing to the hesitancy.</p>
<p>The lack of trust is especially upsetting to public health officials, doctors and other scientists. The issue is especially irksome because a major reason for vaccine reluctance sprang from a <a href="https://time.com/5175704/andrew-wakefield-vaccine-autism/">debunked, retracted and outright false article</a>. </p>
<p>Even though the study was discredited a decade ago, undoing the damage has been difficult. The event showed how easy it is to disseminate incorrect information, particularly over the internet.</p>
<p><a href="https://pharmacy.wsu.edu/directory/terri-levien/">As drug information pharmacists</a>, <a href="https://pharmacy.wsu.edu/directory/anne-kim/">we want</a> to review the ingredients that have caused so much controversy – and to remind you this is a great time to get your flu vaccine. As coronavirus cases soar, threatening not only lives but also the ability of hospitals to care for them, getting a flu vaccine is a crucial part of self-care and health care.</p>
<h2>Flu vaccines 101</h2>
<p>The flu vaccine <a href="https://theconversation.com/getting-a-flu-shot-this-year-is-more-important-than-ever-because-of-covid-19-144034">is different every year</a>; that’s because there are different types of viruses and strains of each virus. The contents of the vaccine depend on the kind of flu that has been circulating in any given year.</p>
<p>The FDA Vaccines and Related Biological Products Advisory Committee <a href="https://www.fda.gov/media/136302/download">determines a vaccine</a> for the coming flu season, using the best scientific evidence at hand to determine which virus strains should be included. </p>
<p>To mass-produce the flu vaccine, a large amount of virus needs to be replicated. Vaccine manufacturers do this in eggs or in animal cell lines from which the virus can be harvested. The final product may contain trace amounts of egg protein. Even individuals with egg allergies can usually receive these vaccines; however, for those with severe allergy to egg proteins, <a href="https://www.cdc.gov/flu/prevent/egg-allergies.htm">flu vaccines that don’t contain egg protein are available</a>.</p>
<h2>Inactivating the virus</h2>
<p>Flu vaccines carry a killed, or dead, version of the virus. In turn, the body mounts an immune response, but <a href="https://theconversation.com/why-the-flu-shot-cannot-give-you-the-flu-and-why-you-should-get-one-now-124257">the vaccine cannot cause the flu</a> because the virus is killed. </p>
<p>One flu vaccine administered as a nasal spray – <a href="https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=64f300d3-e1ba-40bc-a25f-4203ffdb27cf">FluMist</a> – does contain a weakened form of the live virus. In healthy people, <a href="https://theconversation.com/why-the-flu-shot-cannot-give-you-the-flu-and-why-you-should-get-one-now-124257">this won’t cause the flu</a>, but it can cause runny or stuffy nose, headache and sore throat. The live, weakened flu vaccine should not be used if you have a weakened immune system or are caring for someone with a compromised immune system.</p>
<p>Chemical agents are used to inactivate the virus. But the amount of any inactivating agent in the finished flu vaccine is negligible. </p>
<p>One common agent is <a href="https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/common-ingredients-us-licensed-vaccines">formaldehyde</a>. Higher levels of formaldehyde are naturally <a href="https://www.who.int/ipcs/publications/cicad/en/cicad40.pdf">found in fruits</a>. An average apple contains 600 times more formaldehyde than is found in a dose of the flu vaccine. </p>
<figure class="align-center ">
<img alt="The flu vaccine carries only a dead version of the virus." src="https://images.theconversation.com/files/367091/original/file-20201102-28194-swf29q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/367091/original/file-20201102-28194-swf29q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/367091/original/file-20201102-28194-swf29q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/367091/original/file-20201102-28194-swf29q.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/367091/original/file-20201102-28194-swf29q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/367091/original/file-20201102-28194-swf29q.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/367091/original/file-20201102-28194-swf29q.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">Flu vaccines carry a dead version of the virus; the vaccine doesn’t cause the flu.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/pharmacist-giving-customer-flu-shot-royalty-free-image/463247377?adppopup=true">Terry Vine via Getty Images</a></span>
</figcaption>
</figure>
<h2>Keeping the vaccine stable</h2>
<p>Vaccines also must be stabilized to help maintain the effectiveness of the vaccine in case it is exposed to heat, light or moisture, or if it experiences changes in acidity. Vaccine makers use stabilizers such as sucrose, sorbitol, gelatin and monosodium glutamate (MSG). </p>
<p>All are food ingredients found in almost every kitchen. Sucrose and sorbitol are sugars; gelatin, derived from collagen, is used in Jell-O and gummy bears; monosodium glutamate adds flavor to many dishes. And the amount of stabilizer found in flu vaccines is very small. The average person consumes much more of these ingredients per day through normal food consumption. For example, the amount of sugar and gelatin in a vaccine dose is far less than that found in a single gummy bear. And for those with gelatin allergies, a flu vaccine without it is easy to find. </p>
<figure class="align-center ">
