tag:theconversation.com,2011:/uk/topics/vaccine-efficacy-91324/articlesVaccine efficacy – The Conversation2022-03-22T23:23:45Ztag:theconversation.com,2011:article/1797462022-03-22T23:23:45Z2022-03-22T23:23:45ZAs New Zealand relaxes restrictions, here’s what we can still do to limit COVID infections<figure><img src="https://images.theconversation.com/files/453703/original/file-20220322-21-mfo752.jpg?ixlib=rb-1.1.0&rect=18%2C138%2C4007%2C2879&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Phil Walter/Getty Images</span></span></figcaption></figure><p>New Zealanders are about to enjoy cautiously relaxed COVID restrictions under the country’s <a href="https://covid19.govt.nz/traffic-lights/covid-19-protection-framework/">COVID-19 Protection Framework</a>, starting from this weekend.</p>
<p>Prime Minister Jacinda Ardern announced the relaxations today, signalling the end “for now” of vaccine passes, QR codes and vaccine mandates in the education, police and defence sectors from April 4. </p>
<p>Mandates will still apply for health, aged-care, corrections and border control workers, pending more official advice. Settings within the traffic light system have also been revised, but the country remains at the red level and indoor mask use is still required.</p>
<p>New Zealand’s vaccine pass system was designed when we were in the middle of the vaccine rollout, only about one in 400 New Zealanders had had COVID-19, and nobody had even heard of Omicron. </p>
<p>At that time, unvaccinated people had a <a href="https://theconversation.com/your-unvaccinated-friend-is-roughly-20-times-more-likely-to-give-you-covid-170448">much higher risk</a> of catching the virus and spreading it to others. </p>
<p>For this reason, vaccine passes were an important part of safely relaxing the Auckland lockdown. They helped us enjoy a summer with very low case numbers and minimal restrictions. Crucially, this meant we avoided the dual Delta-Omicron epidemic that significantly added to the health burden in places such as <a href="https://www.stuff.co.nz/national/explained/127440590/covid19-the-nsw-omicron-outbreak-is-not-what-you-think">New South Wales</a>. </p>
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<p>The situation we face today is very different. Vaccines remain highly effective at preventing severe illness but aren’t as good at stopping people catching Omicron. And the protection they do provide against infection wanes fairly quickly. </p>
<p>At the same time, increasing numbers of people have some temporary immunity as a result of having had the virus. This means vaccine passes are far less effective as a public health intervention now than they were a few months ago. </p>
<p>But as vaccine passes are phased out, it is important to consider what measures we can use to reduce transmission.</p>
<h2>Vaccines still work</h2>
<p>Vaccines are still highly effective at preventing severe illness and death from COVID-19. Like New Zealand, Hong Kong is now experiencing a major Omicron wave after initially following an elimination strategy. But in the last two months, Hong Kong has had close to 4,000 deaths per five million people compared to New Zealand’s 130. </p>
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<p>Why such a big difference? Vaccines. Hong Kong has much <a href="https://www.ft.com/content/6e610cac-400b-4843-a07b-7d870e8635a3">lower vaccine coverage in older groups</a> than New Zealand does. </p>
<p>But it’s clear vaccines are less effective at preventing infection with Omicron. The <a href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1061532/Vaccine_surveillance_report_-_week_11.pdf">UK Health Security Agency</a> estimates the effectiveness of two doses of the Pfizer vaccine against symptomatic COVID-19 drops to just 10% after about 25 weeks following the second dose. This jumps to 65% after a booster but also wanes quite quickly to around 40% 15 weeks later.</p>
<p>The proportion of unvaccinated people testing positive is <a href="https://www.newsroom.co.nz/tracking-omicron-in-new-zealand-latest-charts-and-data">not that different</a> from fully vaccinated people. So if you go to a cafe, a hairdressers or a bar, whether or not there are unvaccinated people there makes little difference to your risk of catching the virus.</p>
<p>Other risk factors are more important: are people wearing masks, is it crowded, is the venue well ventilated or outdoors, are people staying away if they have symptoms? </p>
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Read more:
<a href="https://theconversation.com/most-covid-patients-in-nzs-omicron-outbreak-are-vaccinated-but-thats-no-reason-to-doubt-vaccine-benefits-179648">Most COVID patients in NZ's Omicron outbreak are vaccinated, but that's no reason to doubt vaccine benefits</a>
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<h2>We still need public health measures to mitigate COVID</h2>
<p>The <a href="https://theconversation.com/to-be-truly-ethical-vaccine-mandates-must-be-about-more-than-just-lifting-jab-rates-169612">limitations</a> the vaccine pass system has placed on people’s freedoms are much harder to justify now. But that doesn’t mean we can end all vaccination requirements or remove all public health measures.</p>
<p>COVID-19 is an airborne disease but a comparison with diseases spread through contaminated water is useful. The spread of cholera from contaminated water is one of the earliest examples of an <a href="https://www.ph.ucla.edu/epi/snow/snowcricketarticle.html">effective public health response</a> to an infectious disease. </p>
<p>The first response was a “boil water” notice, the equivalent of mask wearing to prevent the spread of infections. Longer-term measures involve systemic changes, such as infrastructure for clean water or, in the case of COVID, infrastructure for <a href="https://www.reuters.com/world/europe/italian-study-shows-ventilation-can-cut-school-covid-cases-by-82-2022-03-22/">clean air</a> through ventilation and filtration. </p>
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Read more:
<a href="https://theconversation.com/no-catching-omicron-is-not-inevitable-heres-why-we-should-all-still-avoid-the-virus-178276">No, catching Omicron is not 'inevitable' – here's why we should all still avoid the virus</a>
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<p>The time to remove boil-water notices is not when case numbers are peaking, or even when they are back at half of their peak level. It is when there are sufficient systemic changes in place to keep people safe.</p>
<p>Similarly, isolation periods are intended to stop people from infecting others. For Omicron, studies suggest half of all cases were still <a href="https://dash.harvard.edu/handle/1/37370587">infectious on day five</a> and the infectious period may be as long as ten days. Given wider availability of rapid antigen tests, we could introduce a test-to-return policy to require a negative test before people leave isolation. </p>
<h2>Some vaccine mandates remain</h2>
<p>People working in specific high-risk situations, like healthcare and aged residential care, will still be required to be up to date with their vaccinations to protect the vulnerable people they work with. </p>
<p>We are currently in the middle of a major Omicron wave, with hospitalisations and deaths at record levels. At least as many people will get infected on the way down from the peak as on the way up. </p>
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Read more:
<a href="https://theconversation.com/evidence-supports-mandatory-covid-vaccination-for-aged-care-workers-but-we-need-to-make-it-easier-too-163569">Evidence supports mandatory COVID vaccination for aged-care workers. But we need to make it easier too</a>
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<p>And even when this wave subsides, COVID-19 isn’t going to go away. It’s likely we will continue to see daily case numbers in the thousands for some time. Added to other respiratory illnesses like influenza and RSV, this could cause significant strain on healthcare over the winter months. </p>
<p>Altogether, this means we still need <a href="https://blogs.otago.ac.nz/pubhealthexpert/covid-19-hospitalisations-now-peaking-in-aotearoa-nz-but-key-covid-19-control-measures-still-need-to-be-maintained/">a set of sustainable mitigations</a> to reduce transmission and the health impacts of the virus. This includes strategies to address <a href="https://www.stuff.co.nz/pou-tiaki/300482666/government-breached-treaty-principles-in-covid19-response-waitangi-tribunal-finds">vaccine inequity</a> and increase booster uptake, mask use when cases are high, better ventilation and adequate financial support for people to take time off work when they are sick. </p>
<p>COVID vaccine passes have outlived their usefulness at least for now. But COVID-19 is going to be with us for the forseeable future.</p><img src="https://counter.theconversation.com/content/179746/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael Plank is affiliated with the University of Canterbury and is funded by the New Zealand Government for mathematical modelling of Covid-19.</span></em></p><p class="fine-print"><em><span>Dion O'Neale receives funding from the NZ Department of Prime Minister and Cabinet for providing modelling and analysis related to COVID-19 and from the NZ Health Research Council for research on modeling and equity impacts of COVID-19 in Aotearoa. He is affiliated with COVID Modelling Aotearoa, The University of Auckland, and Te Pūnaha Matatini. </span></em></p><p class="fine-print"><em><span>Emily Harvey receives funding from the NZ Department of Prime Minister and Cabinet for providing modelling and analysis related to COVID-19 and from the NZ Health Research Council for research on modeling and equity impacts of COVID-19 in Aotearoa. She is affiliated with COVID-19 Modelling Aotearoa, ME Research, Te Pūnaha Matatini, and the University of Auckland.</span></em></p>Vaccine passes have outlived their usefulness, at least for now. But as New Zealand’s Omicron wave begins to subside, other public health measures remain vitally important.Michael Plank, Professor in Applied Mathematics, University of CanterburyDion O'Neale, Project Lead - COVID Modeling Aotearoa; Senior Lecturer - Department of Physics, University of Auckland; Principal Investigator - Te Pūnaha Matatini, University of Auckland, Waipapa Taumata RauEmily Harvey, Principal Investigator, Te Pūnaha Matatini, University of Auckland, Waipapa Taumata RauLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1796482022-03-22T04:39:44Z2022-03-22T04:39:44ZMost COVID patients in NZ’s Omicron outbreak are vaccinated, but that’s no reason to doubt vaccine benefits<figure><img src="https://images.theconversation.com/files/453511/original/file-20220322-15-195s6ta.jpg?ixlib=rb-1.1.0&rect=50%2C0%2C4786%2C2915&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Hannah Peters/Getty Images</span></span></figcaption></figure><p>New Zealand’s Omicron wave may be peaking, but we’ll continue to record thousands of new <a href="https://www.health.govt.nz/news-media/news-items/14463-community-cases-1000-hospitalisations-33-icu-9-deaths-reported-today-more-4-million-people">cases</a> each day and most people who test positive or are hospitalised with COVID will have been vaccinated. </p>
<p>This is exactly what we should expect and it’s no reason to doubt vaccine effectiveness.</p>
<p>The principal reason why a lot of COVID cases are vaccinated is because most New Zealanders are now vaccinated. As of today, about 94% of people 12 years and older have had two or more vaccine doses, and even if their risk of catching COVID is significantly lower than for an unvaccinated person, they vastly outnumber those who aren’t. </p>
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<p>In the week ending March 13, about 93% of the 118,000 confirmed cases 12 years and older were in people with two or more doses. But such crude proportions of cases aren’t all that good an indicator of vaccine effectiveness. </p>
<p>Last year, during the Delta outbreak, the proportions were misleading in the other direction. The rate of cases in people who were unvaccinated was about 20 times that in vaccinated people. </p>
<p>Unfortunately, some commentators talked about that ratio as if it was all a real benefit of vaccination. It <a href="https://www.statschat.org.nz/2021/11/22/vaccinate-for-the-holidays/">wasn’t</a>. </p>
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Read more:
<a href="https://theconversation.com/how-effective-are-covid-19-vaccines-heres-what-the-stats-mean-and-what-they-dont-164755">How effective are COVID-19 vaccines? Here's what the stats mean … and what they don't</a>
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<p>The outbreak in Auckland was nearly under control and was spreading among unvaccinated people partly because they had less resistance to infection, but also because they were more likely to come into contact with infected people. Social clustering leads to disease clustering.</p>
<h2>What case numbers can tell us</h2>
<p>For Delta, two doses of the vaccine produced <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2108891">very good immunity</a>, especially in the short term. The vaccine is less effective for <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2119451">Omicron</a>; two doses give only partial immunity even in the short term, and the effectiveness wears off over time. </p>
<p>About 60% of people 12 years and older have had a booster dose, and in the week ending March 13, only 42% of cases were in people who had been boosted. We can see that boosters help.</p>
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<p>Counting cases remains important, because even a non-hospitalised case of COVID can be unpleasant, and because we don’t know how likely a mild case is to lead to long COVID and months or years of disability. We can’t draw strong conclusions from numbers of cases, though. </p>
<p>Many cases, probably most cases, are not being diagnosed at the moment. Unvaccinated people will be less likely to get tested, especially in mild cases of the disease, either because of poor access to the health system or because they don’t think COVID is important. We can’t really tell how much bias this introduces into the numbers.</p>
<p>Hospitalisations and deaths are much more reliably counted than cases. Results from clinical trials and careful population studies of COVID vaccines consistently show the vaccines to be more effective in preventing more serious disease, especially with the new variants. There are plausible biological explanations for this, based on different parts of our immune response. </p>
<p><a href="https://www.nature.com/articles/d41586-022-00063-0">Antibodies against the COVID virus</a> seem to be affected more by differences between strains than T-cells are; antibodies are probably more important for preventing initial infection and less important for fighting serious disease.</p>
<h2>More benefit in protecting from serious disease</h2>
<p>When we look at hospitalisations and deaths, the difference between vaccinated and unvaccinated people is much more dramatic. In the week ending March 13, 65% of people over 12 hospitalised were vaccinated, compared to 94% in the population; 32% had a booster dose, compared to 60% in the population. The 5% of unvaccinated people over 12 contributed 20% of hospitalisations. </p>
<p>The number of deaths is, fortunately, too small for the Ministry of Health to publish detailed weekly breakdowns, but vaccinated people are a minority over the period since August.</p>
<p>The relatively small number of deaths in New Zealand’s Omicron wave also shows the effectiveness of the vaccine. Hong Kong had largely eliminated COVID until Omicron; they are now getting a large outbreak similar to New Zealand’s, but only in the number of cases. Over the past week, Hong Kong averaged 280 deaths per day, in a population less than twice that of New Zealand. </p>
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<p>The vaccination rate in Hong Kong is <a href="https://twitter.com/jburnmurdoch/status/1503420660869214213">much lower</a>. About 71% are fully vaccinated and only 30% have had a booster. Among elderly people, who are at much greater risk from COVID, the vaccination rate is especially lower, with two-thirds of people over 80 and more than a third of those aged 70-80 having been unvaccinated when Omicron hit.</p>
<h2>Towards fair comparisons</h2>
<p>Comparing across whole populations this way gives some indication of the vaccine benefit, but it is very imprecise. We don’t choose randomly who gets the vaccine and who doesn’t. </p>
<p>In New Zealand, for example, essentially everyone over 75 has been vaccinated. Since people over 75 are much more likely to need hospital care than younger people, the higher vaccination rate in people over 75 makes the vaccine look less effective than it really is. </p>
<p>Statisticians call this “confounding by indication”. Auckland has always had more exposure to new outbreaks and had higher vaccination rates than the rest of the country; this again tends to make the vaccine look less effective that it really is.</p>
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Read more:
<a href="https://theconversation.com/how-does-the-immune-system-mobilize-in-response-to-a-covid-19-infection-or-a-vaccine-5-essential-reads-179060">How does the immune system mobilize in response to a COVID-19 infection or a vaccine? 5 essential reads</a>
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<p>More reliable comparisons require either random allocation of vaccine to people, as in the clinical trials performed before the vaccines were approved, or careful statistical matching of vaccinated and unvaccinated groups to get a fair comparison. </p>
<p>Omicron is too recent to have useful clinical trial data, but peer-reviewed statistical analyses of individual case data from the <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2119451">United Kingdom</a>, the <a href="https://www.bmj.com/content/376/bmj-2021-069761">United States</a>, and <a href="https://www.nejm.org/doi/full/10.1056/NEJMc2119270">South Africa</a> all agree the vaccines are beneficial. </p>
<p>There’s some evidence vaccination also <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00460-6/fulltext">reduces the risk and severity of long COVID</a>, the most likely bad outcome for healthy people. But there obviously hasn’t been time to do this sort of comparison specifically for the Omicron variant.</p>
<p>Overall, the most reliable comparisons between vaccinated and unvaccinated people have consistently shown a benefit of vaccination. The effectiveness of the vaccines does wear off over time, and the effectiveness is lower against Omicron than it was against Delta or the original COVID strain, but it still improves your chances of avoiding infection, keeping out of hospital and making a full recovery.</p><img src="https://counter.theconversation.com/content/179648/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Thomas Lumley 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>For hospitalisations and deaths, the difference between vaccinated and unvaccinated people is more dramatic. Only 5% of New Zealanders are unvaccinated, but they account for 20% of hospitalisations.Thomas Lumley, Professor of Biostatistics, University of Auckland, Waipapa Taumata RauLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1764472022-02-07T19:09:26Z2022-02-07T19:09:26ZWhat’s the difference in protection against Omicron between 2 doses and 3 doses of vaccine?<p>Australian Health Minister Greg Hunt <a href="https://www.skynews.com.au/australia-news/coronavirus/health-minister-greg-hunt-expects-atagi-will-redefine-fully-vaccinated-to-include-three-covid19-jabs/news-story/a5750dae90a4b19c6335c6c3e31a92a9">said last week</a> he expects the Australian Technical Advisory Group on Immunisation (ATAGI) to change the definition of “fully vaccinated” to three doses instead of two.</p>
<p>It comes as evidence emerges suggesting the highly infectious Omicron variant has the ability to escape the protection two vaccine doses offer.</p>
<p>So, how effective are two doses compared to three against Omicron?</p>
<p>Let’s break it down.</p>
<h2>Two doses don’t protect much against Omicron</h2>
<p>Vaccine protection against Omicron is reduced for two reasons.</p>
<p>First, antibodies generated by vaccination <a href="https://media.nature.com/original/magazine-assets/d41586-021-02532-4/d41586-021-02532-4.pdf">gradually wane</a> over time. There are now many countries that are more than a year into their COVID vaccine rollout, so many people have received their second COVID jab over six months ago.</p>
<p>Without boosting, their antibody levels will have dropped significantly. Australia was a little slower off the mark – but now finds itself in a similar situation.</p>
<p>The second reason is Omicron can escape vaccine-induced immunity because of its constellation of mutations. Its spike protein (the bit that helps the virus access our cells) is significantly different to Delta’s, and to the original virus from which our vaccines are based. </p>
<p>The critical part of the spike protein is the “receptor binding domain”. It latches onto a protein on our cells called ACE-2 so the virus can gain entry. Delta had two mutations in the receptor binding domain, and Beta had three. Omicron has <a href="https://www.nature.com/articles/d41586-022-00292-3">15 mutations</a> in its receptor binding domain. As a result, only some of the antibodies the vaccine induces will still bind to Omicron’s spike and inhibit it getting into your cells.</p>
<p>For these reasons, emerging evidence suggests two doses of a COVID vaccine provide just <a href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1050721/Vaccine-surveillance-report-week-4.pdf">0-10% protection against infection with Omicron</a> five to six months after the second jab.</p>
<p>So, you really cannot claim you are “fully vaccinated” with just two doses now, particularly if it’s been months since your second dose.</p>
<p>Some protection against severe disease and hospitalisation remains. UK data suggests two doses of AstraZeneca or Pfizer offer <a href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1050721/Vaccine-surveillance-report-week-4.pdf">around 35% protection against hospitalisation</a> by six months after the second dose.</p>
<h2>What about three doses?</h2>
<p>Having a booster dose bumps up your antibodies – which is particularly important for Omicron because only some of those antibodies are protective. Emerging evidence suggests protection from symptomatic Omicron infection is <a href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1050721/Vaccine-surveillance-report-week-4.pdf">restored to 60-75%</a> two to four weeks after a Pfizer or Moderna booster dose.</p>
<p>However, third-dose protection also wanes, down to <a href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1050721/Vaccine-surveillance-report-week-4.pdf">30-40% against Omicron infection</a> after 15 weeks. </p>
<p>So, unfortunately breakthrough infections will still be common. Fortunately, protection against hospitalisation remains much higher, up around 90% after a Pfizer booster dose and only <a href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1050721/Vaccine-surveillance-report-week-4.pdf">dropping to 75% after 10-14 weeks</a>, and 90-95% up to nine weeks after a Moderna booster. </p>
<p><a href="https://www.cnbc.com/2022/01/10/covid-vaccine-pfizer-ceo-says-omicron-vaccine-will-be-ready-in-march.html">Pfizer</a> and <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/moderna-ceo-says-data-omicron-specific-shot-likely-available-march-2022-01-17/">Moderna</a> are currently developing vaccines matched to Omicron, which if approved, should induce better immunity against this variant.</p>
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Read more:
<a href="https://theconversation.com/will-an-omicron-specific-vaccine-help-control-covid-theres-one-key-problem-175137">Will an Omicron-specific vaccine help control COVID? There's one key problem</a>
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<h2>Will we need a new dose every three months?</h2>
<p>Israel is currently rolling out <a href="https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00010-8/fulltext">fourth Pfizer doses</a> to some high-risk groups. </p>
<p>Some people will be concerned this trend means we’ll need a new dose every few months. But I don’t think that will be the case.</p>
<p>We can’t keep boosting people every few months chasing waning immunity. It’s likely after each round of boosting, faith in the vaccines will diminish. It’s worth remembering we have never tried to vaccinate against a respiratory coronavirus so we are still learning about how to best generate protective immunity. </p>
<p>There’s also the ethical question of rolling out multiple rounds of booster doses in wealthy countries when many people in some parts of the world haven’t received their first two doses yet.</p>
<p>While there are high levels of infection in countries with low rates of vaccination, all countries remain at risk of outbreaks, particularly if new viral variants emerge – which is sure to happen while there’s so much transmission globally. </p>
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Read more:
<a href="https://theconversation.com/israel-is-rolling-out-fourth-doses-of-covid-vaccines-should-australia-do-the-same-176145">Israel is rolling out fourth doses of COVID vaccines. Should Australia do the same?</a>
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<p>But better vaccines are coming. Universal COVID vaccines <a href="https://www.nejm.org/doi/full/10.1056/nejmp2118468">are in development</a>, which target areas of the virus that don’t easily mutate, meaning they’ll likely be effective across different variants.</p>
<p>In the future, we may get a yearly COVID vaccine combined with the flu vaccine. Treatments will improve, too, so you can minimise symptoms at home. </p>
<p>These developments will reduce the impact the virus has on us, so eventually COVID will stabilise to a predictable level of transmission that doesn’t cause disruption – that is, it becomes endemic.</p>
<p>Your existing immunity will be boosted with naturally acquired infections every year or so that will almost always be asymptomatic or very low (cold-like) symptoms. </p>
<p>However, for those more vulnerable, such as the elderly and those who are immune compromised or have chronic diseases, vaccines are less effective and the virus will still be able to cause severe illness and death, similar to the flu. So we need to continue to progress research into new treatment approaches that will better protect these individuals. </p>
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<h2>A silver lining</h2>
<p>One silver lining from COVID has been intensified research efforts towards vaccines and treatments. </p>
<p>We’re seeing multiple new anti-viral drugs being approved which will reduce disease and death.</p>
<p>Some of these treatments are likely to be effective across different viruses, not just COVID.</p>
<p>And mRNA vaccine technology can churn out new vaccines in a matter of months, which was completely inconceivable two years ago.</p>
<p>All this means we’re better prepared against COVID, but also future respiratory virus outbreaks and pandemics, whether that’s a new coronavirus, influenza virus or any of the multitude of other respiratory viruses out there.</p><img src="https://counter.theconversation.com/content/176447/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nathan Bartlett 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>Emerging evidence suggests the highly infectious Omicron variant has the ability to escape the protection two vaccine doses offer.Nathan Bartlett, Associate Professor, School of Biomedical Sciences and Pharmacy, University of NewcastleLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1735542021-12-15T19:49:31Z2021-12-15T19:49:31ZHow effective are vaccines against omicron? An epidemiologist answers 6 questions<figure><img src="https://images.theconversation.com/files/437635/original/file-20211214-15-12p1fq7.jpg?ixlib=rb-1.1.0&rect=134%2C0%2C5856%2C3880&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Understanding how much protection a vaccine offers is not as simple as it sounds.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/covid-19-vaccine-royalty-free-image/1287544065?adppopup=true">Andriy Onufriyenko/Moment via Getty Images</a></span></figcaption></figure><p><em>The pandemic has brought many tricky terms and ideas from epidemiology into everyone’s lives. Two particularly complicated concepts are vaccine <a href="https://theconversation.com/pfizer-vaccine-what-an-efficacy-rate-above-90-really-means-149849">efficacy and effectiveness</a>. These are not the same thing. And as time goes on and new variants like omicron emerge, they are changing, too. Melissa Hawkins is an <a href="https://www.american.edu/cas/faculty/mhawkins.cfm">epidemiologist and public health researcher</a> at American University. She explains the way researchers calculate how well a vaccine prevents disease, what influences these numbers and how omicron is changing things.</em></p>
