So-called challenge trials have long been used to study infections, but so far only the U.K. is doing them for Covid-19.
LONDON—Much of the world spent the past year taking vaccines and wearing masks to evade Covid-19. In the U.K., almost four dozen volunteers have had the virus dripped into their noses by syringe in clinical experiments.
Covid-19 Challenge Trials
So-called human challenge studies—which intentionally expose heal thy people to viruses and other pathogens to study illness, vaccines and treatments—aren’t new. Scientists globally have used them for decades to assess how infections and drugs behave from the moment they enter the body.
But only the U.K. has pushed ahead with Covid-19 challenge trials, deliberately infecting volunteers to study a new, sometimes-deadly disease that still harbours many unknowns.
On March 8, 23-year-old Jacob Hopkins, a U.K. university student, watched researchers enter his quarantine room’s air-locked entrance at London’s Royal Free Hospital. They wheeled a cart carrying a big red box, like a picnic cooler, labelled “biohazard.”
“It’s kind of like that scene from ‘Contagion’—well, any scene from ‘Contagion,’ really—all wearing hazmat suits [with] a little ventilator thing to the side,” he said. He lay on the bed with his head tilted back. A droplet of the coronavirus was inserted into his left nostril, then his right. He stayed there; his nose clipped closed for about another 20 minutes.
Mr. Hopkins kept an audio and visual diary during his hospital quarantine, providing details of his experiences. He said he volunteered to get infected to help scientists understand the disease better—and, he hoped, to help end the pandemic sooner.
On March 6, Mr. Hopkins took a taxi to London’s Royal Free Hospital. He was there for a Covid-19 challenge trial. Two days later, researchers dripped coronavirus into his nose.
So yeah, that was it. I’ve now been infected with coronavirus directly as apart of this study. Yeah. Wow, God.
A few days after the virus was dripped into his nose, he was shivering with a mild case of Covid-19, with the antiviral remdesivir pumped through a thin tube inserted into his arm. He spent 19 days in quarantine and said he felt fully recuperated a month later. He will ultimately be paid about £6,000, equivalent to $8,300, for that time, a year of follow-up tests and phone calls, and a parallel study he agreed to. Trial payments are based on U.K. living wages and go through ethical review.
The trials have faced pushback from health advisers and researchers here and abroad. World Health Organisation advisers and top U.S. officials have cast doubt over whether the potential benefits justify the risks. One big issue: the lack of a cure or proven lifesaving “rescue treatment” if a trial subject falls dangerously ill.
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Ezekiel Emanuel, a U.S. oncologist and bioethicist at the University of Pennsylvania, said Covid-19 challenge trials might have made sense last year before multiple vaccines proved effective. But this year, he opposed the idea on ethical grounds. “It’s still a mystery to me what the ultimate justification is.”
Garth Rapeport, a challenge-trial advocate, and former adviser to the U.K. Vaccine Taskforce, said overseas scepticism was high: “You can’t do this, it’s insane, it’s a lethal infection,” he said he heard. Dr. Rapeport, a respiratory-viral infection specialist, said the pandemic called for extraordinary measures and that statistics showed the trials could be conducted safely. “You had to strip the emotion out of the situation,” he said.
A U.K. health-department spokesman said the trials were being conducted in a “very safe and highly controlled environment and will deepen our understanding of pre- and post-symptomatic transmission of Covid-19.”
Matthew Memoli, director of the Laboratory of Infectious Diseases at the U.S. National Institute of Allergy and Infectious Diseases in Bethesda, Md., started planning a Covid-19 challenge trial last year before other U.S. government officials decided it was too risky for the potential payoff. But if the U.K. has breakthroughs from its trials, he said, “that will change the perspective of people in the U.S.”
The view from Mr. Hopkins’s hospital room.
All volunteers are 18 to 30 years old and screened for known risk factors. They are isolated in quarantine suites with full-time medical care and specialised air systems to contain the virus. Researchers hope to publish peer-reviewed initial findings from the first phase of the challenge trials by this autumn.
Planning started in April 2020, led by researchers from the University of Oxford and Imperial College London, officials from the government-appointed U.K. Vaccine Taskforce, and a small London-based biotech called hVivo Services Ltd. that specialises in contract drug testing.
Some of the scientists and hVivo have years of experience with human challenge trials. They say that observing the earliest moments of Covid-19 infection will further development of new vaccines, measure effectiveness of antiviral remedies and help authorities prepare for the next pandemic.
Last year, the UK set up ethical and regulatory reviews, with government pledging more than $40 million in fundraising. A medical ethics panel approved trials here in February.
Views were divided. At Oxford, a group of medical-school academics lobbied government health advisers to pull the plug on planned trials, arguing the risks were too high and could damage the university’s reputation, according to people familiar with the discussions. As trial timelines hit delays, proponents clashed over the study’s design and speed and the release of data, according to people involved.
Mr. Hopkins was in quarantine for 19 days. Before breakfast, he completed a cognitive test. Researchers measured virus levels, including from his breath.
“So yes it’s Friday the 12th now, it’s like just gone midnight, and yeah I’m— I don’t know if you can tell but like I have got the biggest chills on right now.”
The pace reflected caution, the government says. “The safety of volunteers in any clinical study is always paramount,” the U.K. health-department spokesman said.
“Sheer determination got us there in the end,” said Clive Dix, a drug-company executive and investor who served as deputy and then interim chair of the U.K. Vaccine Taskforce until April of this year.
Researchers hope trial data will shed light on the durability of immune protection and how Covid-19 affects breathing, heart function, smell and concentration even before symptoms show. They say the model could test new vaccines and treatments head-to-head, eliminating weaker candidates before expensive, large-scale trials. Transmission data could help authorities prioritise who gets booster doses.
“Already it’s evident that we’re going to learn a huge amount that couldn’t actually be done any other way,” said Helen McShane, an Oxford vaccinologist leading the university’s reinfection trial.
Researchers and the government say there have been no serious safety problems so far. Long Covid, involving prolonged symptoms like fatigue and shortness of breath, remains a concern, but the researchers cite evidence that young volunteers should shed symptoms within a few months.
“You need to really be sure that your participants understand that there is that small risk, even though we’re fairly reassured,” said immunologist Christopher Chiu, the Imperial College’s lead challenge-study researcher.
So far, volunteers have been exposed to the original strain of the virus that first circulated in Wuhan, China. hVivo is working to manufacture a Delta-variant version, a process that takes several months.
Meta Roestenberg, a physician-scientist at Leiden University in the Netherlands, still hopes to persuade wary Dutch regulators to allow Covid-19 challenge trials there. “These studies yield so much data and insights sometimes on things you can’t imagine beforehand,” she said. She also understands the hesitation. “It’s a societal decision to support this kind of work.”
Mr. Hopkins and his father, Andrew, adhered to social-distancing rules at the former’s home in Birmingham, England, before the trials began.
