Researchers in the U.K. have deliberately infected 30 volunteers with the virus that causes Covid-19, in the first human challenge study of the disease. Infecting the volunteers—who are healthy, unvaccinated and range in age from 18 to 30—will allow the scientists to observe in real time how the virus attacks the body and, from the moment of exposure, how the immune system responds.
The volunteers are under 24-hour study in a hospital residential facility, allowing the researchers to, among other things, measure their viral load twice daily in the nose and throat, perform multiple blood tests, collect urine or stool samples if needed and measure antibodies in the mucus from the respiratory tract and in the blood, according to Peter Openshaw, a professor of experimental medicine at Imperial College London and a co-investigator on the study.
“Because we can take so many different samples, we can get extraordinary insight into how the virus causes disease,” Dr. Openshaw said. “We are learning more about the twists and the tails this virus has and the ways it can cause problems in other organs. It’s all very important in learning how to prevent those complications.”
Human challenge studies are different from randomized clinical trials, the primary way researchers find out if vaccines and other therapies are safe and effective. In clinical trials, researchers take a large number of people, give half a vaccine and half a placebo, and send them on their way to be naturally exposed to the virus, said Kathleen Neuzil, director of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine. A clinical trial in the U.S. of Covid-19 vaccines used more than 30,000 volunteers.
In comparison, a human challenge study of a relatively small number of participants offers precise answers to specific questions, often related to immune response. Today, human challenges conducted under the supervision of institutional review boards are routinely used to research diseases such as influenza, malaria, cholera, salmonella, shigellosis and norovirus.
But similar studies have been used for centuries, at times raising ethical concerns.
The first smallpox vaccine was developed in 1796 when a physician exposed a healthy boy to cowpox, a similar but milder virus, and then to the deadly smallpox virus. The boy did not contract smallpox, and vaccination became the primary defense against the incurable disease, which was eradicated in the 20th century.
Other early human challenge studies, including some involving children and babies, were eventually judged immoral.
Before a Covid-19 vaccine or other therapies were available, the idea of intentionally infecting people with the deadly virus that causes the disease also generated debate, and a primary goal of the U.K. study is to determine the lowest possible dose of virus required to make volunteers sick so that scientists can study the disease while placing participants at minimal risk.
Volunteers were admitted to the Royal Free Hospital in London, where they were inoculated with the virus, said Robert
A goal of the study is to determine the lowest possible dose of virus required to make volunteers sick. Above, commuters at the King’s Cross train station in London last month. HENRY NICHOLLS/REUTERS
Read, a professor of infectious diseases at the University of Southampton who helped design the study.
Typically, they remain in the hospital for two weeks for testing, Dr. Openshaw said, but the criteria for release includes becoming negative on a PCR test, a molecular test that detects the genetic material of the virus, so there isn’t a set point at which someone is discharged. For participating, they are paid roughly $5,000.
The study, which began in March and is expected to conclude in September, has revealed new information, researchers said, but they wouldn’t disclose details. The Imperial College London research is supported with an investment of £33.6 million, equivalent to $46 million, from the U.K. government, an amount expected to support this and future research.
“The very first stage was to establish whether it was feasible to do it safely,” Dr. Openshaw said. “The next stage would be to go on and ask questions about those who previously have some immunity induced largely by vaccination but also from natural infection.”
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