<img alt="Adjuvants are often added to flu vaccines to boost immune response." src="https://images.theconversation.com/files/367099/original/file-20201102-27584-1xbtrmm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/367099/original/file-20201102-27584-1xbtrmm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/367099/original/file-20201102-27584-1xbtrmm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/367099/original/file-20201102-27584-1xbtrmm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/367099/original/file-20201102-27584-1xbtrmm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/367099/original/file-20201102-27584-1xbtrmm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/367099/original/file-20201102-27584-1xbtrmm.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">For those over 65, adjuvants can be added to flu vaccines to boost the immune response.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/home-healthcare-nurse-giving-injection-to-senior-royalty-free-image/531179950?adppopup=true">fstop123 via Getty Images</a></span>
</figcaption>
</figure>
<h2>Preservatives</h2>
<p>Vaccines can get contaminated, and to prevent that, thimerosal is sometimes added to prevent bacterial or fungal contamination from using the same vial to deliver multiple doses. The discredited study led many people to believe that thimerosal in vaccines can cause autism. But multiple studies that followed could not establish an association between <a href="https://www.cdc.gov/vaccinesafety/concerns/autism.html">thimerosal-containing vaccines and autism</a>. </p>
<p>Thimerosal contains an organic derivative of mercury called <a href="https://www.cdc.gov/vaccinesafety/concerns/thimerosal/index.html">ethylmercury</a>, one of two types of the element to which people may be exposed. The body eliminates it more easily than the second type, called <a href="https://www.cdc.gov/vaccinesafety/concerns/thimerosal/index.html">methyl mercury</a>, which is found in contaminated fish. </p>
<p>It is true that high exposures to mercury can affect the central nervous system; but the amount of elemental mercury found in a vaccine dose is 25 mcg, which equates to the amount in a 3-ounce can of <a href="https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/thimerosal-and-vaccines#cstat">tuna fish</a>. That said, because thimerosal is found only in multidose vials, it can easily be avoided by receiving a thimerosal-free single-dose flu vaccine. </p>
<h2>Added ingredients</h2>
<p>One flu vaccine, <a href="https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9dbbf304-7be3-4417-8285-a8f5fd20f977">Fluad and Fluad Quadrivalent</a>, is approved to prevent seasonal influenza in adults 65 and older. It contains an extra ingredient, or adjuvant, to boost the immune response. The adjuvant in this vaccine is MF59, an oil-in-water emulsion of squalene oil. </p>
<p><a href="https://www.fda.gov/vaccines-blood-biologics/vaccine-safety-availability/influenza-h5n1-virus-monovalent-vaccine-adjuvanted-manufactured-id-biomedical-corporation-questions#squalene">Squalene</a> is found naturally in plants, animals and the human body. The squalene in the flu vaccine, highly purified, is obtained from shark liver oil. Squalene from shark livers is also present in cosmetics, over-the-counter medicines and dietary health supplements. Each dose of vaccine contains about the amount in 4 teaspoons of olive oil. No severe reactions associated with <a href="https://www.who.int/vaccine_safety/committee/topics/adjuvants/squalene/questions_and_answers/en/">squalene in vaccines</a> have been observed.</p>
<h2>Antibiotics</h2>
<p>Antibiotics are often used in vaccine production to prevent bacterial contamination during manufacturing. In some cases, very small amounts may be in the vaccines. These antibiotics are not the ones commonly associated with severe allergic reactions, such as penicillins, cephalosporins and sulfa drugs. Instead, antibiotics commonly used in flu vaccine manufacturing include neomycin, kanamycin, polymyxin B and gentamicin. </p>
<p>These trace amounts of antibiotics have not been clearly associated with severe <a href="https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/common-ingredients-us-licensed-vaccines">allergic reactions</a>. For those who have experienced an allergic reaction to one of these antibiotics, flu vaccines are available that don’t contain them. </p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p>
<p>Different formulations of the flu vaccine contain a variety of ingredients, but most are in extremely small quantities. They are unlikely to produce negative effects when administered as a single dose once a year. Unless a person has a history of a severe allergic reaction to an ingredient, most flu vaccines can be safely administered. </p>
<p>Centuries ago, the father of toxicology, Paracelsus, said, “What is there that is not poison? All things are poison and nothing is without poison.” Water is healthy for us in appropriate amounts, but too little or too much of it could potentially lead to death. It’s the dose, says Paracelsus, that determines whether or not something is dangerous. Centuries later, consider that sage advice when you think about whether or not to take the flu vaccine.</p><img src="https://counter.theconversation.com/content/146984/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Many people object to the added ingredients in vaccines. But pharmacists explain why those fears are unwarranted.Terri Levien, Professor of pharmacy, Washington State UniversityAnne P. Kim, Clinical assistant professor, Washington State UniversityLicensed as Creative Commons – attribution, no derivatives.