COVID-19 Human Challenge Study
Leading the world's first human challenge study for COVID-19
In February 2021, it was announced that the UK would be the first country in the world to carry out a human infection study (also known as a human challenge study) with SARS-CoV-2, the coronavirus that causes COVID-19.
During this study, young, healthy volunteers will be deliberately infected with the virus so that researchers can learn more about the infection and test new vaccines and treatments in the future. The initial study is supported by a £33.6 million UK government investment and will be delivered by a partnership between Imperial College London, the Royal Free London NHS Foundation Trust and the clinical company hVIVO.
For the initial study, up to 90 volunteers will be given the virus by drops in the nose in a safe and controlled environment. Only volunteers at the lowest risk of becoming severely unwell (young adults between 18-30 years old with no underlying health conditions) can take part. The study is taking place in a controlled facility at the Royal Free Hospital in London, so the virus cannot be passed on to people outside the study. There are medical staff on hand all the time closely monitoring the volunteers.
To begin with, the first small group of volunteers have been given a low dose of coronavirus, then researchers will slowly increase it in subsequent groups of volunteers until they find the minimum dose needed for most of the volunteers to get a positive coronavirus (COVID-19) PCR test result.
Findings from the study have now been published on a pre-print server (not yet been peer-reviewed) and detail the outcomes in 36 healthy, young participants with no immunity to the virus. Read the full news story on the Imperial College news site to learn more.
About the study
The SARS-CoV-2 coronavirus is likely to cause outbreaks of COVID-19 in the UK and around the world for years to come, even with vaccines available. There is still an urgent need to better understand the infection and continue efforts to develop new vaccines and treatments.
Human infection studies can help to address this need. This kind of study can provide an efficient platform for rapidly testing new vaccines and treatments. Human infection studies can also give researchers very detailed information about the infection, some of which can only be found in this way and will have important public health benefits.
Vaccines and treatments
Even though some COVID-19 vaccines are available, there are good reasons why we need continued research into new vaccines and treatments for COVID-19.
- It will take a long time to vaccinate everyone around the world. New vaccines will increase availability, especially if they do not require cold storage (and therefore can be used in more remote places or countries without the infrastructure to keep them cold).
- The virus is changing, so we will likely need to keep updating the vaccines and testing them against new emerging variants of the coronavirus.
- Having ‘single shot’ vaccines (highly effective after a single dose) would mean we could protect the population faster. Furthermore, finding new ways to deliver vaccines (for example, via a nasal spray) could also be beneficial by making them easier to administer and more acceptable.
- Some people won’t respond to the current vaccines or can’t be given them for medical reasons (or don’t want a vaccine). We still need better treatments for this group of people to help prevent them from being infected, or from becoming seriously ill or dying from COVID-19.
Human infection studies will also be able to help answer fundamental questions about vaccines, including whether they stop people passing on the virus as well as preventing them from becoming seriously unwell. If vaccines can block transmission too, they will be more effective because they create herd immunity and protect those who aren’t vaccinated (including vulnerable groups who may be unable to receive a vaccine). This kind of study could also help determine the best timing of second doses and boosters, and to understand how long immunity from the vaccines last.
Understanding COVID-19 and the immune response to the virus
There are many aspects of SARS-CoV-2 infection that scientists still don’t understand that human infection studies could help answer. Because volunteers taking part in such a study can be monitored from the moment they are given the virus, researchers can get very detailed information about the infection which wouldn’t be possible from people who have caught it naturally.
A human infection study can provide critical insights including:
- The incubation period of COVID-19 (the time from a person catching the virus to when they start to feel unwell), during which people can be infectious.
- The overall length of time that people are infectious (from first being exposed to when the virus is no longer detectable) and the best tests to identify infectious people.
- The risk of reinfection (some people have caught COVID-19 more than once). Researchers can use this kind of study to find out how long natural immunity lasts, factors that put people at higher risk of reinfection, whether new variants pose a higher risk of reinfection, and if reinfected people can spread the virus to others.
- Why many people infected with coronavirus have no symptoms (asymptomatic) but are still major spreaders of the infection.
Understanding more about the infection will help to inform public health measures like self-isolation and travel quarantine periods, track and trace efforts, how to reduce asymptomatic spread and community testing programmes.
Study design and managing risk
No clinical study is completely risk-free, but the researchers who designed the human infection study have done everything possible to minimise the risks to the volunteers who are taking part, the study staff, and the wider society. The team have also ensured that potential volunteers are fully informed about the risks before agreeing to take part.