<h2>1. What do vaccines do?</h2>
<p>A <a href="https://www.cdc.gov/vaccinesafety/ensuringsafety/history/index.html">vaccine</a> activates 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">immune system to produce antibodies</a> that remain in your body to fight against exposure to a virus in the future. All three vaccines currently approved for use in the U.S. – the Pfizer-BioNTech, Moderna and Johnson & Johnson vaccines – showed <a href="https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html">impressive success in clinical trials</a>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/437637/original/file-20211214-19-kx4h5b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A medical professional getting a shot." src="https://images.theconversation.com/files/437637/original/file-20211214-19-kx4h5b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/437637/original/file-20211214-19-kx4h5b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/437637/original/file-20211214-19-kx4h5b.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/437637/original/file-20211214-19-kx4h5b.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/437637/original/file-20211214-19-kx4h5b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/437637/original/file-20211214-19-kx4h5b.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/437637/original/file-20211214-19-kx4h5b.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">Clinical trials are used to calculate the efficacy of a vaccine but don’t necessarily represent real-world conditions.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/VirusOutbreakGeorgiaVaccineTrial/47e7e14cbd864228b79581d3e5bd8c23/photo?Query=vaccine%20trial&mediaType=photo&sortBy=&dateRange=Anytime&totalCount=605&currentItemNo=5">AP Photo/Ben Gray</a></span>
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<h2>2. What is the difference between vaccine efficacy and effectiveness?</h2>
<p>All new vaccines must undergo clinical trials in which researchers test the vaccines on thousands of people to examine how well they work and whether they are safe. </p>
<p><a href="https://www.cdc.gov/csels/dsepd/ss1978/lesson3/section6.html">Efficacy</a> is the measure of <a href="https://theconversation.com/pfizer-vaccine-what-an-efficacy-rate-above-90-really-means-149849">how well a vaccine works</a> in clinical trials. Researchers design the trials to include two groups of people: those who receive the vaccine and those who receive a placebo. They calculate the vaccine’s efficacy by comparing how many cases of the illness occur in each group, vaccinated versus placebo.</p>
<p><a href="https://www.cdc.gov/csels/dsepd/ss1978/lesson3/section6.html">Effectiveness</a>, on the other hand, describes how well a vaccine performs in the real world. It is calculated the same way, by comparing illness among vaccinated and unvaccinated people.</p>
<p>Efficacy and effectiveness are usually close to each other but won’t necessarily be the same. How the vaccines work will vary a bit from the trial results once millions of people are getting vaccinated.</p>
<p>Many factors influence how a vaccine performs in the real world. New variants like delta and omicron may change things. The number and age of people enrolled in the trials matter. And the health of those receiving the vaccine is also important.</p>
<p><a href="https://doi.org/10.1001/jamapsychiatry.2021.2497">Vaccine uptake</a> – the proportion of a population that gets vaccinated – can also influence vaccine effectiveness. When a large enough proportion of the population is vaccinated, herd immunity begins to come into play. Vaccines with <a href="https://www.cdc.gov/flu/vaccines-work/effectivenessqa.htm">moderate or even low efficacy can work very well</a> at a population level. Likewise, vaccines with high efficacy in clinical trials, like coronavirus vaccines, may have <a href="https://www.nature.com/articles/d41586-021-00728-2">lower effectiveness</a> and a small impact if there isn’t high vaccine uptake in the population.</p>
<p>The distinction between efficacy and effectiveness is important, because one describes the risk reduction achieved by the vaccines under trial conditions and the other describes how this may vary in populations with different exposures and transmission levels. Researchers can calculate both, but they can’t design a study that will measure both simultaneously. </p>
<h2>3. How do you calculate efficacy and effectiveness?</h2>
<p>Both <a href="https://pubmed.ncbi.nlm.nih.gov/33301246/">Pfizer</a> and <a href="https://www.cdc.gov/mmwr/volumes/69/wr/mm695152e1.htm?s_cid=mm695152e1_w">Moderna</a> reported that their vaccines demonstrated more than 90% efficacy in preventing symptomatic COVID-19 infection. Stated another way, among those individuals who received the vaccine in the clinical trials, the risk of getting COVID-19 was reduced by 90% compared with those who did not receive the vaccine. </p>
<p>Imagine conducting a vaccine trial. You randomize 1,000 people to receive the vaccine in one group. You randomize another 1,000 to be given a placebo in the other group. Say 2.5% of people in the vaccinated group get COVID-19 compared with 50% in the unvaccinated group. That means the vaccine has 95% efficacy. We determine that because (50% – 2.5%)/50% = .95. So 95% indicates the reduction in the proportion of disease among the vaccinated group. However, a vaccine with 95% efficacy does not mean 5% of vaccinated people will get COVID-19. It’s even better news: Your risk of illness is reduced by 95%.</p>
<p>Vaccine effectiveness is calculated the exact same way but is determined through <a href="https://dx.doi.org/10.17269%2Fs41997-021-00554-z">observational studies</a>. Early on, vaccines were well over <a href="https://www.statnews.com/2021/03/29/real-world-study-by-cdc-shows-pfizer-and-moderna-vaccines-were-90-effective/">90% effective</a> at preventing severe illness in the real world. But, by their very nature, <a href="https://doi.org/10.1038/d41586-021-03619-8">viruses change</a>, and this can change effectiveness. For example, a study found that by August 2021, when delta was surging, the Pfizer vaccine was <a href="http://dx.doi.org/10.15585/mmwr.mm7034e3">53% effective at preventing severe illness in nursing home residents</a> who had been vaccinated in early 2021. Age, health issues, waning immunity and the new strain all lowered effectiveness in this case.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/437638/original/file-20211214-23-1e9wqqp.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A model of the coronavirus." src="https://images.theconversation.com/files/437638/original/file-20211214-23-1e9wqqp.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/437638/original/file-20211214-23-1e9wqqp.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/437638/original/file-20211214-23-1e9wqqp.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/437638/original/file-20211214-23-1e9wqqp.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/437638/original/file-20211214-23-1e9wqqp.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/437638/original/file-20211214-23-1e9wqqp.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/437638/original/file-20211214-23-1e9wqqp.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">New variants of the coronavirus are all slightly different from the original strain that vaccines were based on, so immunity to variants may be different.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Coronavirus._SARS-CoV-2.png#/media/File:Coronavirus._SARS-CoV-2.png">Alexey Solodovnikov, Valeria Arkhipova/WikimediaCommons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<h2>4. What about the omicron variant?</h2>
<p>The preliminary data about omicron and vaccines is <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/pfizer-covid-19-vaccine-partially-protective-against-omicron-bloomberg-news-2021-12-07/">coming in quickly</a> and is revealing lower vaccine effectiveness. Best estimates suggest vaccines are around <a href="https://www.medpagetoday.com/special-reports/exclusives/96172">30%-40% effective at preventing infections</a> and <a href="https://www.reuters.com/business/healthcare-pharmaceuticals/pfizer-vaccine-protecting-against-hospitalisation-during-omicron-wave-study-2021-12-14/">70% effective at preventing severe disease</a>.</p>
<p>A <a href="https://www.medrxiv.org/content/10.1101/2021.12.07.212%2067432v1">preprint study</a> – one not formally reviewed by other scientists yet – that was conducted in Germany found that antibodies in blood collected from people fully vaccinated with Moderna and Pfizer showed <a href="https://doi.org/10.1038/d41586-021-03672-3">reduced efficacy in neutralizing the omicron variant</a>. Other small preprint <a href="https://doi.org/10.1101/2021.12.08.21267417">studies in South Africa</a> and <a href="https://www.medrxiv.org/content/10.1101/2021.12.10.21267534v1.full">England</a> showed a significant decrease in how well antibodies target the omicron variant. More <a href="https://www.npr.org/sections/goatsandsoda/2021/12/14/1063947940/vaccine-protection-vs-omicron-infection-may-drop-to-30-but-does-cut-severe-disea">breakthough infections are expected</a>, with decreased immune system ability to recognize omicron compared with other variants. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/437636/original/file-20211214-15-862uwa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A sign outside of a pharmacy saying vaccines are available for walk-in appointments." src="https://images.theconversation.com/files/437636/original/file-20211214-15-862uwa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/437636/original/file-20211214-15-862uwa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/437636/original/file-20211214-15-862uwa.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/437636/original/file-20211214-15-862uwa.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/437636/original/file-20211214-15-862uwa.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/437636/original/file-20211214-15-862uwa.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/437636/original/file-20211214-15-862uwa.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">Most people in the U.S. are now eligible to get a booster coronavirus vaccine which could help protect against the omicron variant.</span>
<span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/VirusOutbreakIllinois/07e30f89e82f47a8a6a575d3c2e8080b/photo?Query=booster%20vaccine%20sign&mediaType=photo&sortBy=&dateRange=Anytime&totalCount=50&currentItemNo=4">AP Photo/Nam Y. Huh</a></span>
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<h2>5. Do boosters boost immunity against omicron?</h2>
<p>Initial data reinforces that <a href="https://theconversation.com/should-i-get-my-covid-vaccine-booster-yes-it-increases-protection-against-covid-including-omicron-172965">a third dose would help boost</a> immune response and protection against omicron, with estimates of <a href="https://www.cnbc.com/2021/12/10/boosters-give-70percent-75percent-protection-against-mild-disease-from-omicron-uk-health-security-agency-says.html">70%-75% effectiveness</a>. </p>
<p><a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-provide-update-omicron-variant">Pfizer has reported</a> that people who have received two doses of its vaccine are susceptible to infection from omicron, but that a <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-provide-update-omicron-variant">third shot improves antibody activity against the virus</a>. This was based on lab experiments using the blood of people who have received the vaccine. </p>
<p>Booster doses can increase the amount of antibodies and the ability of a person’s immune system to protect against omicron. However, unlike the U.S., much of the <a href="https://ourworldindata.org/covid-vaccinations">world does not have access</a> to booster doses.</p>
<h2>6. What does this all mean?</h2>
<p>Despite the lowered effectiveness of vaccines against omicron, it is clear that vaccines do work and are among the <a href="https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6019a5.htm">greatest public health achievements</a>. Vaccines have varying levels of effectiveness and are still useful. The flu vaccine is usually <a href="https://www.cdc.gov/flu/vaccines-work/vaccineeffect.htm">40%-60% effective</a> and prevents illness in millions of people and hospitalizations in more than 100,000 people in the U.S. <a href="https://www.cdc.gov/flu/about/burden-averted/2019-2020.htm">annually</a>.</p>
<p>Finally, vaccines protect not only those who are vaccinated, but those who can’t get vaccinated as well. Vaccinated people are <a href="https://theconversation.com/no-vaccinated-people-are-not-just-as-infectious-as-unvaccinated-people-if-they-get-covid-171302">less likely to spread</a> COVID-19, which reduces new infections and offers protection to society overall.</p>
<p>[<em><a href="https://memberservices.theconversation.com/newsletters?nl=science&source=inline-science-corona-important">Get The Conversation’s most important coronavirus headlines, weekly in a science newsletter</a></em>]</p><img src="https://counter.theconversation.com/content/173554/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Melissa Hawkins receives funding from USDA/NIFA. </span></em></p>For a number of reasons, as time goes on vaccines become less effective. So how do researchers calculate how well vaccines are working?Melissa Hawkins, Professor of Public Health, American UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1695132021-10-15T11:34:57Z2021-10-15T11:34:57ZHow many lives have coronavirus vaccines saved? We used state data on deaths and vaccination rates to find out<figure><img src="https://images.theconversation.com/files/425999/original/file-20211012-15-dzt98d.jpg?ixlib=rb-1.1.0&rect=145%2C218%2C5246%2C3370&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Clinical trials demonstrate how effective vaccines are individually, but the real world shows how effective they are at a population level.</span> <span class="attribution"><a class="source" href="https://newsroom.ap.org/detail/APTOPIXVirusOutbreakPfizerVaccineNewYork/f7e1e80cffb948e9aeca625578ba6487/photo?Query=pfizer%20AND%20vaccine&mediaType=photo&sortBy=&dateRange=Anytime&totalCount=4431&currentItemNo=8">AP Photo/Mark Lennihan, Pool</a></span></figcaption></figure><figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/426256/original/file-20211013-27-1g7zmpv.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/426256/original/file-20211013-27-1g7zmpv.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/426256/original/file-20211013-27-1g7zmpv.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=255&fit=crop&dpr=1 600w, https://images.theconversation.com/files/426256/original/file-20211013-27-1g7zmpv.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=255&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/426256/original/file-20211013-27-1g7zmpv.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=255&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/426256/original/file-20211013-27-1g7zmpv.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=321&fit=crop&dpr=1 754w, https://images.theconversation.com/files/426256/original/file-20211013-27-1g7zmpv.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=321&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/426256/original/file-20211013-27-1g7zmpv.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=321&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="attribution"><a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<p>More than 200 million U.S. residents have gotten at least one shot of a COVID-19 vaccine with the expectation that the vaccines slow virus transmission and save lives. </p>
<p>Researchers know the efficacy of the vaccines from <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine">large-scale clinical trials</a>, the gold standard for medical research. The studies found the vaccines to be <a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm7009e4.htm?s_cid=mm7009e4_w">very effective at preventing severe COVID–19</a> and <a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm7037e1.htm">especially good at preventing death</a>. But it’s important to track any new treatment in the real world as the population-level benefits of vaccines could <a href="https://www.who.int/news-room/feature-stories/detail/vaccine-efficacy-effectiveness-and-protection">differ from the efficacy found in clinical trials</a>. </p>
<p>For instance, some people in the U.S. have <a href="https://www.newsweek.com/texas-reporting-second-shot-hesitancy-nearly-2m-skipped-last-covid-vaccine-dose-1629100">only been getting the first shot</a> of a two-shot vaccine and are therefore <a href="https://abc7.com/pfizer-vaccine-moderna-covid-19-first-dose-of/10458064/">less protected than a fully vaccinated person</a>. Alternatively, vaccinated people are <a href="https://www.nbcnews.com/health/health-news/vaccinated-people-are-less-likely-spread-covid-new-research-finds-n1280583">much less likely to transmit COVID-19 to others</a>, including those who are not vaccinated. This could make vaccines more effective at a population level than in the clinical trials. </p>
<p><a href="https://scholar.google.com/citations?user=2flNbOIAAAAJ&hl=en&oi=ao">I am a health economist</a>, and my team and I have been studying the effects of public policy interventions like vaccination have had on the pandemic. We wanted to know how many lives vaccines may have saved due to the states’ COVID-19 vaccination campaigns in the U.S. </p>
<h2>Building an accurate model</h2>
<p>In March 2021, when weekly data on state COVID-19 vaccinations started to become reliably available from state agencies, my team began to analyze the association between state vaccination rates and the subsequent COVID-19 cases and deaths in each state. Our goal was to build a model that was accurate enough to measure the effect of vaccination within the complicated web of factors that influence COVID–19 deaths.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/426254/original/file-20211013-27-avfc28.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A map of the U.S. with coronavirus particles connecting different areas." src="https://images.theconversation.com/files/426254/original/file-20211013-27-avfc28.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/426254/original/file-20211013-27-avfc28.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/426254/original/file-20211013-27-avfc28.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/426254/original/file-20211013-27-avfc28.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/426254/original/file-20211013-27-avfc28.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/426254/original/file-20211013-27-avfc28.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/426254/original/file-20211013-27-avfc28.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">State data for vaccination rates and COVID–19 deaths can shed light on the real-world effectiveness of the vaccines.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/america-virus-propagation-map-community-royalty-free-illustration/1213737233?adppopup=true">DeskCube/iStock via Getty Images</a></span>
</figcaption>
</figure>
<p>To do this, our model compares COVID-19 incidence in states with high vaccination rates against states with low vaccination rates. As part of the analysis, we controlled for things that influence the spread of the coronavirus, like state–by–state differences in <a href="https://dx.doi.org/10.1016%2Fj.scitotenv.2020.143783">weather</a> and <a href="https://doi.org/10.1371/journal.pone.0242398">population density</a>, <a href="https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/safe-activities-during-covid19/art-20489385">seasonally driven changes in social behavior</a> and <a href="https://statepolicies.com/">non-pharmaceutical interventions</a> like stay-at-home orders, mask mandates and overnight business closures. We also accounted for the fact that there is a delay between when a person is first vaccinated and when their <a href="https://news.weill.cornell.edu/news/2021/02/covid-19-vaccines-and-immunity-how-long-does-it-take-for-the-vaccines-to-provide">immune system has built up protection</a>. </p>
<h2>Vaccines saved lives</h2>
<p>To check the strength of our model before playing with variables, we first compared reported deaths with an estimate that our model produced.</p>
<p>When we fed it all of the information available – including vaccination rates – the model calculated that by May 9, 2021, there should have been 569,193 COVID-19 deaths in the U.S. The <a href="https://www.nytimes.com/interactive/2021/us/covid-cases.html">reported death count</a> by that date was 578,862, less than a 2% difference from our model’s prediction.</p>
<p>Equipped with our well-working statistical model, we were then able to “turn off” the vaccination effect and see how much of a difference vaccines made. </p>
<p>Using near real-time <a href="https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution/">data of state vaccination rates</a>, coronavirus cases and deaths in our model, we found that in the absence of vaccines, 708,586 people would have died by May 9, 2021. We then compared that to our model estimate of deaths with vaccines: 569,193. The difference between those two numbers is just under 140,000. Our model suggests that vaccines <a href="https://doi.org/10.1377/hlthaff.2021.00619">saved 140,000 lives</a> by May 9, 2021.</p>
<p>Our study only looked at the few months just after vaccination began. Even in that short time frame, COVID-19 vaccinations saved many thousands of lives despite vaccination rates still being fairly low in several states by the end of our study period. I can say with certainty that vaccines have since then saved many more lives – and will continue to do so as long as the coronavirus is still around.</p><img src="https://counter.theconversation.com/content/169513/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sumedha Gupta receives funding from National Institute of Health, National Pharmaceutical Council, and Fairbanks Foundation. </span></em></p>Using a robust statistical model, researchers estimate that coronavirus vaccines had prevented 140,000 deaths by May 9, 2021.Sumedha Gupta, Associate Professor of Economics, IUPUILicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1682942021-09-27T15:30:02Z2021-09-27T15:30:02ZWe can’t banish COVID-19. But we can end the pandemic with vaccinations<figure><img src="https://images.theconversation.com/files/423097/original/file-20210924-15-9xe9vi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A vaccination done at a pop-up site in Johannesburg. Not enough South Africans are coming forward to get their shots.</span> <span class="attribution"><span class="source">Photo by Sharon Seretlo/Gallo Images via Getty Images</span></span></figcaption></figure><p>South Africa’s daily rate of new infections has been <a href="https://www.sabcnews.com/sabcnews/sa-seeing-promising-decline-in-confirmed-cases-csir/">on a steady decline for some time</a>. But, truth be told, a fourth wave is probably just on the horizon – and a fifth, and a sixth, and a seventh. This is true of every country in the world.</p>
<p>These waves could be instigated by various phenomena. Perhaps a “super-spreader” event or two, or the arrival of a new and more contagious variant.</p>
<p>Thanks to a successful vaccination programme, smallpox was <a href="https://www.cdc.gov/smallpox/history/history.html">eradicated worldwide by 1977</a>. But as leading American science journalist Christie Aschwanden recently argued, COVID-19 is unlikely to disappear in the same way. Current vaccines just don’t provide enough protection <a href="https://www.nature.com/articles/d41586-021-00728-2">against infection to provide herd immunity</a>. They provide substantial protection against infection as well as severe illness, but they aren’t bullet proof, and reinfection is a reality. </p>
<p>What does this say about the pandemic?</p>
<p>Epidemics do not require the total eradication of the disease to end. More important than the existence of the disease, is the harm it is causing the population. But will the harms of COVID-19 ever be low enough? Will the epidemic ever end? </p>
<p>In short: Yes, it will - so long as enough people get vaccinated and vaccine efficacy continues to protect people from severe illness with new variants. Although exactly what percentage of the population need to be vaccinated to achieve this is hard to say at this stage.</p>
<h2>The pandemic’s end</h2>
<p>This won’t happen with a bang. What we can expect to see is a fading-away. Waves might well still continue, and even increase in magnitude. But fatalities will reduce and severe illness become less common as vaccination rates improve. </p>
<p>As medical historians Erica Charters and Kristin Heitman put it, <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/1600-0498.12370">epidemics end</a> once the disease is</p>
<blockquote>
<p>accepted into people’s daily lives and routines, becoming endemic— domesticated—and accepted. </p>
</blockquote>
<p>Whereas diseases become epidemics and pandemics through purely biostatistical means – a matter of how many people are infected and where those people are – they end once the biomedical harms they cause are sufficiently reduced. In other words, when relatively few people are getting seriously ill.</p>
<p>There are currently multiple vaccines that are <a href="https://www.bmj.com/content/374/bmj.n2282">extremely effective</a> in reducing the effects of the virus from a life-threatening disease, to (for the vast majority of people) nothing more than a mild cold. </p>
<p>Even in the face of further waves of infection, were the entire population fully vaccinated, the biomedical harm the disease would cause would be (relative to many diseases we are already dealing with) sufficiently low to call an end to the epidemic. </p>
<p>This would mark the point at which governments could stop implementing many of the economically and socially devastating non-pharmaceutical interventions. </p>
<h2>How far down the road are we?</h2>
<p>The answer to this question depends on which country you’re living in.</p>
<p>If you are in Europe, you’re closer than those of us living in an African country.</p>
<p>Despite the initial shortages, South Africa currently has more than enough vaccines to satisfy demand. Initially, the slow roll out might have been blamed on supply issues, but now the country faces one big problem: <a href="https://businesstech.co.za/news/trending/512982/south-africas-vaccine-headache-switches-from-supply-to-demand/">not enough people are choosing to vaccinate</a>. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/south-africas-immunisation-record-risks-being-dented-by-anti-vaccination-views-153549">South Africa's immunisation record risks being dented by anti-vaccination views</a>
</strong>
</em>
</p>
<hr>
<p>The scourge of disinformation and anti-vax propaganda has people afraid to accept these life-saving vaccines. All too often, this ends in tragedy. </p>
<h2>A call to arms</h2>
<p>Unfortunately, it is quite natural to listen to anecdotal evidence and take it seriously – to think that because “Uncle Richard” took the vaccine and then had a heart attack, the vaccine caused the heart attack. But this is not good evidence of a causal relationship. </p>
<p>Evidence-based medicine is routed in large-scale randomized trials, with many thousands of people participating (and now, many millions have taken the vaccine). </p>
<p>Both the trials and now large-scale roll-outs have conclusively shown that vaccines massively reduce people’s chances of <a href="https://www.bmj.com/content/374/bmj.n2282">hospitalization and death</a>, and further, that by all standard measures of pharmaceutical safety, that they are not harmful. </p>
<p>We do not advocate for legally mandated vaccinations (or indeed for any legally mandated medical treatment). But we must come to terms with the fact that COVID-19 is probably here to stay, and that the only way to end this epidemic is to stop the enormous harm it is doing. </p>
<p>The only way to prevent healthcare systems being periodically clogged up with suffering COVID-19 patients, and to end this epidemic, is to ensure that as many people as possible are vaccinated, and as soon as possible.</p><img src="https://counter.theconversation.com/content/168294/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Epidemics do not require the total eradication of the disease to end.Benjamin T H Smart, Associate Professor, University of JohannesburgHerkulaas MvE Combrink, Lecturer, University of the Free StateLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1670462021-09-01T22:54:49Z2021-09-01T22:54:49ZI work at a COVID-19 vaccine clinic. Here’s what people ask me when they’re getting their shot — and what I tell them<figure><img src="https://images.theconversation.com/files/418799/original/file-20210901-17-5618xv.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3647%2C2528&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">People getting vaccinated may still have questions about COVID-19 vaccines, like why it takes two doses — and then two weeks — to take full effect.
