Why a COVID-19 Challenge Trial Is So Controversial

Doctor giving person a vaccine.

A. Martin UW Photography / Getty Images

Key Takeaways

  • Researchers in the U.K. received approval to conduct a COVID-19 challenge trial, which involves deliberately infecting people with the virus in an effort to find a safe and effective vaccine.
  • The trials will be conducted in a contained biohazard unit.
  • This trial is controversial, given the unknown long-term effects of COVID-19.

Researchers in the U.K. received approval from government officials to conduct the first COVID-19 human challenge studies, in which healthy people will be purposefully infected with SARS-CoV-2, the virus that causes COVID-19.

According to a U.K. government press release, up to 90 volunteers between the ages of 18 and 30 will be exposed to COVID-19 in a safe and controlled environment so researchers can better examine and understand how the virus affects people.

While the study received ethics approval in February, pharmaceutical company Open Orphan originally announced the news on October 20 in a press release. According to the release, Open Orphan will develop a model to manufacture the challenge virus and the study. The study, which is expected to begin within a month, will allow researchers to identify “the most appropriate dose of the challenge virus for use in future human challenge studies, which play a vital role in helping to develop vaccines and antivirals for infectious diseases such as COVID-19.”

The study is sponsored by Imperial College London and conducted by hVIVO, a subsidiary of Open Orphan, at The Royal Free Hospital's specialist research unit in London.

Open Orphan says researchers will monitor participants 24 hours a day in a clinical facility. Once the initial phase of the trial is over, participants will be monitored for up to a year after being infected with the virus “to ensure their long-term well-being.”

Trial participants will be given the “very smallest dose” of the virus, Martin Johnson, MB ChB, senior medical director at hVIVO, told CNN. And, if a patient displays symptoms of COVID-19, they will be given the antiviral drug remdesivir.

The COVID-19 challenge trial is controversial, though, and the news also raises ethical questions about challenge trials in general.

What This Means For You

A challenge trial for COVID-19 can potentially speed up approval for a vaccine for the virus, but it’s controversial.

What Is a Challenge Trial?

Human challenge trials are scientific trials where participants are deliberately infected with an infectious disease, whether they have been vaccinated against the disease or not, according to the World Health Organization (WHO).

Under the WHO’s guidelines, a challenge organism can be similar to what is widely circulating among the public, adapted, or genetically modified.

This is a different technique from those used in currently ongoing clinical trials for a COVID-19 vaccine. Trials that are in phase 3 of testing, the final phase, give participants an experimental vaccine and then have them go about their usual life, Thomas Russo, MD, a professor and chief of infectious disease at the University at Buffalo, tells Verywell. The thought, he says, is that they may be naturally exposed to the virus. But a challenge trial purposefully infects people in an effort to speed up the timeline.

“Rarely do we do these sorts of things in humans unless we’re sure that, if you’re being challenged, that the chances of something bad happening to the volunteer is extraordinarily low,” Russo says. “It’s also desirable to have a treatment available in case things go sideways.”

This Challenge Trial Is Controversial

Russo calls the COVID-19 challenge trial a “very bad idea” and cites several reasons. “There is still some uncertainty about the infectious dose of the virus—how much we have to give to infect a person,” he says. “There’s a general rule of infectious disease that the more of a pathogen you’re exposed to, the more likely you are to develop severe disease.” Researchers run the risk of giving too high a dose—potentially giving participants serious illness, Russo says.

Russo also expresses concerns about the potential long-term effects of being infected with COVID-19. “We originally thought this was a respiratory virus and now it’s clear that there are potentially long-term effects on the heart, gastrointestinal system, and central nervous system,” he says. “It’s not just about the treatment and whether the vaccine is protective in the short-term. It could also be that there are some untoward consequences in the immediate and long-term.”

It’s also important to note that there is no cure yet for COVID-19, Peter Smith, DSc, a professor at the London School of Hygiene & Tropical Medicine who co-authored a scientific paper on using challenge trials for COVID-19 in March, tells Verywell. “There is a risk of serious disease or even death,” he says. “That’s been the source of controversy. Is it ethical to do these studies when there is a small, but not non-zero risk of either developing serious illness or dying?”

But Smith says the idea of doing a challenge trial for COVID-19 has been “debated in ethical circles over a number of months,” noting that “there are very many, including ethicists, who think that the potential benefits of challenge studies outweigh the risks.”

“Obviously, any individual who entered into it would have to be fully informed about the known potential risk,” he says.

But still, Russo says, the current treatment for COVID-19 “is a little shaky.” While studies show remdesivir often helps hospitalized patients, recent research sponsored by the WHO found it didn’t prevent deaths.

Challenge Trials Have Been Conducted in the Past

Challenge trials aren’t a new concept. In fact, Open Orphan previously conducted them for other illnesses, including the flu.

“Challenge trials have been done for a number of different pathogens—malaria, typhoid, cholera,” Smith says. “All of those can potentially cause serious illness or even kill people, but there are effective treatments.” If people in a challenge trial for one of those illnesses does become sick, they can “be very sure that they can be treated,” Smith says.

Overall, Smith thinks doing challenge trials for COVID-19 will be helpful toward finding the right vaccine. Initially, he and his fellow co-authors thought a challenge trial would be helpful in getting an effective vaccine created. But now that several vaccines are in phase 3 trials, Smith says there may be more benefit in using challenge trials to verify and evaluate the efficacy of new vaccines. “It’s going to be very difficult to carry on doing large-scale trials with tens of thousands of people, particularly when there are some vaccines that are partially efficacious available,” he says.

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.

5 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Cision PR Newswire. Open Orphan/hVIVO Signs Contract with UK Government for the Development of a COVID-19 Human Challenge Study Model. October 20, 2020.

  2. Open Orphan. The Human Challenge Programme.

  3. World Health Organization. Expert Committee on Biological Standardization. October 16, 2016.

  4. Eyal N, Lipsitch M, Smith P. Human challenge studies to accelerate coronavirus vaccine licensureJ Infect Dis. 2020;221(11):1752-1756. doi:10.1093/infdis/jiaa152

  5. Pan H, Peto R, Karim Q et al. Repurposed antiviral drugs for COVID-19–interim WHO SOLIDARITY trial results. 2020. doi:10.1101/2020.10.15.20209817

By Korin Miller
Korin Miller is a health and lifestyle journalist who has been published in The Washington Post, Prevention, SELF, Women's Health, The Bump, and Yahoo, among other outlets.