Questions on the COVID-19 Vaccine? We've Got Answers

At a recent CGD staff presentation of our work into COVID-19 vaccines, our colleagues raised a large number of interesting questions, many of which went beyond our initial project that analysed and estimated timelines for when a vaccine could be approved and manufactured. It made us realize that there are varying understandings about the state of the COVID-19 vaccine pipeline, and that it’s hard to find simple answers to key questions right now. So, we asked our colleagues to send in their questions on the COVID-19 vaccine portfolio. Below we answer nine of them.

1. How soon will vaccinations start to have an impact at the population level, and how will this vary by country?

This depends both on the vaccine and how quickly it is rolled out. The Pfizer BioNtech vaccine starts to give people some immunity about 12 days after their first dose; three weeks after the first dose patients get a second dose; and a week after that they achieve full immunity. Other vaccines might take a few weeks longer to reach this immunity level.

The UK and US are currently expected to receive enough of the Pfizer BioNTech vaccine to inoculate about 4 percent of their population before the end of December (based on these US and UK estimates and the authors calculations, new reports suggest this might be an underestimate), with the US receiving more of the Moderna vaccine this month too (though they might not be able to use all those vaccines in this time period). Three percent coverage on its own is a long way off what we need to start building herd immunity, but because vaccines are going to the highest-risk groups first, it is likely enough that we might start to see mortality rates slowly drop starting in late January.

2. Is there anything in place to stop richer countries buying up supplies of vaccines before poorer countries?

There are no global rules to stop rich countries from buying up large amounts of vaccine supply. The EU, US, UK, and Canada have already purchased four or five doses for every person in their country or region, this is done in case some leading candidates fail, and because they want to ensure they have their choice of the best and earliest vaccines, as more information on them becomes available. There is a facility called COVAX which is purchasing and allocating vaccines to countries across the world, with priority given to those countries that do not already have deals with pharmaceutical companies. But recent reports suggest there are problems getting this facility up, because countries might decide not to purchase the vaccines COVAX has already bought, putting COVAX at financial risk and making it hard for it to negotiate deals with manufacturers.

COVAX is aiming to distribute two billion vaccines in 2021, which will be enough to inoculate a billion people, about 20 percent of the population of the lower and middle-income countries it serves. In contrast, high-income countries hope to inoculate the majority of their populations in 2021. It is in all of our interest to make sure there aren’t areas of the world left behind by vaccination, so high-income countries should work to redistribute the doses they’re not going to use. Some, like Canada, appear to be planning to do so.

3. As more vaccines come to market, who will decide who gets which vaccine—both internationally and within countries?

Different countries will have different needs, and as more vaccines come to market, we expect that this will play a large part in different purchasing decisions. For example, vaccines requiring an ultra-cold chain like Pfizer BioNTech’s will likely not be deployable in resource-constrained settings, as deployment will require advanced and reliable infrastructure. Countries are unlikely to buy vaccines that are not suitable for them, but their options will be limited by which candidates they can get their hands on.

There has been some discussion about how to “choose” which vaccine to take, but the reality is that very few patients will receive a choice over which vaccine to receive. If some vaccines prove to be more effective in younger populations than older populations—such as the early results for Sanofi’s vaccine indicate—or are not suitable for those with severe allergies—like Pfizer BioNtech’s might be—then the most likely scenario is that their health system and provider will decide to give them whichever vaccine suits them best. This of course requires their country to have purchased a range of vaccines.

4. How does each country decide the order of priority in which people will be vaccinated, and how does that differ by country?

Each country will come up with a framework for who should get the vaccine first. Health staff and people in care homes are likely to be the two highest-priority groups, followed by other older people, those with comorbidities that make them at a greater risk of contracting the illness ,and other front line staff. The US CDC has recommended that “Healthcare personnel and residents of long-term care facilities should be offered the first doses of COVID-19 vaccines.” The New York Times has a tracker estimating when different individuals are likely to get access to vaccines, which has used data from the Surgo Foundation and Ariadne Labs (who have their own tracker). The UK government has outlined 10 priority groups for receiving the vaccine, starting with “residents in a care home for older adults and their carers,” followed by other adults over 80 and healthcare workers. Some countries will have different priorities though, New Zealand which has very low infection rates and keeps new arrivals in quarantine for two weeks, is prioritising its border force, who are the most likely people to interact with COVID-19 in that country. If you are interested to learn more about your own country, we recommend checking the department of health’s guidance in your country of residence.