</span> <span class="attribution"><span class="source">THE CANADIAN PRESS/Ryan Remiorz </span></span></figcaption></figure><iframe style="width: 100%; height: 175px; border: none; position: relative; z-index: 1;" allowtransparency="" src="https://narrations.ad-auris.com/widget/the-conversation-canada/i-work-at-a-covid-19-vaccine-clinic--here-s-what-people-ask-me-when-they-re-getting-their-shot---and-what-i-tell-them" width="100%" height="400"></iframe>
<p>As a medical student working with Alberta Health Services to vaccinate people against COVID-19, I have been asked my fair share of questions about the COVID-19 vaccines — from the need for booster doses to rare side effects.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><a class="source" href="https://theconversation.com/ca/topics/vaccine-confidence-in-canada-107061">Click here for more articles in our series about vaccine confidence.</a></span>
</figcaption>
</figure>
<p>A few days ago, I told an individual who was about to receive her second dose of the Moderna vaccine, “We are expecting about 95 per cent immunity two weeks from today.” She paused and asked, “What does that even mean?” </p>
<p>That scenario has repeated itself a few more times since then. I usually respond with, “It means you have 95 per cent less chance of developing COVID-19 two weeks after you have been vaccinated with the second dose of an mRNA vaccine.” </p>
<p>But what’s the long story behind that?</p>
<h2>mRNA vaccines</h2>
<p>There are multiple vaccines against COVID-19. I’ll focus on the Moderna and Pfizer-BioNTech mRNA vaccines used in Canada. They both received emergency use authorization from the <a href="https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-vaccines">U.S. Food and Drug Administration (FDA)</a> and <a href="https://covid-vaccine.canada.ca/">Health Canada</a> in December 2020. The Pfizer-BioNTech vaccine also <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-first-covid-19-vaccine">received full FDA approval in August 2021</a>. Now that it is fully approved, the Pfizer-BioNTech vaccine is also known by a brand name — Comirnaty — but it’s the exact same vaccine that’s been in use since December 2020. </p>
<p>Both the Moderna and Pfizer-BioNTech vaccines require two doses given at least three to four weeks apart. The mRNA (or messenger RNA) in the vaccines contains the instructions for how to make the now-well-known <a href="https://theconversation.com/know-your-target-fundamental-science-will-lead-us-to-coronavirus-vaccines-136952">spike protein</a> on the surface of SARS-CoV-2, the virus that causes COVID-19. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/418805/original/file-20210901-19-1tpc2kl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="An arm getting an injection" src="https://images.theconversation.com/files/418805/original/file-20210901-19-1tpc2kl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/418805/original/file-20210901-19-1tpc2kl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/418805/original/file-20210901-19-1tpc2kl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/418805/original/file-20210901-19-1tpc2kl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/418805/original/file-20210901-19-1tpc2kl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/418805/original/file-20210901-19-1tpc2kl.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/418805/original/file-20210901-19-1tpc2kl.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Once the mRNA vaccine is injected, it carries instructions to cells for how to make the SARS-CoV-2 virus’s spike protein, so the immune system can learn to recognize it and build an immune response to it.</span>
<span class="attribution"><span class="source">(AP Photo/Rogelio V. Solis)</span></span>
</figcaption>
</figure>
<p>Once it is injected into a muscle in the upper arm, this mRNA gives the muscle’s cells the instructions to make the spike protein. The immune system practises combating this protein and learns how to react when it recognizes something that has that spike protein on it. </p>
<p>Down the line, if we are exposed to the actual SARS-CoV-2 virus, our body knows how to defend against the virus because it has built immunity by making antibodies against the spike protein on the surface of the virus. These antibodies are our bodies’ protective proteins against SARS-CoV-2.</p>
<h2>Efficacy vs. effectiveness</h2>
<p>The Pfizer-BioNTech and the Moderna vaccines are extremely efficacious and effective against COVID-19. But what do efficacious and effective mean in the context of a vaccine? </p>
<p>Vaccine efficacy is defined as the reduction in the rate of developing disease in vaccinated people compared to unvaccinated people. First, we would calculate the difference in cases between the two groups and then divide it by the rate of unvaccinated cases. For example, if eight out of 21,830 vaccinated people and 162 out of 21,830 unvaccinated people develop the disease, the efficacy of that vaccine would be calculated as:</p>
<blockquote>
<p>(162 / 21830 - 8 / 21830) / (162 / 21830) = 95 per cent </p>
</blockquote>
<p>These numbers are the actual numbers out of <a href="https://www.nytimes.com/2020/12/13/learning/what-does-95-effective-mean-teaching-the-math-of-vaccine-efficacy.html">the Pfizer-BioNTech trial</a>, which reported <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine">95 per cent efficacy</a> in its clinical trials. Moderna reported a <a href="https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy">similar number (94.5 per cent efficacy)</a> in its trials. </p>
<p>Vaccine efficacy is usually measured under specific controlled environments and in the setting of double-blind <a href="https://theconversation.com/how-effective-are-covid-19-vaccines-heres-what-the-stats-mean-and-what-they-dont-164755">randomized controlled trials</a> (RCTs). A double-blind RCT is a study in which the participants are randomly assigned to either a placebo (no vaccine) or intervention (vaccine) group and neither the researchers nor the participants are aware which group they are assigned to. This setting reduces bias and increases the accuracy of the studies. </p>
<p>Now that we know how efficacy is measured, let’s see what 95 per cent efficacy really means. In simple terms, 95 per cent efficacy means that vaccinated people have a 95 per cent lower chance of developing COVID-19. So, if out of 10,000 unvaccinated people, 100 people get the disease, out of 10,000 vaccinated people, only five people might get the disease.</p>
<h2>Real-world effectiveness</h2>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/418809/original/file-20210901-21-11tx0j.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="People getting vaccinated at an arena set up as a mass vaccination clinic" src="https://images.theconversation.com/files/418809/original/file-20210901-21-11tx0j.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/418809/original/file-20210901-21-11tx0j.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/418809/original/file-20210901-21-11tx0j.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/418809/original/file-20210901-21-11tx0j.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/418809/original/file-20210901-21-11tx0j.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/418809/original/file-20210901-21-11tx0j.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/418809/original/file-20210901-21-11tx0j.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">People receive a dose of the COVID-19 vaccine at a mass vaccination clinic at Scotiabank Arena in Toronto on June 27, 2021. For those getting a second dose, the vaccine would take full effect two weeks later.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Cole Burston</span></span>
</figcaption>
</figure>
<p>Vaccine effectiveness, however, is different from efficacy. Effectiveness is how well a vaccine works in reducing the rate of disease in vaccinated people compared to unvaccinated people under real-world conditions.</p>
<p>It’s worth noting that most studies have defined developing disease as testing positive for COVID-19 and having at least one symptom. The efficacy numbers can change based on the circumstances under which the vaccines are tested. For example, the location of testing, the method of testing, the presence of specific strains or variants of a disease-causing virus and the diversity of the participants can affect the efficacy numbers. That’s why demographic information is collected in clinical trials, <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/Moderna.html">including Moderna</a>’s and <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/Pfizer-BioNTech.html">Pfizer-BioNTech</a>’s vaccine trials. </p>
<p>This means we can’t directly compare the efficacy of one vaccine to another if they have not been tested under the exact same conditions.</p>
<h2>How well are the mRNA vaccines working?</h2>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/418810/original/file-20210901-19-1fkk48n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Empty vials of Moderna's COVID-19 vaccine" src="https://images.theconversation.com/files/418810/original/file-20210901-19-1fkk48n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/418810/original/file-20210901-19-1fkk48n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/418810/original/file-20210901-19-1fkk48n.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/418810/original/file-20210901-19-1fkk48n.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/418810/original/file-20210901-19-1fkk48n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/418810/original/file-20210901-19-1fkk48n.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/418810/original/file-20210901-19-1fkk48n.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">Preliminary studies suggest mRNA vaccines are about 90 per cent effective under real-world circumstances.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Lars Hagberg</span></span>
</figcaption>
</figure>
<p>With <a href="https://ourworldindata.org/covid-vaccinations">more than five billion doses</a> administered around the world, we are at a point where we can also look at the effectiveness of the COVID-19 vaccines. <a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/effectiveness.html">Preliminary studies</a> have shown that both mRNA vaccines are about 90 per cent effective in the real world against COVID-19. <a href="https://edmonton.ctvnews.ca/here-s-how-effective-covid-19-vaccines-have-been-in-alberta-1.5456656">The Alberta government has reported</a> 93 per cent effectiveness from the Moderna and 90 per cent effectiveness from the Pfizer-BioNTech vaccine.</p>
<p>And why does it take two weeks to develop that level of immunity? The process of a vaccine making our bodies immune against a disease has <a href="https://theconversation.com/covid-19-vaccines-how-pfizers-and-modernas-95-effective-mrna-shots-work-149957">multiple steps</a>. Remember the protective proteins called antibodies? One of the last steps in the immunity process is making those antibodies. </p>
<p><a href="https://www.theatlantic.com/health/archive/2021/03/how-long-wait-fully-vaccinated/618303/">Based on the studies done by the vaccine makers</a>, at around 14 days after the second dose, our bodies have made enough antibodies to recognize and fight SARS-CoV-2, hence the two-week rule before you are considered fully vaccinated.</p>
<p>One important statistic that needs to be mentioned is that both mRNA vaccines have been shown to prevent hospitalizations and deaths. This means that even in the rare case of a vaccinated individual developing COVID-19, the likelihood of them being hospitalized or dying is very much lower than if they hadn’t been vaccinated.</p>
<h2>How do COVID-19 vaccines compare to others?</h2>
<p>Another question I’ve been asked is how the effectiveness from the COVID-19 vaccines compares to the vaccines made for other diseases. Well, the MMR vaccine is <a href="https://www.cdc.gov/vaccines/vpd/mmr/public/index.html">97 per cent effective against measles and rubella and 88 per cent against mumps</a>. The effectiveness of the DTaP vaccine (diphtheria, tetanus, acellular pertussis) is between <a href="https://www.immunize.org/askexperts/experts_per.asp">80-85 per cent</a>. The effectiveness of the flu vaccine hovers <a href="https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates.html">between 10-60 per cent</a> depending on the year, the strains the vaccine protects against each year and the actual strains causing influenza and influenza-like diseases.</p>
<p>These numbers all reflect the reduction in the rate of disease between vaccinated and unvaccinated people. So next time you hear a vaccine is 95 per cent effective, that doesn’t mean five per cent of the people who got the vaccine will develop the disease; it means that vaccinated people have 95 per cent less chance of developing the disease compared to unvaccinated people.</p>
<p><em>Do you have a question about COVID-19 vaccines? Email us at <a href="mailto:ca-vaccination@theconversation.com">ca‑vaccination@theconversation.com</a> and vaccine experts will answer questions in upcoming articles.</em></p><img src="https://counter.theconversation.com/content/167046/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ehsan Misaghi 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>A medical student answers questions he gets asked at a COVID-19 vaccine clinic: Efficacy versus real-world effectiveness, immune response and how the mRNA vaccines compare to vaccines already in wide use.Ehsan Misaghi, Clinician-Scientist Trainee, Faculty of Medicine & Dentistry and Faculty of Science, University of AlbertaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1647552021-08-09T15:04:07Z2021-08-09T15:04:07ZHow effective are COVID-19 vaccines? Here’s what the stats mean … and what they don’t<figure><img src="https://images.theconversation.com/files/415041/original/file-20210806-17-q0azks.jpg?ixlib=rb-1.1.0&rect=0%2C860%2C3400%2C2651&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Vaccine efficacy statistics are often based on the results of randomized controlled trials.</span> <span class="attribution"><span class="source">(Art-Aleatoire.com)</span>, <span class="license">Author provided</span></span></figcaption></figure><iframe style="width: 100%; height: 175px; border: none; position: relative; z-index: 1;" allowtransparency="" src="https://narrations.ad-auris.com/widget/the-conversation-canada/how-effective-are-covid-19-vaccines--here-s-what-the-stats-mean---and-what-they-don-t" width="100%" height="400"></iframe>
<p>The <a href="https://www.who.int/emergencies/diseases/novel-coronavirus-2019">COVID-19 pandemic</a> brought the term <em>vaccine efficacy</em> into the public eye. But what do the efficacy numbers mean? </p>
<p>For example, at first glance, a vaccine efficacy of 70 per cent might suggest that in 30 per cent of cases, people are not protected by the vaccine and could get sick. But this cannot be, as clearly 30 per cent of people who get vaccinated do not become sick. The percentage seems to sow confusion. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/410911/original/file-20210712-19-geybnm.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><a class="source" href="https://theconversation.com/ca/topics/vaccine-confidence-in-canada-107061">Click here for more articles in our series about vaccine confidence.</a></span>
</figcaption>
</figure>
<p>As professors of statistics who explain technical concepts to non-specialists, we propose to shed light on these numbers. The concept is related to randomized controlled trials (RCT), like the <a href="http://doi.org/10.1056/NEJMoa2035389">Moderna</a>, <a href="http://doi.org/10.1056/NEJMoa2034577">Pfizer-BioNTech</a> or <a href="https://doi.org/10.1016/S0140-6736(20)32661-1">Astra Zeneca</a> Phase 3 vaccine trials. </p>
<p>Typically, a RCT follows two large groups, called cohorts, that are similar in relevant ways (in age distribution and ethnicity, for instance). One cohort is injected with the new vaccine, the other one a placebo with no impact on immunity. </p>
<p>Participants are randomly assigned to receiving vaccine or placebo (that’s why it’s called a randomized trial), but not all on the same calendar day. At determined times after the first inoculation a second dose is administered. During the follow-up, people who tested positive for the condition, as well as those who required hospitalization or died from the condition, are counted and compared between cohorts.</p>
<h2>Vaccine efficacy: a relative measure</h2>
<p>For getting to the gist of <a href="https://www.cdc.gov/csels/dsepd/ss1978/lesson3/section6.html">vaccine efficacy</a>, we use simple hypothetical values. This makes calculations straightforward while remaining close to what is observed in trials. </p>
<p>Imagine two studies for two vaccines, vaccine A and vaccine B and, in each study, two cohorts — vaccinated and unvaccinated — with 10,000 participants each. Twenty days after injecting the vaccine we count those who tested positive for the disease and report vaccine efficacies (VE): VE(A) = 60 per cent for vaccine A and VE(B) = 80 per cent for vaccine B. How were these values calculated? What do they mean? The clue is in comparing vaccinated with unvaccinated.</p>
<p>To illustrate, assume that during the time of the study in the general population there is an incidence of one infected case among 10,000 people per day. So, in a cohort of 10,000 unvaccinated we have on average one infection a day and, after 20 days, we end up with 20 infected among the unvaccinated. What about the vaccinated? </p>
<p>Suppose we find eight infected in Study A and four infected in Study B. By comparing with the placebo cohorts where there are 20 infected, we can see that the vaccine has reduced the number of infected people by 12 in Study A and by 16 in Study B. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/412260/original/file-20210720-21-1uqlntq.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Line graph with three lines showing infection numbers for three groups " src="https://images.theconversation.com/files/412260/original/file-20210720-21-1uqlntq.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/412260/original/file-20210720-21-1uqlntq.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=310&fit=crop&dpr=1 600w, https://images.theconversation.com/files/412260/original/file-20210720-21-1uqlntq.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=310&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/412260/original/file-20210720-21-1uqlntq.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=310&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/412260/original/file-20210720-21-1uqlntq.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=390&fit=crop&dpr=1 754w, https://images.theconversation.com/files/412260/original/file-20210720-21-1uqlntq.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=390&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/412260/original/file-20210720-21-1uqlntq.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=390&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">History of infections during 20 days, two vaccines and a placebo: every step gives the number of new cases in a specific day. Assumptions: one case per 10 000 daily, VE(A)=60%, VE(B)=80%.</span>
</figcaption>
</figure>
<p>This protective effect is the <em>vaccine efficacy</em> computed as follows:</p>
<ul>
<li><p>Study A: VE(A) = (20-8)/20 = 12/20 = 0.6 = 60 per cent </p></li>
<li><p>Study B: VE(B) = (20-4)/20 = 16/20 = 0.8 = 80 per cent</p></li>
</ul>
<p>The formula above illustrates the fact that VE quantifies the reduction in risk of getting infected where one compares a vaccinated with an unvaccinated person and not the risk itself.</p>
<p>In our numerical example the risk of infection with no vaccine is one in 10,000 per day. If VE = 80 per cent, this risk is reduced by 80 per cent: infections in vaccinated are one-fifth (or 100-80=20 per cent) of infections in unvaccinated. Thus the risk of infection in vaccinated is one in 50,000 per day. </p>
<p>What if VE = 0 per cent? Vaccinated have the same risk as unvaccinated! And if VE = 100 per cent? There are no infected among vaccinated.</p>
<p>In conclusion, VE is neither a cohort percentage, nor a population percentage; VE is the percentage of potential infected who are protected by the vaccine. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/412164/original/file-20210720-13-e96fa0.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Bar graph showing expected number of infections in 10 days" src="https://images.theconversation.com/files/412164/original/file-20210720-13-e96fa0.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/412164/original/file-20210720-13-e96fa0.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=428&fit=crop&dpr=1 600w, https://images.theconversation.com/files/412164/original/file-20210720-13-e96fa0.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=428&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/412164/original/file-20210720-13-e96fa0.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=428&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/412164/original/file-20210720-13-e96fa0.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=538&fit=crop&dpr=1 754w, https://images.theconversation.com/files/412164/original/file-20210720-13-e96fa0.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=538&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/412164/original/file-20210720-13-e96fa0.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=538&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Expected number of infected after 10 days: incidence 10 in 100,000 per day; VE=80 per cent.</span>
</figcaption>
</figure>
<p>Timing also plays a key role.</p>
<h2>Can we compare vaccination strategies?</h2>
<p>Another issue that has come up in the news is <a href="https://theconversation.com/which-age-group-old-or-young-should-get-the-covid-19-vaccine-first-may-depend-on-timing-150412">vaccination policies</a>. We propose to compare two vaccination strategies, postponing or not the distribution of a second dose of a vaccine in a 40-day time window. We suppose:</p>
<ul>
<li><p>unvaccinated infection rate: one in 10,000; </p></li>
<li><p>VE1 = 60 per cent: efficacy after the first dose;</p></li>
<li><p>VE2 = 80 per cent: efficacy after the second dose;</p></li>
<li><p>We administrate the vaccine to a group of 20,000 divided in two halves, H1 and H2.</p></li>
</ul>
<p>The COVID-19 vaccines have no immediate immunization effect because it takes approximately 14 days for a noticeable outcome, but for illustration we assume there is no immunization lag. In Scenario 1 we vaccinate H1 only, at day one with dose one and at day 21 with dose two; in Scenario 2 we vaccinate both H1 and H2 but with one dose only. </p>
<figure class="align-center ">
<img alt="Diagram illustrating two infection scenarios" src="https://images.theconversation.com/files/412903/original/file-20210723-19-qlq73y.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/412903/original/file-20210723-19-qlq73y.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=239&fit=crop&dpr=1 600w, https://images.theconversation.com/files/412903/original/file-20210723-19-qlq73y.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=239&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/412903/original/file-20210723-19-qlq73y.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=239&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/412903/original/file-20210723-19-qlq73y.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=300&fit=crop&dpr=1 754w, https://images.theconversation.com/files/412903/original/file-20210723-19-qlq73y.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=300&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/412903/original/file-20210723-19-qlq73y.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=300&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Two vaccination scenarios with 10 000 jabs on day 1 and 21.</span>
</figcaption>
</figure>
<p>What scenario is the winner? Which one ends up with fewer infected after 40 days? The answer is illustrated in the graphs below: </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/412479/original/file-20210721-27-fohgy1.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Two line graphs comparing infection scenarios" src="https://images.theconversation.com/files/412479/original/file-20210721-27-fohgy1.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/412479/original/file-20210721-27-fohgy1.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=298&fit=crop&dpr=1 600w, https://images.theconversation.com/files/412479/original/file-20210721-27-fohgy1.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=298&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/412479/original/file-20210721-27-fohgy1.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=298&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/412479/original/file-20210721-27-fohgy1.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=374&fit=crop&dpr=1 754w, https://images.theconversation.com/files/412479/original/file-20210721-27-fohgy1.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=374&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/412479/original/file-20210721-27-fohgy1.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=374&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Expected number of infected at days 20 and 40: two scenarios.</span>
</figcaption>
</figure>
<p>There are 18 per cent more cases in Scenario 1 but why? In this scenario, even if the people in H1 get fully vaccinated with two doses, those in H2 keep getting infected at the non-reduced rate as they receive no vaccine. So, this simplified example suggests that to postpone the second dose and continue vaccinating with dose one for a while could be advantageous. </p>
<p>This being said, in practice more considerations are at stake, like severity and mortality or administration constraints. Indeed, if people in H1 are more prone to severe forms of the disease, during the last 20 days the number of such serious cases double in Scenario 2 as compared with Scenario 1. Thus, there is no clear winner, since in Scenario 2 there may be more serious cases, while in Scenario 1 there are more infected. These numerical illustrations point to the challenge of finding <a href="https://www.inspq.qc.ca/en/publications/3103">best vaccination strategies</a>.</p>
<h2>Cases per day: Many or few?</h2>
<p>Why bother with an incidence of one case in 10,000 per day? It sounds low. Well, it is high <a href="https://www.cdc.gov/coronavirus/2019-ncov/travelers/how-level-is-determined.html">by the standards of the U.S. Centers for Disease Control</a>. Just check: in a population like Canada’s of 38 million, it comes to 26,600 new cases per week — 10 times higher than what <a href="https://health-infobase.canada.ca/covid-19/epidemiological-summary-covid-19-cases.html">Canada experienced </a> at the beginning of July 2021. Last summer, in 2020, in placebo cohorts of RCT vaccine studies the incidence was <a href="http://doi.org/10.1056/NEJMoa2034577">almost two</a> or <a href="https://doi.org/10.1016/S0140-6736(20)32661-1">roughly four</a> in 10,000 per day. </p>
<h2>Finally: What about 50% vaccine efficacy?</h2>
<p>In June 2020, the FDA placed the threshold for acceptable vaccine efficacy at <a href="https://www.fda.gov/media/139638/download">VE = 50 per cent or higher</a>. This goal was greatly surpassed, with reports of <a href="http://doi.org/10.1056/NEJMoa2034577">VE = 95 per cent</a> or <a href="http://doi.org/10.1056/NEJMoa2035389">VE = 94.1 per cent</a> after two doses. </p>
<p>Still, even a vaccine 50 per cent effective is very worthy: it can cut the risk of infections or hospitalizations in half. Actually, the same vaccine could present different efficacies, depending on the event: for severe cases and hospitalizations, Astra Zeneca <a href="https://doi.org/10.1016/S0140-6736(20)32661-1">reported 100 per cent efficacy</a>. </p>
<p>There are more complex analyses in ongoing field studies that involve the related concept of <em>vaccine effectiveness</em>. We touch upon these issues in a <a href="http://arxiv.org/abs/2107.12336">recent manuscript not yet published</a>, but this is another chapter in the vaccine story.</p>
<p><em>Do you have a question about COVID-19 vaccines? Email us at <a href="mailto:ca-vaccination@theconversation.com">ca-vaccination@theconversation.com</a> and vaccine experts will answer questions in upcoming articles.</em></p><img src="https://counter.theconversation.com/content/164755/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Vaccine efficacy is usually expressed as a percentage, but what is it actually measuring? Statisticians explain what the numbers mean, and what they say about how well a vaccine can protect us.Sorana Froda, Professeure Associée, Département de mathématiques; Chercheure émérite, STATQAM, Université du Québec à Montréal (UQAM)Fabrice Larribe, Professeur de Statistique, Département de Mathématiques, Université du Québec à Montréal (UQAM)Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1629262021-07-01T19:53:30Z2021-07-01T19:53:30ZHow well do COVID vaccines work in the real world?<figure><img src="https://images.theconversation.com/files/409222/original/file-20210701-21240-j7md96.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C998%2C597&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/coronavirus-faces-collage-composition-different-multi-1774439057">www.shutterstock.com</a></span></figcaption></figure><p>Many Australians will be <a href="https://www.theguardian.com/australia-news/2021/jul/01/confused-about-whether-you-can-get-an-astrazeneca-vaccine-heres-what-you-need-to-know">weighing up</a> whether to be vaccinated with the AstraZeneca vaccine, which is widely available, or to wait for Pfizer later in the year. </p>
<p>There are many factors to consider. One is how well these COVID-19 vaccines work in the “real world” of those getting vaccines now.</p>
<p>Real-world data data can tell us how well vaccines protect against currently circulating variants — including the Delta variant, which is dominant in the UK and the subject of lockdowns in Australia. Though less reliable than clinical trials, real-world data can tell us how well vaccines work in some parts of the population excluded from clinical trials. They can also tell us whether we can effectively mix vaccines and what the main side-effects are, almost in real time.</p>
<p>You might be surprised by the results.</p>
<h2>Where did these data come from?</h2>
<p>Results of the crucial randomised clinical trials, which led to COVID vaccines being approved around the world, led to extraordinary media coverage. The vaccines have since become household names. But those trials were only the beginning.</p>
<p>Data collected during health-care delivery including medical consultations, hospital admissions, vaccine registers, laboratory tests and death records give us more, and different information about the vaccines.</p>
<p>These are data about millions of individual people, which are de-identified before analysis. Analysed properly, they tell us how well vaccines work, and their side-effects, in the real world.</p>
<h2>How well do COVID vaccines protect you from serious disease?</h2>
<p>The most important finding from analysing these data is vaccines from AstraZeneca, Pfizer and Moderna appear equivalent in reducing your chance of serious illness from COVID-19. As we show <a href="https://www.mja.com.au/journal/2021/effectiveness-covid-19-vaccines-findings-real-world-studies">in our recent review</a>, they do this by more than 80%.</p>
<p>These results extend the findings of the randomised trials by showing all ages benefit from the vaccines, and people with underlying chronic diseases experience reduced, but still worthwhile, protection from serious illness.</p>
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Read more:
<a href="https://theconversation.com/which-covid-vaccine-is-best-heres-why-thats-really-hard-to-answer-161185">Which COVID vaccine is best? Here's why that's really hard to answer</a>
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<h2>How about reducing transmission?</h2>
<p>The next question is how well these vaccines reduce transmission of the virus from person to person, which the randomised clinical trials were not designed to measure directly.</p>
<p>Researchers in the UK linked data from the vaccination register with laboratory results and residential addresses. They showed a vaccinated household member who then developed COVID-19 was <a href="https://www.nejm.org/doi/full/10.1056/NEJMc2107717">half as likely</a> to transmit the virus to another household member as someone who had not been vaccinated.</p>
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<p>However, researchers did not measure the impact of vaccination on transmissibility of the Delta variant in this study as it was conducted before this became dominant in the UK.</p>
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Read more:
<a href="https://theconversation.com/mounting-evidence-suggests-covid-vaccines-do-reduce-transmission-how-does-this-work-160437">Mounting evidence suggests COVID vaccines do reduce transmission. How does this work?</a>
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<h2>How about effectiveness against viral variants?</h2>
<p>Researchers in the UK have released estimates of vaccine effectiveness against coronavirus variants. </p>
<p>The most <a href="https://media.tghn.org/articles/Effectiveness_of_COVID-19_vaccines_against_hospital_admission_with_the_Delta_B._G6gnnqJ.pdf">recent report</a> from England found a single dose of the AstraZeneca or Pfizer vaccines provides only modest protection (30-40%) against infection with the Delta variant. Full vaccination with two doses of Pfizer offers greater protection (88%) than two doses of AstraZeneca (67%).</p>
<p>However, the same report found full vaccination with either vaccine provides more than 90% protection against hospitalisation from COVID-19.</p>
<p>A study in Scotland found <a href="https://www.thelancet.com/action/showPdf?pii=S0140-6736%2821%2901358-1">very similar results</a>.</p>
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Read more:
<a href="https://theconversation.com/should-i-get-my-second-astrazeneca-dose-yes-it-almost-doubles-your-protection-against-delta-163259">Should I get my second AstraZeneca dose? Yes, it almost doubles your protection against Delta</a>
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<h2>What about vaccine side effects?</h2>
<p>Common side-effects of vaccines are tracked by the <a href="https://covid.joinzoe.com/">Zoe COVID Symptom Study</a>. This allows over four million people, mainly in the UK, to report any side-effects via an app.</p>
<p>Reported side-effects are <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00224-3/fulltext">generally mild</a> (headache and fatigue). About 13% report common side-effects after the first dose of the Pfizer vaccine, 22% after the second dose. With AstraZeneca, it’s more than 33% after the first dose. Data from the second AstraZeneca dose were not available for this study.</p>
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<img alt="Middle-aged woman sitting on sofa scrolling smartphone" src="https://images.theconversation.com/files/409223/original/file-20210701-21135-1yd70d1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/409223/original/file-20210701-21135-1yd70d1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/409223/original/file-20210701-21135-1yd70d1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/409223/original/file-20210701-21135-1yd70d1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/409223/original/file-20210701-21135-1yd70d1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/409223/original/file-20210701-21135-1yd70d1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/409223/original/file-20210701-21135-1yd70d1.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">Millions of people can report any suspected side-effects of COVID vaccines via an app.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pleasant-senior-older-lady-resting-on-1667439751">from www.shutterstock.com</a></span>
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<p>The Zoe app has not quantified the risk of rare severe complications of vaccination. However, real-world data have provided <a href="https://www.bmj.com/content/373/bmj.n1114">early estimates</a> of the risk of a blood clot (thrombosis) after receiving the AstraZeneca vaccine in Norway and Denmark. </p>
<p>The overall rate of a blood clot in the veins anywhere in the body was approximately doubled compared to the general population. This included an extra risk of cerebral venous thrombosis (a type of brain blood clot) of 2.5 out of every 100,000 who received a first vaccination (compared with the general population). Although elevated, this is a very low risk.</p>
<p>The researchers did not have access to appropriate control groups receiving other COVID-19 vaccines to compare the levels of risk. This will likely be a priority in future studies.</p>
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Read more:
<a href="https://theconversation.com/concerned-about-the-latest-astrazeneca-news-these-3-graphics-help-you-make-sense-of-the-risk-162175">Concerned about the latest AstraZeneca news? These 3 graphics help you make sense of the risk</a>
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<h2>How do we know all this?</h2>
<p>The science of analysing and interpreting real-world data from vaccine and other treatments has developed over the past 20 years.</p>
