The U.K. plans to deliberately infect dozens of healthy young adult volunteers in the coming weeks with SARS-CoV-2 to learn more about how the virus affects people and the effectiveness of experimental vaccines. The research, the first so-called human challenge study for Covid-19 announced anywhere, has been approved by the country’s clinical trials ethics body and aims to start by mid-March. Yet it throws up a number of questions, including the availability of reliable “rescue treatments” in the event that participants develop a serious illness.
1. What is a human challenge study?
It’s a controlled human infection study in which healthy volunteers are deliberately “challenged” with an infectious disease organism. The World Health Organization says such research can be particularly valuable for testing vaccines because fewer participants need to be given experimental inoculations to gauge their efficacy and safety, potentially speeding the development of immunizations. Human challenge studies may also be used to glean information about a pathogen, such as its ability to cause disease, factors that put people at risk of illness and clues about the way the body generates immunity in response to an infection. Organizers of the U.K. study say this type of research has been used over many decades and for diseases including malaria, typhoid, cholera, norovirus and flu.
2. What is the U.K. proposing to study?
As many as 90 healthy adults ages 18 to 30 years are being recruited for two areas of research, according to a Feb. 17 statement from the U.K. government. The first will test varying amounts of virus to determine the smallest amount needed to cause an infection and generate an immune response. Organizers said the research would help identify factors that influence how the virus is transmitted, including how a person who is infected with SARS-CoV-2 transmits infectious particles into the environment. After that, Covid-19 vaccine candidates proved safe in clinical trials could be administered to groups of volunteers who are then exposed to SARS-CoV-2. This would help identify the immunological response needed to protect people from re-infection, as well as the most effective vaccines.
3. Who is doing the research?
It’s being run by a group comprising the U.K. government’s Vaccines Taskforce, Imperial College London, the Royal Free London NHS Foundation Trust and clinical research company hVIVO Plc. The U.K. is investing 33.6 million pounds ($47 million) in the research. Volunteers will compensated for the time they spend in the study. Their payment for being isolated while infectious and for a year’s worth of follow-up appointments will be 4,500 pounds, the New York Times reported.
4. Are they really volunteering?
Covid-19 has killed more than 2.4 million people globally since late 2019. Morally, those volunteering would need to be free from coercion and their consent vetted by ethics committees, Stanley Plotkin, a physician from Doylestown, Pennsylvania, who helped develop a vaccine against rubella virus, and New York University bioethicist Arthur Caplan wrote in a paper in the journal Vaccine in May. “Asking volunteers to take risks without pressure or coercion is not exploitation, but benefiting from altruism,” they said.
5. What precautions are being taken?
No study is completely risk-free, but the researchers said safety is paramount. The virus characterization study would use the version of SARS-CoV-2 that has been circulating in the U.K. since March 2020 and has been shown to be of “low risk” in young healthy adults, the government said. (It didn’t say whether more-transmissible variants would be studied later.) An expert team “will closely monitor the effect of the virus on volunteers and will be on hand to look after them 24 hours a day.” The researchers are working closely with the Royal Free Hospital and the North Central London Adult Critical Care Network to ensure the study won’t compromise care for other Covid-19 patients. Criteria for participation includes no history or symptoms of Covid-19, no underlying health conditions and no known adverse risk factors for Covid-19 such as heart disease, diabetes, or obesity, the BMJ medical journal reported in October. Participants who develop Covid-19 will be treated with Gilead Sciences Inc.’s antiviral remdesivir as soon as the infection is confirmed, the BMJ said.
6. What are the concerns with human challenge studies?
The WHO formed an advisory group last year to consider such research in the context of Covid-19. In a December report it said that some concerns were highlighted, such as the potential for severe sickness, including blood-clotting complications, and the lack of reliable, effective remedies to thwart the disease. Some critics have raised concern about the possibility of long-term effects from a SARS-CoV-2 infection. The WHO report also cautioned that human challenge studies can lead to misinterpretation and confusion among the public, resulting in increased fear and hesitancy toward vaccines — especially if a participant becomes seriously ill or dies, or if there’s a containment breach. “The current environment is extremely volatile due to the politicization of the pandemic and the historical association of abuse with human subjects, in particular among different ethnicities and marginalized communities,” it said. There have been numerous questionable — and in some cases cruelly exploitative — human challenge studies in the past. A notable example is the 1932 Tuskegee Syphilis Study in which Black men were misled about the purpose of the research and suffered unnecessarily as a consequence of untreated disease.
7. What is the WHO doing?
WHO plans to organize an open forum call with technical experts to discuss the study protocols in detail, and to reconvene its advisory group before the end of March to review the situation and to “provide advice and support in making informed decisions.”
The Reference Shelf:
- Related QuickTakes on how the coronavirus is transmitted, what we know about Covid-19 in children, severe reactions to pandemic vaccines, vaccine passports, and SARS-CoV-2 variants, whether you can be forced to get vaccinated, challenges deploying vaccines, Covid-19 treatments, and the unanswered questions about the virus.
- Study protocol as posted on a clinical trials registry.
- Stanley Plotkin and Arthur Caplan discuss human challenge trials in a paper in Vaccine, and researchers at the University of Oxford’s Ethox Centre provide an overview of the ethics of human challenge studies.
- The WHO advisory group reports on its work considering the feasibility, potential value and limitations of establishing a closely monitored challenge model of experimental Covid-19 in healthy young adult volunteers.
- The journals Nature, The Lancet, BMJ and Science report on the proposed research.