The volunteers allowed to join the study are at the lowest risk of becoming severely unwell with COVID-19; they are young (18-30 years old) and in good health. During the study, they might get common symptoms of COVID-19 (including fever, tiredness, a cough, and changes to taste/smell), but these are expected to be mild and of short duration (1-2 weeks).
There is a small risk (1%) of the volunteers getting long COVID. Volunteers will be monitored for a year after being exposed to the virus, and if anyone develops long COVID they will be supported (both in terms of care via specialist clinics and compensation for loss of earnings).
Severe disease or death due to COVID-19 in young people is very uncommon, but there is still a small risk. However, the risk of the volunteers in the study becoming seriously unwell or dying is relatively lower, because they are screened for underlying health conditions and other factors that increase the chances of severe disease.
There are also other measures in place during the study to minimise these risks, including giving the volunteers the smallest amount of virus needed for infection and constantly monitoring them for early signs of more serious symptoms.
If any of the volunteers show any concerning symptoms, they will be moved from the quarantine unit where the study is taking place into the main hospital (The Royal Free Hospital), which has one of the best infectious disease teams in the world and would take over their care. The study is fully insured should any volunteer experience any serious consequences.
The first human infection study with coronavirus was approved as being ethical by an independent Research Ethics Committee. You can find out more about Research Ethics Committees (RECs) and the Health Research Authority (HRA) approvals on the HRA website. A REC is made up of experts from different backgrounds (for example doctors, clinical trial experts, and scientists) and members of the public.
Review by an ethics committee is one of a series of safeguards intended to protect people taking part in all clinical research studies. It is a thorough process and there are many principles that are considered during the review, including weighing up the benefits against the risks. Another important consideration is making sure the potential participants receive high-quality, comprehensive information about the study in a timely fashion. The information about the human infection study sent to and discussed with potential volunteers is very detailed and there are measures in place to make sure it is understood, so potential volunteers have a full picture of what the risks are and what the study entails before agreeing to take part (this is known as informed consent).
If you are interested in the general principles underpinning ethical review, you might find this website created by a research ethics advisor of interest.
The programme of activities (including surveys and online focus groups) to consult and involve members of the public began in April 2020, around 10 months before the human infection study with coronavirus was approved. The activities enabled public input into the concept and design of the human infection study throughout the study’s planning process. The findings from all the public consultation and involvement activities supported the Research Ethics Committee to review the study, helped shape the design of the study, and improved the study information material for potential participants.
The public involvement programme
Following the publication of the WHO key criteria for the ethical acceptability of COVID-19 human infection studies in May 2020, a team at the University of Southampton carried out the first public consultation to explore public acceptability of a human infection study with coronavirus (COVID-19). In a series of small discussion groups, they posed a series of questions to probe whether those taking part thought the concept of deliberately infecting people with coronavirus was acceptable, what concerns volunteers might have, and whether and how much they should be compensated for taking part. The full results of this study have since been published online.
To build upon this work, HIC-Vac funded a more extensive public consultation programme to include a larger, more diverse group of people across the UK. Teams from Imperial College London and the University of Southampton worked together to explore and capture public perspectives from different geographic regions reflecting a balance of ages, ethnicities and gender. The consultation activities included a wide-reaching survey and several in-depth focus groups to explore the survey findings in more detail.
Once the official partnership leading the human infection study with coronavirus had been decided and announced, the teams engaged and involved a broad range of individuals across the UK for more specific discussions relating to perspectives and feedback on potential participation in this kind of study, study design, and study information and consent.
The findings from all the activities have been collected and analysed and were discussed with the wider team designing the human infection study and considered during the ethical review. Involving the public at this early stage enabled the team to capture broad public attitudes on a human infection study with coronavirus, respond to any concerns raised and implement suggested study improvements to make it more acceptable to potential participants.
The findings from all the public consultation and involvement activities were discussed with the wider team designing the human infection study with coronavirus, as well as being submitted to the Research Ethics Committee as part of the ethics application. The impact of the findings included:
- Supporting the Research Ethics Committee by providing them with views from the public about such a study taking place in the UK
- Improving the description of risk to potential volunteers
- Capturing what details potential volunteers wanted to understand about taking part and follow-up care/support
- Informing the inclusion/exclusion criteria
- Optimising the participant information sheet and informed consent
The findings from the public consultation activities are being written up for publication. The HIC-Vac website will be updated when the findings are published to provide a fuller picture of this work.
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This page has been developed based on materials provided by HIC-Vac, an international network of researchers who are developing human infection challenge (HIC) studies to accelerate the development of vaccines against pathogens of high global impact. Learn more on the HIC-Vac website.
Image: 'Transmission electron micrograph of SARS-CoV-2 virus particles, isolated from a patient' - NIAID.
Page updated on 4 February 2022.