<p>In clinical trials randomisation of participants to treatment or control results in very similar comparison groups. This means any differences in trial outcomes should be due to the treatment, not some other factor. Real-world comparisons do not provide this guarantee. </p>
<p>If elderly people, with underlying disease, receive their vaccine early in the rollout, this may create a sicker group of people (or cohort) to follow and analyse. This may make the vaccine appear less-effective than it really is.</p>
<p>Conversely, a more open rollout may lead to more healthy people getting vaccinated. So, the vaccine will appear better (more effective) than it really is. </p>
<p>This complex interplay of biases makes it difficult for researchers to tease out the true effects of vaccines; hence real-world studies require more sophisticated designs and analyses than randomised trials.</p>
<p>However, it’s not so simple. Randomised trials can also be “real world” when they include broad criteria of who to include. While we need <a href="http://www.bmj.com/content/372/bmj.n435">more randomised trials</a>, they will never answer all the emerging questions soon enough. That’s why real-world data are so powerful in the middle of a pandemic.</p>
<h2>Where to next?</h2>
<p>Despite some limitations, analyses of real-world data have become increasingly important with the emergence of new, more infectious strains of SARS-CoV-2 as they can provide answers to important questions more quickly than randomised trials.</p>
<p>However, not all governments provide secure access to de-identified population-scale data to allow researchers to do this. So it’s essential suitably qualified researchers have this access to perform this important work.</p><img src="https://counter.theconversation.com/content/162926/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Henry also has an affiliation with Gold Coast University Hospital, Queensland, Australia</span></em></p><p class="fine-print"><em><span>Paul Glasziou 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>AstraZeneca, Pfizer and Moderna appear equivalent in reducing your chance of serious illness from COVID-19.David Henry, Professor of Evidence-Based Practice, Institute for Evidence-Based Healthcare, Bond UniversityPaul Glasziou, Professor of Medicine, Bond UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1622582021-06-21T09:20:42Z2021-06-21T09:20:42ZWhat are the Sinopharm and Sinovac vaccines? And how effective are they? Two experts explain<figure><img src="https://images.theconversation.com/files/407355/original/file-20210621-35169-12f6dad.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C6000%2C3997&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Rahmat Gul/AP/AAP</span></span></figcaption></figure><p>Last weekend, China reached a milestone of having administered more than <a href="https://edition.cnn.com/2021/06/20/asia/china-one-billion-doses-intl/index.html">one billion doses</a> of its homegrown COVID-19 vaccines, the majority of which were developed by local companies Sinovac and Sinopharm.</p>
<p>What’s more, hundreds of millions of doses of these vaccines have been shipped to <a href="https://www.eastasiaforum.org/2021/04/29/why-chinas-vaccine-diplomacy-is-winning/">more than 80 countries worldwide</a>.</p>
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<p>Sinopharm was given emergency approval by the <a href="https://www.who.int/teams/regulation-prequalification/eul/#:%7E:text=The%20WHO%20Emergency%20Use%20Listing,by%20a%20public%20health%20emergency.">World Health Organization</a> (WHO) <a href="https://www.who.int/news/item/07-05-2021-who-lists-additional-covid-19-vaccine-for-emergency-use-and-issues-interim-policy-recommendations">in May</a> this year, and Sinovac in <a href="https://www.who.int/news/item/01-06-2021-who-validates-sinovac-covid-19-vaccine-for-emergency-use-and-issues-interim-policy-recommendations">June</a>.</p>
<p>But what do we know about these vaccines? How do they work, are they safe, and how effective are they in the real world?</p>
<h2>What type of vaccine are they?</h2>
<p>Both are inactivated virus vaccines. This means they’re made from viral particles produced in a lab, which are then inactivated so they can’t infect you with COVID-19. Many other vaccines use similar platforms, including injectable polio, Hepatitis A and flu vaccines.</p>
<p>Both companies use similar technology, and the vaccines are mixed with an adjuvant, which is a substance added to vaccines to stimulate a stronger immune response.</p>
<p>The vaccines contain many proteins the immune system can respond to, stimulating the production of antibodies to fight COVID-19.</p>
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Read more:
<a href="https://theconversation.com/which-covid-vaccine-is-best-heres-why-thats-really-hard-to-answer-161185">Which COVID vaccine is best? Here's why that's really hard to answer</a>
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<h2>Are they safe?</h2>
<p>Side-effects common after most other COVID-19 vaccines, such as fever and fatigue, were found to be uncommon after <a href="https://www.thelancet.com/article/S1473-3099(20)30843-4/fulltext">Sinovac</a> or <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30831-8/fulltext">Sinopharm</a>.</p>
<p>Once vaccines are approved and being used in large populations, they’re continuously monitored for very rare side effects. <a href="https://cdn.who.int/media/docs/default-source/immunization/sage/2021/april/5_sage29apr2021_critical-evidence_sinovac.pdf?sfvrsn=2488098d_5">No significant safety concerns</a> have been identified amid Sinovac’s rollout in China, Brazil, Indonesia and Chile.</p>
<p>In saying that, there were very low numbers of adverse events identified overall, which would suggest substantial under-reporting.</p>
<p>For example, there were only <a href="https://cdn.who.int/media/docs/default-source/immunization/sage/2021/april/5_sage29apr2021_critical-evidence_sinovac.pdf?sfvrsn=2488098d_5">49 serious adverse events</a> reported following 35.8 million Sinovac doses administered in China. </p>
<p>In a population of that size, we’d expect to see a larger number of illnesses and deaths recorded in the few weeks after vaccination just by coincidence alone, even if not causally related to the vaccine.</p>
<p>Only <a href="https://cdn.who.int/media/docs/default-source/immunization/sage/2021/april/2_sage29apr2021_critical-evidence_sinopharm.pdf?sfvrsn=3dfe32c1_5">79 people</a> reported mostly mild adverse events following 1.1 million doses of Sinopharm in China, much lower than usual rates of <a href="https://www.tga.gov.au/periodic/covid-19-vaccine-weekly-safety-report-03-06-2021">adverse event reporting following immunisation</a>.</p>
<p>A potential side effect of particular concern is what’s called “vaccine-associated enhanced disease”. This is a very rare side effect of some other vaccines which use a similar “inactivated” technology to the Sinopharm and Sinovac vaccines.</p>
<p>It occurs when a vaccinated person is exposed to the virus and develops a serious inflammatory condition, and results in them getting <a href="https://www.sciencedirect.com/science/article/pii/S0264410X21000943">more severe symptoms</a> than they would have without the vaccination.</p>
<p>This hasn’t been reported for these vaccines to date, although <a href="https://apps.who.int/iris/bitstream/handle/10665/341454/WHO-2019-nCoV-vaccines-SAGE-recommendation-Sinovac-CoronaVac-2021.1-eng.pdf">WHO recommends ongoing safety monitoring</a> to identify any cases that occur.</p>
<h2>What was their efficacy in clinical trials?</h2>
<p><a href="https://cdn.who.int/media/docs/default-source/immunization/sage/2021/april/5_sage29apr2021_critical-evidence_sinovac.pdf?sfvrsn=2488098d_5">Sinovac’s efficacy at preventing symptomatic infection</a> was 51% in Brazil, 67% in Chile, 65% in Indonesia, and 84% in Turkey. The differences in results may be due to different variants circulating in each country at the time and differences in the populations included in the studies.</p>
<p>Sinopharm’s efficacy in preventing symptomatic infection was 78% in <a href="https://cdn.who.int/media/docs/default-source/immunization/sage/2021/april/2_sage29apr2021_critical-evidence_sinopharm.pdf?sfvrsn=3dfe32c1_5">UAE, Bahrain, Egypt and Jordan combined</a>.</p>
<p>As with all the COVID-19 vaccines for which data are available, efficacy against the more severe outcomes is greater. Efficacy against hospitalisation for Sinovac in Chile, Brazil and Turkey was <a href="https://www.who.int/news-room/events/detail/2021/04/29/default-calendar/extraordinary-meeting-of-the-strategic-advisory-group-of-experts-on-immunization-(sage)-29-april-2021">85%, 100% and 100%</a>, respectively.</p>
<p>However, few elderly people with underlying health issues were enrolled into these studies. </p>
<p>For Sinopharm, efficacy against <a href="https://cdn.who.int/media/docs/default-source/immunization/sage/2021/april/2_sage29apr2021_critical-evidence_sinopharm.pdf?sfvrsn=3dfe32c1_5">hospitalisation was 79%</a>, although few women were enrolled in these studies. </p>
<h2>How effective are they in the real world?</h2>
<p><a href="https://www.minsal.cl/wp-content/uploads/2021/04/Effectiveness-of-the-inactivated-CoronaVac-vaccine-against-SARS-CoV-2-in-Chile.pdf">Data published in April</a> from a large real world study in Chile suggests Sinovac is 67% effective in preventing symptomatic COVID-19 infection. It’s effectiveness against hospitalisation was 85%, ICU admission 89%, and death 80%.</p>
<p>Sinopharm’s effectiveness against symptomatic infection in <a href="https://cdn.who.int/media/docs/default-source/immunization/sage/2021/april/2_sage29apr2021_critical-evidence_sinopharm.pdf?sfvrsn=3dfe32c1_5">Bahrain was 90%</a>. </p>
<p>However, it’s concerning there have been increases in infections in some countries where these vaccines have been extensively used, but detailed reports are not available.</p>
<p>For example, Seychelles has <a href="https://coronavirus.jhu.edu/vaccines/international">fully vaccinated 68%</a> of its population, mostly with Sinopharm and the remainder with AstraZeneca. </p>
<p>Seychelles has recently experienced a surge in cases, which suggests the <a href="https://theconversation.com/covid-is-surging-in-the-worlds-most-vaccinated-country-why-160869">herd immunity threshold may not have been reached</a>. The exact threshold for this is unknown but is influenced by variants in circulation, the number of people vaccinated, and the effectiveness of the vaccines. </p>
<p>Detailed epidemiological studies are required to investigate this but news reports suggest <a href="https://www.nytimes.com/2021/05/12/business/economy/covid-seychelles-sinopharm.html?referringSource=articleShare">20% of those hospitalised and 37% of new active cases are fully vaccinated</a>.</p>
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Read more:
<a href="https://theconversation.com/covid-is-surging-in-the-worlds-most-vaccinated-country-why-160869">COVID is surging in the world's most vaccinated country. Why?</a>
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<p>Bahrain and the United Arab Emirates have also achieved high vaccination coverage, predominantly with Sinopharm. They also experienced recent COVID-19 surges, and are <a href="https://www.wsj.com/articles/bahrain-facing-a-covid-surge-starts-giving-pfizer-boosters-to-recipients-of-chinese-vaccine-11622648737">offering a booster dose</a> of Pfizer six months after two Sinopharm doses, because of concerns two doses of Sinopharm may not provide sufficient protection. </p>
<p>However, there’s no data publicly available to determine whether this mix and match schedule is safe and produces a protective immune response.</p>
<p>In Mongolia, the rapid vaccine rollout of four different vaccines, including Sinopharm, suggests initial good effectiveness but a recent increase in cases suggests short-term protection only, and perhaps little effect on transmission. </p>
<p>There’s increasing concern about surging cases in Indonesia. Almost all health workers have been vaccinated with the Sinovac vaccine but <a href="https://www.straitstimes.com/asia/se-asia/hundreds-of-indonesian-doctors-contract-covid-19-despite-vaccination-dozens">some are now developing severe disease</a>.</p>
<p>Chile has also achieved high vaccine coverage, mostly with Sinovac. Around 75% of the adult population <a href="https://www.abc.net.au/news/2021-06-11/chile-santiago-vaccinated-covid-19-surge-lockdown/100209768">has received one dose</a>, and 58% two doses. </p>
<p>Despite this, a current surge in infections and consistent high numbers of deaths has prompted a <a href="https://www.abc.net.au/news/2021-06-11/chile-santiago-vaccinated-covid-19-surge-lockdown/100209768">blanket lockdown</a> across the capital, Santiago. The spread may be related to the more transmissible Gamma variant, which first emerged in Brazil.</p>
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<p>However, in a small town of 45,000 in Brazil, very high vaccination coverage with Sinovac of 95% of adults, reportedly decreased <a href="https://www.globaltimes.cn/page/202106/1225031.shtml">symptomatic infections by 80% and deaths by 95%</a>.</p>
<p>There’s currently no data on how effective Sinopharm is against any variant of concern despite its <a href="https://covid19.trackvaccines.org/vaccines/5/">use in more than 50 countries</a>. </p>
<p>For Sinovac, effectiveness against symptomatic infection with the Alpha and Gamma variants in <a href="https://www.who.int/news-room/events/detail/2021/04/29/default-calendar/extraordinary-meeting-of-the-strategic-advisory-group-of-experts-on-immunization-(sage)-29-april-2021">Chile was 67%</a>. </p>
<p>In Brazil, with circulation of the Gamma variant, one pre-print study suggested <a href="https://www.medrxiv.org/content/10.1101/2021.05.19.21257472v1.full-text">effectiveness against symptomatic infection was 42%</a>. </p>
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<a href="https://theconversation.com/coronavirus-variants-have-new-names-we-can-finally-stop-stigmatising-countries-159652">Coronavirus variants have new names: we can finally stop stigmatising countries</a>
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<p>Both vaccines are effective against severe COVID-19. </p>
<p>However, it is critical that researchers and health authorities determine vaccine effectiveness against variants and their effect on transmission, and their safety profiles. For countries that have community transmission this includes “vaccine-associated enhanced disease”. </p>
<p>As for any vaccine, we also need to understand how effective these vaccines are in older people, adolescents, pregnant women and immunocompromised groups, and how long protection lasts.</p>
<p>We need as many vaccines as possible to tackle the pandemic. But now these vaccines are in widespread use and will be further distributed by <a href="https://www.gavi.org/vaccineswork/covax-explained">COVAX</a>, a global alliance which provides vaccine doses to low-and middle-income nations, it’s essential the safety and effectiveness of all vaccines continues to be closely monitored.</p><img src="https://counter.theconversation.com/content/162258/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Fiona Russell receives funding from NHMRC, the Wellcome Trust, the World Health Organization, the Bill & Melinda Gates Foundation and DFAT. </span></em></p><p class="fine-print"><em><span>John Hart 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>China has administered more than one billion doses of its homegrown COVID-19 vaccines, the majority of which were developed by local companies Sinovac and Sinopharm. So what do we know about them?John Hart, Clinical researcher, Murdoch Children's Research InstituteFiona Russell, Senior Principal Research Fellow; paediatrician; infectious diseases epidemiologist, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1611852021-06-16T20:10:21Z2021-06-16T20:10:21ZWhich COVID vaccine is best? Here’s why that’s really hard to answer<figure><img src="https://images.theconversation.com/files/406594/original/file-20210615-13-1g97ouf.jpg?ixlib=rb-1.1.0&rect=2%2C4%2C995%2C661&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/photo-pretty-lady-social-distancing-not-1748934254">Shutterstock</a></span></figcaption></figure><p>With the rollout of COVID-19 vaccines accelerating, people are increasingly asking <a href="https://trends.google.com/trends/explore?q=which%20vaccine%20is%20the%20best%20for%20covid">which vaccine is best</a>?</p>
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<img alt="" src="https://images.theconversation.com/files/406650/original/file-20210616-3721-ufb675.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/406650/original/file-20210616-3721-ufb675.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=438&fit=crop&dpr=1 600w, https://images.theconversation.com/files/406650/original/file-20210616-3721-ufb675.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=438&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/406650/original/file-20210616-3721-ufb675.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=438&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/406650/original/file-20210616-3721-ufb675.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=551&fit=crop&dpr=1 754w, https://images.theconversation.com/files/406650/original/file-20210616-3721-ufb675.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=551&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/406650/original/file-20210616-3721-ufb675.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=551&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">According to Google Trends, more and more people want to know.</span>
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<p>Even if we tried to answer this question, defining which vaccine is “best” is not simple. Does that mean the vaccine better at protecting you from serious disease? The one that protects you from whichever variant is circulating near you? The one that needs fewer booster shots? The one for your age group? Or is it another measure entirely?</p>
<p>Even if we could define what’s “best”, it’s not as if you get a choice of vaccine. Until a suite of vaccines become available, the vast majority of people around the world will be vaccinated with whichever vaccine is available. That’s based on available clinical data and health authorities’ recommendations, or by what your doctor advises if you have an underlying medical condition. So the candid answer to which COVID vaccine is “best” is simply the one available to you right now. </p>
<p>Still not convinced? Here’s why it’s so difficult to compare COVID vaccines.</p>
<h2>Clinical trial results only go so far</h2>
<p>You might think clinical trials might provide some answers about which vaccine is “best”, particularly the large phase 3 trials used as the basis of approval by regulatory authorities around the world.</p>
<p>These trials, usually in tens of thousands of people, compare the number of COVID-19 cases in people who get the vaccine, versus those who get a placebo. This gives a measure of efficacy, or how well the vaccine works under the tightly controlled conditions of a clinical trial.</p>
<p>And we know the efficacy of different COVID vaccines differ. For instance, we learned from clinical trials that the Pfizer vaccine reported an <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2034577">efficacy of 95%</a> in preventing symptoms, whereas AstraZeneca had an efficacy of <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext">62-90%</a>, depending on the dosing regime.</p>
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Read more:
<a href="https://theconversation.com/how-to-read-results-from-covid-vaccine-trials-like-a-pro-149916">How to read results from COVID vaccine trials like a pro</a>
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<p>But direct comparison of phase 3 trials <a href="https://www.nature.com/articles/d41586-021-00409-0">is complex</a> as they take place at different locations and times. This means rates of infection in the community, public health measures and the mix of distinct viral variants can vary. Trial participants can also differ in age, ethnicity and potential underlying medical conditions.</p>
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<figcaption><span class="caption">It’s tempting to compare COVID vaccines. But in a pandemic, when vaccines are scarce, that can be dangerous.</span></figcaption>
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<h2>We might compare vaccines head to head</h2>
<p>One way we can compare vaccine efficacy directly is to run head-to-head studies. These compare outcomes of people receiving one vaccine with those who receive another, in the same trial.</p>
<p>In these trials, how we measure efficacy, the study population and every other factor is the same. So we know any differences in outcomes must be down to differences between the vaccines.</p>
<p>For instance, a head-to-head trial is <a href="https://www.globenewswire.com/news-release/2021/04/21/2214528/0/en/Valneva-Initiates-Phase-3-Clinical-Trial-for-its-Inactivated-Adjuvanted-COVID-19-Vaccine-Candidate-VLA2001.html">under way in the UK</a> to compare the AstraZeneca and <a href="https://theconversation.com/whats-the-valneva-covid-19-vaccine-the-french-shot-thats-supposed-to-be-variant-proof-160345">Valneva</a> vaccines. The phase 3 trial is expected to be completed later this year.</p>
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<h2>How about out in the real world?</h2>
<p>Until we wait for the results of head-to-head studies, there’s much we can learn from how vaccines work in the general community, outside clinical trials. Real-world data tells us about vaccine effectiveness (not efficacy).</p>
<p>And the effectiveness of COVID vaccines can be compared in countries that have rolled out different vaccines to the same populations. </p>
<p>For instance, the latest data from the UK show both Pfizer and AstraZeneca vaccines have <a href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/988193/Vaccine_surveillance_report_-_week_20.pdf">similar effectiveness</a>. They <a href="https://www1.racgp.org.au/newsgp/clinical/evidence-indicates-astrazeneca-and-pfizer-covid-va">both reliably prevent COVID-19</a> symptoms, hospitalisation and death, even after a single dose.</p>
<p>So what at first glance looks “best” according to efficacy results from clinical trials doesn’t always translate to the real world.</p>
<h2>What about the future?</h2>
<p>The COVID vaccine you get today is not likely to be your last. As immunity naturally wanes after immunisation, periodic boosters will become necessary to maintain effective protection.</p>
<p>There is now <a href="https://www.nature.com/articles/d41586-021-01359-3">promising data from Spain</a> that mix-and-matching vaccines is safe and can trigger very potent immune responses. So this may be a viable strategy to maintain high vaccine effectiveness over time.</p>
<p>In other words, the “best” vaccine might in fact be a number of different vaccines.</p>
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<p>Variant viruses have started to circulate, and while current vaccines show reduced protection against these variants, <a href="https://theconversation.com/whats-the-indian-variant-responsible-for-victorias-outbreak-and-how-effective-are-vaccines-against-it-161574">they still protect</a>.</p>
<p><a href="https://www.afr.com/policy/health-and-education/australia-negotiating-with-three-vaccine-makers-for-boosters-variants-20210427-p57ms6">Companies</a>, <a href="https://www.bmj.com/content/372/bmj.n232">including Moderna</a>, are rapidly updating their vaccines to be administered as variant-specific boosters to combat this.</p>
<p>So, while one vaccine might have a greater efficacy in a phase 3 trial, that vaccine might not necessarily be “best” at protecting against future variants of concern circulating near you.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/can-i-get-astrazeneca-now-and-pfizer-later-why-mixing-and-matching-covid-vaccines-could-help-solve-many-rollout-problems-161404">Can I get AstraZeneca now and Pfizer later? Why mixing and matching COVID vaccines could help solve many rollout problems</a>
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<h2>The best vaccine is the one you can get now</h2>
<p>It is entirely rational to want the “best” vaccine available. But the best vaccine is the one available to you right now because it stops you from catching COVID-19, <a href="https://theconversation.com/mounting-evidence-suggests-covid-vaccines-do-reduce-transmission-how-does-this-work-160437">reduces transmission</a> to vulnerable members of our community and substantially reduces your risk of severe disease. </p>
<p>All available vaccines do this job and do it well. From a collective perspective, these benefits are compounded. The more people get vaccinated, the more the community becomes immune (also known as herd immunity), further curtailing the spread of COVID-19. </p>
<p>The global pandemic is a highly dynamic situation, with emerging viral variants of concern, uncertain global vaccine supply, patchy governmental action and potential for explosive outbreaks in many regions. </p>
<p>So waiting for the perfect vaccine is an unattainable ambition. Every vaccine delivered is a small but significant step towards global normality.</p><img src="https://counter.theconversation.com/content/161185/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Even if we came up with a definition of what makes the “best” vaccine, we don’t have the luxury of choice, when vaccines are in short supply.Wen Shi Lee, Postdoctoral researcher, The Peter Doherty Institute for Infection and ImmunityHyon Xhi Tan, Postdoctoral researcher, The Peter Doherty Institute for Infection and ImmunityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1608692021-05-19T07:00:48Z2021-05-19T07:00:48ZCOVID is surging in the world’s most vaccinated country. Why?<figure><img src="https://images.theconversation.com/files/401478/original/file-20210519-13-fhzfc2.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C6250%2C3957&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Houses in the city of Victoria, the capital of Seychelles.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>The small archipelago nation of Seychelles, northeast of Madagascar in the Indian Ocean, has emerged as the world’s most vaccinated country for COVID-19. </p>
<p>Around <a href="https://ourworldindata.org/covid-vaccinations">71% of people</a> have had at least one dose of a COVID vaccine, and 62% have been fully vaccinated. Of these, <a href="https://www.nytimes.com/2021/05/12/business/economy/covid-seychelles-sinopharm.html">57% have received the Sinopharm vaccine</a>, and 43% AstraZeneca.</p>
<p>Despite this, there has been a recent surge in cases, with 37% of new active cases and 20% of hospital cases <a href="https://www.nytimes.com/2021/05/12/business/economy/covid-seychelles-sinopharm.html?referringSource=articleShare">being fully vaccinated</a>. The country has had to <a href="https://www.bloomberg.com/news/articles/2021-05-04/world-s-most-vaccinated-nation-reintroduces-curbs-as-cases-surge">reimpose some restrictions</a>. </p>
<p>How can this be happening? There are several possible explanations:</p>
<ol>
<li><p>the herd immunity threshold has not been reached — 62% vaccination is likely not adequate with the vaccines being used</p></li>
<li><p>herd immunity is unreachable due to inadequate efficacy of the two vaccines being used</p></li>
<li><p>variants that escape vaccine protection are dominant in Seychelles</p></li>
<li><p>the B1617 Indian variant is spreading, which appears to be more infectious than other variants</p></li>
<li><p>mass failures of the cold-chain logistics needed for transport and storage, which rendered the vaccines ineffective. </p></li>
</ol>
<p>What does the country’s experience teach us about variants, vaccine efficacy and herd immunity?</p>
<p>Let’s break this down.</p>
<h2>Variants can escape vaccine protection</h2>
<p>There are <a href="https://www.bloomberg.com/news/articles/2021-05-04/world-s-most-vaccinated-nation-reintroduces-curbs-as-cases-surge">reports</a> of the South African B.1.351 variant circulating in Seychelles. This variant shows the greatest ability to escape vaccine protection of all COVID variants so far.</p>
<p>In South Africa, one study showed AstraZeneca has <a href="https://www.nejm.org/doi/full/10.1056/nejmoa2102214">0-10% efficacy against this variant</a>, prompting the South African government to <a href="https://www.bbc.com/news/world-africa-56944400">stop using that vaccine</a> in February.</p>
<p>The efficacy of the Sinopharm vaccine against this variant is unknown, but lab studies <a href="https://www.dailysabah.com/life/health/chinese-covid-19-vaccine-effective-against-south-africa-variant">show some reduction in protection, based on blood tests</a>, but probably some protection. </p>
<p>However, no comprehensive surveillance exists in the country to know what proportion of cases are due to the South African variant.</p>
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<p>The UK variant B117, which is more contagious than the original strain, became the dominant variant in the United States. But the US still <a href="https://www.nytimes.com/2021/05/14/health/coronavirus-variants-united-states-of-america.html">achieved a dramatic reduction in COVID-19</a> cases through vaccination, with most people receiving the Pfizer and Moderna vaccines.</p>
<p>Israel, where the UK variant was dominant, also has a very high vaccination rate, having vaccinated nearly 60% of its population with Pfizer. It found <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2101765">92% effectiveness</a> against any infection including asymptomatic infection, and Israel has seen a <a href="https://ourworldindata.org/coronavirus/country/israel">large drop in new cases</a>. </p>
<p>The United Kingdom has used a combination of Pfizer and AstraZeneca vaccines. <a href="https://ourworldindata.org/covid-vaccinations">More than 50% of the population</a> have had a single dose and almost 30% are fully vaccinated. The country has also seen a significant decline in case numbers. </p>
<p>But there’s a current <a href="https://www.bbc.com/news/health-57094274">surge of cases in northwest England</a>, with most new cases in the city of Bolton being the Indian variant. This variant is also causing <a href="https://www.todayonline.com/singapore/new-b1617-coronavirus-strain-appears-be-attacking-younger-children-more-covid-19-task-force">outbreaks in Singapore</a>, which had previously controlled the virus well.</p>
<p>Seychelles needs to conduct urgent genome sequencing and surveillance to see what contribution variants of concern are making, and whether the Indian variant is present.</p>
<p>If the South African variant is dominant, the country needs to use a vaccine that works well against it. Many companies are making boosters targeted to this variant, but for now, Pfizer would be an option. In Qatar, local researchers found Pfizer had <a href="https://www.nejm.org/doi/full/10.1056/NEJMc2104974">75% effectiveness against the South African variant</a>.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/new-covid-variants-have-changed-the-game-and-vaccines-will-not-be-enough-we-need-global-maximum-suppression-157870">New COVID variants have changed the game, and vaccines will not be enough. We need global 'maximum suppression'</a>
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<h2>We need to use high-efficacy vaccines to achieve herd immunity</h2>
<p>The <a href="https://www.dw.com/en/coronavirus-confusion-over-efficacy-of-chinese-vaccines/a-57181029">reported efficacy</a> of Sinopharm is 79% and AstraZeneca is <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext">62-70% from phase 3 clinical trials</a>.</p>
<p>Our research at the Kirby Institute showed that, in New South Wales, Australia, using a vaccine with 90% efficacy against all infection means herd immunity could be achieved <a href="https://www.sciencedirect.com/science/article/pii/S0264410X21005016?via%3Dihub">if 66% of the population was vaccinated</a>. </p>
<p>However, using lower efficacy vaccines means more people need to be vaccinated. If the vaccine is 60% effective, the proportion needing to be vaccinated rises to 100%.</p>
<p>When you get an efficacy of less than 60%, herd immunity is not achievable.</p>
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<p>However, these calculations were done for the regular COVID-19 caused by the D614G variant <a href="https://www.who.int/csr/don/31-december-2020-sars-cov2-variants/en/">which dominated in 2020</a>. This has a reproductive number (R0) of 2.5, meaning people infected with the virus on average infect 2.5 others.</p>
<p>But the B117 variant is <a href="https://science.sciencemag.org/content/372/6538/eabg3055">43-90% more contagious</a> than D614G, so the R0 may be up to 4.75. This will require higher vaccination rates to control spread.</p>
<p>What’s more, the Indian variant B1617 has been estimated to be at least <a href="https://www.npr.org/sections/goatsandsoda/2021/05/07/994710459/is-the-variant-from-india-the-most-contagious-coronavirus-mutant-on-the-planet">50% more contagious than B117</a>, which could take the R0 to over 7, and takes us into uncharted territory.</p>
<p>This could explain the catastrophic situation in India, but also raises the stakes for vaccination, as lower efficacy vaccines will not be able to contain such highly transmissible variants effectively.</p>
<p>Herd immunity is still possible, but <a href="https://www.publish.csiro.au/ma/Fulltext/MA21009">depends on the efficacy of the vaccine used and the proportion of people vaccinated</a>.</p>
<p>A <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00079-7/fulltext">UK modelling study found</a> using very low efficacy vaccines would result in the economy barely breaking even over ten years because it would fail to control transmission. On the other hand, using very high efficacy vaccines would result in much better economic outcomes.</p>
<h2>Vaccinating the world is the only way to end the pandemic</h2>
<p>As the pandemic continues to worsen in some parts of the world, the risk increases of more dangerous mutations that are vaccine-resistant or too contagious to control with current vaccines.</p>
<p>Keeping up with mutations is like whack-a-mole while the pandemic is raging.</p>
<p>The take-home message for our pandemic exit strategy is that the sooner we get the whole world vaccinated, the sooner we will control emergence of new variants.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/3-ways-to-vaccinate-the-world-and-make-sure-everyone-benefits-rich-and-poor-155943">3 ways to vaccinate the world and make sure everyone benefits, rich and poor</a>
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<img src="https://counter.theconversation.com/content/160869/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>C Raina MacIntyre receives funding from NHMRC and MRFF. She has consulted for or been on advisory boards on COVID-19 vaccines for AstraZeneca, Seqirus and Janssen.</span></em></p>What does the Seychelles experience tell us about variants, vaccine efficacy and herd immunity?C Raina MacIntyre, Professor of Global Biosecurity, NHMRC Principal Research Fellow, Head, Biosecurity Program, Kirby Institute, UNSW SydneyLicensed 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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<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>
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<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/1545692021-03-09T18:51:21Z2021-03-09T18:51:21ZCOVID-19 vaccine FAQs: Efficacy, immunity to illness vs. infection (yes, they’re different), new variants and the likelihood of eradication<figure><img src="https://images.theconversation.com/files/388207/original/file-20210308-21-uj0n7f.JPG?ixlib=rb-1.1.0&rect=51%2C0%2C5678%2C3663&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A COVID-19 vaccine is administered at a clinic at Olympic Stadium in Montréal on March 1, 2021, marking the beginning of mass vaccination in the Province of Québec based on age.</span> <span class="attribution"><span class="source">THE CANADIAN PRESS/Paul Chiasson</span></span></figcaption></figure><p>As of March 8, four COVID-19 vaccines have been approved for emergency use in Canada. Two of them, the <a href="https://theconversation.com/covid-19-vaccine-update-pfizer-may-be-the-frontrunner-but-canada-has-hedged-its-bets-149962">mRNA vaccines</a> from <a href="https://www.cbc.ca/news/politics/vaccine-rollout-plan-phac-1.5833912">Pfizer/BioNTech</a> and <a href="https://www.cbc.ca/news/politics/canada-approves-moderna-vaccine-1.5852848">Moderna</a> vaccines, were approved for use in Canada in December 2020. The <a href="https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222-oxford-phase-iii-trials-interim-analysis-results-published-in-the-lancet.html">Oxford/AstraZeneca</a> vaccine was approved on Feb. 26, followed by the <a href="https://www.jnj.com/johnson-johnson-announces-single-shot-janssen-covid-19-vaccine-candidate-met-primary-endpoints-in-interim-analysis-of-its-phase-3-ensemble-trial">Johnson & Johnson</a> vaccine on March 5. </p>
<p>A fifth vaccine was submitted on Jan. 29 by <a href="https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3">Novavax</a> for <a href="https://www.macleans.ca/news/novavaxs-vaccine-covid-19-canada/">approval in Canada</a>. If approved, the vaccine would be produced in Canada. </p>
<p>How effective these vaccines may be in ending the COVID-19 pandemic has been equated to their “efficacy rates.” It’s important to know what these numbers mean to understand what can be expected from these vaccines and the ones that follow.</p>
<h2>What is a vaccine’s efficacy rate?</h2>
