First human challenge study of Covid-19 yields valuable insights about how we get sick

By Brenda Goodman, CNN

It takes just a tiny virus-laden droplet — about the width of a human blood cell — to infect someone with Covid-19.

That’s just one of the findings from research that deliberately infected healthy volunteers with the SARS-CoV-2 virus. The findings were published Thursday in the journal Nature Medicine.

Challenge studies can be controversial because they involve intentionally giving someone a virus or other pathogen in order to study its effects on the human body. Even with safeguards in place, there’s an element of risk, particularly when studying a new virus.

But they are also hugely valuable for understanding the course of an infection.

“Really, there’s no other type of study where you can do that, because normally, patients only come to your attention if they have developed symptoms, and so you miss all of those preceding days when the infection is brewing,” said lead study author Dr. Christopher Chiu, an infectious disease physician and immunologist at Imperial College London.

Volunteers were carefully screened

The study began in March 2021. The 36 volunteers were between the ages of 18 and 30. They were allowed to participate only if they didn’t have any risk factors for severe Covid-19, such as being overweight, having reduced kidney or liver function, or having any heart, lung or blood problems. They also signed an extensive informed consent form to participate.

To further minimize the risks, researchers conducted the study in phases. The first 10 infected volunteers got the antiviral drug remdesivir to reduce their chances of progressing to severe disease. Researchers also had monoclonal antibodies at the ready in case anyone took a turn for the worse. Ultimately, the remdesivir proved unnecessary, and researchers never had to give anyone antibodies.

The volunteers got a tiny drop of fluid containing the originally detected strain of the virus through a long, thin tube inserted into their nose.

They were medically monitored 24 hours a day and stayed for two weeks in rooms at London’s Royal Free Hospital that had special air flow to keep the virus from escaping.

Half were infected

A total of 18 participants became infected, two of whom never developed symptoms. Among the people who got sick, their illnesses were mild. They had stuffy noses, congestion, sneezing and sore throats.

Most of the study participants who caught Covid-19 — 83% — lost their sense of smell, at least to a degree. Nine couldn’t smell at all.

This now-well-known symptom got better for most people, but six months after the study ended, there’s one person whose sense of smell isn’t back to normal but is improving.

That’s a concern because another recent study found that this loss of smell was tied to changes in the brain.

Chiu says the researchers gave the participants cognitive tests to check their short-term memory and reaction time. They’re still looking at that data, but he thinks those tests “will really be informative.”

None of the study volunteers developed lung involvement in their infections. Chiu thinks this is because they were young and healthy and inoculated with tiny amounts of virus.

Beyond the loss of smell, no other symptoms persisted.

A closer look at infection as it moves through the body

Under these carefully controlled conditions, researchers were able to learn a lot about the virus and how it moves through the body:

• Tiny amounts of virus, about 10 microns — the amount in a single droplet someone sneezes or coughs — can make someone sick.
• Covid-19 has a very short incubation period. It takes about two days after infection for a person to start shedding virus.
• People shed high amounts of virus before they show symptoms (confirming something epidemiologists had figured out).
• On average, the young, healthy study volunteers shed virus for 6½ days, but some shed virus for 12 days.
• Infected people can shed high levels of virus without any symptoms.
• About 40 hours after the virus was introduced, it could be detected in the back of the throat.
• It took about 58 hours for virus to show up on swabs from the nose, where it eventually grew to much higher levels.
• Lateral flow tests, the rapid at-home kind, work really well for detecting when a person is contagious. The study found that these kinds of tests could diagnose infection before 70% to 80% of viable virus had been generated.

Chiu says his study emphasizes a lot of what we already know about Covid-19 infections, not least of which is why it’s so important to cover both your mouth and nose when sick to help protect others.

More challenge studies planned

This challenge study was so successful that Chiu plans to do it again, this time with vaccinated people infected with the Delta variant to study their immune response.

He says his team also plans to continue studying the people who didn’t get sick.

“That’s what’s really interesting,” he said. About half of the study participants never got sick and never developed antibodies, despite getting exactly the same dose of the virus.

Everyone was screened for antibodies to closely related viruses, like the original SARS virus. So it wasn’t cross-protection that kept them safe; it was something else.

“There are lots of other things that help protect us,” Chiu said. “There are barriers in the nose. There are different kinds of proteins and things which are very ancient, primordial, protective systems, and they are likely to have been contributing to them not being infected, and we’re really interested in trying to understand what those are.”

Understanding what other factors may be at play could help us provide more generalized protection to people in case of a future pandemic.

Dr. Kathryn Edwards, a pediatric infectious disease specialist at Vanderbilt University who wrote an editorial published alongside the study, said the research offers important information about infection and contagion with the SARS-CoV-2 virus.

Blood and tissue samples collected for the study will continue to be analyzed for years to come, she said. “I think those are all in the freezer, so to speak, and are being dissected. So I think that should be very powerful.”

In the end, she thinks the study has put many of the fears about human challenge studies to rest and paved the way for others.

“We won’t be doing challenge studies in babies, and we won’t be doing it in, you know, 75-year-old people with chronic lung disease,” she said. But in young, healthy people, “I think these are studies that will be helpful.”

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