LONDON -- U.K. researchers are preparing to infect healthy young volunteers with the virus that causes covid-19, becoming the first to announce plans to use the controversial technique to study the disease and potentially speed up development of a vaccine that could help end the pandemic.
This type of research, known as a human challenge study, is used infrequently because some consider the risk involved in infecting otherwise healthy people to be unethical. But researchers racing to combat covid-19 say that risk is warranted because such studies have the potential to quickly identify the most effective vaccines and help control a disease that has killed more than 1.1 million people worldwide.
"Deliberately infecting volunteers with a known human pathogen is never undertaken lightly, said professor Peter Openshaw, co-investigator on the study. "However, such studies are enormously informative about a disease, even one so well studied as covid-19."
Human challenge studies have been previously used to develop vaccines for diseases, including typhoid, cholera and malaria.
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Imperial College London said Tuesday that the study, involving volunteers ages 18-30, would be conducted in partnership with the government's Department for Business, Energy and Industrial Strategy, the Royal Free London National Health Service Foundation Trust and hVIVO, a company that has experience conducting challenge studies. The government plans to invest $43.4 million in the research.
Governments around the world are funding efforts to develop a vaccine in hopes of ending the pandemic that has pummeled the international economy, closing businesses and putting millions of people out of work. Forty-six potential vaccines are already in human testing, with 11 of them in late-stage trials -- several expected to report results later this year or in early 2021.
The Imperial College partnership expects to begin work in January, with results expected by May. Before any research begins, the study must be approved by ethics committees and regulators.
While one or more vaccines are likely to be approved before then, the study will still be relevant because the world may need multiple vaccines to adequately protect different groups within the population, as well as treatments for those who continue to get sick, said Dr. Michael Jacobs, a consultant in infectious diseases at the Royal Free London National Health Service Foundation Trust who will take part in the research.
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"I don't think many people think that what we're doing as scientists is searching for a silver bullet," Jacobs said. "We're going to need a whole raft of interventions in order to control this pandemic."
VOLUNTEERS LINE UP
Tens of thousands of volunteers around the world have already signed up to participate in more traditional trials of covid-19 vaccines. Critics of challenge studies question the need to expose healthy people to the virus when the disease remains widespread and vaccine development is moving quickly.
In the first phase of the U.K. challenge study, researchers will expose 90 paid volunteers to the virus using nasal drops in an effort to determine the smallest level of exposure needed to cause covid-19. Ultimately, the same model will be used to test the effectiveness of potential vaccines by exposing volunteers to the virus after they've received one of the candidate vaccines.
The research will be conducted at Royal Free Hospital in London, which has a specially designed area to contain the disease. While quarantined, volunteers will be monitored in a 22-bed biosecure unit for at least a year to ensure they don't suffer any long-term effects. They will undergo daily, even hourly, tests over two to three weeks.
Kate Bingham, chairman of the government's Vaccine Taskforce, which is to promote development of a vaccine for covid-19, said the project will improve understanding of the virus and help scientists make decisions about research.
"There is much we can learn in terms of immunity, the length of vaccine protection and reinfection," she said in a statement.
Later in the spring, the scientists hope to enlist more volunteers, who will be inoculated with promising vaccines and then exposed to the virus to see how well the vaccines protect them.
Challenge studies are typically used to test vaccines against mild infections to avoid exposing volunteers to a serious illness if the vaccine doesn't work. While the coronavirus causes only mild or moderate symptoms in most people and seems to be especially mild in young, healthy individuals, the long-term effects of the disease aren't well understood, and there have been reports of lingering problems in the heart and other organs even in those who don't ever feel sick.
Challenge experiments have a long history in biomedical research, dating to Edward Jenner's development of a smallpox vaccine in 1796. In the modern era, challenge trials have been used extensively to study and find treatments for influenza, malaria, typhoid, dengue fever and cholera.
Covid-19, though, is different. Without a medication to reliably "rescue" volunteers from the disease, many scientists are hesitant to infect people.
The challenge trial participants will be given the antiviral drug remdesivir, which has been approved or authorized for temporary use to treat covid-19 in more than 50 countries. The World Health Organization, however, recently reported that in large clinical trials in 30 countries, remdesivir had no substantial effect on mortality. That study has not yet been peer-reviewed.
TRIALS AND RISKS
In the U.S., the National Institutes of Health has downplayed the need for challenge studies given the speed with which vaccines are being developed, but it has taken preliminary steps to prepare for such research in case the approach eventually is required. Those steps include examining the ethics of a challenge study and funding research to create lab-grown virus strains that potentially could be used.
But even if they are needed, "human challenge trials would not replace Phase 3 trials" of covid-19 vaccines, according to a September statement from the National Institutes of Health that called the standard, rigorous studies its priority.