5. Have the clinical trials tested whether vaccines limit asymptomatic spread?

All vaccine producers will eventually release information on whether being vaccinated prevents the recipient from asymptomatically spreading the disease to other people, but whether they release that data alongside other results depends on the trial. Pfizer BioNTech has not released data on asymptomatic people yet; it says this information is currently being collected but it will be several months before this is released. Moderna has said they have not completed full analysis on the efficacy against asymptomatic infection, but early indications suggest that it does provide protection. The Oxford AstraZenica vaccine significantly reduces asymptomatic cases, but it appears that it reduces these by less than it reduces symptomatic infections.

There is a worry that vaccines can lead to more asymptomatic spread if they result in people who would have otherwise been symptomatic becoming asymptomatic, rather than being fully protected. This might lead to increased transmission if these people are then more likely to pass the virus on, because they do not realise they are spreading it. So, this is clearly really important information for understanding how we can use these vaccines to eradicate the illness and get back to near-normal life. We hope researchers prioritise collecting it.

6. What does “90 percent efficacious” mean, and how has this been calculated?

The main measurement in most COVID-19 vaccines trials is the chance that you catch a symptomatic case of COVID-19. A 90 percent effective vaccine will be one that reduces your chance of getting symptomatic COVID-19 by 90 percent, compared to not getting the vaccine. This is measured as the percentage of people in the study’s treatment group (those who receive the vaccine) who get sick as a percentage of those in the control group (who do not receive the vaccine). If 1000 people in the control group were to contract COVID, but only 100 people in the treatment group, then the vaccine would be said to be 90 percent effective, because it prevented 90 percent of people from contracting the virus. Because clinical trials are conducted under ideal conditions and frequently exclude people who have some other condition or illness, the effectiveness of the vaccine as it is rolled out in the general population may be somewhat lower than the clinical efficacy.

If everyone in society was to get a vaccine that was 90 percent effective, it would reduce the infection rate by far more than 90 percent. That’s because people who have been immunised would be 90 percent less likely to contract the illness when they come into contact with it, and when vaccination is widespread, each of those people who is less likely to contract the illness is also less likely to spread it to others—drastically slowing the rate of spread.

For example: if you provide care for a vulnerable person and you’re the only person they ever interact with, if they get a vaccine, their risk of infection will fall by the rate of efficacy (say, 90 percent). Should the vaccine reduce asymptomatic cases by the same amount, and if you also get the vaccine, their chances of being infected fall substantially again because you’re much less likely to meet them whilst infectious, and even if you were, they’re less likely to contract the illness. The benefits compound. However, as mentioned in question 5, stopping asymptomatic infection is crucial for societal vaccine benefits.

7. Has the information about these vaccines been released in the usual way? Why did the press release come out before the peer-reviewed journal articles?

There is nothing to cause suspicion about the current approach. Companies are obliged to notify shareholders of “material” news that impact their share price. This is often taken to mean anything that will change the price by more than 5 percent. For this reason, important clinical trial results often need to be made public immediately via press release, to limit the risk of insider trading. Usually, companies try to limit the amount of information contained in these releases, because scientific journals will not accept results that are given in full elsewhere, and companies rely on journals to share their trial results with clinicians. COVID-19 vaccine press releases appear to contain more information than usual, probably because of reduced concerns that a journal would not accept the results, or even that journals are needed to publicise their results (because many journals want to publish up-to-date COVID-19 findings). The media is also paying much closer attention to the results of these clinical trials than would be expected for a normal clinical trial, and reporting any findings at great pace.

8. Companies have outlined the cost of purchasing the vaccines themselves, but are there differences in the costs of the rollout, in terms of infrastructure and personnel?

As we mentioned, some of these vaccines have very poor thermostability (meaning they must be kept at a specific temperature, often very cold), particularly the Pfizer BioNTech vaccine. This is creating huge logistical challenges for distributing these vaccines. We are not aware of any public costing for what distributing the different vaccines will be, but costs will depend on the infrastructure that countries already have for ultra-cold storage. Cold-storage freezers, for example, cost $10,000-$15,000 to purchase and then up to $1,000 a year to run.

Please do get in touch with us if you have been researching this and can share resources on what this might look like at the country level.

9. When can we expect to see pregnant and lactating people included in trials?

Most of the leading vaccine candidates have now committed to running trials for people who are pregnant or breastfeeding. These could start as early as January 2021, and results from these trials would be expected to take several months. The US FDA, however, has decided that the benefits of vaccination outweigh any potential risk, and has given those who are pregnant or breastfeeding the option to opt in to receiving the vaccine now.

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We recognise that information about vaccines is being released at a great pace, and it can be hard to keep up. At CGD, we have a strong body of work on COVID-19 vaccines, with recent commentary from our experts in a range of media outlets. While we have pulled this first blog together with questions from our colleagues, we welcome you to share your questions with us, please do get in touch if you have questions you would like us to consider.

Update 12/18: Answers to questions 5 and 6 have been updated following feedback from colleagues.