Facts about COVID-19 Vaccines

--- title: Facts about COVID-19 Vaccines tags: test permalink: https://c19vax.scibeh.org/pages/c19vaxfacts ---  {%hackmd GHtBRFZdTV-X1g8ex-NMQg %} ASSUMING THIS IS THE LIVE VERSION # Facts about COVID-19 vaccines [TOC] Vaccines provide a possible path out of the COVID19 pandemic, and it is therefore fortunate that scientists have now developed several vaccines against COVID-19. Those vaccines have been found to be highly effective against the disease, and some provide a protection level of around 95% in controlled trials. * For facts about the disease COVID-19 see [our page here](https://hackmd.io/mkPIpGVSRiyd1k7TQOA36A). * Find out how successful vaccines have been in the past at [our page here](https://hackmd.io/gWXZ-K07RBWE3TLYzN5lCQ). * Find out more about how the COVID-19 vaccines were developed at [our page here](https://c19vax.scibeh.org/pages/vaxprocess). --- ## How do the vaccines work? Here is a two-minute introduction by Dr Asher Williams at Cornell University about how the mRNA vaccines, by Pfizer/BioNTech and Moderna, work: {%youtube 4keWTrpKTYM %} --- ## How many people have received the COVID-19 vaccines? As of 3 February 2021, more than 100 million doses of COVID-19 vaccines have been delivered worldwide. Several live trackers allow you to get up-to-date statistics on vaccinations: * The tracker by [Our World in Data](https://ourworldindata.org/covid-vaccinations). * The [New York Times Coronovirus vaccine tracker](https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html) (it also provides a lot of in-depth information regarding the different vaccines) * The [Bloomberg COVID-19 vaccine tracker](https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution/). --- ## How safe are the vaccines? The _Metafact_ fact-checking site asked 14 independent experts from around the world to indicate whether they think the COVID-19 vaccines are safe: [Their unanimous judgment was, yes, the vaccines are safe](https://metafact.io/factchecks/1716). We have a page **[dedicated to side effects of the vaccines](https://c19vax.scibeh.org/pages/sideeffects)**. Several national and international regulatory agencies have examined the data and have authorized vaccines before they can be used: * The U.S. Food and Drug Administration gave [emergency approval to the Pfizer-BioNTech COVID-19 Vaccine](https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/pfizer-biontech-covid-19-vaccine) in December 2020. This graph explains how emergency approval is granted (click for full size image): [![](https://i.imgur.com/AUJJDaW.png =350x)](https://www.fda.gov/media/143890/download) It shows that "emergency approval" requires a series of steps that [ensure the safety of the vaccine](https://www.fda.gov/vaccines-blood-biologics/vaccines/emergency-use-authorization-vaccines-explained) notwithstanding the emergency: >For an EUA [emergency approval] to be issued for a vaccine, for which there is adequate manufacturing information to ensure quality and consistency, FDA must determine that the known and potential benefits outweigh the known and potential risks of the vaccine. An EUA request for a COVID-19 vaccine can be submitted to FDA based on a final analysis of a phase 3 clinical efficacy trial or an interim analysis of such trial, i.e., an analysis performed before the planned end of the trial once the data have met the pre-specified success criteria for the study’s primary efficacy endpoint. * The World Health Organization (WHO) gave [emergency validation to the Pfizer/BioNTech vaccine](https://www.who.int/news/item/31-12-2020-who-issues-its-first-emergency-use-validation-for-a-covid-19-vaccine-and-emphasizes-need-for-equitable-global-access) on 31 December 2020---the first vaccine to receive validation since the outbreak began. * More details about safety can be found at this [_Metafact_ page](https://metafact.io/consensus/the-approved-covid-19-vaccines-are-safe). * A great resource about vaccine safety generally is the [Vaccine Safety Net](https://www.vaccinesafetynet.org/). * _National Geographic_ has a synopsis of the current state of the [most promising vaccine developments](https://www.nationalgeographic.com/science/health-and-human-body/human-diseases/coronavirus-vaccine-tracker-how-they-work-latest-developments-cvd/) * The [European Medicines Agency](https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/covid-19-vaccines-development-evaluation-approval-monitoring#accelerated-evaluation) has a detailed page about the development, approval, and monitoring of COVID-19 vaccines.  --- ## How are vaccines being tested? :::info Two key terms are used to describe the success of a vaccine: **[Efficacy](https://www.gavi.org/vaccineswork/what-difference-between-efficacy-and-effectiveness)** refers to the degree to which a vaccine prevents a disease in controlled clinical trials. The numbers reported below therefore refer to efficacy. **[Effectiveness](https://www.gavi.org/vaccineswork/what-difference-between-efficacy-and-effectiveness)**, by contrast, refers to the success of a vaccine in the real world, established by observational studies. A vaccine with high efficacy would be expected to also be highly effective in the real world, but the actually achieved effectiveness may differ from the controlled studies. ::: The Centre for Disease Control (CDC) provides a summary of vaccine testing procedures [here](https://www.cdc.gov/vaccines/basics/test-approve.html). There are 3 test phases that any vaccine goes through before it is licenced: * During **Phase 1**, a small number of people receive the trial vaccine. This phase mainly checks for adverse side effects, but also verifies the body's immune response. * During **Phase 2**, the vaccine is administered to people who are similar (in terms of age and physical health) to the population for whom the new vaccine is intended. * During **Phase 3**, the vaccine is given to thousands or tens of thousands of people. The emphasis here is on efficacy---does the vaccine prevent illeness?---and also safety. For all practical intents and purposes, **Phase 3 is the most important part of testing because it tells us about safety and efficacy on a large scale**. If all phases are completed successfully, and the vaccine has been shown to be effective and without serious side effects, regulatory bodies approve the new vaccine for release. Once a vaccine is approved and licensed, "testing" continues during actual use, a stage known as **Phase 4**. This phase consists of monitoring the side effects, if any, of the vaccine while it is being administered to the public. We have an **[entire page devoted](https://c19vax.scibeh.org/pages/vaxprocess)** to the way in which the COVID-19 vaccines were developed, and why they could become available so quickly despite being thoroughly tested. --- ## Efficacy of COVID-19 Vaccines Vaccinated individuals have a lower risk of contracting COVID-19 compared to unvaccinated individuals. For example, in one study the risk of contracting COVID was reduced by 95% in the group that received the COVID-19 vaccine compared to the control group. Vaccinated individuals also have a lower risk of developing severe symptoms if contracting the disease compared to unvaccinated individuals. We summarize the method and results for the Phase 3 tests of the three main vaccines rolled out to date: Pfizer-BioNTech, Morderna, and Oxford-AstraZeneca. In all three studies, volunteer participants were randomly assigned either to a placebo control group that did not receive the vaccine or to a vaccine group that was administered the COVID-19 vaccine. Because the assignment was random, the only thing that differed between groups was whether or not people received the vaccine. In consequence, if we find a difference in the incidence of the disease, then we can be certain that it reflects the effect of the vaccine. Altogether, the trials involved more than 85,000 participants from around the world. ### The Pfizer-BioNTech vaccine The [Pfizer-BioNtech trial](https://www.nejm.org/doi/full/10.1056/NEJMoa2034577?query=featured_home) involved 43,448 individuals (older than 16) who were randomly assigned to two groups: One that received the vaccine and one that received a placebo. Ultimately, 18,556 people received two doses of the vaccine 21 days apart, and 18,530 received a placebo. (Some participants withdrew along the way, so the two numbers do not add up to the original 43,448.) The figure shows the trial design: ![](https://i.imgur.com/QYojdNF.png =500x) Once both doses of the vaccine (or placebo) were administered, the incidence of COVID-19 was monitored for both groups (i.e., around 37,000 people). The bottom line was that only 8 people in the vaccine group contracted the disease, compared to 162 in the placebo. In other words, **the vaccine was 95% effective.