<p>The high efficacy rates of the first approved vaccines <a href="https://theconversation.com/covid-19-vaccines-how-pfizers-and-modernas-95-effective-mrna-shots-work-149957">made headlines</a>, but what do these numbers actually mean? Efficacy rates indicate how well a vaccine met specified primary and secondary “<a href="https://doi.org/10.7326/M20-6169">end point(s)</a>,” which, in lay terms, are the goals determined at the outset of a clinical trial: what the study is measuring. In the case of COVID-19 pandemic, these goals had to do with the ability of the vaccines to lower the risk of a symptomatic disease — especially a severe one — hospitalization and death.</p>
<p>The term efficacy, as opposed to effectiveness, specifically refers to a drug or vaccine’s performance under clinical trial conditions, by meeting the primary and secondary end points.</p>
<p>For example, in the case of the Pfizer/BioNTech Phase 3 clinical trial, the primary end point was the efficacy rate of the vaccine in preventing <em>symptomatic</em> COVID-19 (including mild, moderate and severe disease) with the onset at least seven days after the second dose. The secondary end point on this trial was the efficacy rate against severe COVID-19. </p>
<figure class="align-center ">
<img alt="A hand in a purple glove holding a vial of vaccine" src="https://images.theconversation.com/files/388209/original/file-20210308-13-zva9mh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/388209/original/file-20210308-13-zva9mh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/388209/original/file-20210308-13-zva9mh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/388209/original/file-20210308-13-zva9mh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/388209/original/file-20210308-13-zva9mh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/388209/original/file-20210308-13-zva9mh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/388209/original/file-20210308-13-zva9mh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A vial of AstraZeneca’s COVID-19 vaccine at a facility in Milton, Ont. on March 3, 2021.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Carlos Osorio - POOL</span></span>
</figcaption>
</figure>
<p>In the case of the <a href="https://www.jnj.com/johnson-johnson-announces-single-shot-janssen-covid-19-vaccine-candidate-met-primary-endpoints-in-interim-analysis-of-its-phase-3-ensemble-trial">Johnson & Johnson</a> vaccine, which requires only one shot, the primary end point was defined as protection against moderate and severe COVID-19, assessed at day 14 and day 28 after the vaccination.</p>
<p>So the efficacy rates of these vaccines, as determined from their Phase 3 clinical trials, indicate protection against different forms of <em>symptomatic</em> COVID-19 (mild, moderate and/or severe disease), and outcomes of the disease (hospitalization and death).</p>
<h2>What do the vaccines protect against?</h2>
<p>In general, a <a href="https://www.who.int/news-room/feature-stories/detail/how-do-vaccines-work">vaccine teaches the body to recognize a specific pathogen</a> (virus or bacterium) without having to experience a disease. As a result, future exposure to the pathogen leads to a fast immune response whereby the body recognizes the pathogen by its antibodies (humoral response) and can destroy the pathogen and the infected cells through the means of specialized immune cells (cellular response). </p>
<p>Moreover, the vaccines can also induce long-term immune memory of the pathogen whereby dormant specialized immune cells reactivate and produce a humoral response.</p>
<p>In the case of the approved COVID-19 vaccines, or those currently awaiting approval, the efficacy rate indicates how well these vaccines protect against symptomatic COVID-19 disease. </p>
<p>Indeed, a study in Israel — where 42 per cent of the population had received at least one dose of the Pfizer/BioNTech vaccine at the time of the study — found that this vaccine <a href="https://doi.org/10.1101/2021.02.05.21251139">is 87-96 per cent effective</a> in preventing severe cases (the study has not yet been peer reviewed).</p>
<h2>Does vaccination prevent infection?</h2>
<p>Although the reported efficacy rates are a reflection of the vaccine’s ability to protect against symptomatic COVID-19 illness, it is not currently known whether these vaccines protect against infection: whether a vaccinated person’s immune response can eliminate the virus before it replicates in the body. </p>
<figure class="align-center ">
<img alt="Roll of round pink stickers reading 'I got my COVID-19 shot!'" src="https://images.theconversation.com/files/388208/original/file-20210308-13-1o8zube.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/388208/original/file-20210308-13-1o8zube.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/388208/original/file-20210308-13-1o8zube.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/388208/original/file-20210308-13-1o8zube.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/388208/original/file-20210308-13-1o8zube.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/388208/original/file-20210308-13-1o8zube.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/388208/original/file-20210308-13-1o8zube.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">COVID-19 stickers at the Invista Centre in Kingston, Ont., which will be used as a vaccination site, on March 1, 2021.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Lars Hagberg</span></span>
</figcaption>
</figure>
<p>If the novel coronavirus can infect a vaccinated host (replicate within that host), it can also use that host to “jump” to another host, and lead to further transmission of the virus, and possibly illness if other hosts are not vaccinated.</p>
<p>By the same token, if you are not vaccinated and are surrounded by people who are vaccinated, they may not catch the disease (they will not get sick). However, they can catch the virus from you and pass it on to others who are not vaccinated and who may get sick as a result.</p>
<p>However, all these vaccines, through their interaction with the immune system, are expected to reduce infection (virus replication) and hence virus transmission at some level. <a href="https://www.research.ox.ac.uk/Article/2021-02-02-oxford-coronavirus-vaccine-shows-sustained-protection-of-76-during-the-3-month-interval-until-the-second-dose">Oxford/AstraZeneca</a>, <a href="https://ir.novavax.com/news-releases/news-release-details/novavax-announces-covid-19-vaccine-clinical-development-progress">Novavax</a> and <a href="https://doi.org/10.1038/d41586-021-00450-z">Moderna</a> have all reported that their vaccines reduce virus transmission. </p>
<p>These preliminary data appear to be supported by countries that have vaccinated a large portion of their population, such as Israel and the <a href="https://www.ox.ac.uk/news/2021-02-02-oxford-coronavirus-vaccine-shows-sustained-protection-76-during-3-month-interval">United Kingdom</a>. <a href="https://doi.org/10.1038/d41586-021-00140-w">Israel, which has vaccinated 75 per cent of its older population</a>, reported a 33 per cent decrease in the transmission rate in this age group.</p>
<p>In a nutshell, while the current COVID-19 vaccines provide immunity to the disease, their impact on transmission of the virus has yet to be fully determined. We must understand their impact on the pandemic to protect those who have underlying health conditions and may not respond to vaccination or cannot be vaccinated.</p>
<h2>How do COVID-19 vaccines compare to other vaccines?</h2>
<p>Many existing vaccines work in the same way as the approved COVID-19 vaccines: they protect us from diseases, but they do not eliminate the virus during the replication process (or prevent infection). </p>
<p>The <a href="https://www.cdc.gov/smallpox/prevention-treatment/index.html">smallpox vaccine</a> is the poster child among the vaccines that do prevent infection, also referred to as vaccines that induce sterilizing immunity. That is how smallpox was eradicated after 200 years of vaccination efforts. A few other vaccines that induce sterilizing immunity are the <a href="https://www.npr.org/sections/health-shots/2014/04/18/304155213/why-mumps-and-measles-can-spread-even-when-were-vaccinated">measles vaccine</a> and the <a href="https://doi.org/10.1016/S0140-6736(06)68439-0">human papillomavirus vaccine</a>.</p>
<p>However, vaccines against many diseases such as <a href="https://doi.org/10.1053/j.gastro.2013.07.044">hepatitis B</a>, <a href="https://www.cdc.gov/vaccines/hcp/vis/vis-statements/rotavirus.html">rotavirus</a> and <a href="https://doi.org/10.1586/14760584.2015.1052800">polio</a> (all caused by viruses), or <a href="https://doi.org/10.1093/infdis/jit491">whooping cough</a> or <a href="https://doi.org/10.1016/s1473-3099(19)30279-8">chlamydia</a> (both caused by bacteria) do not prevent infection (replication of the virus in the body), but they prevent their respective diseases. </p>
<figure class="align-center ">
<img alt="Hands preparing a syringe" src="https://images.theconversation.com/files/388210/original/file-20210308-20-1fkj4f6.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/388210/original/file-20210308-20-1fkj4f6.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=406&fit=crop&dpr=1 600w, https://images.theconversation.com/files/388210/original/file-20210308-20-1fkj4f6.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=406&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/388210/original/file-20210308-20-1fkj4f6.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=406&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/388210/original/file-20210308-20-1fkj4f6.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=511&fit=crop&dpr=1 754w, https://images.theconversation.com/files/388210/original/file-20210308-20-1fkj4f6.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=511&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/388210/original/file-20210308-20-1fkj4f6.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=511&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A dose of COVID-19 vaccine is prepared at a vaccination clinic in Montréal’s Olympic Stadium on Feb. 23, 2021.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Paul Chiasson</span></span>
</figcaption>
</figure>
<p>The <a href="https://www.who.int/bulletin/volumes/86/2/07-040089/en/">World Health Organization</a> explains that, “Many vaccines are primarily intended to prevent disease and do not necessarily protect against infection.” However, all these vaccines rely on high vaccination coverage and vaccine efficacy rates to protect the population from the disease through <a href="http://doi.org/10.1001/jama.2020.20895">herd immunity</a>. Where the vaccination rate is low, we get outbreaks, as is the case of <a href="https://www.npr.org/sections/health-shots/2014/04/18/304155213/why-mumps-and-measles-can-spread-even-when-were-vaccinated">mumps</a> in recent years.</p>
<h2>Will immunity lead to eradication of COVID-19?</h2>
<p>There is still more to learn about the immune response against SARS-CoV-2, the virus that causes COVID-19. One thing for certain is that the current vaccines provide immunity at various efficacy rates against symptomatic COVID-19. </p>
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Read more:
<a href="https://theconversation.com/covid-19-vaccine-rollout-why-a-mask-and-social-distancing-are-still-needed-even-if-you-get-the-shot-152351">COVID-19 vaccine rollout: Why a mask and social distancing are still needed, even if you get the shot</a>
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<p>Eradication often is reached when there is sterilizing immunity, induced by the virus or by a vaccine. While the coronavirus and the COVID-19 vaccines are not believed to elicit sterilizing immunity, they are likely to reduce infection and hence transmission. So high vaccination coverage with a vaccine with a high efficacy rate, and compliance with existing prevention measures, are key to protecting the general population from COVID-19, but not necessarily eradicating the virus.</p>
<h2>Do the vaccines protect against SARS-CoV-2 variants?</h2>
<p>Considering the potential impact of the emergence of SARS-CoV-2 variants, <a href="https://www.who.int/publications/m/item/covid-19-weekly-epidemiological-update">WHO recently provided the definitions for variants of concern and variants of interest</a> in order to assess their public health relevance.</p>
<p>Variants of concern are those that show an increase in transmissibility or severity of the disease, or a reduction in vaccine effectiveness. Variants of interest are those that call for research and closer monitoring based on community transmission (a number of outbreaks) or detection in a number of countries.</p>
<p>Because the Phase 3 clinical trials were carried out at different times coinciding with the emergence of different dominant virus variants in different participating countries, efficacy rates of different vaccines cannot translate directly to their ability to protect against different variants of concern.</p>
<figure class="align-center ">
<img alt="Red sign reading 'Vaccination' with an illustration of a syringe and a vial" src="https://images.theconversation.com/files/388211/original/file-20210308-19-1g5n8rb.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/388211/original/file-20210308-19-1g5n8rb.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=410&fit=crop&dpr=1 600w, https://images.theconversation.com/files/388211/original/file-20210308-19-1g5n8rb.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=410&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/388211/original/file-20210308-19-1g5n8rb.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=410&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/388211/original/file-20210308-19-1g5n8rb.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=515&fit=crop&dpr=1 754w, https://images.theconversation.com/files/388211/original/file-20210308-19-1g5n8rb.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=515&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/388211/original/file-20210308-19-1g5n8rb.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">A sign at a COVID-19 vaccination clinic in Montréal’s Olympic Stadium on Feb. 23, 2021.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Paul Chiasson</span></span>
</figcaption>
</figure>
<p>However, <a href="https://www.jnj.com/johnson-johnson-announces-single-shot-janssen-covid-19-vaccine-candidate-met-primary-endpoints-in-interim-analysis-of-its-phase-3-ensemble-trial">Johnson & Johnson</a> Phase 3 clinical trial shows that its vaccine has an efficacy rate of 60 per cent against moderate to severe COVID-19 caused by the B.1.351 variant (dominant in South Africa) and 66 per cent against moderate to severe COVID-19 caused by the P1 variant (dominant in Brazil). The vaccine has an overall efficacy rate of 85 per cent against severe COVID-19 across these variants. </p>
<p>The <a href="https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3">Novavax</a> vaccine fared very well against B.1.1.7, which is dominant in the U.K., with an efficacy rate of 85.6 per cent against symptomatic COVID-19, but only 60 per cent against B.1.351 (after removing the HIV positive volunteers). </p>
<p>The mRNA vaccines’ Phase 3 clinical trials were done in the United States only, at a time when there was no circulation of any of those virus variants. Both <a href="https://doi.org/10.1101/2021.01.25.427948">Moderna</a> and <a href="https://doi.org/10.1101/2021.01.27.427998">Pfizer/BioNTech</a> have shown their vaccines have a reduced efficacy rate against the B.1.1.7 and B.1.351 variants, compared to the non-variant strain, but their efficacy is still considerable. </p>
<p>Recently, Oxford/AstraZeneca reported that its vaccine is efficacious <a href="https://dx.doi.org/10.2139/ssrn.3779160">against B.1.1.7</a> but not <a href="https://www.bloomberg.com/news/articles/2021-02-06/astra-vaccine-less-effective-against-south-africa-variant-ft">against B.1.351</a>.</p><img src="https://counter.theconversation.com/content/154569/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dasantila Golemi-Kotra 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>With four COVID-19 vaccines approved for use in Canada, it’s time to answer FAQs about efficacy, immunity, eradication and variants.Dasantila Golemi-Kotra, Professor, Biology, York University, CanadaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1559212021-03-02T10:10:33Z2021-03-02T10:10:33ZCOVID vaccines: how to make sense of reports on their effectiveness<p>I feel desperately sorry for the public trying to make head or tail of some of the scientific discussions on the pandemic right now.</p>
<p>Science is being done, disseminated, argued about – sometimes peer-reviewed if we are lucky – and then immediately rewritten days later. Even with some experience – I’m a clinician-scientist – it’s hard to keep up. Data and reports come thick and fast, with little time to assess what they really mean.</p>
<p>One particularly fast-moving topic at the moment is vaccine efficacy. The emerging data from vaccination programmes looks great and seems to strongly back up the findings of clinical trials. However, in keeping with these frenzied times, on closer inspection what’s being presented is actually more complex.</p>
<h2>Assessing real-world effectiveness</h2>
<p>A “leaked” <a href="https://news.sky.com/story/covid-19-risk-of-illness-drops-95-8-after-second-pfizer-vaccine-dose-israel-says-12224403">paper</a> from Israel, since widely reported on, has suggested that the Pfizer/BioNTech vaccine is highly effective at preventing disease – and possibly transmission – in the real world. An additional unreviewed <a href="https://www.thelancet.com/action/showPdf?pii=S0140-6736%2821%2900448-7">study</a> has looked at the effectiveness of the Pfizer/BioNTech vaccine in health workers in Israel and is similarly positive. Almost immediately, a <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2101765?query=featured_home">peer-reviewed paper</a> looking at a wider Israeli population then emerged. It too suggests the vaccine is very effective.</p>
<p>UK <a href="https://www.ft.com/content/20576254-422b-4545-91ab-20b4d005bbf3">data</a> on both the Oxford/AstraZeneca and Pfizer/BioNTech vaccines was also recently revealed. All of these real-world studies are pointing at vaccine efficacy being around the 80-90% mark or above, though with some variation. So far, so straightforward. But from here on, things get a bit more complicated.</p>
<p>There has already been extensive and public critiquing of this work. These trials are “observational”. This means we are just watching what happens, rather than guiding or directing it. This is what a real-world trial usually is, but it comes with some problems.</p>
<p>Let’s take some of the UK data – Scotland’s specifically. The <a href="https://www.theguardian.com/world/2021/feb/22/scotland-covid-vaccination-drive-linked-to-big-drop-in-hospital-admissions">headlines</a> were focused on the vaccine cutting hospitalisations: Oxford/AstraZeneca by 94% and Pfizer/BioNtech by 85%. Social media immediately began comparing the two – missing arguably the biggest challenge that comes with observational studies: confounding variables.</p>
<p>These are additional factors that can influence results (rather than the thing being studied – in these cases, the vaccines). They are why in trials we try to guide what happens to some extent by randomising things where possible, to try to minimise the risk of things we’re not assessing influencing the result.</p>
<p>In the Scottish data, of the various possible confounding factors, two stand out. First is the different times at which the vaccines were rolled out. This is important because the amount of circulating virus significantly changed during the second wave, which muddies comparisons between the two vaccine types. The second factor is who was targeted for vaccination, as there were differences in who got what. As well as potentially accounting for differences in the two vaccines’ perceived effects, these and other confounding factors may also explain differences between how effective the vaccines were in trials versus the real world.</p>
<p>And speaking of the trials, hospitalisation wasn’t their focus. You need to look at very large numbers of people to prove or disprove differences in hospitalisation with COVID-19. Rather, the trials looked at whether vaccines prevented symptomatic disease – so measured effectiveness in a related but different way. </p>
<h2>What about mutations?</h2>
<p>Complicating things further are debates about how well the vaccines work against emerging variants, such as the B1351 variant first reported in South Africa. As with everything else in the pandemic, the data on this is still in evolution. The first thing we in the scientific community need to acknowledge is what we don’t know.</p>
<p>We think that some of these variants are likely <a href="https://theconversation.com/concerning-coronavirus-mutation-now-found-in-uk-variant-heres-what-you-need-to-know-153248">escaping</a> some of the effects of the vaccines, though the size of these effects and differences between specific vaccines is still unclear. The variants we are worried about now might not end up being the same ones we are worrying about in six months.</p>
<p>We don’t know for sure yet what the effects of the variants will be on vaccine efficacy because we have different things to look at – transmission, cases, more severe cases, hospitalisations and deaths. We will continue to collect real-world data, and when it becomes clear, this will change policies. Updates to the existing vaccines will almost certainly be a rolling process, and the great news is that these are <a href="https://www.cnbc.com/2021/02/24/moderna-covid-vaccine-booster-shots-south-africa-variant-trials.html">already underway</a>.</p>
<figure class="align-center ">
<img alt="Scientists in a lab using a pipette" src="https://images.theconversation.com/files/387024/original/file-20210301-20-17cdwul.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/387024/original/file-20210301-20-17cdwul.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/387024/original/file-20210301-20-17cdwul.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/387024/original/file-20210301-20-17cdwul.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/387024/original/file-20210301-20-17cdwul.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/387024/original/file-20210301-20-17cdwul.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/387024/original/file-20210301-20-17cdwul.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">
<figcaption>
<span class="caption">Boosters for the emerging coronavirus variants are already being created for the Pfizer, Oxford and Moderna vaccines.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/female-research-scientist-uses-micropipette-filling-691541080">Gorodenkoff/Shutterstock</a></span>
</figcaption>
</figure>
<p>In the meantime, I think scientists and commentators need to have an eye on the bigger picture. All of the licensed vaccines have excellent safety profiles. So far, they are dramatically reducing serious infections, significantly affecting milder cases, and transmission data will probably soon follow. </p>
<p>Debates about which vaccines are best are for the moment moot because we have no good head-to-head data and most importantly are in a situation where we have limited supplies of licensed vaccines that we need to quickly get into people. Debates around optimum strategies often don’t acknowledge the real world. And as time advances, it’s likely we will all end up being re-vaccinated with whatever emerges as the best options.</p>
<p>So what should you make of all this? Well, if you are offered a vaccine – any vaccine – take it enthusiastically. You should feel confident that it is safe and by the positive nature of both the <a href="https://theconversation.com/pfizer-vaccine-final-results-its-highly-protective-but-how-long-for-151966">trial</a> <a href="https://theconversation.com/astrazeneca-vaccine-delaying-the-second-dose-increases-protection-according-to-new-data-154617">data</a> and the experience of countries that are rolling them out in high numbers already – even if we don’t have highly precise measures of their real-world effectiveness yet.</p>
<p>But acknowledge too that because of the variants, you’re likely to end up getting a booster down the road. That booster may be a different vaccine entirely and be reassured that work is already underway to make sure it is based on the best evidence available.</p><img src="https://counter.theconversation.com/content/155921/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Toshner receives funding from the National Institute for Health Research, British Heart Foundation and Medical Research Council. He has received grants and personal fees from Bayer, personal fees from MSD, grants and personal fees from Actelion and personal fees from GSK, all unrelated to vaccine work.</span></em></p>Real-world studies of vaccines aren’t directly comparable with clinical trials, but their results are still good news.Mark Toshner, Lecturer in Translational Respiratory Medicine, University of CambridgeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1528562021-02-10T20:57:50Z2021-02-10T20:57:50Z5 factors that could dictate the success or failure of the COVID-19 vaccine rollout<figure><img src="https://images.theconversation.com/files/382964/original/file-20210208-17-in1iqm.jpg?ixlib=rb-1.1.0&rect=55%2C0%2C3299%2C2228&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Tamara Dus, director of University Health Network Safety Services, administers a Pfizer-BioNTech COVID-19 vaccine in Toronto. </span> <span class="attribution"><span class="source">THE CANADIAN PRESS/Frank Gunn</span></span></figcaption></figure><p>As a viral immunologist who develops immunization strategies to prevent infectious diseases and treat cancers, I would like to highlight outstanding questions about the emergency use of vaccines against <a href="https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/biosafety-directives-advisories-notifications/novel-coronavirus-january-27.html">SARS-CoV-2</a>, the coronavirus that causes <a href="https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it">COVID-19</a>.</p>
<p>These vaccines have raised hopes that the pandemic is <a href="https://www.bbc.com/news/health-54949799">nearing an end</a>. Hopefully this is true, but here are some potential sticking points.</p>
<h2>1. Long-term safety profile of COVID-19 vaccines</h2>
<p>Because COVID-19 vaccines have received regulatory approval in record-shattering time, these vaccines are being distributed with uniquely short safety profiles: only months’ worth of data are available. </p>
<p>Short-term safety of approved COVID-19 vaccines <a href="http://doi.org/10.1056/NEJMoa2035389">looks</a> <a href="http://doi.org/10.1056/NEJMoa2034577">good</a>. However, induction of <a href="https://www.mayoclinic.org/diseases-conditions/anaphylaxis/symptoms-causes/syc-20351468#:%7E:text=Anaphylaxis%20causes%20your%20immune%20system,rash%3B%20and%20nausea%20and%20vomiting.">anaphylactic reactions</a> in <a href="https://www.cbc.ca/news/canada/hamilton/covid-19-vaccine-allergic-reaction-1.5856827#:%7E:text=Canada-,Hamilton%20PSW%20says%20allergic%20reaction%20to%20COVID%2D19%20vaccine%20led,get%20a%20COVID%2D19%20vaccine.">some vaccine recipients</a> hasn’t helped the optics for those with <a href="https://www.ecdc.europa.eu/en/immunisation-vaccines/vaccine-hesitancy">vaccine hesitancy</a>. But these cases are rare and usually associated with pre-existing severe allergies. </p>
<p><a href="https://www.cfn-nce.ca/frailty-matters/what-is-frailty/">Twenty-three frail elderly</a> individuals in Norway <a href="https://doi.org/10.1136/bmj.n149">died shortly after receiving the Pfizer vaccine</a>. It is difficult to ascertain the reason for these deaths and they may have had nothing to do with the vaccine. It has put pressure on physicians in that country to try to determine which members of this demographic at high risk for COVID-19 mortality should and should not be vaccinated. </p>
<p>If too many unpredicted severe long-term side-effects were to accrue over time, this could be cause for withdrawal of approval for a vaccine.</p>
<h2>2. Duration of immunity of COVID-19 vaccines</h2>
<p><a href="https://www.sciencemag.org/news/2019/04/how-long-do-vaccines-last-surprising-answers-may-help-protect-people-longer">Duration of immunity</a> refers to how long a person is protected after being vaccinated. For previous vaccines, we could have reasonable confidence that immunity would last at least a few years prior to public rollouts. COVID-19 vaccines only have a few months’ worth of <a href="http://doi.org/10.1056/NEJMc2032195">data on duration of immunity</a>. </p>
<p>If <a href="https://science.sciencemag.org/content/364/6437/224.full">immunity declines</a> before “<a href="https://www.jhsph.edu/covid-19/articles/achieving-herd-immunity-with-covid19.html">herd immunity</a>” is achieved, previously vaccinated individuals will become susceptible to infection again and the rollout could fail.</p>
<figure class="align-center ">
<img alt="A person wearing a hooded coat and a face masks walks past a sign pointing to the entrance of COVID-19 vaccination clinic." src="https://images.theconversation.com/files/382965/original/file-20210208-13-rla7q4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/382965/original/file-20210208-13-rla7q4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=449&fit=crop&dpr=1 600w, https://images.theconversation.com/files/382965/original/file-20210208-13-rla7q4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=449&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/382965/original/file-20210208-13-rla7q4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=449&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/382965/original/file-20210208-13-rla7q4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=565&fit=crop&dpr=1 754w, https://images.theconversation.com/files/382965/original/file-20210208-13-rla7q4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=565&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/382965/original/file-20210208-13-rla7q4.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">
<figcaption>
<span class="caption">A man walks past the COVID-19 vaccination site at Maimonides long-term care facility in Montréal.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Ryan Remiorz</span></span>
</figcaption>
</figure>
<h2>3. Effectiveness of COVID-19 vaccines</h2>
<p>There were public declarations of greater than 90 per cent effectiveness for the <a href="https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-primary-efficacy-analysis-phase-3-cove-study">Moderna</a> and <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-vaccine-candidate-against">Pfizer</a> vaccines. Unfortunately, Pfizer did not publicly disclose the fact that there were large numbers of suspected, but unconfirmed cases of COVID-19 that were excluded from their calculation of efficacy. This was revealed in a <a href="https://www.fda.gov/media/144245/download">summary report</a> issued by the United States Food and Drug Administration (FDA).</p>
<p>Re-analysis of the data with this new information accounted for was performed by the associate editor of the <em>British Medical Journal</em>, who reported his non-peer-reviewed findings in the journal’s opinion column. His estimate suggests the true effectiveness of the vaccine might be as low as <a href="https://blogs.bmj.com/bmj/2021/01/04/peter-doshi-pfizer-and-modernas-95-effective-vaccines-we-need-more-details-and-the-raw-data/">19 to 29 per cent</a>. This can’t be confirmed or refuted until raw data not included in the FDA report are released. </p>
<p>The effectiveness reported for Sinovac Biotech’s currently unapproved vaccine <a href="https://edition.cnn.com/world/live-news/coronavirus-pandemic-vaccine-updates-01-08-21/h_ab72abc621a3b254838b7897a7a3c32b">dropped from 78 per cent</a> early in a clinical trial being run in Brazil to <a href="https://www.cnn.com/2021/01/13/asia/sinovac-covid-vaccine-efficacy-intl-hnk/index.html">50.38</a> per cent in the late stages of the trial. The cut-off for approval of COVID-19 vaccines has been set at <a href="https://www.nbcnews.com/health/health-news/fda-s-cutoff-covid-19-vaccine-effectiveness-50-percent-what-n1245506">50 per cent effectiveness</a>. If efficacy during public rollouts ends up being less than “advertised,” COVID-19 vaccines will under-perform relative to expectations.</p>
<h2>4. Risk of variants that can evade vaccine-induced immunity</h2>
<p><a href="https://www.who.int/csr/don/21-december-2020-sars-cov2-variant-united-kingdom/en/">Several</a> <a href="https://www.the-scientist.com/news-opinion/south-african-sars-cov-2-variant-alarms-scientists-68317">novel</a> <a href="https://www.who.int/csr/don/03-december-2020-mink-associated-sars-cov2-denmark/en/#:%7E:text=On%205%20November%2C%20the%20Danish,from%20August%20to%20September%202020.">variants</a> of SARS-CoV-2 have been identified recently. Coronaviruses copy their genetic material in a way that inherently <a href="https://media.nature.com/original/magazine-assets/d41586-020-02544-6/d41586-020-02544-6.pdf">induces random mutations</a>. If these mutations promote survival of the virus in vaccinated people, it could spell disaster for the current immunization strategy.</p>
<p>Although the risk of mutations that can evade vaccine-induced immunity cannot be accurately quantified, the way COVID-19 vaccines are being rolled out will likely increase the potential for this to occur for at least two reasons. First, the current vaccines confer narrowly focused immunity that targets a single <a href="https://doi.org/10.1038/s41467-020-15562-9">viral spike protein</a>. That means SARS-CoV-2 only needs to mutate one protein to evade vaccine-induced immunity. In contrast, it would be more difficult for the virus if it had to mutate several proteins to become immune-evasive.</p>
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Read more:
<a href="https://theconversation.com/the-mink-link-how-covid-19-mutations-in-animals-affect-human-health-and-vaccine-effectiveness-149947">The mink link: How COVID-19 mutations in animals affect human health and vaccine effectiveness</a>
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<p>Secondly, the <a href="https://www.canada.ca/en/public-health/services/diseases/2019-novel-coronavirus-infection/prevention-risks/covid-19-vaccine-treatment/vaccine-rollout.html#a4">vaccination program</a> is being rolled out in piece-meal fashion. This slow expansion of narrowly focused immunity among people who are surrounded by others who are not immune provides the time and contact with a “reservoir population” that a virus would need to generate random variants that can probe their potential to infect vaccinated people. </p>
<p>If a variant emerges that has altered its spike protein enough to bypass vaccine-induced immunity, the vaccine rollout could fail. If this happens, vaccines may need to be re-engineered to express a novel version of the spike protein, preferably with other proteins added to broaden immunity.</p>
<p>Importantly, acquisition of natural immunity, which targets multiple components of the virus, may reduce the risk of re-infection with variants that can bypass spike protein-specific immunity.</p>
<h2>5. Untested COVID-19 vaccine regimens</h2>
<p>Due to logistical challenges of rolling out two-shot vaccines and with the goal of maximizing how many and how quickly people can be vaccinated, <a href="https://www.healio.com/news/primary-care/20210106/could-a-singledose-vaccine-strategy-be-more-beneficial-in-covid19">single-dose</a> regimens, combining <a href="https://www.krem.com/article/news/verify/verify-covid-19-vaccine-mixing/293-89be6a9e-196c-414c-affa-dea94915963f">vaccines from different manufacturers</a>, and regimens that alter the <a href="https://doi.org/10.1136/bmj.n18">intervals between doses</a> are all being considered.</p>
<p>Note that the efficacy of Pfizer’s and Moderna’s vaccines only holds true beginning one to two weeks after the second shot, and using the recommended interval and dose. The performance of vaccines cannot be guaranteed if administered differently than the way in which they obtained regulatory approval. Indeed, results of a single-dose regimen with the Pfizer vaccine in Israel were <a href="https://www.theguardian.com/world/2021/jan/22/israeli-covid-chiefs-remarks-on-vaccine-inaccurate-say-officials">reported as disappointing</a>, although this is being debated.</p>
<p>The overall magnitude and/or quality of immune responses could be compromised by lengthening the interval between the two doses. Deviations in protocols <a href="https://www.fda.gov/news-events/press-announcements/fda-statement-following-authorized-dosing-schedules-covid-19-vaccines">should not be tolerated</a> unless backed up by clinical trial data.</p>
<h2>Herd immunity without rollout success?</h2>
<figure class="align-center ">
<img alt="A woman in a face mask with her hands in the air in celebration." src="https://images.theconversation.com/files/382967/original/file-20210208-21-1ujjv68.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/382967/original/file-20210208-21-1ujjv68.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/382967/original/file-20210208-21-1ujjv68.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/382967/original/file-20210208-21-1ujjv68.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/382967/original/file-20210208-21-1ujjv68.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/382967/original/file-20210208-21-1ujjv68.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/382967/original/file-20210208-21-1ujjv68.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">Registered nurse Sherry Plett celebrates after receiving a COVID-19 vaccine shot in the COVID-19 vaccination clinic at the Winnipeg Health Sciences Centre, Dec. 16, 2020.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/John Woods</span></span>
