The UK plans to run the world’s first COVID-19 ‘human challenge’ trial to assess the efficacy of possible vaccine candidates. On the 20th of October it was announced that the UK government will invest £33.6 million to fund the studies, which will be conducted in partnership with Imperial College London, viral challenge study expert hVIVO, and the Royal Free London NHS Foundation Trust. Rapidly rising case numbers have led to the announcement of a second lockdown in the UK, emphasising the need for effective measures to counter the spread of the virus and protect the population. If final ethical approval is granted, these trials have the potential to dramatically accelerate vaccine research. However, some scientists have concerns about the value of this research and the ethical implications.

Human challenge trials typically involve deliberately infecting young, healthy volunteers with a disease-causing agent to assess how well vaccines or drugs work to prevent the disease or reduce its symptoms. This is done in a laboratory environment, with 24-hour medical attention and observation by scientists to check for side effects and to deal with any medical problems. These trials are well-established in other diseases, with influenza challenge trials dating back to 1937.

Scientists plan to infect small groups of 18-30 year olds, who have no known underlying health conditions, with SARS-CoV-2 (the virus that causes COVID-19), by spraying droplets containing laboratory-produced virus into their nose. Their first task is to find the lowest possible dose of SARS-CoV-2 that can reliably cause infection, followed by trials to see how effective different vaccines are at preventing COVID-19. These studies are due to start in January 2021, with results expected by May.

The major benefit of these trials is that they could reduce the time it takes to approve an effective COVID-19 vaccine. Current phase III vaccine trials rely on some of their many thousands of volunteers being naturally exposed to the virus in order for them to assess if the vaccine is better at preventing infection than a placebo. It can take many months for enough infections to occur naturally to be sure that the vaccine is making a difference. Challenge trials can speed up this process by exposing a much smaller number of participants to the virus soon after vaccination, potentially providing results in a number of weeks. Given that there have been well over 1 million deaths globally due to COVID-19 since the start of the year, accelerating vaccine approval by months could save a huge number of lives.

“The major benefit of these trials is that they could reduce the time it takes to approve an effective COVID-19 vaccine”

However, some scientists doubt the value of these trials. An important criticism is that the trials will only tell us if the vaccines are effective in a small number of young and healthy people, not the elderly, immunocompromised and chronically ill people who are most at risk. Despite this, they could provide a faster way of screening which vaccine candidates are likely to be effective and safe, before investing time and money in testing them in other demographics.

As with all clinical studies in the UK, the proposed trials will be carefully considered by ethics committees before the research begins. A particular ethical concern for COVID-19 challenge trials is that there are currently few successful treatments for the disease, which has higher mortality rates than other diseases previously investigated using this kind of trial, such as influenza. Once volunteers show signs of infection they will be given the anti-viral drug remdesivir, but the latest research has disagreed on whether this drug has a meaningful effect on the progression of the disease, with no research at all done on patients at early-stages of infection.

The study organisers have said the trial will be paused if a participant becomes severely ill, but their expectation is that most won’t even get any symptoms. Young, healthy people have a very low risk of complications, but we can’t completely rule out the possibility of participants having pre-existing conditions that they are unaware of. Despite these good odds, there have been many cases of young, otherwise healthy people sadly dying due to COVID-19.

“Young, healthy people have a very low risk of complications, but we can’t completely rule out the possibility of participants having pre-existing conditions that they are unaware of”

Another concern is the prospect of ‘long COVID’ - a phenomenon experienced by 1 in 10 infected people, where symptoms last for three weeks or more, sometimes continuing for months. Experts have warned that even mild cases may cause lasting damage to internal organs, and there is currently no way to predict who will recover quickly and who will be affected long-term.

Despite this, many believe that the level of risk is justified. The trials have been compared to altruistic kidney donations, which have a comparable risk of death to participation in a COVID-19 challenge trial. These procedures are considered ethically acceptable, despite saving only one life. In an interview with Nature, director of the Center for Population-Level Bioethics at Rutgers University Nir Eyal said “We […] let humans volunteer to do risky things all the time. We let people, for example, volunteer to be emergency medical services during this period. That significantly elevates their risk of getting infected. But it’s also very important.”

Though potential risks of the trial will be communicated clearly to participants, some are concerned that the payment on offer raises the possibility for exploitation of low-income people. The trial organisers have not yet disclosed the amount participants will be paid, but influenza challenge trials in the UK can pay up to £3,750. Given that many people are finding themselves under extraordinary financial pressure due to the impact of the pandemic, there are concerns that some may volunteer for financial reasons without fully considering the risks. The recent announcement of a second lockdown in the UK has led many to fear further job losses as economic recovery from the initial lockdown grinds to a halt, putting more people in financial distress.

Over 38,000 people from 166 countries have indicated that they are interested in volunteering on 1daysooner.org, a website advocating for the benefits of COVID-19 challenge trials. Interestingly, many quotes from these volunteers suggest that they are not motivated by the money, with one USA resident saying: “the potential benefit to global public health and economic recovery that could come from a challenge trial is far greater than any personal risk to me.”

This is a pivotal but controversial development in COVID-19 research, with the potential to provide vital insights into vaccines and treatments. If granted full approval, the study is expected to begin in early 2021, with further information on participant recruitment and study design to be published soon.

If you are interested in volunteering for a challenge trial you should visit www.UKCovidChallenge.com where you can read more about the risks involved and sign up to their mailing list of potential participants.