illustration of green viral particles flowing into a person's nostril
illustration of green viral particles flowing into a person's nostril

First COVID-19 Human Challenge Trial Reveals Uneven Susceptibility

Only half of volunteers deliberately exposed to SARS-CoV-2 developed an infection. None developed serious symptoms, paving the way for further challenge trials.

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Shawna Williams

Shawna joined The Scientist in 2017 and is now a senior editor and news director. She holds a bachelor's degree in biochemistry from Colorado College and a graduate certificate and science communication from the University of California, Santa Cruz.

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Feb 3, 2022

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Update (April 1): This study was published yesterday in Nature Medicine.

Since the early months of the COVID-19 pandemic, some researchers and organizations have been mulling the possibility of organizing human challenge trials on the disease, meaning that people would be deliberately infected under controlled conditions in order to better study its course. The first such trial, using the original strain of SARS-CoV-2, got underway in April 2021. On February 1, the authors posted their results as a preprint. They report no safety issues in their study cohort of 36 young adults and some preliminary data on the trajectory of a bout of COVID-19. 

“This study has already generated intriguing insights into the timeline of infection, particularly in the early phase,” Doug Brown, the chief executive of the British Society for Immunology who was not involved in the study, says in comments to the Science Media Centre. “In the longer-term, the hope is that these findings will now open up a new research avenue to develop a platform that will allow us to speed up the development of new vaccines, antivirals and diagnostics against COVID-19.”  

See “Q&A: Human Challenge Studies of COVID-19 Underway in UK” 

For the study, researchers recruited people between the ages of 18–29 who had not been previously infected or vaccinated against the virus and exposed them to SARS-CoV-2 made from a sample that was collected early in the pandemic before variants emerged. Half of the participants—18—became infected. Sixteen of those infected participants experienced symptoms that began two days after exposure. In those who became infected, it took about 42 hours for the virus to become detectable in the throat, the researchers report. It took longer for the subjects’ noses to begin shedding virus but when they did, the noses produced far more infectious particles than the throat had. Infectiousness peaked at five days after infection and lasted an average of nine days, with some subjects remaining infectious for up to 12 days, the researchers report.  

Participants developed cold-like symptoms such as sneezing and sore throats, the researchers report, with some also experiencing headaches, muscle aches, fever, or tiredness. Thirteen lost their sense of smell, and all but three of those people had regained it by 90 days later.  

The study, which has not yet been peer-reviewed, also found that lateral flow tests, also known as rapid tests, were effective in detecting when participants were shedding enough virus to potentially infect other people. “We found that overall, lateral flow tests correlate very well with the presence of infectious virus,” says the trial’s chief investigator, Christopher Chiu of Imperial College London, in a press release. “Even though in the first day or two they may be less sensitive, if you use them correctly and repeatedly, and act on them if they read positive, this will have a major impact on interrupting viral spread.” 

See “Opinion: What COVID-19 Has Taught Us About the Importance of Testing

“One interesting observation is that only 53% of infected individuals developed PCR-confirmed infection with no obvious differences between the groups” who got infected or didn’t, says Lawrence Young, a virologist at Warwick Medical School who was not involved with the study, to the Science Media Centre. “What factors are responsible for this difference are unknown but are likely due to immune factors that will be examined in on-going studies.”  

See “A Challenge Trial for COVID-19 Would Not Be the First of Its Kind