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<p>Can herd immunity still be achieved if COVID-19 vaccines underperform? Probably! Mounting evidence suggests most people that have been infected with SARS-CoV-2 have <a href="https://doi.org/10.1101/2020.12.18.20248336">naturally acquired immunity</a> that can <a href="http://doi.org/10.1126/science.abf4063">protect them from re-infection</a>. In fact, we have much longer duration data for naturally acquired immunity than for vaccine-induced immunity against SARS-CoV-2. </p>
<p>There is even evidence that pre-existing immunity against other coronaviruses, including those that merely cause colds, can <a href="http://doi.org/10.1126/science.abd3871">cross-protect</a> some people against SARS-CoV-2. This is not surprising because this is what our immune system is designed to do. All these people will contribute to the acquisition of herd immunity. </p>
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Read more:
<a href="https://theconversation.com/can-antibody-tests-tell-us-who-is-immune-to-covid-19-138240">Can antibody tests tell us who is immune to COVID-19?</a>
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<p>At the beginning of the pandemic most governments decided against using naturally acquired immunity as a primary way to achieve herd immunity to allow hospitals time to deal with severe illnesses. However, one year into the pandemic a huge unanswered question is: how close/far are we from natural herd immunity? </p>
<p>In Canada, we have done a poor job of tracking this. A starting point would be extensive antibody testing. If someone has antibodies in their blood against SARS-CoV-2, then they were infected at some point. If this had been combined with the direct detection of SARS-CoV-2 being done at testing centres, we could have had a massive data set in-hand.</p>
<p>Natural immunity acquired by an ever-growing number of people means fewer people require vaccination to reach herd immunity. As a bonus, natural immunity also equates to broader immunity; these people should be less susceptible to re-infection if an immuno-evasive SARS-CoV-2 variant emerges. </p>
<p><a href="https://www.statcan.gc.ca/eng/survey/household/5339/brochure">Statistics Canada</a> is initiating a large-scale study to conduct antibody testing on randomly selected Canadians. A smaller study by a <a href="https://www.utoronto.ca/news/u-t-epidemiologist-leads-study-tracking-covid-19-immunity-10000-canadians">researcher at the University of Toronto</a> was started in June 2020. Data from these studies could be used to estimate how much natural immunity exists in the general population. However, looking only for circulating antibodies against SARS-CoV-2 will likely underestimate immunity. These will often disappear, but the memory B cells that produce them <a href="https://doi.org/10.1101/2020.11.15.383323">are usually long-lasting</a> and can <a href="https://doi.org/10.1038/s41577-020-00436-4">confer protection</a>.</p><img src="https://counter.theconversation.com/content/152856/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Byram Bridle received funding from the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, the Canada Foundation for Innovation, and Ontario COVID-19 Rapid Research Funding.</span></em></p>The arrival of COVID-19 vaccines has raised hope for an end to the pandemic. Hopefully that’s true, but there are variables. Here are some factors that could affect the success of the vaccine rollout.Byram W. Bridle, Associate Professor of Viral Immunology, Department of Pathobiology, University of GuelphLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1546172021-02-05T13:46:37Z2021-02-05T13:46:37ZAstraZeneca vaccine: delaying the second dose increases protection, according to new data<figure><img src="https://images.theconversation.com/files/382519/original/file-20210204-22-zu1vq8.jpg?ixlib=rb-1.1.0&rect=97%2C272%2C5955%2C3658&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/doctor-giving-senior-woman-vaccination-virus-1868898253">Yuganov Konstantin/Shutterstock</a></span></figcaption></figure><p>The Oxford/AstraZeneca vaccine is effective at preventing people from developing COVID-19 and could reduce viral transmission, according to a new <a href="https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3777268">scientific paper</a> from the team behind the vaccine.</p>
<p>The paper also suggests that delaying the second dose to 12 weeks after the first works especially well. The protective effect of the first dose doesn’t appear to wane during these 12 weeks, and leaving a longer gap between doses ultimately seems to make the second more protective.</p>
<p>These promising new findings come from an analysis of clinical trial data, updating a <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext">previous paper</a> on the vaccine’s trial results published in early December. However, it’s important to keep in mind that the paper is a preprint – meaning its results haven’t yet been scrutinised formally by other scientists.</p>
<p>The main difference between this paper and the last is that more cases of COVID-19 have been included. In the December paper, 192 cases of illness were included in the analysis, enough to give a general estimate of the amount by which the vaccine reduces the risk of developing symptomatic COVID-19 – otherwise known its efficacy. This new paper analyses 332 cases.</p>
<p>More cases appearing among trial participants doesn’t mean the vaccine isn’t working as well. As before, the majority occurred in those who didn’t get the vaccine, meaning its overall efficacy is broadly the same: 67% (still lower than other authorised COVID-19 vaccines, but nevertheless offering important protection). </p>
<p>Rather, having more cases to look at means the authors can now make more robust estimates of the vaccine’s efficacy. It’s also allowed them to address the dosing regimen, whether the vaccine prevents asymptomatic infection and how protective a single dose actually is.</p>
<h2>The half-dose debate</h2>
<p>One surprising trial outcome reported in the earlier paper was that efficacy seemed to be much higher in volunteers given only half a dose in their first injection. The half-dosing was apparently an <a href="https://www.theguardian.com/uk-news/2020/nov/23/oxford-covid-vaccine-hit-90-success-rate-thanks-to-dosing-error">error</a> and so was considered to be a serendipitous mistake. In the UK part of the trial, giving two standard doses resulted in 59% efficacy, whereas the efficacy of a half dose followed by a standard dose was 90%. </p>
<p>In an <a href="https://theconversation.com/oxford-covid-19-vaccine-newly-published-results-show-it-is-safe-but-questions-remain-over-its-efficacy-151774">earlier Conversation article</a>, I raised concerns about the reliability of any conclusions drawn on starting with a half-dose. The UK Medicines and Health Products Regulatory Agency <a href="https://www.gov.uk/government/publications/regulatory-approval-of-covid-19-vaccine-astrazeneca/information-for-healthcare-professionals-on-covid-19-vaccine-astrazeneca">licensed</a> the standard-dosing schedule, <a href="https://www.reuters.com/article/uk-health-coronavirus-britain-vaccine-mh-idUSKBN294128">saying</a> that when assessing the data, the benefits of the initial half-dose “were not borne out by the full analysis”.</p>
<figure class="align-center ">
<img alt="A gloved hand holding half a vial of vaccine" src="https://images.theconversation.com/files/382523/original/file-20210204-22-x6tv9d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/382523/original/file-20210204-22-x6tv9d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=402&fit=crop&dpr=1 600w, https://images.theconversation.com/files/382523/original/file-20210204-22-x6tv9d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=402&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/382523/original/file-20210204-22-x6tv9d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=402&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/382523/original/file-20210204-22-x6tv9d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=505&fit=crop&dpr=1 754w, https://images.theconversation.com/files/382523/original/file-20210204-22-x6tv9d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=505&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/382523/original/file-20210204-22-x6tv9d.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">Giving people half a dose in the first injection wasn’t meant to happen – it came about because of a mistake.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/doctors-hand-blue-gloves-hold-vial-1812635860">Soho A Studio/Shutterstock</a></span>
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<p>It’s very clear in this second paper that the dosing error was not serendipitous at all. Rather, the greater efficacy for those receiving an initial half-dose appears to be down to many of them receiving their second injection much later. </p>
<p>This new analysis shows that vaccine efficacy after the second dose was only 55% if the gap between doses was less than six weeks, but was 81% if the gap was 12 weeks or more. Although not directly presented in the paper, it appears that with a 12-week gap between doses there was very little difference in efficacy for those receiving an initial half or full dose.</p>
<h2>Mind the gap</h2>
<p>One of the more intense debates around the UK vaccine rollout has concerned increasing the gap between doses to 12 weeks. The <a href="https://theconversation.com/delaying-the-second-covid-vaccine-dose-a-medical-expert-answers-key-questions-152771">thinking</a> was that although a single injection may not be as protective as two, delaying the second dose would allow more people to be given some protection with the first, leading to fewer deaths. </p>
<p>In light of this, this paper also looks at the efficacy of a single injection of the Oxford/AstraZeneca vaccine. Of course, this is only relevant to people receiving this vaccine. Anyone receiving the Pfizer/BioNTech or Moderna vaccines in the UK will also have their doses spaced out by 12 weeks, but we don’t have a clear view yet of what effect – if any – this has on these vaccines’ efficacy.</p>
<p>From 22 days after being given, the paper states that the efficacy of the first dose of the Oxford/AstraZeneca vaccine is 76%. The paper also finds no evidence of efficacy declining during the 90 days following the first injection – meaning a first dose should remain protective until the second is given 12 weeks later. </p>
<p>At first sight, it appears that a single-dose regimen may even provide better protection than two doses (76% vs 63%). However, the <a href="https://www.simplypsychology.org/confidence-interval.html">confidence intervals</a> for these figures overlap, meaning that in reality these results may not be that different.</p>
<p>Indeed, overall we need to be a little cautious here. Testing the vaccine’s efficacy after delaying the second dose for different amounts of time wasn’t an original aim of the trial. This means that people weren’t <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/randomization">randomly assigned</a> how long they would have to wait for their second dose to eliminate potential bias.
Because of this, it could be that these findings have been influenced by other factors.</p>
<h2>Preventing transmission?</h2>
<p>One aspect of this paper <a href="https://www.bbc.co.uk/news/health-55910964">picked up by the media</a> is the suggestion that the vaccine could substantially cut the spread of the virus. However, we also have to be somewhat cautious with accepting this conclusion. </p>
<p>As well as recording symptomatic infections, the authors also took regular throat swabs for PCR testing to see what effect the vaccine had on asymptomatic infections. The overall efficacy at preventing symptomatic infections after two standard doses was 67%, but for preventing any infection (as measured by a positive PCR test) it was 50% – a worthwhile reduction, but not enough to prevent all transmission. </p>
<p>Any vaccine that reduces the incidence of symptomatic infections <a href="https://theconversation.com/coronavirus-few-vaccines-prevent-infection-heres-why-thats-not-a-problem-152204">will also reduce</a> the transmission of the virus somewhat. But people with asymptomatic infections <a href="https://journals.plos.org/plosmedicine/article?id=10.1371%2Fjournal.pmed.1003346">can still spread the virus</a>, albeit rather less effectively. So unless a vaccine is highly effective at preventing these, it won’t be able to fully prevent the disease spreading.</p>
<p>And, as <a href="https://www.statnews.com/2021/02/03/with-a-seductive-number-astrazeneca-study-fueled-hopes-that-eclipsed-its-data/">others have noted</a>, seeing a reduction in the number of people carrying the virus as a result of being vaccinated doesn’t definitively prove that it will reduce transmission – this is still quite a big inference to make.</p><img src="https://counter.theconversation.com/content/154617/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Paul Hunter consults to The World Health Organisation. He receives funding from National Institute for Health Research, World Health Organization and The European Regional Development Fund. </span></em></p>New trial data appears to support pushing back the second dose to 12 weeks.Paul Hunter, Professor of Medicine, University of East AngliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1543062021-01-29T16:59:22Z2021-01-29T16:59:22ZGermany may not give the Oxford-AstraZeneca vaccine to over-65s, but that doesn’t mean it won’t work<figure><img src="https://images.theconversation.com/files/381380/original/file-20210129-20349-g79bze.jpg?ixlib=rb-1.1.0&rect=263%2C136%2C5931%2C4045&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/black-woman-doctor-nurse-medical-uniform-1875121819">Studio Romantic/Shutterstock</a></span></figcaption></figure><p>The Oxford-AstraZeneca vaccine has been receiving <a href="https://theconversation.com/what-is-behind-the-eus-dispute-with-astrazeneca-over-covid-19-vaccines-154161">a lot of attention</a> recently. The EU has been dissatisfied with <a href="https://theconversation.com/covid-vaccine-supply-is-causing-an-eu-crisis-so-whats-being-done-to-speed-up-production-154153">production hold-ups</a>, while the German health ministry has raised questions over its efficacy in older age groups. As a result, Stiko – the German Standing Committee on Vaccination – has suggested in a draft recommendation that the vaccine should not be given to people over 65. </p>
<p>If Germany does decide not to authorise the vaccine for over-65s, this will be because it considers there were insufficient people over 55 included in the vaccine’s phase 3 trials to give a good estimate of efficacy in older age groups. This is an issue that has been <a href="https://theconversation.com/oxford-covid-19-vaccine-newly-published-results-show-it-is-safe-but-questions-remain-over-its-efficacy-151774">raised before</a>. </p>
<p>In fact, in the <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext">peer-reviewed write-up</a> of the Oxford-AstraZeneca trials, the authors admitted that following their tests, “vaccine efficacy in older age groups could not be assessed”. But while this isn’t ideal, it’s not a reason to panic.</p>
<p>Indeed, the European Medicines Agency has now <a href="https://www.ema.europa.eu/en/news/ema-recommends-covid-19-vaccine-astrazeneca-authorisation-eu">authorised the vaccine</a> for use in Europe in all adults over 18, despite German concerns. The EMA acknowledged that efficacy data for over-55s was lacking, but said that it expected the vaccine to be protective “given that an immune response is seen in this age group and based on experience with other vaccines”.</p>
<h2>Over-65s should still take the jab if offered</h2>
<p>Even though there’s not currently sufficient data in the public domain to estimate efficacy of the Oxford-AstraZeneca vaccine in older age groups, there is still a lot of evidence that the vaccine will be effective in older people.</p>
<p>As we grow older, we tend to respond less well to vaccines and natural infections, in a process known as <a href="https://immunityageing.biomedcentral.com/articles/10.1186/s12979-019-0164-9">immunosenescence</a>. But this is not a sudden drop in immunity once you get past a certain age. For example, the mRNA vaccines against COVID-19 made by <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2034577">Pfizer</a> and <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2035389">Moderna</a> – for which there is more data – show very little drop, if any, in effectiveness in older age groups.</p>
<p>We also know from Oxford’s <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32466-1/fulltext">earlier phase 2 trials</a> (which checked that the vaccine stimulated an immune response in humans) that there is very little difference in the amount of “IgG” antibodies produced in people over 70 years old compared to people in the 18-55 and 56-69 age groups. And there’s <a href="https://www.nejm.org/doi/full/10.1056/NEJMe2034495">emerging evidence</a> that these IgG antibodies protect against severe disease, thanks to trials that are looking at using certain antibodies as a treatment for COVID-19.</p>
<p>There’s also <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32466-1/fulltext">good evidence</a> that the vaccine is safe in this age group. And older people report fewer side-effects from it than younger people.</p>
<p>The vaccine makers have since recruited more older people into their ongoing phase 3 trials, and so better data on efficacy will be available soon. The UK is also putting a lot of effort into post-vaccine surveillance, and this should lead to good data on the vaccine’s effectiveness in the UK in coming weeks – especially in the 80+ age group, who were initially offered the vaccine.</p>
<h2>What about the 8% efficacy claim?</h2>
<p>A further claim – made by the German newspaper Handelsblatt – that the vaccine is only 8% effective in older age groups is almost certainly false. The German ministry of health has <a href="https://www.theguardian.com/world/2021/jan/26/german-government-challenges-astrazeneca-covid-vaccine-efficacy-reports">suggested</a> that this figure arose from a misunderstanding of the vaccine’s trial data by the newspaper.</p>
<p>Indeed, looking at <a href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/951851/uk-clean-spc-covid-19-vaccine-astrazeneca-reg174.pdf">data available in the public domain</a>, it seems there were only two cases of infection reported in older people during the trials. One was in the group receiving the vaccine, and one in another group receiving a placebo. With this data, it’s just not possible to estimate the true efficacy with any precision. </p>
<p>The overwhelming balance of evidence is that the Oxford-AstraZeneca vaccine is safe in older people and will provide high protection against severe disease, hospitalisation and death. Speaking as someone in his mid-60s, I would happily accept whatever vaccine I am offered when I eventually make it to the front of the queue.</p><img src="https://counter.theconversation.com/content/154306/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Paul Hunter receives funding from National Institute for Health Research, World Health Organization and The European Regional Development Fund.</span></em></p>The vaccine is still very likely to be protective in over-65s, even if efficacy in this age group is unknown.Paul Hunter, Professor of Medicine, University of East AngliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1518332021-01-06T13:10:55Z2021-01-06T13:10:55ZWhat is a margin of error? This statistical tool can help you understand vaccine trials and political polling<figure><img src="https://images.theconversation.com/files/377225/original/file-20210105-21-1a370vy.jpg?ixlib=rb-1.1.0&rect=457%2C147%2C4718%2C3298&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">All predictions, whether scientific or political, include uncertainty.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/monitoring-the-power-of-high-frequency-laser-used-royalty-free-image/1007669174?adppopup=true"> CasarsaGuru/E+ via Getty Images</a></span></figcaption></figure><p>In the last year, statistics have been unusually important in the news. How <a href="https://theconversation.com/coronavirus-tests-are-pretty-accurate-but-far-from-perfect-136671">accurate is the COVID-19 test</a> you or others are using? How do researchers know the <a href="https://theconversation.com/trump-is-taking-the-latest-in-covid-19-treatments-heres-what-doctors-know-works-against-the-virus-147398">effectiveness of new therapeutics</a> for COVID-19 patients? How can television networks <a href="https://www.vox.com/policy-and-politics/21535103/when-will-we-get-election-results-calls-networks">predict the election results</a> long before all the ballots have been counted? </p>
<p>Each of these questions involves some uncertainty, but it is still possible to make accurate predictions as long as that uncertainty is understood. One tool statisticians use to quantify uncertainty is called the margin of error.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/376295/original/file-20201221-19-q2d6lo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A graphic of people separated into a pie chart." src="https://images.theconversation.com/files/376295/original/file-20201221-19-q2d6lo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/376295/original/file-20201221-19-q2d6lo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/376295/original/file-20201221-19-q2d6lo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/376295/original/file-20201221-19-q2d6lo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/376295/original/file-20201221-19-q2d6lo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/376295/original/file-20201221-19-q2d6lo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/376295/original/file-20201221-19-q2d6lo.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">In the real world, it is impossible to test or sample every relevant person, so statisticians rely on smaller samples drawn from a population.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/pie-chart-with-people-on-white-background-royalty-free-illustration/826228744?adppopup=true">Guzaliia Filimonova/iStock via Getty Images Plus</a></span>
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<h2>Limited data</h2>
<p><a href="https://scholar.google.com/citations?hl=en&user=T1RlT7gAAAAJ">I am a statistician</a>, and part of my job is to make inferences and predictions. With unlimited time and money, I could simply test or survey the entire group of people I am interested in to evaluate the question in mind and find the exact answer. For example, to find out the COVID-19 infection rate in the U.S., I could simply test the entire U.S. population. However, in the real world, you can never access 100% of a population. </p>
<p>Instead, statisticians sample a small portion of the population and build a model to make a prediction. Using statistical theory, that result from the sample is extrapolated to represent the whole population.</p>
<p>Ideally, a good sample should be representative of the total population, including gender, racial diversity, socioeconomic diversity, lifestyle patterns and other demographic measures. The larger the sample, the more similar it would be to the true population, and with a larger sample, the more confident statisticians become in their predictions. But there will always be some uncertainty.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/376293/original/file-20201221-15-1xre90f.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A graph showing margins of error for different sample sizes." src="https://images.theconversation.com/files/376293/original/file-20201221-15-1xre90f.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/376293/original/file-20201221-15-1xre90f.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=567&fit=crop&dpr=1 600w, https://images.theconversation.com/files/376293/original/file-20201221-15-1xre90f.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=567&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/376293/original/file-20201221-15-1xre90f.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=567&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/376293/original/file-20201221-15-1xre90f.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=713&fit=crop&dpr=1 754w, https://images.theconversation.com/files/376293/original/file-20201221-15-1xre90f.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=713&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/376293/original/file-20201221-15-1xre90f.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=713&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 larger the sample size, the more accurate the prediction and the smaller the margin of error.</span>
<span class="attribution"><a class="source" href="https://en.wikipedia.org/wiki/Margin_of_error#/media/File:Marginoferror95.PNG">Fadethree via Wikimedia Commons</a></span>
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<h2>Quantifying uncertainty</h2>
<p>Take drug development, for example. It is always true to predict that a new medication will be somewhere between 0% and 100% effective for everyone on Earth. But that isn’t a very useful prediction. It is a statistician’s job to narrow that range to something more useful. Statisticians usually call this range a confidence interval, and it is the range of predictions within which statisticians are very confident the true number will be found.</p>
<p>If a medication was tested on 10 individuals and seven of them found it effective, the estimated drug efficacy is 70%. But since the goal is to predict the efficacy in the whole population, statisticians need to account for the uncertainty of testing only 10 people. </p>
<p>[<em>The Conversation’s science, health and technology editors pick their favorite 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-favorite">Weekly on Wednesdays</a>.]</p>
<p>Confidence intervals are calculated using a mathematical formula that encompasses the sample size, the range of responses and the laws of probability. In this example, the confidence interval would be between 42% and 98% – a range of 56 percentage points. After testing only 10 people, you could say with high confidence that the drug is effective for between 42% and 98% of people in the whole population.</p>
<p>If you divide the confidence interval in half, you get the margin of error – in this case, 28%. The larger the margin of error, the less accurate the prediction. The smaller the margin of error, the more accurate the prediction. A margin of error that is almost 30% is still quite a wide range. </p>
<p>However, imagine that the researchers tested this new drug on 1,000 people instead of 10 and it was effective in 700 of them. The estimated drug efficacy is still going to be around 70%, yet this prediction is much more accurate. The confidence interval for the larger sample will be between 67% and 73% with a margin of error of 3%. You could say this drug is expected to be 70% effective, plus or minus 3%, for the entire population.</p>
<p>Statisticians would love to be able to predict with 100% accuracy the success or failure of a new medication or the exact outcomes of an election. However, this is not possible. There is always some uncertainty, and the margin of error is what quantifies that uncertainty; it must be considered when looking at results. In particular, the margin of error defines the range of predictions within which statisticians are very confident the true number will be found. An acceptable margin of error is a matter of judgment based on the degree of accuracy required in the conclusions to be drawn.</p><img src="https://counter.theconversation.com/content/151833/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ofer Harel receives funding from The National Science Foundation, US Food and Drug Administration and The National Institute of Health. He is also sits on the Bureau of Labor Statistics Technical Advisory Committee.</span></em></p>Whether you are predicting the outcome of an election or studying how effective a new drug is, there will always be some uncertainty. A margin of error is how statisticians measure that uncertainty.Ofer Harel, Professor of Statistics, University of ConnecticutLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1507322020-11-24T06:14:37Z2020-11-24T06:14:37ZAstraZeneca’s results signal more good vaccine news — but efficacy is only the beginning of the story<figure><img src="https://images.theconversation.com/files/370975/original/file-20201124-23-rcvunp.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C6720%2C4466&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>AstraZeneca has become the latest pharmaceutical company to reveal <a href="https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222hlr.html">promising results</a> in clinical trials, for its viral vector vaccine developed with the University of Oxford.</p>
<p>In a group given two full doses of the vaccine at least one month apart, the vaccine demonstrated <a href="https://www.abc.net.au/news/health/2020-11-24/do-coronavirus-vaccines-prevent-infection-or-disease/12905654">62% efficacy</a> at preventing COVID. Interestingly, in another group initially given a half dose of vaccine, followed by a full dose, the efficacy was 90%.</p>
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<p>This news follows similarly promising results for both <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine">Pfizer/BioNTech</a> and <a href="https://www.nih.gov/news-events/news-releases/promising-interim-results-clinical-trial-nih-moderna-covid-19-vaccine">Moderna’s</a> mRNA vaccines. Press announcements indicated both had efficacy above 90% in preventing symptomatic COVID-19. </p>
<p>It’s important to remember none of these results have yet been published in a peer-reviewed journal. It’s also important to consider that while these figures are encouraging, they don’t necessarily tell us everything we need to know about how well the vaccines will work in the real world.</p>
<h2>What does efficacy mean?</h2>
<p>When clinical trials report their results — and the media follow — the <a href="https://pubmed.ncbi.nlm.nih.gov/9855432/">correct term</a> is “efficacy”, rather than “effectiveness”. </p>
<p>Vaccine efficacy is the extent to which a vaccine achieves its intended effect under ideal circumstances, such as in a randomised clinical trial. </p>
<p>Vaccine effectiveness is the extent to which a vaccine achieves its intended effect in the usual clinical setting — so, when it’s used in the real world.</p>
<p>We never really know how effective vaccines are until they’re used in large numbers of people outside of a trial. This is partly because trials select those who can and can’t take part. </p>
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Read more:
<a href="https://theconversation.com/why-the-oxford-astrazeneca-vaccine-is-now-a-global-gamechanger-150660">Why the Oxford AstraZeneca vaccine is now a global gamechanger</a>
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<h2>Who is allowed to take part in a vaccine trial?</h2>
<p>Many thousands of volunteers are currently taking part in phase 3 trials for COVID vaccines. Pfizer has more than 43,000 participants; Moderna more than 30,000; and AstraZeneca more than 11,000.</p>
<p>But it’s important to recognise that although the participants are great in number, they’re not necessarily representative of all members of the population.</p>
<p>All clinical trials have inclusion and exclusion criteria. These are rules the researchers set at the outset of the trial to determine who is and isn’t allowed to take part. They may exclude certain people due to potential safety concerns.</p>
<p>In general, participants don’t have any severe underlying medical conditions, or if they do, they are usually under good control. </p>
<p>The phase 3 protocols for the <a href="https://media.tghn.org/medialibrary/2020/11/C4591001_Clinical_Protocol_Nov2020_Pfizer_BioNTech.pdf">Pfizer</a>, <a href="https://www.modernatx.com/sites/default/files/mRNA-1273-P301-Protocol.pdf">Moderna</a>, and <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32466-1/fulltext">AstraZeneca</a> vaccines all have similar exclusion criteria, as you can see in this table.</p>
<iframe title="Exclusion criteria for participation in selected phase 3 trials" aria-label="chart" id="datawrapper-chart-JzxN3" src="https://datawrapper.dwcdn.net/JzxN3/2/" scrolling="no" frameborder="0" style="border: none;" width="100%" height="380"></iframe>
<p>People who have previously had COVID-19, are pregnant, have weakened immune systems, have had recent blood transfusions, or have an unstable medical condition (for example, they’ve recently been hospitalised for their disease) were not allowed to take part in the trials. </p>
<p>The blood transfusions point is not because of safety concerns, but because the transfusion may <a href="https://immunisationhandbook.health.gov.au/vaccination-for-special-risk-groups/vaccination-for-people-who-have-recently-received-normal-human">inhibit the immune response</a> to the vaccine.</p>
<p>But this all means efficacy data from the trials so far reflect how generally healthy, non-pregnant people respond to the vaccines. It may not be the same in those people who have been excluded.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-to-read-results-from-covid-vaccine-trials-like-a-pro-149916">How to read results from COVID vaccine trials like a pro</a>
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<h2>What’s next? From efficacy to effectiveness</h2>
<p>At this stage, Australia has signed up for the <a href="https://www.health.gov.au/sites/default/files/documents/2020/11/australian-covid-19-vaccination-policy_1.pdf">Pfizer and AstraZeneca vaccines</a> should they meet the relevant safety and efficacy standards and gain regulatory approval.</p>
<p><a href="https://www.cnbc.com/2020/11/20/covid-19-vaccine-pfizer-will-apply-for-fda-emergency-use-authorization.html">Pfizer</a> has applied to the US Food and Drug Administration (FDA) for an emergency use authorisation, while AstraZeneca has said it will “<a href="https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222hlr.html">immediately</a>” prepare to submit its data to regulatory authorities around the world.</p>
<p>The FDA and any other regulators that receive applications — likely including the Therapeutic Goods Administration in Australia — will assess the vaccines on a case-by-case basis. They will consider the target population to receive the vaccine (for example, older people or health-care workers), the characteristics of the vaccine, and all relevant evidence on the vaccine’s safety and efficacy we have so far from preclinical and human trials. </p>
<p>The regulators will also need to decide whether to authorise the vaccine for groups who were excluded from the trial, such as pregnant women. In any event, this emergency use authorisation is an early, or conditional approval, as the phase 3 trials are still ongoing.</p>
<p>Over time, we’ll accumulate more data on the safety and efficacy on these three vaccine candidates, as participants complete the phase 3 trials, and possibly from <a href="https://www.medical-reference.net/2013/10/bridging-studies-definition-history-importance.html">further clinical trials</a> including different groups who were initially excluded. For example, further studies might evaluate the vaccine’s safety and efficacy in immunosuppressed people or pregnant women.</p>
<p>Monitoring how well the vaccine works and how safe it is will continue as the vaccine is rolled out in the community, outside of a tightly controlled clinical trial.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/modernas-covid-vaccine-reports-95-efficacy-it-means-we-might-have-multiple-successful-vaccines-150266">Moderna's COVID vaccine reports 95% efficacy. It means we might have multiple successful vaccines</a>
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<p>The early efficacy results from the Pfizer, Moderna and AstraZeneca trials are very encouraging. They may lead to an emergency use authorisation in selected populations, with vaccines potentially rolling out in the coming months. </p>
<p>However, we’re only at the beginning of the story. As we transition from these trials to the real world, we must continue to monitor whether any approved vaccine is safe and effective — not just efficacious — across the spectrum of the population.</p><img src="https://counter.theconversation.com/content/150732/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Nicholas Wood receives funding from the NHMRC for a Career Development Fellowship. He has received funding from the MRFF to conduct a COVID-19 Phase 1 vaccine trial.</span></em></p>Data coming through from phase 3 trials are encouraging. But participants don’t represent the whole community — so we can’t be sure these vaccines will work as well in everyone.Nicholas Wood, Associate Professor, Discipline of Childhood and Adolescent Health, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1502702020-11-23T22:42:41Z2020-11-23T22:42:41ZHow pharma can build trust in COVID-19 vaccines: Transparency on trials and side-effects<figure><img src="https://images.theconversation.com/files/370843/original/file-20201123-21-7rxk7n.jpg?ixlib=rb-1.1.0&rect=103%2C0%2C2505%2C2164&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A woman walks by graffiti reading 'No vaccine, No tracking, No COVID', in Montréal on Aug. 16, 2020.