**. The next figure provides another snapshot of the data, by plotting the cumulative number of cases (severe cases are identified by solid plotting symbols) in both groups over time after the first dose (the inset is showing the same data but on a different time scale). ![](https://i.imgur.com/GAYszhc.png) The divergence between the placebo and vaccination group is striking. Note that the time axis starts after the first dose, and that full protection would not be expected to kick in until 7 days after the second dose --- corresponding to day 28 in the graph. ### The Moderna vaccine The [Moderna trial](https://www.nejm.org/doi/full/10.1056/NEJMoa2035389?query=featured_home) used a very similar design to the Pfizer-BioNTech trial. A total of 30,420 participants were randomly assigned to either the placebo or the vaccine group. Participants were again observed for around 90 days after receiving the second dose. Altogether, 269 cases were observed in the placebo group, compared to 19 in the vaccinated group. The efficacy of the vaccine was estimated to be around 93-94%. ### The Oxford-AstraZeneca vaccine The [Oxford-Astrazeneca](https://linkinghub.elsevier.com/retrieve/pii/S0140673620326611) randomized 23,848 participants into the usual two groups, of whom 11,636 were included in the interim analysis reported in the paper. Vaccine efficacy was estimated to be 90% in a regime involving a low dose followed by a standard dose (it was 62% under a regime of two standard doses). ### How to interpret the results The vaccines were shown to be 95% effective (or more). What exactly does "95% efficacy" mean? We explain this by considering the [Pfizer-BioNTech clinical trial](https://www.nejm.org/doi/full/10.1056/NEJMoa2034577?query=featured_home). Results from the clinical trial in Phase 3 indicate that vaccine efficacy one week after the _first_ dose was **52%** (95% credible interval 29.5% to 68.4%), with 39 cases of COVID-19 in the vaccine group and 82 cases in the placebo group. Seven or more days after the _second_ dose, the participants were again examined for COVID-19 symptoms. In total, 162 people in the placebo group and 8 people in the vaccine group were found to have at least one of the COVID-19 specific symptoms, indicating they were sick from COVID-19. Thus, vaccine efficacy after the second injection was **95%** (90.3% to 97.6%), with 8 covid-19 cases reported in the vaccine group and 162 cases in the placebo group.  To understand where the percentages come from, we work out that in the vaccine group, 154 people _escaped_ the disease: We know that 162 would have likely gotten the disease without vaccination, and because only 8 did, we protected 154 people from the disease. This is what we call efficacy of the vaccine: 154 / 162 = 0.9506 = 95%. You can see a more detailed analysis (albeit with slightly changed numbers) in this [New York Times article](https://www.nytimes.com/2020/12/13/learning/what-does-95-effective-mean-teaching-the-math-of-vaccine-efficacy.html). :::info **We can scale up those numbers to illustrate how effective the vaccine is**. If we had vaccinated 1,000,000 people, only 430 would be expected to get sick. Out of 1,000,000 people who were not vaccinated, 8,760 would get sick from COVID-19. The difference between the two scenarios would be 8,760 - 430 = 8,330. This is the number of people who would be saved from getting sick with COVID-19 thanks to having been vaccinated. In total, this means that, in a population of 1,000,000, out of the 8,760 people who would get sick without vaccination, 8,330 would avoid the disease thanks to the vaccination. The effectiveness again is 8,330 / 8,760 = 0.9509 = 95%. (Note that in reality, the effectiveness of the vaccine may be lower than the efficacy observed in laboratory studies, as noted above, so these numbers are illustrative only.) ::: ### Points to note about interpretation 1. The efficacy of a Phase 3 clinical trial only estimates the protection provided by vaccination to the people who get vaccinated in **a short period after vaccination**. It is not meant to explore long-term effects ('duration of immunity'), as this is something that is evaluated once the vaccination begins in the general population. 