A study of people who were intentionally infected with SARS-CoV-2 has provided a wealth of insights into viral transmission — showing, for example, that a select group of people are ‘supershedders’ who spew vastly more virus into the air than do others1.
The publication describes data from a controversial ‘challenge study’, in which scientists deliberately infected volunteers with the virus that causes COVID-192. Although the approach drew opposition, the work has now yielded data on questions central to public health, such as whether the severity of symptoms correlates with how contagious people are and whether home COVID-19 tests can play a part in reducing viral spread.
The results highlight how widely and unpredictably disease severity and contagiousness vary between people. “And it’s that variability among humans that has made this virus so difficult to control,” says infectious-disease doctor Monica Gandhi at the University of California, San Francisco, who was not involved in the work. The study, published on 9 June in Lancet Microbe, also suggests that human physiology, not the virus, is to blame for some of the inconsistency of COVID-191.
Design with benefits
Challenge studies are “very bold”, says Gandhi. Some people argue that it’s unethical to give people an infection that can cause severe illness, but the research design comes with benefits. Challenge studies can substantially speed up vaccine testing, and they’re the only way to understand certain aspects of COVID-19, such as the stage before people test positive or develop symptoms.
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Researchers inoculated 34 healthy young participants by squirting a known quantity of viral particles up their noses. Eighteen developed infections and spent at least 14 days confined to hospital rooms. Each day, researchers measured viral levels in the participants’ noses and throats, in the air, and on the participants’ hands and various surfaces in the rooms.
The symptoms and severity of naturally acquired COVID-19 might vary depending on transmission route, viral strain and how much virus a person was exposed to. But in the challenge study, “we know that that was all controlled”, says infectious-disease researcher Anika Singanayagam at Imperial College London, a co-author of the paper.
Of the 18 participants who developed infections, 2 shed 86% of the airborne virus detected over the course of the entire study — even though both had only mild symptoms. Previous research3 has provided evidence for the existence of superspreaders who infect large numbers of people. But whether such people are also ‘supershedders’ who emit copious amounts of virus, or simply have many social contacts, was up for debate, says disease ecologist Pablo Beldomenico at the Institute of Veterinary Sciences of the Coast in Esperanza, Argentina. This study “supports the existence of supershedders”, he says.
Rapid tests show their value
Participants used lateral flow tests, also known as rapid antigen tests, on each day that they were in isolation. None of the participants emitted a detectable level of virus into the air before testing positive, and only a small proportion of them left detectable virus on their hands, on surfaces or on masks that they donned temporarily.
By the time they tested positive, most participants had already experienced mild symptoms, such as tiredness or muscle aches. That means that if people test as soon as they detect symptoms, rapid tests “can be a powerful tool” for controlling viral spread, says infectious-disease researcher Christopher Brooke at the University of Illinois at Urbana-Champaign.
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Some researchers question the relevance of the study’s results to today’s world. The route of infection — drops administered through the nose — differs from that of most natural infections, says airborne-infectious-disease researcher Donald Milton at the University of Maryland in College Park. As a result, viral shedding might differ between study participants and infected people in the real world. The now-dominant Omicron variant also spreads differently from the 2020 strain the researchers used, his colleague Kristen Coleman adds.
Despite these limitations, the work “still gives us really useful information”, Singanayagam says, adding that the results are in line with what she and her colleagues have observed with naturally acquired infections. The team plans to perform similar challenge studies with more-recent variants.