</span> <span class="attribution"><span class="source">THE CANADIAN PRESS/Graham Hughes</span></span></figcaption></figure><p>Promising results from large clinical trials testing three vaccines to prevent COVID-19 bring us a step closer to a widely available vaccine. </p>
<p>On Nov. 9, Pfizer’s <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-vaccine-candidate-against#:%7E:text=The%20Phase%203%20clinical%20trial,racially%20and%20ethnically%20diverse%20backgrounds">interim analysis</a> from its Phase 3 vaccine trial revealed it prevented 90 per cent of COVID-19 cases. (The vaccine’s efficacy was revised to 95 per cent in a recent <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine">more complete analysis of the data</a>.) Just one week later, Moderna announced <a href="https://www.nih.gov/news-events/news-releases/promising-interim-results-clinical-trial-nih-moderna-covid-19-vaccine">interim results</a> from its own Phase 3 trial: its vaccine conferred 94.5 per cent protection against illness. </p>
<p>On Nov. 23, AstraZeneca reported an <a href="https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222hlr.html">interim analysis</a> from two separate Phase 3 trials that looked at two dosing regimens. Its COVID-19 vaccine, developed with the University of Oxford in the United Kingdom, was 70 per cent efficacious overall, with one dosage regimen protecting against the disease 90 per cent of the time.</p>
<p>But a vaccine that works is useless if people are unwilling to take it. </p>
<h2>Vaccine hesitancy</h2>
<p>Polling in the United States and Canada reveals increasing distrust of COVID-19 vaccines. This distrust threatens the widespread uptake of the vaccine required to bring an end to the pandemic.</p>
<p>The proportion of <a href="https://morningconsult.com/2020/11/16/coronavirus-vaccine-willingness-mid-november/">Americans surveyed</a> who “would get a potential coronavirus vaccine” has dropped to 52 per cent in November from 72 per cent in April. Notably, the November poll was conducted after Pfizer’s announcement.</p>
<p>A similar trend is seen in Canada. In July, 46 per cent of <a href="http://angusreid.org/canada-covid-19-vaccine/">Canadians polled</a> indicated they would get vaccinated “as soon as possible,” 32 per cent would “wait for others to go first and immunize later,” and 14 per cent would not get vaccinated. After Pfizer’s announcement, Canadians surveyed were slightly more reluctant: only 40 per cent would get a vaccine right away, while 36 per cent would wait.</p>
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<a href="https://images.theconversation.com/files/370882/original/file-20201123-17-1rdjja2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A woman in jeans and a denim shirt sits on the end of an exam table in a medical exam room." src="https://images.theconversation.com/files/370882/original/file-20201123-17-1rdjja2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/370882/original/file-20201123-17-1rdjja2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/370882/original/file-20201123-17-1rdjja2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/370882/original/file-20201123-17-1rdjja2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/370882/original/file-20201123-17-1rdjja2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/370882/original/file-20201123-17-1rdjja2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/370882/original/file-20201123-17-1rdjja2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Jennifer Haller waits in an exam room before being given a shot in the first-stage study of Moderna’s coronavirus vaccine on March 16, 2020, at the Kaiser Permanente Washington Health Research Institute in Seattle. Haller was the first person to receive the shot.</span>
<span class="attribution"><span class="source">(AP Photo/Ted S. Warren)</span></span>
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<p>The World Health Organization defines vaccine hesitancy as “the reluctance or refusal to vaccinate despite the availability of vaccines,” and has identified it as a <a href="https://www.who.int/news-room/spotlight/ten-threats-to-global-health-in-2019">leading threat to global health</a>. While vaccine hesitancy is a complex social phenomenon, with COVID-19 it is clear that the <a href="https://www.pewresearch.org/science/2020/09/17/u-s-public-now-divided-over-whether-to-get-covid-19-vaccine/">rapid pace of vaccine development</a> and its <a href="https://www.ctvnews.ca/health/coronavirus/scientists-raise-alarm-over-signs-of-vaccine-hesitancy-1.5152604">perceived politicization</a> are driving distrust. </p>
<h2>Transparency builds trust</h2>
<p>As vaccine developers and sponsors of ongoing trials, pharmaceutical companies are uniquely situated to help <a href="https://www.msn.com/en-us/video/superbowl-chiefs/modernas-covid-19-vaccine-and-public-trust/vp-BB1b4ud3">promote public trust</a> in COVID-19 vaccines. </p>
<p>Pharma must ensure greater transparency in vaccine trials. Transparency will allow independent scientists to assess the rigour of trial designs and the reliability of results. Further, transparency may increase public understanding of and confidence in vaccine development. </p>
<p>Pharma has taken some steps in the right direction.</p>
<p>In September, nine companies developing COVID-19 vaccines issued a public pledge to be bound by science — not politics. They affirmed that vaccine development will be guided by “high ethical standards and sound scientific principles” and that applications for regulatory approval will only be made “after demonstrating safety and efficacy through a Phase 3 clinical study.”</p>
<p>Subsequently, four companies (<a href="https://s3.amazonaws.com/ctr-med-7111/D8110C00001/52bec400-80f6-4c1b-8791-0483923d0867/c8070a4e-6a9d-46f9-8c32-cece903592b9/D8110C00001_CSP-v2.pdf">AstraZeneca</a>, <a href="https://www.jnj.com/coronavirus/covid-19-phase-3-study-clinical-protocol">Johnson & Johnson</a>, <a href="https://www.modernatx.com/sites/default/files/mRNA-1273-P301-Protocol.pdf">Moderna</a> and <a href="https://pfe-pfizercom-d8-prod.s3.amazonaws.com/2020-11/C4591001_Clinical_Protocol_Nov2020.pdf">Pfizer</a>) took the unusual step of making the protocols for their Phase 3 vaccine trials public. The protocol is the detailed plan for the trial, and it contains information on recruitment of volunteers, vaccine administration, participant followup and statistical analysis. </p>
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<a href="https://images.theconversation.com/files/370883/original/file-20201123-17-1n8b6sw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A man wearing a hat and a face mask gets an inject from a health-care worker out of frame." src="https://images.theconversation.com/files/370883/original/file-20201123-17-1n8b6sw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/370883/original/file-20201123-17-1n8b6sw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=361&fit=crop&dpr=1 600w, https://images.theconversation.com/files/370883/original/file-20201123-17-1n8b6sw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=361&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/370883/original/file-20201123-17-1n8b6sw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=361&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/370883/original/file-20201123-17-1n8b6sw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=453&fit=crop&dpr=1 754w, https://images.theconversation.com/files/370883/original/file-20201123-17-1n8b6sw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=453&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/370883/original/file-20201123-17-1n8b6sw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=453&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">A volunteer is injected with AstraZenica’s COVID-19 vaccine candidate at the Chris Hani Baragwanath hospital in Soweto, Johannesburg, South Africa on June 24, 2020.</span>
<span class="attribution"><span class="source">(AP Photo/Siphiwe Sibeko)</span></span>
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<p>Two companies (<a href="https://www.covid19vaccinetrial.co.uk/participate-oxford">AstraZeneca</a> and <a href="https://www.modernatx.com/sites/default/files/u1421/Moderna_mRNA-1273-P301-Informed-Consent.pdf">Moderna</a>) additionally made available consent documents provided to volunteers.</p>
<p>But pharma must go further.</p>
<h2>Data monitoring committees</h2>
<p>Phase 3 trials have independent <a href="https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-data-monitoring-committees_en.pdf">data monitoring committees</a> that review in real time any serious adverse events and trends in accumulating data. Traditionally, the membership of these committees is confidential, and their work is done in secret. </p>
<p>Of the data monitoring committees overseeing current COVID-19 vaccine trials, we know next to nothing. This may be business as usual, but in the face of a global pandemic, business as usual is not good enough.</p>
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Read more:
<a href="https://theconversation.com/canadas-covid-19-vaccine-task-force-needs-better-transparency-about-potential-conflicts-of-interest-147323">Canada’s COVID-19 Vaccine Task Force needs better transparency about potential conflicts of interest</a>
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<p>Membership of data monitoring committees should be public. Trust would be enhanced by knowledge that people making key decisions about safety in COVID-19 trials have the requisite expertise, and they are not encumbered by conflicts of interest.</p>
<h2>Adverse events</h2>
<p>On Sept. 8, AstraZeneca’s vaccine trials were <a href="https://www.statnews.com/2020/09/08/astrazeneca-covid-19-vaccine-study-put-on-hold-due-to-suspected-adverse-reaction-in-participant-in-the-u-k/">paused due to a serious adverse event</a>. The next day, while a <a href="https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/statement-on-astrazeneca-oxford-sars-cov-2-vaccine-azd1222-covid-19-vaccine-trials-temporary-pause.html">press release</a> referred only to a “single event of an unexplained illness,” AstraZeneca’s CEO revealed in a <a href="https://www.statnews.com/2020/09/09/astrazeneca-covid19-vaccine-trial-hold-patient-report/">phone call to investors</a> that the adverse event involved a woman hospitalized with transverse myelitis, an inflammation of the spinal cord.</p>
<p>One month later, Johnson & Johnson’s Phase 3 vaccine trial <a href="https://www.statnews.com/2020/10/12/johnson-johnson-covid-19-vaccine-study-paused-due-to-unexplained-illness-in-participant/">was paused</a> “due to an unexplained illness in a study participant.” No further details would be provided, said a company representative: “We must respect this participant’s privacy.”</p>
<p>If one were seeking to inflame distrust in vaccine trials, it is difficult to imagine a more effective strategy.</p>
<p>Pharma should publicly disclose details of any serious adverse event in a vaccine trial. Given the global attention focused on these trials, a pause — and the obvious inference that something bad has happened — is certain to become international news. In trials involving tens of thousands of people, sufficient details of the adverse event can be released without imperilling participant privacy. </p>
<p>Revealing the steps taken to investigate the adverse event and the reasons for restarting the trial are an opportunity to reinforce the careful oversight of vaccine trials and reassure an anxious public.</p>
<h2>Open access to data</h2>
<p>Finally, pharma should commit to making <a href="https://doi.org/10.1136/bmj.j2372">de-identified participant data from vaccine trials publicly available</a> as soon as possible. This allows independent scientists to investigate and confirm the reliability of analyses. In the case of discrepant interpretations, these can be mediated and resolved in plain view.</p>
<p>Responding to COVID-19 vaccine hesitancy requires unprecedented — and no doubt uncomfortable — transparency from pharma. But the <a href="https://doi.org/10.1038/d41586-020-02738-y">stakes could not be higher</a>: “History has shown that once public trust in vaccines has been compromised it is difficult to win back.”</p><img src="https://counter.theconversation.com/content/150270/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Charles Weijer consults with Cardialen, Eli Lilly & Company, and Research Triangle Institute (RTI) International.</span></em></p>COVID-19 vaccines are at risk of being undermined by vaccine hesitancy. Pharma must take steps to ensure transparency in data monitoring committees and trial data to build public trust in vaccines.Charles Weijer, Professor of medicine, epidemiology & biostatistics, and philosophy, Western UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1481682020-11-17T18:51:59Z2020-11-17T18:51:59ZWe may have to accept a ‘good enough’ COVID-19 vaccine, at least in 2021<figure><img src="https://images.theconversation.com/files/368988/original/file-20201112-17-100cgy6.jpg?ixlib=rb-1.1.0&rect=1%2C1%2C997%2C661&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/ampoules-covid19-vaccine-on-laboratory-bench-1696929460">Shutterstock</a></span></figcaption></figure><p>Australian health minister Greg Hunt <a href="https://www.abc.net.au/news/2020-11-11/coronavirus-australia-live-news-covid-19-latest-remembrance-day/12870516">said recently</a> the government is on track to deliver COVID-19 vaccines from March 2021.</p>
<p>US biotech firm Moderna has just announced its COVID-19 vaccine has <a href="https://theconversation.com/modernas-covid-vaccine-reports-95-efficacy-it-means-we-might-have-multiple-successful-vaccines-150266">95% efficacy</a>, following on the heels of Pfizer’s claimed <a href="https://theconversation.com/90-efficacy-for-pfizers-covid-19-mrna-vaccine-is-striking-but-we-need-to-wait-for-the-full-data-149818">90% efficacy</a> and the Russian Sputnik V vaccine’s <a href="https://sputnikvaccine.com/newsroom/pressreleases/the-first-interim-data-analysis-of-the-sputnik-v-vaccine-against-covid-19-phase-iii-clinical-trials-/">92% efficacy</a>, albeit based on limited data and yet to be peer-reviewed. </p>
<p>We’ll likely see more preliminary results from other vaccine trials reported in the media in coming weeks and months.</p>
<p>While an effective vaccine will provide the best chance of controlling the disease, it is sadly not so simple. No vaccine will be perfect or end the pandemic instantly. The first vaccines are also likely to have significant limitations.</p>
<p>The issue is how good a vaccine is good enough? We also need to think about what imperfections we — as individuals, regulators or governments — will be prepared to accept.</p>
<h2>How safe is safe enough?</h2>
<p>Safety is obviously the major concern. Vaccines are designed to be given to very large numbers of healthy people. This means even an extremely rare, serious adverse event, when applied to a population of millions, can produce major harm.</p>
<p>Short-term trials on small population samples relative to the numbers expected to receive the vaccine may also not be able to pick up relatively rare but important risks. This is a problem we may not be able to avoid because the only way to find out is to give the vaccine to large numbers of people and then allow long periods of time to elapse, for any long-term adverse events to become evident.</p>
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<p>Obviously, all therapeutic agents carry the possibility of adverse effects and in individual cases decisions have to be made about whether the potential benefits justify taking the risks. It is arguable that the extreme dangers associated with COVID-19 justify accepting a higher level of risk for the vaccine. However, while the US and Australian regulatory authorities have <a href="https://www.fda.gov/files/vaccines,%20blood%20&%20biologics/published/Ensuring-the-Safety-of-Vaccines-in-the-United-States.pdf">broad guidelines relating to vaccine safety</a>, neither has issued guidelines regarding the levels of risk that are considered justified for a coronavirus vaccine, and there has been only limited public debate on this subject. </p>
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Read more:
<a href="https://theconversation.com/who-pays-compensation-if-a-covid-19-vaccine-has-rare-side-effects-heres-the-little-we-know-about-australias-new-deal-147846">Who pays compensation if a COVID-19 vaccine has rare side-effects? Here's the little we know about Australia's new deal</a>
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<h2>How effective is good enough?</h2>
<p>Efficacy — the vaccine’s ability to produce clinical and public health benefits — is also uncertain.</p>
<p>Ideally, a vaccine should prevent any person who receives it from catching the disease. However, at least with the first vaccines, it is likely the benefits will be <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31976-0/fulltext">more limited</a>. For example, they may slightly reduce the severity of the illness, or they may only benefit a small subset of the population. No current trials are looking at purely whether the vaccine will reduce the chance of dying from COVID-19 of individuals in <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30773-8/fulltext">specific risk groups</a>.</p>
<p>In fact, different clinical trials have different “efficacy end points”, including (among others) effects on susceptibility to infection, severity of disease, time to recovery and mortality, in <a href="https://journals.sagepub.com/doi/full/10.1177/1740774520939938">different age and population groups</a>.</p>
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<a href="https://images.theconversation.com/files/368996/original/file-20201112-13-1c0hq8c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Elderly people in a nursing home doing group exercise sitting down" src="https://images.theconversation.com/files/368996/original/file-20201112-13-1c0hq8c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/368996/original/file-20201112-13-1c0hq8c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/368996/original/file-20201112-13-1c0hq8c.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/368996/original/file-20201112-13-1c0hq8c.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/368996/original/file-20201112-13-1c0hq8c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/368996/original/file-20201112-13-1c0hq8c.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/368996/original/file-20201112-13-1c0hq8c.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">There is no guarantee vaccines will provide significant protection for those in most need, such as people in older age groups.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/large-group-happy-enthusiastic-elderly-ladies-367740026">Shutterstock</a></span>
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<p>There is no guarantee vaccines under development will provide significant protection for those in most need, such as people in older age groups or those with existing medical conditions. Not all trials are specifically recruiting such participants and there is a real possibility benefits will not extend to them. In other words, a clinical trial might show “efficacy” in a formal sense but might not solve the key problems we are facing in the real world.</p>
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Read more:
<a href="https://theconversation.com/pfizer-vaccine-what-an-efficacy-rate-above-90-really-means-149849">Pfizer vaccine: what an 'efficacy rate above 90%' really means</a>
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<p>Earlier this year, the US Food and Drug Administration <a href="https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-takes-action-help-facilitate-timely-development-safe-effective-covid">said</a> it would only consider approving vaccines that “prevent disease or decrease its severity in at least 50% of people who are vaccinated”. Australia’s equivalent, the Therapeutic Goods Administration, has not issued any <a href="https://www.tga.gov.au/clinical-trial-processes">similarly precise guidance</a>.</p>
<h2>How equitable is good enough?</h2>
<p>Access and distribution of any vaccine pose major problems. Some of these are built into the nature of the product itself. </p>
<p>For example, vaccines like the mRNA vaccine developed by Pfizer that need to be transported and stored at around -70°C, will have limited utility in low and middle income countries with limited health infrastructure and in rural and remote communities all over the world – meaning other vaccines may need to be found for these populations. </p>
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Read more:
<a href="https://theconversation.com/keeping-coronavirus-vaccines-at-subzero-temperatures-during-distribution-will-be-hard-but-likely-key-to-ending-pandemic-146071">Keeping coronavirus vaccines at subzero temperatures during distribution will be hard, but likely key to ending pandemic</a>
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<p>The role of minorities in relation to clinical studies of therapeutic products in the US is very uneven, in terms of <a href="https://link.springer.com/article/10.1007/s11019-020-09984-x#Fn35">participation, exposure to risk and access to benefits</a>. There is a serious chance that in the search for a COVID-19 vaccine those least likely ultimately to receive the final product will be the ones who <a href="https://www.nybooks.com/articles/2020/07/02/ethical-path-covid-19-vaccine/">carry the greatest risk</a>. This creates a possibility the social divisions already exposed by the COVID crisis will be further exacerbated.</p>
<p>Further, while there has been widespread <a href="https://www.who.int/initiatives/act-accelerator/covax">acknowledgement</a> of the need for access and supply of COVID vaccines to poorer nations there is no legal structure to ensure this and no guarantee it will actually happen. </p>
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Read more:
<a href="https://theconversation.com/australias-just-signed-up-for-a-shot-at-9-covid-19-vaccines-heres-what-to-expect-146750">Australia's just signed up for a shot at 9 COVID-19 vaccines. Here's what to expect</a>
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<h2>Where to next?</h2>
<p>A number of COVID-19 vaccines will likely become available during 2021 that offer either limited protection from infection or lower the risk somewhat of severe disease. However, these benefits may not necessarily be for those most at risk. </p>
<p>Robust regulatory systems, and independent scrutiny of clinical trial results, mean COVID-19 vaccines will likely be safe in the short-term. However, no-one will know about long-term risks and distribution may be limited, for logistic, economic and cultural reasons.</p>
<p>Even if we develop a “good enough” vaccine, there are no guarantees. Although many will be prepared to chance the first vaccines, many others will refuse them, despite government attempts at persuasion.</p>
<p>So herd immunity via vaccination, which for the coronavirus requires effective immunisation of <a href="https://www.nature.com/articles/d41586-020-02948-4">at least two-thirds of the population</a>, will remain a long way away. </p>
<p>This means strategies to reduce the spread, such as physical distancing, use of face masks and hand hygiene and, where necessary, rigorous quarantine measures, will be with us for some time.</p><img src="https://counter.theconversation.com/content/148168/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>We will struggle to find a vaccine that works perfectly for people who need it most, despite what the headlines say is coming in 2021.Paul Komesaroff, Professor of Medicine, Monash UniversityIan Kerridge, Professor of Bioethics & Medicine, Sydney Health Ethics, Haematologist/BMT Physician, Royal North Shore Hospital and Director, Praxis Australia, University of SydneyRoss Upshur, Professor, Dalla Lana School of Public Health, University of TorontoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1495222020-11-05T05:56:22Z2020-11-05T05:56:22ZWhat do we know about the Novavax and Pfizer COVID vaccines that Australia just signed up for?<figure><img src="https://images.theconversation.com/files/367599/original/file-20201104-23-1xy5a9j.jpg?ixlib=rb-1.1.0&rect=1%2C1%2C1024%2C530&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-vector/development-creation-covid19-vaccine-design-by-1782359774">Shutterstock</a></span></figcaption></figure><p>The federal government’s <a href="https://www.abc.net.au/news/2020-11-04/two-new-coronavirus-vaccine-deals-50-million-doses-government/12849572">announcement</a> of agreements to supply vaccines from Novavax and Pfizer/BioNTech <a href="https://www.pm.gov.au/media/australia-secures-further-50-million-doses-covid-19-vaccine">potentially increases</a> the pool of COVID-19 vaccines Australians will be able to access.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1324101696289648641"}"></div></p>
<p>These two vaccines are in addition to supply arrangements for vaccines from Oxford University/AstraZeneca and the University of Queensland/CSL, <a href="https://theconversation.com/putting-our-money-on-two-covid-vaccines-is-better-than-one-why-australias-latest-vaccine-deal-makes-sense-145693">announced in September</a>. Australia will also have access to vaccines via the World Health Organisation-backed <a href="https://theconversation.com/australias-just-signed-up-for-a-shot-at-9-covid-19-vaccines-heres-what-to-expect-146750">COVAX initiative</a>.</p>
<p>However, these arrangements depend on whether the vaccines are shown to be safe and effective in clinical trials, which are still ongoing. So what do we know about the two vaccines in this latest deal?</p>
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Read more:
<a href="https://theconversation.com/scott-morrison-to-announce-two-new-covid-vaccine-deals-149458">Scott Morrison to announce two new COVID vaccine deals</a>
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<h2>What do we know about the Novavax vaccine?</h2>
<p>The Novavax vaccine, NVX-CoV2373, contains <a href="https://ir.novavax.com/news-releases/news-release-details/novavax-present-covid-19-vaccine-data-world-vaccine-congress">purified pieces</a> of the spike protein of SARS-CoV-2, the virus that causes COVID-19. </p>
<p>These proteins are administered with an adjuvant, a molecule that enhances the immune response. The idea is that when this vaccine is administered, the body recognises its contents as “foreign” and mounts a protective immune response.</p>
<p>Early clinical trials were performed <a href="https://www.nejm.org/doi/10.1056/NEJMoa2026920?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed">in Australia</a>. In the phase 1 clinical trials, the vaccine was generally well-tolerated and produced <a href="https://www.nejm.org/doi/10.1056/NEJMoa2026920?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed">strong antibody responses</a>, stronger than what we see in patients recovering from COVID-19.</p>
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Read more:
<a href="https://theconversation.com/from-adenoviruses-to-rna-the-pros-and-cons-of-different-covid-vaccine-technologies-145454">From adenoviruses to RNA: the pros and cons of different COVID vaccine technologies</a>
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<p>In September, Novavax launched a phase 3 clinical trial <a href="https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-004123-16/GB">in the United Kingdom</a>. Further large-scale clinical trials are planned for other countries in late 2020 and early 2021. </p>
<p>If the Novavax vaccine is successful <a href="https://www.health.gov.au/resources/publications/coronavirus-covid-19-information-about-the-novavax-vaccine-for-covid-19">40 million doses</a> are expected to be available in Australia during 2021, with the option to buy a further 10 million. </p>
<h2>What do we know about the Pfizer vaccine?</h2>
<p>The vaccine developed by Pfizer, BNT162b2, is based on the genetic material mRNA (or messenger ribonucleic acid). Such mRNA vaccines carry a piece of genetic material that codes for viral proteins, or parts of them. Once inside your cells, the mRNA instructs your cells’ protein factories to make copies of these viral proteins. These then stimulate your immune system to mount a protective immune response.</p>
<p>Pfizer’s BNT162b2 vaccine <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-choose-lead-mrna-vaccine-candidate-0">codes for</a> the virus’ full-length spike protein.</p>