2. The efficacy of a Phase 3 clinical trial only estimates the **direct** protection to the people who get vaccinated. This means that it cannot account for the people who are protected indirectly thanks to herd immunity. This means that the actual number of people who are protected thanks to vaccination directly and indirectly is even larger. 3. In case of only one injection of the Pfizer-BioNTech vaccine, 39 cases of COVID-19 were found in the vaccine group and 82 in the placebo group, leading to a 52% efficacy. This means that if people receive only one injection, half of the people who got vaccinated would be spared from the disease. Although not as impressive as the 95% of the two injections, saving half the population from getting sick would be still a huge accomplishment. However, it is not known at the moment how long the protection offered by a single shot lasts. 4. For more information on statistical literacy regarding health statistics, see: [Gigerenzer, et. al. (2007)](https://journals.sagepub.com/doi/10.1111/j.1539-6053.2008.00033.x) 5. The actual statistics used by some of the trials to compute efficacy were more complicated and sophisticated than the illustrative computations shown here. **The trials also recorded side effects from the vaccination, which we discuss in a [separate dedicated page](https://c19vax.scibeh.org/pages/sideeffects).** --- ## Effectiveness of COVID-19 Vaccines Data on the effectiveness of the vaccines in "real-life" situations are beginning to become available in early 2021. Some of these results are from Israel, which has been leading the world in its vaccination drive. According to the [_Times of Israel_](https://www.timesofisrael.com/vaccine-found-92-effective-in-israel-in-first-controlled-result-outside-trials/), Pfizer's vaccine has been 92 percent effective, based on data from 163,000 people vaccinated by one healthcare service. Only 31 out of those 163,000 (or .02%) were diagnosed with COVID-19 in their first 10 days of full-strength protection. In an equivalent sample of unvaccinated Israelis, that rate was 11 times higher, yielding an estimated efficiency of 92%. This number is gratifyingly close to the 95% efficacy observed in controlled trials. --- ## What about the new variant of COVID-19? In late 2020, a new variant of COVID-19, named B.1.1.7, emerged. This new variant has 23 mutations compared to the old virus, [8 of which are affecting the spike protein that the virus uses to attach itself to our cells](https://theconversation.com/why-it-matters-that-the-coronavirus-is-changing-and-what-this-means-for-vaccine-effectiveness-152383). Thus, it is possible that B.1.1.7 might create an increased vaccine-virus mismatch, leading to potentially reduced effectiveness of the mRNA vaccines (Pfizer and Moderna). This would be of particular concern given that the new variant seems to be more contagious. At present, it is not entirely clear whether the existing vaccines would be less effective against the new variant. [Some experts are concerned, others less so](https://www.livescience.com/south-africa-variant-coronavirus-vaccines.html). However, a recent publication seems to indicate that the Pfizer vaccine is able to protect from the new variant ([Xie et. al., 2021](https://www.biorxiv.org/content/10.1101/2021.01.07.425740v1?fbclid=IwAR1sTUnngQK0wemjvmYPpbEI-EgV4zvPYSLLIl3VhmXsBl9UXxD1ULVK9L0)). --- ## Facts against disinformation Unfortunately, misinformation about the COVID-19 vaccines has been circulating online. There are a number of reputable sources that counter disinformation: * The Center for Disease Control has a page [dedicated to the COVID-19 vaccines](https://www.cdc.gov/coronavirus/2019-ncov/vaccines/vaccine-benefits/facts.html). We excerpt some of their main points below. * The European Medicines Agency has a page [dedicated to the COVID-19 vaccines](https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/covid-19-vaccines-key-facts). * A rich resource regarding COVID-19 vaccination is [the CDC website](https://www.cdc.gov/vaccines/covid-19/index.html). * The [European Vaccination Information Portal](https://vaccination-info.eu/en/covid-19/covid-19-vaccines) has a fact page with many interesting links. **We have a separate page that is dedicated to addressing [common myths about the COVID-19 vaccine](https://c19vax.scibeh.org/pages/misinfo_myths).** </div>