First human challenge study on Covid-19 provides valuable insights into how we get sick

That’s just one of the takeaways research who intentionally 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 to study its effects on the human body. Even when safety precautions have been taken, there is still some risk, especially when investigating a new virus.

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

“Really, there’s no other type of study where you can do that because you usually only become aware of patients when they’ve developed symptoms and you miss out on all the previous days of the infection brewing,” he said the lead author of the study Dr. Christopher Chiu, Infectious Diseases Physician and Immunologist at Imperial College London.

The volunteers were carefully screened

The study started in March 2021. The 36 subjects were between 18 and 30 years old. They were only allowed to take part if they had no risk factors for severe Covid-19 disease, such as being overweight, reduced kidney or liver function, or had heart, lung or blood problems. They also signed a detailed consent form to participate.

To further minimize the risks, the researchers conducted the study in phases. The first 10 volunteers who were infected were given the antiviral drug remdesivir to reduce their chances of developing serious illness. The researchers also had monoclonal antibodies on hand in case someone got worse. Ultimately, the remdesivir proved unnecessary and the researchers didn’t have to give anyone antibodies.

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

They were kept under 24-hour medical surveillance and stayed for two weeks in rooms at London’s Royal Free Hospital, which have special airflow to stop the virus 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 study participants who contracted Covid-19 – 83% – lost at least some of their sense of smell. Nine couldn’t smell at all.

This now-known symptom got better in most people, but six months after the study ended, there is one person whose sense of smell is not back to normal but is improving.

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

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

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

Apart from the loss of smell, no other symptoms persisted.

A closer look at the infection as it moves through the body

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

  • Tiny amounts of virus, around 10 microns — the amount in a single droplet that 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 the virus.
  • Humans shed large amounts of virus before showing symptoms (confirming what epidemiologists had found).
  • On average, the young, healthy volunteers in the study shed the virus for 6½ days, but some shed the virus for 12 days.
  • Infected individuals can shed high levels of virus without symptoms.
  • About 40 hours after the introduction of the virus, it could be detected in the pharynx.
  • It took about 58 hours for the virus to show up on nasal swabs, where it eventually grew to much higher levels.
  • Lateral flow tests, the quick at-home kind, are very good for determining if a person is contagious. The study found that these types of tests could diagnose infection before 70% to 80% of viable virus had been produced.

Chiu says his study underscores much of what we already know about Covid-19 infections, not least because it’s so important to cover both your mouth and nose when you’re sick to protect others.

More challenge studies planned

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

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

“That’s the really interesting thing,” he said. About half of the study participants never got sick or developed antibodies despite receiving the exact same dose of the virus.

Each was screened for antibodies to closely related viruses, such as the original SARS virus. So it wasn’t mutual protection that protected them; it was something else.

“There are many other things that help us protect ourselves,” Chiu said. “There are barriers in the nose. There are different types of proteins and things that are very old, primordial protective systems, and they probably helped keep them from getting infected, and we’re really interested in trying to understand what those are.”

Understanding what other factors might be at play could help us provide people with broader protections in the event of a future pandemic.

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

Blood and tissue samples collected for the study will be analyzed for years to come, she said. “I think they’re sort of all in the freezer being dissected. So I think that should be very powerful.”

In the end, she believes the study has allayed many of the fears about human challenge studies and paved the way for others.

“We’re not going to do provocation studies in babies, and we’re not going to do it in 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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