<p>In <a href="https://clinicaltrials.gov/ct2/show/NCT04380701">early clinical trials</a>, the vaccine was generally safe with no serious side-effects. The vaccine also produced a <a href="https://pubmed.ncbi.nlm.nih.gov/33053279/">robust immune response</a> after two doses.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/367656/original/file-20201105-24-155ysu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Illustration of single-stranded RNA" src="https://images.theconversation.com/files/367656/original/file-20201105-24-155ysu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/367656/original/file-20201105-24-155ysu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/367656/original/file-20201105-24-155ysu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/367656/original/file-20201105-24-155ysu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/367656/original/file-20201105-24-155ysu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/367656/original/file-20201105-24-155ysu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/367656/original/file-20201105-24-155ysu.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>
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<span class="caption">Vaccines based on RNA use your cells’ protein factories to make viral protein, which stimulates your immune system.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/single-strand-ribonucleic-acid-rna-research-1094792225">Shutterstock</a></span>
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<p>When older adults (65-85 years of age) were vaccinated, they produced a <a href="https://pubmed.ncbi.nlm.nih.gov/33053279/">greater neutralising antibody response</a> than seen in patients who contracted SARS-CoV-2 naturally.</p>
<p>Interestingly, BNT162b2 is one of the first COVID-19 vaccines to be tested <a href="https://www.pfizer.com/science/coronavirus/vaccine">in adolescents</a> (12-18 years of age).</p>
<p><a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-choose-lead-mrna-vaccine-candidate-0">In July</a>, Pfizer announced the launch of large-scale phase 2/3 trials. Trials are under way in <a href="https://www.health.gov.au/sites/default/files/documents/2020/11/coronavirus-covid-19-information-about-the-pfizer-biontech-vaccine-for-covid-19.pdf">several countries</a>, including the United States, Germany, Argentina, Brazil and South Africa, involving 44,000 participants. </p>
<p>One of the challenges facing this vaccine is distribution, as it needs to be stored below -70°C. This is costly and makes transportation difficult, particularly in developing regions. </p>
<p>If BNT162b2 is successful, <a href="https://www.pm.gov.au/media/australia-secures-further-50-million-doses-covid-19-vaccine">10 million doses</a> <a href="https://www.health.gov.au/sites/default/files/documents/2020/11/coronavirus-covid-19-information-about-the-pfizer-biontech-vaccine-for-covid-19.pdf">will be available</a> in Australia from early 2021.</p>
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Read more:
<a href="https://theconversation.com/australias-just-signed-up-for-a-shot-at-9-covid-19-vaccines-heres-what-to-expect-146750">Australia's just signed up for a shot at 9 COVID-19 vaccines. Here's what to expect</a>
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<h2>What happens next?</h2>
<p>Both vaccines, if successful in clinical trials, will be manufactured outside Australia. </p>
<p>This will <a href="https://theconversation.com/australia-may-miss-out-on-several-covid-vaccines-if-it-cant-make-mrna-ones-locally-148996">allay fears</a> Australia might miss out on mRNA vaccines as the country does not have the technology and capacity to make these vaccines itself.</p>
<p>A successful COVID-19 vaccine will also need to navigate the rigorous assessment and approval processes of the Therapeutic Goods Administration for use in Australia.</p>
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<strong>
Read more:
<a href="https://theconversation.com/australia-may-miss-out-on-several-covid-vaccines-if-it-cant-make-mrna-ones-locally-148996">Australia may miss out on several COVID vaccines if it can't make mRNA ones locally</a>
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<h2>Hedging our bets</h2>
<p>It is unlikely all COVID-19 vaccines currently in development will be successful. We have already seen COVID-19 vaccine trials <a href="https://theconversation.com/the-oxford-vaccine-trial-has-been-paused-but-this-is-no-reason-to-panic-145882">temporarily halted</a> due to safety issues. And not all vaccines will provide a consistent level of immunity. Some vaccines may only provide immunity for limited periods of time and require a booster shot.</p>
<p>By investing in numerous front-running candidates, the Australian government’s strategy of not putting all its eggs in one basket is a wise one. </p>
<p>Investing in a range of vaccine technologies also has benefits, should more than one vaccine become available. This is because different vaccine technologies may be more effective or safe in different populations. This increases the likelihood all sections of society — young and old, with or without existing medical complications — could be targeted.</p><img src="https://counter.theconversation.com/content/149522/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Adam Taylor receives funding from The National Health and Medical Research Council of Australia, the National Foundation for Medical Research and Innovation and the New South Wales Department of Primary Industries. </span></em></p>Two more COVID-19 vaccines may now be on the cards for Australia, should they pass clinical trials. But, as with earlier vaccine deals, there are no guarantees.Adam Taylor, Early Career Research Leader, Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1460912020-09-22T18:59:19Z2020-09-22T18:59:19ZHow and when will we know that a COVID-19 vaccine is safe and effective?<figure><img src="https://images.theconversation.com/files/358194/original/file-20200915-20-141c8is.jpg?ixlib=rb-1.1.0&rect=26%2C66%2C4415%2C3856&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">How much longer must society wait for a vaccine?</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/hourglass-inside-syringe-artwork-royalty-free-illustration/488635523?adppopup=true">ANDRZEJ WOJCICKI/Getty Images</a></span></figcaption></figure><p>With COVID-19 vaccines currently in the final phase of study, you’ve probably been wondering how the FDA will decide if a vaccine is safe and effective.</p>
<p>Based on the status of the <a href="https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html">Phase 3 trials</a> currently underway, it is unlikely that the results of these trials will be available before November. But it is likely that not just one but several of the competing COVID-19 vaccines will be shown to be safe and effective by the end of 2020. </p>
<p><a href="https://scholar.google.com/citations?hl=en&user=6yMIM1MAAAAJ&view_op=list_works&sortby=pubdate">I am a scientist and infectious diseases specialist</a> at the University of Virginia, where I care for patients with COVID-19 and conduct research on the pandemic. I am also a member of the World Health Organization Expert Group on COVID-19 Vaccine Prioritization. </p>
<h2>What is the status of COVID-19 vaccines in human clinical trials?</h2>
<p><a href="https://partners.mediasite.com/mediasite/Play/968f633a874c4f1a80c368496f49d4661d">Phase 3 studies are underway</a> for the Moderna and BioNTech/Pfizer vaccines, the Oxford/AstraZeneca viral vector vaccine and now the <a href="https://www.washingtonpost.com/health/2020/09/23/coronavirus-vaccine-jj-single-shot/">Johnson & Johnson viral vector vaccine</a>. </p>
<p>Each of these vaccines uses the SARS-CoV-2 spike glycoprotein, which the virus uses to infect cells, to trigger the immune system to generate protective antibodies and a cellular immune response to the virus. Protective antibodies act by preventing the spike glycoprotein from attaching the virus to human cells, thereby neutralizing the SARS-CoV-2 virus that causes COVID-19.</p>
<p>In the case of <a href="https://theconversation.com/coronavirus-a-new-type-of-vaccine-using-rna-could-help-defeat-covid-19-133217">Moderna’s nucleic acid vaccine</a>, the messenger RNA encoding the spike glycoprotein is encased in a fat droplet – called a liposome – to protect the mRNA from degradation and enable it to enter cells. Once these instructions are inside the cells, the mRNA is read by the human cell machinery and made into many spike proteins so that the immune system can respond and begin producing antibodies against this coronavirus. </p>
<p>The Oxford/AstraZeneca and <a href="https://www.jnj.com/johnson-johnson-initiates-pivotal-global-phase-3-clinical-trial-of-janssens-covid-19-vaccine-candidate">Johnson & Johnson</a> vaccines use a different strategy to activate an immune response. Here an adenovirus found in chimpanzees shuttles the instructions for manufacturing the spike glycoprotein into cells.</p>
<p><a href="http://doi.org/10.1126/science.abc5312">Phase 1 and 2 studies by pharmaceutical companies Janssen and Merck</a> also use viral vectors similar to the Oxford/AstraZeneca and J&J vaccines, while vaccines by Novavax and GSK-Sanofi use the actual spike protein itself. </p>
<h2>Animal tests show the vaccines provide protection from coronavirus infection</h2>
<p>Studies in animal models of COVID-19 provide convincing evidence that vaccination with the spike glycoprotein will protect from COVID-19. Experiments have show that when the immune system is shown the spike protein – which alone cannot trigger disease – the immune system will generate an antibody response that protects from infection with SARS-CoV-2.</p>
<p><a href="https://doi.org/10.1038/s41591-020-1070-6">In studies in hamsters</a> an adenovirus viral vector – the approach used by Oxford/AstraZeneca, for example – was used to immunize with the Spike glycoprotein. When the hamsters were infected with SARS-CoV-2 they were protected from pneumonia, weight loss and death.</p>
<p><a href="http://doi.org/10.1126/science.abc6284">In nonhuman primates</a>, DNA vaccines – which deliver the gene for the spike glycoprotein – reduced the amount of virus in the lungs. Animals that produced antibody that prevented virus attachment to human cells were most likely to be protected.</p>
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<figcaption><span class="caption">History of vaccines: Smallpox to SARS-CoV-2.</span></figcaption>
</figure>
<h2>What have the early Phase 1 and 2 studies in humans shown?</h2>
<p>Overall, <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2026920?query=featured_coronavirus">vaccination has triggered a more potent neutralizing antibody response</a> than even that seen in patients recovering from COVID-19. </p>
<p>This has also been the case for <a href="http://doi.org/10.1056/NEJMoa2022483">Moderna’s vaccine currently in Phase 3 trials</a> and for vaccines from <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31611-1/fulltext">CanSino Biologics and Oxford/ AstraZeneca.</a> </p>
<h2>What side effects have been observed?</h2>
<p><a href="https://doi.org/10.1016/S0140-6736(20)31605-6">Physicians have recorded</a> <a href="https://doi.org/10.1016/S0140-6736(20)31604-4">mild to moderate reactions</a> <a href="http://doi.org/10.1056/NEJMoa2022483">when the subjects were observed</a> up to 28 days after vaccination. These side effects included mild pain, warmth and tenderness at the site of injection, and fever, fatigue, joint and muscle pain. </p>
<p>But Phase 1 and 2 studies are by small by design, with just hundreds of participants. So these trials will not be large enough to detect uncommon or rare side effects. </p>
<p>The emphasis on safety as the primary goal was recently demonstrated in the Phase 3 Oxford/AstraZeneca vaccine trial <a href="https://www.nature.com/articles/d41586-020-02594-w">where one vaccinated individual developed inflammation of the spinal cord</a>. It isn’t clear whether the vaccine caused this reaction – it might be a new case of multiple sclerosis unrelated to the vaccine – but the Phase 3 trial was halted in the U.S. until more is known.</p>
<h2>How is the FDA ensuring that a vaccine will be safe yet quickly produced?</h2>
<p>The <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/development-and-licensure-vaccines-prevent-covid-19">FDA has issued guidance for industry</a> on the steps required for developing and ultimately licensing vaccines to prevent COVID-19 – these are the same rigorous safety standards required for all vaccines.</p>
<p>There are, however, ways to speed the process of approval that are centered on “platform technology.” What this means is that if a vaccine is using an approach such as an adenovirus that has previously been shown to be safe, it may be possible for a company to use previously collected data on toxicity and pharmacokinetics to fast-track clinical trial approval. </p>
<p>While speed and safety may appear conflicting goals, it is also encouraging to note that the <a href="https://www.wsj.com/articles/covid-19-vaccine-developers-prepare-joint-pledge-on-safety-standards-11599257729">rival vaccine manufacturers have jointly pledged</a> not to bow to any political pressures to rush vaccine approval, but to maintain the most rigorous safety standards. </p>
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<figcaption><span class="caption">How to develop a vaccine, quickly.</span></figcaption>
</figure>
<h2>How protective does a vaccine need be to receive FDA approval?</h2>
<p>The FDA has set the bar for the primary endpoint of a Phase 3 trial of 50% protection for approval of a COVID-19 vaccine. </p>
<p>Protection is defined as protection from symptomatic COVID-19 infection, defined as laboratory-confirmed SARS-CoV-2 infection plus symptoms such as fever or chills, cough, shortness of breath, fatigue, muscle aches, loss of taste or smell, congestion or runny nose, diarrhea, nausea or vomiting. </p>
<p>This means that an effective vaccine is considered one that will reduce the number of infections in vaccine recipients by half. This is the <a href="https://doi.org/10.1016/S0140-6736(20)31821-3">minimal protection that is anticipated to be clinically useful</a>. That is, in part, because lower levels of efficacy could paradoxically increase COVID-19 infections if it leads vaccinated people to decrease mask wearing or social distancing because they think they are completely protected.</p>
<p>Since a vaccine might be more effective at preventing severe COVID-19, the FDA instructs that <a href="https://www.fda.gov/media/139638/download">protection from severe COVID-19</a> should be a secondary endpoint.</p>
<h2>How many people have to be vaccinated to know if a vaccine works in Phase 3?</h2>
<p>The current Phase 3 trials are enrolling 30,000-40,000 subjects. Most of these participants will receive the vaccine and some a placebo.</p>
<p>When, exactly, the results of Phase 3 studies will be released depends in large part on the rate of infection in the placebo recipients. The way that these vaccine studies work is that they test if naturally acquired new coronavirus infections are lower in the group that received the vaccine compared with the group receiving the placebo. </p>
<p>So while it is good news that COVID-19 infections have dropped recently in the U.S. from <a href="https://www.nytimes.com/interactive/2020/us/coronavirus-us-cases.html?auth=login-email&login=email">70,000 to 40,000 cases per day</a>, this drop in new infections may slow the vaccine studies.</p>
<h2>Will Emergency Use Authorization fast-track vaccine?</h2>
<p>In an emergency such as we are faced with the COVID-19 pandemic, with approximately 700 new deaths and 40,000 new cases per day right now, the FDA is authorized to allow the use of unapproved products for the diagnosis, treatment and prevention of disease. That includes a vaccine.</p>
<p><a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/development-and-licensure-vaccines-prevent-covid-19">The standard approval process for vaccines</a> can require more than one year of observation after vaccination. If the short-term safety is good and the vaccine works to prevent COVID-19, then the vaccine should be approved for use under an Emergency Use Authorization while it is still being studied.</p>
<p>Under Emergency Use Authorization, the FDA will <a href="https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization">continue to collect information</a> from the companies producing the vaccines for benefit and harm, including surveillance for vaccine-associated enhanced respiratory disease or other potentially rare complications that might be observed in only one in a million.</p>
<h2>What should we expect in terms of approvals?</h2>
<p>I expect that the FDA will approve several vaccines by the end of 2020 under its Emergency Use Authorization authority so that vaccination can begin immediately, starting with high-risk groups including first responders, health care personnel, and the elderly and those with preexisting medical conditions. </p>
<p>This will be followed rapidly with <a href="https://theconversation.com/video-who-should-get-a-covid-19-vaccine-first-146285">roll-out of vaccination</a> to the population at large, while all of the time the FDA and vaccine manufacturers will continue to monitor for side effects and work to improve upon these first vaccines. This process is <a href="https://www.usatoday.com/story/news/health/2020/09/02/covid-19-vaccine-rollout-plan-united-states-worries-experts/5694037002/">expected to take months</a>.</p>
<p>It may not be life back to normal next year, but all signs point to a healthier 2021.</p>
<p><em>This article was updated on September 25 with information on the Johnson & Johnson vaccine trial.</em></p><img src="https://counter.theconversation.com/content/146091/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>William Petri receives funding from the NIH and the Bill & Melinda Gates Foundation.</span></em></p>Several vaccines are in Phase 3 trials. So when will we know whether any of these will protect against COVID-19?William Petri, Professor of Medicine, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1443322020-08-12T12:00:59Z2020-08-12T12:00:59ZA COVID-19 vaccine needs the public’s trust – and it’s risky to cut corners on clinical trials, as Russia is<figure><img src="https://images.theconversation.com/files/352381/original/file-20200811-20-179mzzz.jpg?ixlib=rb-1.1.0&rect=187%2C22%2C743%2C551&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">On Aug. 11, Russian President Vladimir Putin announced that a coronavirus vaccine developed in the country has been registered for use.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/photo-shows-vials-of-vaccine-called-gamcovidvac-in-moscow-news-photo/1228002428?adppopup=true">Russian Health Ministry/Handout/Anadolu Agency via Getty Images</a></span></figcaption></figure><p>Russia’s announcement that a <a href="https://www.politico.com/news/2020/08/11/russia-coronavirus-vaccine-putin-daughter-393455">fast-tracked COVID-19 vaccine</a> is registered there, with plans for quick distribution in the general population this fall, is being <a href="https://www.nature.com/articles/d41586-020-02386-2">condemned by scientists worldwide</a>.</p>
<p>Findings from scientific studies of this vaccine, named “Sputnik V,” are not available. Large safety and efficacy trials <a href="https://sputnikvaccine.com/about-vaccine/clinical-trials/">are only now getting underway</a>. But despite only two months of preliminary testing in people, Russian President Vladimir Putin called the vaccine “<a href="https://www.bbc.com/news/world-europe-53735718">quite effective</a>” and it’s <a href="https://www.bloomberg.com/news/articles/2020-08-11/putin-says-russia-has-registered-world-s-first-covid-19-vaccine">received regulatory approval</a>.</p>
<p>In other places, notably the <a href="https://www.weforum.org/agenda/2020/06/vaccine-development-barriers-coronavirus/">United States, China and the European Union</a>, even as <a href="https://www.nationalgeographic.com/science/health-and-human-body/human-diseases/coronavirus-vaccine-tracker-how-they-work-latest-developments-cvd/">researchers rush to develop vaccines</a>, they continue to publish studies of these vaccines at a more measured pace than is happening in Russia.</p>
<p>As an <a href="https://scholar.google.com/citations?user=RNembkwAAAAJ&hl=en&oi=ao">epidemiologist who studies vaccine hesitancy and vaccine-preventable disease</a>, I’m concerned about this news from Russia. After essential workers and high-risk groups are vaccinated, I would want to be among the first in line for an approved COVID-19 vaccine, but the medical research system must make sure any vaccine is safe and effective before distributing it to the population at large.</p>
<h2>Clinical trials have a valuable role</h2>
<p>Before any drug, vaccine or medical device is licensed for use in the general population, it needs to go through <a href="https://www.historyofvaccines.org/content/articles/vaccine-development-testing-and-regulation">several rounds of large-scale testing</a>. These studies are designed to make sure the intervention is safe and effective, and to understand what the appropriate dosage will be.</p>
<p><iframe id="zGYqv" class="tc-infographic-datawrapper" src="https://datawrapper.dwcdn.net/zGYqv/2/" height="400px" width="100%" style="border: none" frameborder="0"></iframe></p>
<p>Under normal conditions, the research required to bring a vaccine to market <a href="https://doi.org/10.1186/s12961-020-00571-3">can take decades</a>. For example, before the HPV vaccine was <a href="https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5920a4.htm">licensed in the U.S. in 2006</a>, a phase III clinical trial <a href="https://doi.org/10.1016/S0140-6736(09)61248-4">enrolled 18,644 participants in 2004-2005</a>, a phase II clinical trial had <a href="https://doi.org/10.1016/S0140-6736(04)17398-4">enrolled 1,113 participants in 2000</a>, and the laboratory studies that led to a vaccine candidate had been <a href="https://doi.org/10.2147/tcrm.2006.2.3.259">published in the early 1990s</a>.</p>
<p>In the face of the coronavirus pandemic, scientists around the globe are focusing their efforts on developing a COVID-19 vaccine. <a href="https://www.knowablemagazine.org/article/health-disease/2020/getting-covid-19-vaccine-quickly-and-safely">They’re working at an</a> <a href="https://theconversation.com/what-needs-to-go-right-to-get-a-coronavirus-vaccine-in-12-18-months-136816">unprecedented pace to move through the necessary clinical trials</a> to end up with a safe and effective vaccine. One of the most time-consuming parts of clinical trials is enrolling participants, and pharmaceutical companies have <a href="https://doi.org/10.1186/s12961-020-00571-3">sped up this process</a> by lining up volunteers early, obtaining important baseline data from them even before a vaccine candidate is available.</p>
<figure>
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<figcaption><span class="caption">Here’s how drugs are tested and approved in the U.S.</span></figcaption>
</figure>
<h2>Problems if the vaccine is released too early</h2>
<p>Carefully conducted clinical trials are necessary to identify any problems with the vaccine. For example, studies of a new type of measles vaccine in the early 1990s found that it was <a href="https://apps.who.int/iris/bitstream/handle/10665/228552/WER6748_357-361.PDF">detrimental to baby girls</a>, and so it was never licensed to the general population. The existing measles or measles-mumps-rubella vaccine available in the U.S. and other countries is <a href="https://www.cdc.gov/vaccinesafety/vaccines/mmr/mmr-studies.html">highly safe and effective</a>. </p>
<p>It could also be that the vaccine is not effective in some categories of people. Phase I and II clinical trials have small sample sizes and may not include individuals from high-risk groups. For example, a recently published phase II clinical trial of a COVID-19 vaccine <a href="https://doi.org/10.1016/S0140-6736(20)31605-6">excluded obese people, those with chronic diseases and pregnant women</a>. However, these are all groups that should be able to get the vaccine in the future. More studies, including phase III trials, are necessary to discover if the vaccine works in the general population. Preliminary results should be <a href="https://www.reuters.com/article/us-health-coronavirus-vaccines-explainer/when-will-a-coronavirus-vaccine-be-ready-idUSKCN2571H2">available by the end of 2020</a>.</p>
<p>The concern is that by introducing the vaccine early, without adequate testing of safety, effectiveness and dosing, the population may be presented with a vaccine which is not safe or not effective, and with little information on which vaccine schedule is best.</p>
<p>Food and Drug Administration Commissioner Dr. Stephen Hahn has said the FDA <a href="https://www.mercurynews.com/2020/08/10/commissioner-fda-wont-cut-corners-on-covid-19-vaccine/">will not “cut corners”</a> in approving a COVID-19 vaccine in the U.S. despite an accelerated program, <a href="https://abcnews.go.com/Politics/public-health-experts-scientists-confident-vaccine-process-criticism/story?id=72216320">dubbed Operation Warp Speed</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/352382/original/file-20200811-14-292m13.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="archival photo of packing vials of polio vaccine into boxes" src="https://images.theconversation.com/files/352382/original/file-20200811-14-292m13.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/352382/original/file-20200811-14-292m13.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=492&fit=crop&dpr=1 600w, https://images.theconversation.com/files/352382/original/file-20200811-14-292m13.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=492&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/352382/original/file-20200811-14-292m13.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=492&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/352382/original/file-20200811-14-292m13.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=619&fit=crop&dpr=1 754w, https://images.theconversation.com/files/352382/original/file-20200811-14-292m13.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=619&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/352382/original/file-20200811-14-292m13.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=619&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">In 1956, boxes of polio vaccine were rushed for delivery, but only after clinical trials concluded and it was approved by the FDA.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/indianapolis-in-at-the-eli-lilly-and-company-plant-in-the-news-photo/514874700?adppopup=true">Bettmann via Getty Images</a></span>
</figcaption>
</figure>
<h2>Rushing to market</h2>
<p>But is there ever an ethical reason to release a vaccine early, even without going through all phases of clinical trials?</p>
<p>Although it would be wonderful to get a vaccine into the population quickly, there could be substantial downsides if researchers and manufacturers cut corners. Imagine a vaccine that often had serious side effects that weren’t caught in small trials before it was widely administered.</p>
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<p>An untested vaccine wouldn’t just harm the people vaccinated. If negative perceptions about the safety or efficacy of a COVID-19 vaccine spread throughout the population, it could limit how many people are willing to get the shot and perpetuate disease transmission.</p>
<p>Trust in vaccination programs is crucial. Russia, in fact, provides an important historical example. In the 1990s, trust in the country’s public health system rapidly decreased, and rates of diphtheria-tetanus-pertussis vaccination fell as a result. A large outbreak of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2640235/?tool=pmcentrez&report=abstract">diphtheria then spread through eastern Europe</a>, leaving over 4,000 people dead.</p>
<p>Hasty rollout of a COVID-19 vaccine could prime people not only to not trust the COVID-19 vaccine, but also to doubt vaccination and public health systems as a whole. </p>
<p>Vaccinations should be developed by impartial scientists and evaluated by nonpartisan government officials. By cutting red tape, procedures can be prioritized and sped up, but they must not be skipped.</p><img src="https://counter.theconversation.com/content/144332/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Abram L. Wagner receives funding from the NIH and NSF. </span></em></p>As Russia fast tracks a coronavirus vaccine, scientists worry about skipped safety checks – and the potential fallout for trust in vaccines if something ends up going wrong.Abram L. Wagner, Research Assistant Professor of Epidemiology, University of MichiganLicensed as Creative Commons – attribution, no derivatives.