Human Challenge Trials for Covid19

At a time when most of us are doing our best to avoid catching coronavirus, it seems surprising that there will soon be some individuals in the UK getting infected on purpose. But that's the goal of a new study announced this week by UK scientists who, supported by a £34 million Pound investment from the British government, are setting up what are called "challenge studies". Volunteers, isolated in a laboratory, will be exposed to the SARS-Cov-2 virus that causes Covid-19 so researchers can study how the body responds to the infection. The initiative will help to speed along the development of safe and effective vaccines. Chris Smith spoke to Chris Chiu, who is leading the project...

Chris C - This is likely to be the first time that anyone has developed a human challenge model for SARS-CoV-2. Human challenge models are a special kind of clinical study where we deliberately infect volunteers with a virus to look at how they respond to the infection.

Chris S - Who are you going to recruit?

Chris C - Our immediate top priority is safety. It's really important to us that the participants in this study are at as low a risk as possible of developing more severe symptoms. So that means that we'll be focusing on people who are young, aged 18 to 30; and who are essentially completely healthy, so people who have no other medical conditions such as diabetes, high blood pressure, anything wrong with their lungs or their heart.

Chris S - And when you do these sorts of studies, how are they done? How do you actually get the people, where do you put them, and how do you infect them?

Chris C - We recruit from the general population, and we go through a very complex process of working out whether they are completely healthy. Then we will bring them in to, in this case, the Royal Free Hospital in North London. They have a unit there specially built to have the highest quality of air handling, which means that infected people who are staying with us will not be at risk of transmitting the virus to people outside. When these volunteers come in, we will take some virus and we'll drop tiny drops in their noses. At that point they may or may not become infected, but we will keep them with us in the units for at least two weeks to monitor them as they develop the infection, and then as they get better.

Chris S - And how are you going to study them? What sorts of samples will you be collecting, and what are you hoping to learn by doing this?

Chris C - So one of the major strengths of these types of studies, human challenge studies, is that we can measure immunity and inflammation in these volunteers before they get the infection, during the course of their infection, and as they get better, to better understand how their immune system is responding to the infection. And what's really unique about these studies is that you can look at their immune responses even before infection has got going. In any kind of normal study, you would only be able to detect if people were infected by their onset of symptoms, and so at that point you're already five days or more into the infection; whereas here, we know exactly when they received the virus, and so we can start looking to see the development of immune responses straightaway, and potentially the immune responses which may help them from more severe infection.

Chris S - How do you know how much virus to expose an individual to, to guarantee that they're standing a good chance of catching it? And presumably there are some people who it'll take more virus to infect than others; so how do you make sure that's safe but also informative? Because people have made a case for -  perhaps the amount of virus we're exposed to at the onset of infection makes a difference to our clinical outcome.

Chris C - Yes, you're absolutely right. And I think part of that is based on our experience. But obviously this is a brand new virus, and we don't know exactly how much virus is going to be needed, so what we're planning on doing is starting with an extremely low dose. If those first few people don't develop any infection, then we will increase to the next level. And we will gradually do that until we reach an optimal dose.

Chris S - Given that the people who tend to have a problem with this infection are not young people, is there not quite a significant limitation to this study? Because you're studying people in whom you expect - and for very good reason - they will just recover. May we not therefore be completely missing the thing we really need to capture, which is what happens when people don't end up with that trivial infection?

Chris C - That's a completely valid point, but I think there are some really unique strengths to human challenge; you can really study the immune response in uniquely detailed ways. And we need to understand those to make better vaccines, make better treatments. The other application is in vaccine development and drug development, because you can do a study with perhaps only a hundred people and you will get a very early indication whether or not your vaccine does anything at all. And if it does nothing at all, then you might decide to deprioritize it; and if it does really well, then you can really put a lot of extra effort into it, and you can compare different vaccines in a short amount of time to be able to triage those.

Chris S -  When does it kick off?

Chris C - We'll be starting recruitment quite soon - within the next few weeks, we hope - and then if all goes well, then we should be inoculating the first volunteers at the beginning of January 2021.