Friday, 1 Jul 2022

First COVID-19 Human Challenge Study Provides Insights

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.

A small droplet that contains the coronavirus can infect someone with COVID-19, according to recent results from the first COVID-19 human challenge study, which were published in the journal Nature Medicine.

Human challenge trials deliberately infect healthy volunteers to understand how an infection occurs and develops. In the first human challenge study for COVID-19, people were infected with the SARS-CoV-2 virus to better understand what has happened during the pandemic.

“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,” Christopher Chiu, the lead study author and an infectious disease doctor and immunologist at Imperial College London, told CNN.

Starting in March 2021, Chiu and colleagues carefully selected 36 volunteers between ages 18-30 who didn’t have any risk factors for severe COVID-19, such as being overweight or having kidney, liver, heart, lung or blood problems. Participants also signed an extensive informed consent form, CNN reported.

The researchers conducted the trial in phases for safety. The first 10 participants who were infected received remdesivir, the antiviral drug, to reduce their chances of progressing to severe COVID-19. The research team also had monoclonal antibodies on hand in case any volunteers developed more severe symptoms. Ultimately, the researchers said, remdesivir was unnecessary, and they didn’t need to use the antibodies.

As part of the study, the participants had a small droplet of fluid that contained the original coronavirus strain inserted into their nose through a long tube. They stayed at London’s Royal Free Hospital for two weeks and were monitored by doctors 24 hours a day in rooms that had special air flow to keep the virus from spreading.

Of the 36 participants, 18 became infected, including two who never developed symptoms. The others had mild cases with symptoms such as congestion, sneezing, stuffy nose and sore throat. Some also had headaches, muscle and joint pain, fatigue and fever.

About 83% of participants who contracted COVID-19 lost their sense of smell to some degree, and nine people couldn’t smell at all. The symptom improved for most participants within 90 days, though one person still hadn’t fully regained their sense of smell about six months after the study ended.

The research team reported several other findings:

  • Small amounts of the virus can make someone sick. About 10 microns, or the amount in a single droplet that someone sneezes or coughs, can lead to infection.

  • About 40 hours after the virus was inserted into a participant’s nose, the virus could be detected in the back of the throat.

  • It took about 58 hours for the virus to appear on swabs from the nose, where the viral load eventually increased even more.

  • COVID-19 has a short incubation period. It takes about two days after infection for someone to begin shedding the virus to others.

  • People become contagious and shed high amounts of the virus before they show symptoms.

  • In addition, infected people can shed high levels of the virus even if they don’t develop any symptoms.

  • The study volunteers shed the virus for about six days on average, though some shed the virus for up to 12 days, even if they didn’t have symptoms.

  • Lateral flow tests, which are used for rapid at-home tests, work well when an infected person is contagious. These tests could diagnose infection before 70% to 80% of the viable virus had been generated.

The findings emphasize the importance of contagious people covering their mouth and nose when sick to protect others, Chiu told CNN.

None of the study volunteers developed lung issues as part of their infection, CNN reported. Chiu said that’s likely because they were young, healthy and received tiny amounts of the virus. All of the participants will be followed for a year to monitor for potential long-term effects.

Throughout the study, the research team also conducted cognitive tests to check the participants’ short-term memory and reaction time. The researchers are still analyzing the data, but the results “will really be informative,” Chiu told CNN.

Now the research team will conduct another human challenge trial, which will include vaccinated people who will be infected with the Delta variant. The researchers intend to study participants’ immune responses, which could provide valuable insights about new variants and vaccines.

“While there are differences in transmissibility due to the emergence of variants, such as Delta and Omicron, fundamentally, this is the same disease and the same factors will be responsible for protecting it,” Chiu said in a statement.

The research team will also study the 18 participants who didn’t get sick in the first human challenge trial. They didn’t develop antibodies, Chiu told CNN, despite receiving the same dose of the virus as those who got sick.

Before the study, all of the participants were screened for antibodies to other viruses, such as the original SARS virus. That means the volunteers weren’t cross-protected, and other factors may play into why some people don’t contract COVID-19. Future studies could help researchers provide better advice about protection if new variants emerge or a future pandemic occurs.

“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 we’re really interested in trying to understand what those are.”

Sources

Nature Medicine: “Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults.”

CNN: “First human challenge study of Covid-19 yields valuable insights about how we get sick.”

Imperial College London: “COVID-19 human challenge study reveals detailed insights into infection.”

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