Gavriel Kleinwaks wants to get COVID-19, and she can’t understand why I find that surprising. The 23-year-old grad student is one of more than 30,000 volunteers who have signed up with an organization to be potential participants in a human challenge trial for COVID-19 vaccines. If selected, she would be given a dose of the vaccine and then given a dose of the live virus to see how well the vaccine works.
When I asked her why this was important to her, she struggled to respond.
“I don’t know how to answer that. Why is saving lives important to me?” she said.
Given the urgency to find a vaccine for COVID-19, these kinds of trials are attracting a lot of attention from researchers, bioethicists and the public at large. It’s encouraging that there are tens of thousands of people like Kleinwaks willing to put their health, and their lives, on the line to get a vaccine sooner. But human challenge trials are not as simple a proposition as they seem, and there’s ongoing debate within the scientific community about whether the risks outweigh the benefits.
In the normal course of vaccine development, the vaccine is tested for efficacy in what’s called a phase 3 trial. A large number of people are given either the vaccine or a placebo and then sent back to live their lives, assuming that some of them, at some point, will be exposed to the virus. If a large percentage of the people who got the vaccine never become infected, and people who got the placebo do, you know the vaccine works. In a human challenge trial, rather than waiting for participants to encounter the virus naturally, the researchers go ahead and expose participants to the virus directly (this can be done in a variety of ways, from ingesting it orally, to dripping a virus-laced fluid into their noses). Participants in the trial stay in a secure medical facility and are treated if they get sick.
In theory, it’s a really practical design. Want to see how someone with the vaccine does when exposed to the virus? Just expose them to the virus! But even in the best-case scenario, these kinds of trials require a lot of ethical considerations. And the novel coronavirus, a pathogen we’re still only just beginning to understand, is not the best-case scenario.
Human challenge trials have been used in the past to study everything from seasonal flu to malaria, but there are noticeable differences between those diseases and COVID-19. In the case of flu, the risk of serious illness or death for healthy participants is low. In the case of malaria, we have proven treatments that cure the disease. We don’t have the same luxuries with COVID-19, which means it doesn’t meet some of the regulations that medical ethicists have laid out for researchers considering using a human challenge model.
“We traced a pretty clear line in the sand saying that you couldn’t do challenge studies if participants would be exposed to risk of irreversible, incurable or possibly fatal infections,” said Charles Weijer, a bioethicist at Western University in Canada who co-authored expert criteria for human challenge trials. As a result, he said, COVID-19 trials, are “not currently ethical.”
Researchers who have proposed considering human challenge trials for COVID-19 vaccines say those risks can be mitigated by enrolling healthy, young participants at a lower risk of serious or deadly infection and providing access to high-quality medical treatment.
“Some people are many thousands of times less at risk for severe disease following infection than others,” said Nir Eyal, a bioethicist at Rutgers University who co-authored a paper in support of human challenge trials for COVID-19 vaccines. “If you select those at lowest risk, the remaining risk is not nil, but it is very low indeed.”
Typically, risks of serious negative outcomes are only taken if the participant has some potential benefit (think of experimental cancer treatments, for example), but that’s not exclusively the case. Eyal pointed to live kidney donation, a practice that carries risk and no physical benefit for the donor, but is widely accepted.
Kleinwaks said she is well aware of the risks, but feels as though the potential benefits — helping develop a vaccine more quickly — would be worth it. And she noted that not participating in a human challenge trial is no guarantee that she won’t get COVID-19 anyway.
“I don’t think infection is completely avoidable through my own actions,” said Kleinwaks, who lives in Boulder, Colorado. “The risks [after infection] might be a little better and certainly not worse if I undergo a challenge trial where I’ll be under really close medical observation and have access to the best care available.”
But Weijer stressed that because there’s so much we still don’t know about COVID-19, especially its potential long-term effects, it’s really difficult to estimate the risks, even for young, healthy participants.
The most compelling argument against human challenge trials for a COVID-19 vaccine, though, is that it might not actually be any faster. In order to infect people with the virus, we have to have a tested viral dose — one that is strong enough to infect people, but not so strong it gives an infection worse than natural spread — which can take up to a year to develop, according to Weijer.
Meanwhile, seven vaccine candidates have entered phase 3 trials. Researchers are developing these vaccines faster than any vaccines have been made in history, and by the time a viral dose is created for a human challenge trial, we might not need it.
Still, some researcher groups have started pursuing the idea. Participants are being recruited for a human challenge trial at the University of Oxford, and the University of Antwerp is building a facility specifically designed to conduct these kinds of trials. While the current development of vaccines might outpace a challenge trial, they could play a role going forward.
Seema Shah, a bioethicist at Lurie Children’s Hospital of Chicago, said researchers should be preparing for human challenge trials and keeping it as a possibility in their back pocket. “That would be especially important if the first vaccine out of the gate is one that isn’t as effective as we would like,” she said.
Until then, there are tens of thousands of volunteers like Kleinwaks waiting and willing to be called in if needed. After thinking about it a bit, Kleinwaks was able to give me an answer to why she’s willing to do all this.
“I feel incredibly lucky to have good health,” she said. “I’m a grad student, I don’t have a lot of time or money to donate. But this is a way I can donate my health. This is the thing I can do.”