Many more infected with Omicron variant than reported, says UK scientists Photograph:( AFP )
In the past, scientists have deliberately exposed volunteers to diseases like typhoid and cholera to test vaccines. But infected people could be cured of those diseases; COVID-19 has no known cure, putting the scientists in charge of the British study in largely uncharted ethical territory
In the coming weeks, a small, carefully selected group of volunteers is expected to arrive on the 11th floor of a London hospital to be given what the rest of the world’s 7.8 billion people have been trying to avoid: a coronavirus infection.
They will be administered tiny droplets of the virus into their nostrils as part of a plan authorized by British regulators Wednesday to deliberately infect unvaccinated volunteers with the coronavirus.
The scientists hope to eventually expose vaccinated people to the virus as a way of comparing the effectiveness of different vaccines. But before that, the project’s backers have to expose unvaccinated volunteers in order to determine the lowest dose of the virus that will reliably infect them.
By controlling the amount of the virus people are subjected to and monitoring them from the moment they are infected, scientists hope to discover things about how the immune system responds to the coronavirus that would be impossible outside a lab — and to develop ways of directly comparing the efficacy of treatments and vaccines.
“We are going to learn an awful lot about the immunology of the virus,” Peter Openshaw, an Imperial College London professor involved in the study, said Wednesday. He added that the study would be able “to accelerate not only understanding of diseases caused by infection, but also to accelerate the discovery of new treatments and of vaccines.”
The idea of such a study, called a human challenge trial, has been hotly debated since the early months of the pandemic.
In the past, scientists have deliberately exposed volunteers to diseases like typhoid and cholera to test vaccines. But infected people could be cured of those diseases; COVID-19 has no known cure, putting the scientists in charge of the British study in largely uncharted ethical territory.
To ensure that participants do not become seriously ill, the British study will be restricted to healthy volunteers, in an 18 to 30 age range.
But there have been severe COVID-19 cases even in those types of patients, and the long-term consequences of an infection are also largely unknown. The age restrictions also may make it difficult to translate the findings to older adults or people with preexisting conditions, whose immune responses might be different and who are the target group for treatments and vaccines.
“It will be a limited study,” said Ian Jones, a professor of virology at the University of Reading who is not part of the study. “And you could argue that, by definition, it’s not going to study those in whom it’s most important to know what’s going on.”
For now, the only part of the study to be formally authorized by British regulators is the experiment to determine the lowest dose of virus needed to infect people.
After being exposed to the virus, the participants will be isolated for two weeks in the hospital. For that and the year’s worth of follow-up appointments that are planned, they will be paid 4,500 pounds, or about $6,200. The researchers said that would compensate people for time away from jobs or families without creating too large an economic incentive for people to participate.
When the idea of human challenge trials was first floated last year, some scientists saw it as a way of shaving off crucial time in the race to identify a vaccine. Unlike in large clinical trials, in which scientists wait for vaccinated people to encounter the virus in their communities, researchers in this project would eventually purposely infect vaccinated people.
Now that several vaccines have been authorized, the goals of this human challenge trial are somewhat different.
For now, the researchers will be exposing people to the version of the virus that has been circulating in Britain since last spring, and not the more contagious and potentially deadlier variant that has taken hold more recently. But eventually, they said, they could give people experimental vaccines designed to address the effect of new, worrisome variants and then subject them to those versions of the virus.
They could also directly compare different vaccine doses and dosing intervals for the same vaccine.
And once the pandemic wanes and there are fewer hospitalized patients to enroll in drug trials, the scientists behind the study said that additional such trials where people are directly infected would allow them to continue investigating new treatments.
“In the future, we won’t have large numbers of people you can do studies on in the field,” said Robert Read, a professor of infectious diseases at the University of Southampton, who helped design the study.
Infecting unvaccinated people with even low doses of the virus could yield important insights, said Andrew Catchpole, the chief scientific officer at hVIVO, a company specializing in human challenge trials that is involved in the study.
As intensely as the coronavirus has been studied, relatively little is understood about how people’s immune systems react in the immediate aftermath of being infected.
Nor do scientists yet know the specific type or level of immune responses that are necessary to completely protect most people from infection, a clue to how the dozens of vaccines that are still being studied will perform against the virus.
“One of the things we don’t understand is what is a truly protective response,” said Lawrence Young, a virus expert at Warwick Medical School, who is not involved in the study. “It’s a good way of understanding the host-pathogen interaction, though it does come with a whole heap of ethical issues, obviously.”
In the first part of the study, the scientists will administer tiny doses of the virus to a small cohort of volunteers. If they do not become infected, the scientists will give slightly bigger doses to a different group of volunteers, repeating the process in up to 90 participants until they have determined the right dose.
By this spring, the scientists hope to repeat a version of their experiment by exposing vaccinated people to the virus. The British government, which is helping fund the study, will help choose the vaccines. Those and other future stages of the trial would require new regulatory approvals.
There has been no shortage of interest among potential volunteers in these types of trials, with thousands of people around the world registering their interest with 1Day Sooner, a group that advocates human challenge trials as a way of speeding the development of enough vaccines to inoculate people in parts of the world still waiting for doses.
It is not clear how drug regulators in Britain or around the world would evaluate results from a human challenge trial, given the age restrictions and the small numbers of people involved.
But Catchpole said Britain’s drug regulator had indicated it would take any of the group’s findings into consideration as it evaluates future vaccine candidates.
With the virus now acquiring dangerous mutations, one question facing the scientists is whether they will be able to keep up with its evolution.
Just as making new vaccines takes time, so does manufacturing new viral particles to infect people. Catchpole said that it would take the researchers three or four months to make a new coronavirus variant in a lab before they could begin putting droplets of it into the noses of volunteers.