Young adults who were intentionally infected with a small dosage of the coronavirus mostly developed either mild symptoms or no symptoms at all, and the majority had their sense of smell and taste affected, according to a preprint study posted online on Wednesday.

The study was the first so-called "human challenge" trial for Covid-19, meaning that researchers deliberately exposed volunteers to learn more about the disease. Covid-19 human challenge trials have been controversial, with critics arguing that such trials unacceptably expose volunteers to serious risks, while proponents say they can offer a powerful way to better understand Covid-19's course.

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Study details

For the study, researchers gave 34 individuals ages 18 to 30 a low dosage of a strain of the coronavirus that was prevalent in the United Kingdom in early 2020—around the amount of virus that would be present in one respiratory droplet.

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The study was conducted by U.K. researchers affiliated with Open Orphan, Imperial College London, and Britain's vaccines task force.

To reduce the risks to study participants, the researchers restricted participation to young, healthy volunteers. Further, the volunteers were housed in "individual negative pressure rooms in an in-patient quarantine unit, with 24-hour medical monitoring and access to higher level clinical support," the authors wrote.

More than half of the participants were infected by the dose, with first symptoms developing and PCR tests returning positive results less than two days after exposure, on average. The speed of infection surprised researchers, as previous epidemiological research had suggested the virus's incubation period was around five days.

The majority of patients had live virus present in their nose for 6.5 days, the researchers found.

The most common symptoms reported by the participants were sore throats, runny noses, and sneezing. Fever was reported as well but was less common, and none of the participants developed a persistent cough.

The researchers also found that some asymptomatic patients had the same high levels of the virus in their upper airways as those who presented symptoms.

Of those who developed Covid-19, 70% reported losing their sense of smell or taste to some degree. These problems lasted for more than six months in five of the participants and for more than nine months in one participant.

Still, the researchers argued the study showed "no serious safety signals" and demonstrates that Covid-19 human challenge trials can be conducted safely.

Discussion

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The study authors said they want to determine why so many participants didn't become infected with the virus despite being exposed to it. According to Christopher Chiu, a physician-scientist at Imperial College London who led the study, some of these participants did briefly show very low viral levels, which suggests their immune systems were fighting the virus.

"We're trying to understand the fundamentals of why people are protected even though they've not been exposed to a virus like this before," Chiu said. He added that his team will launch another trial that will expose vaccinated participants to the delta variant to determine what immune factors protect people from breakthrough infections.

Miles Davenport, an immunologist at the University of New South Wales, who was not involved in the study, said the research "presents a potentially important advance in how to assess future vaccine and drug efficacy" and "opens a number of important possibilities to study immunity in a controlled environment."

However, some experts argued the study's results don't justify the risk of exposing participants to the coronavirus.

"In my mind, it's still not entirely clear whether these studies are ethically justified, and I'm waiting to see what else they've found," Seema Shah, a bioethicist at Lurie Children's Hospital and Northwestern University, said.

Meagan Deming, a vaccine scientist and virologist at the University of Maryland in Baltimore, said the study confirms other findings from Covid-19 studies, but also hasn't assuaged her concerns about exposing participants to a version of the coronavirus that has not been weakened, noting that over a quarter of participants had smell or taste problems that lasted over six months.

"It sounds like this is the most serious risk that materialized. This is the one to keep an eye on," Shah said, adding that the study "reads like a promissory note that ultimately, in conjunction with the other research they're doing, there will eventually be substantial scientific and social benefits. But we're not really seeing that yet." (Callaway, Nature, 2/2; Mason/Rigby, Reuters, 2/2)