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The first study on the human challenge of Covid-19 gives valuable insights into how we get sick

This is just one of the findings of research that deliberately infected healthy volunteers with the SARS-CoV-2 virus. The results 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 is an element of risk, especially when studying a new virus.

But they are also extremely valuable in 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’ve developed symptoms, and so you miss all those previous days where infection is brewing,” said the study’s lead author. Dr Christopher Chiu, infectious disease physician and immunologist at Imperial College London.

The volunteers have been carefully selected

The study began in March 2021. The 36 volunteers were between the ages of 18 and 30. They were only allowed to participate if they had no serious Covid-19 risk factors, such as being overweight, a reduction in the kidneys or liver. function, or having heart, lung or blood problems. They also signed a detailed informed consent form to participate.

To further minimize risk, the researchers conducted the study in phases. The first 10 infected volunteers were given the antiviral drug remdesivir to reduce their risk of progression to serious disease. The researchers also had monoclonal antibodies on hand in case anyone got worse. In the end, remdesivir proved useless, and the researchers never had to give anyone antibodies.

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

They were medically monitored around the clock and stayed for two weeks in rooms at London’s Royal Free Hospital which had special airflow to prevent the virus from escaping.

Half were infected

A total of 18 participants were infected, two of whom never developed symptoms. Of those who fell ill, 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 some extent. Nine couldn’t smell at all.

This now well-known symptom has improved for most people, but six months after the study ended, there is one person whose sense of smell has not returned to normal but is improving.

The first study on the human challenge of Covid-19 gives valuable insights into how we get sick
This is a concern because another recent study found that this loss of sense of smell was linked 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 be really informative.”

None of the study volunteers developed pulmonary involvement in their infections. Chiu thinks it’s because they were young and healthy and inoculated with small amounts of virus.

Beyond the loss of smell, no other symptoms persisted.

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

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

  • Tiny amounts of virus, around 10 microns – the amount contained 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.
  • People shed large amounts of virus before showing symptoms (confirming something epidemiologists had understood).
  • On average, healthy young volunteers in the study shed virus for 6.5 days, but some shed virus for 12 days.
  • Infected people can shed high levels of virus without any symptoms.
  • About 40 hours after the introduction of the virus, it could be detected at the back of the throat.
  • It took around 58 hours for the virus to appear on swabs from the nose, where it eventually rose to much higher levels.
  • Lateral flow tests, the rapid at-home type, work very well for detecting when someone is contagious. The study found that these types of tests could diagnose infection before 70-80% viable virus had been generated.

Chiu says her study emphasizes much of what we already know about Covid-19 infections, including why it’s so important to cover both your mouth and nose when you’re is sick to help protect others.

Further provocation 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 people who haven’t gotten sick.

“That’s what’s really interesting,” he said. About half of the study participants never got sick and never developed antibodies, despite receiving exactly the same dose of 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 a lot of other things that help protect us,” Chiu said. “There are barriers in the nose. There are different types of proteins and things that are very old, primordial protection systems, and they probably contributed to them not getting infected, and we’re really interested trying to figure out what it is.”

Understanding what other factors may be at play could help us provide more widespread protection for people in the event 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 insights into SARS-CoV-virus infection and contagion. 2.

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

Ultimately, she believes the study put to rest many fears about human challenge studies and paved the way for others.

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


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