In July, the National Institutes of Health's vaccine working group published a paper in The New England Journal of Medicine pointing out the risks of doing a challenge study with a virus that so far has no good treatment and is wildly unpredictable, occasionally killing even some young, otherwise healthy people.
But 1Day Sooner, which advocates for covid-19 challenge trial volunteers, praised the decision and called on the government to build a testing center.
"We are glad the U.K. government is embracing the altruism of the thousands of our British volunteers who want these studies," the group said in a statement. "Challenge trials will be key to making multiple safe and effective covid-19 vaccines available for the whole world, including those in low-income countries bearing the brunt of this pandemic."
"Young people are not immune from that outcome," Francis Collins, director of the National Institutes of Health, told The Washington Post last week. "Is it actually justifiable to intentionally infect anybody -- no matter their current health status? I think that's a very open question, ethically."
Nonetheless, more than 38,000 people have indicated a willingness to volunteer by signing up with vaccine advocacy group 1Day Sooner.
"Why? Altruism, basically," he said.
'EXTRA DEATHS'
Meanwhile, the pandemic has killed about 299,000 more people in the United States than would be expected in a typical year, two-thirds of them of covid-19 and the rest from other causes, the Centers for Disease Control and Prevention reported Tuesday.
The CDC said the novel coronavirus, which causes covid-19, has taken a disproportionate toll on Hispanic and Black Americans, as previous analyses have noted. But the CDC also found that it has struck people ages 25-44 very hard. Their "excess death" rate is up 26.5% over previous years, the largest change for any age group.
Lauren Rossen, a senior health statistician at the National Center for Health Statistics and lead author of Tuesday's report, said the death rate in the young-adult age group "was trending up before the pandemic." But it's still not clear why excess deaths for people ages 25-44 rose so quickly.
As the coronavirus races across the country, it has reached every corner of a nursing home in Kansas, infecting all 62 residents. There are so few hospital beds available in North Dakota that patients sick with the virus are being ferried by ambulance to facilities 100 miles away. And in Ohio, more people are hospitalized with the virus than at any other time during the pandemic.
After weeks of warnings that cases were again on the rise, a third surge of coronavirus infection has firmly taken hold in the United States. The nation is averaging 59,000 new cases a day, the most since the beginning of August, and the country is on pace to record the most new daily cases of the entire pandemic in the coming days.
"The majority of states are on the rise," said Dr. Tom Inglesby, an infectious-disease expert at the Johns Hopkins Bloomberg School of Public Health. And at the same time, "there are very few places where things are stable and going down."
Governors of states including Tennessee, Oklahoma, Nebraska and North Dakota are all facing calls from doctors and public health officials to require masks.
In Utah, a spike in cases since school reopened has created a dynamic that Republican Gov. Gary Herbert has called "unsustainable."
But Herbert, who has been pressured by an outspoken contingent of residents opposed to masks, has resisted a statewide mandate.
AROUND THE WORLD
Elsewhere in the world, Ireland's Prime Minister Micheal Martin announced a lockdown starting at midnight today that will close all nonessential stores, limit restaurants to carryout service, require people to stay within 3 miles of their homes and ban visits to other households.
It marks a near-return to restrictions imposed by the government in March, although schools, construction sites and manufacturing industries will remain open. If people comply with the restrictions, which will be in place until Dec. 1, the country will be able to celebrate Christmas "in a meaningful way," Martin said.
Decisions by some European leaders to impose new restrictions are facing stiff opposition at the local level. After a tense face-off, Britain's government said Tuesday that it had failed to reach agreement with Greater Manchester Mayor Andy Burnham, who has rejected tough new measures without money to support the workers and businesses that will be most affected.
Britain's Communities Secretary Robert Jenrick expressed disappointment with Burnham, saying the mayor "has been unwilling to take the action that is required to get the spread of the virus under control." Prime Minister Boris Johnson said Tuesday that he would impose the restrictions, drawing criticism from Burnham.
"It cannot be right to close people's place of work, to shut somebody's business, without giving them proper support," Burnham said. He said Manchester had sought $117 million from the national government to help people get through the winter. It was unclear how much the city would receive.
Meanwhile, an arthritis drug that showed promise to treat coronavirus infections -- at least in small studies early in the pandemic -- did not produce consistent results across three large trials published Tuesday in JAMA Internal Medicine.
The drug, named tocilizumab, blocks specific immune molecules from triggering inflammation. Clinical observations in the outbreak's first months suggested that the drug could tamp down the hyperactive, and sometimes fatal, immune reactions in critically ill patients with covid-19.
Information for this article was contributed by Danica Kirka, Brady McCombs, Adam Geller, Adam Causey, Dave Kolpack, Jill Lawless and Sylvia Hui of The Associated Press; by William Booth, Carolyn Y. Johnson, Ben Guarino and Lenny Bernstein of The Washington Post; and by Sarah Mervosh and Lucy Tompkins of The New York Times.
