Are COVID-19 Human Infection Trials Ethical?

John Whyte, MD, MPH; Peter Openshaw, MD, PhD

Disclosures

March 15, 2021

Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

  • The United Kingdom has a long history of conducting experimental human infection trials. People in the UK vacationed at "flu camps" where they were paid to be infected with flu viruses. The camps closed in the 1980s, but some universities replicated the concept, and it's now being done for COVID-19.

  • These challenge studies allow researchers to learn about COVID-19 in its early stages.

  • Healthy volunteers, ages 18-30, have been selected because they are at low risk of developing COVID-19. They are given the lowest dose of the original SARS-CoV-2 — not a variant — to cause nasal colonization. They are then treated with remdesivir before symptoms occur.

  • Studies could provide efficacy comparisons of different doses of vaccines or regimens of antiviral drugs.

  • The United Kingdom is the first country to give ethical approval for human infection challenge trials for COVID-19, though other countries, such as the Netherlands, are planning to implement such trials.

This transcript has been edited for clarity.

John Whyte, MD, MPH: Welcome, everyone. You're watching Coronavirus in Context. I'm Dr John Whyte, chief medical officer at WebMD. Would you be willing to purposely get infected with the coronavirus so we could study you over time? That's exactly what approximately 100 people are doing in the United Kingdom in the so-called challenge trials.

To help explain this, I asked Dr Peter Openshaw to join us. He is a professor of experimental medicine at the Imperial College in London. Dr Openshaw, thanks for joining.

Peter Openshaw, MD, PhD: It's a pleasure.

Whyte: What are these challenge trials and why are we doing them?

Openshaw: In the UK, we've been doing experimental infections of human volunteers for years. There is actually quite a long tradition which goes back several centuries to the time when Edward Jenner was developing the smallpox vaccine. In more recent times, after the Second World War, there was a facility which was set up on Salisbury Plain — actually funded by the Americans — called the Harvard Hospital, which was established in order to do experimental common cold infections with many viruses, including coronaviruses. Many of us who've grown up with that sort of history in the UK are familiar with the idea that you might go off and be infected with influenza at "flu camp."

Whyte: Flu camp — I had not heard of that.

Openshaw: Yeah, it was called flu camp. You could take a couple of weeks' holiday out on Salisbury Plain, have everything looked after, and the chances of actually getting flu were quite low. Many people were in control groups, and it became quite an established way of getting a completely inexpensive holiday, to be paid to be infected with these viruses. So, when that closed in the 1980s, a number of universities started doing their own versions of this, and again, that tradition has continued. We've been infecting people with common cold viruses, the rhinoviruses, more recently influenza virus, and a virus that I've worked on for about 30 years called respiratory syncytial virus.

Whyte: But we have treatments for those conditions.

Openshaw: Well, there are treatments for influenza. You can use oseltamivir, and in the old days, they used to use the adamantane drugs, but it's become resistant to that.

Whyte: But why do it for COVID-19?

Openshaw: There's so much that you can learn by these challenge studies. If you just wait for people to become naturally infected, you can only really study the disease in its later course. You can't study the early effects of infection, the interval between inoculation of the virus and the development of symptoms, and you can't establish what's the minimal dose that's needed in order to become infected because those are not controlled studies. They're studies which are just opportunist.

Whyte: So, you take these healthy volunteers and you intentionally infect them with COVID-19 and then you study them over time?

Openshaw: Yes. The most important thing is that these volunteers are selected because they are at very low risk of developing serious disease; they're aged 18-30. We rigorously exclude anyone with any preexisting health condition. We start with the very smallest dose that we think might possibly cause nasal colonization with the virus, and then we use remdesivir (an antiviral drug) to terminate the infection before symptoms appear. So, we're not really intending to cause disease. We're just intending to cause nasal colonization with the virus.

Whyte: Some people will say that this is unethical, that you're intentionally infecting someone with a virus that we do not yet have good treatments for, and we have a vaccine to help prevent infection. Is it unethical?

Openshaw: We don't believe it is, and it's been through the most rigorous series of ethical considerations. The dossier that we've had to produce for the ethics committee is extremely extensive. We've gone over the literature on this virus, which by now is actually one of the most intensively studied viruses known to mankind. We do know an awful lot about the virus that we are now using to infect, and as I said, we are going to be using the very smallest dose we can. We're not using one of the new variants, which we have less information about. We are using virus which was circulating last summer, where we really do have a lot of information about exactly how it behaves.

Whyte: To play devil's advocate, if you say we already know a great deal about COVID-19, and you're selecting a population that by definition is much healthier and at less risk, what are we really going to learn from these trials?

Openshaw: Well, we can do very careful comparisons of the effects of different vaccines on virus shedding and compare different doses, vaccines, regimens, or antiviral drugs. We can determine their efficacy with very small studies rather than wait for the very large studies on thousands of people in order to observe natural disease. That's especially true as we begin to drive down the rates of infection. When we have much less virus circulating in the community, it becomes extraordinarily difficult (or sometimes impossible) to design clinical trials in order to answer these vital questions without doing a human infection challenge.

Whyte: Other than the UK, are these trials being conducted anywhere else around the world?

Openshaw: We are the first country in the world to give ethical approval for these trials. They are being planned in a number of other countries. The Netherlands, in particular, is also a world leader in human infection challenge studies, and they are certainly planning to do these studies, but they don't yet have ethical approval.

Whyte: Dr Openshaw, I want to thank you for giving us some insights into this concept of the human infection challenge trials and why we need to do them to gain more information about COVID-19.

Openshaw: Thank you.

Whyte: And if you have questions about coronavirus, drop us a line. You can email them to me at drjohn@webmd.net as well as post on Facebook, Instagram, and Twitter. Thanks for watching.

Follow Medscape on Facebook, Twitter, Instagram, and

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....