What deliberately infecting people with SARS-CoV-2 is teaching us about COVID-19
The first COVID-19 human challenge study is yielding new insights into how healthy young adults respond to infection.
- 8 February 2022
- 4 min read
- by Linda Geddes
While most people were going out of their way to avoid catching COVID-19, a few plucky individuals signed up to be infected with SARS-CoV-2. Now some of the first results from this “human challenge trial” suggest that COVID-19 symptoms may develop sooner than previously estimated, and that at the peak of infection, the virus is significantly more abundant in the nose than in the throat.
The study also confirmed that lateral flow tests (LFTs) – a type of rapid antigen test – are a reliable indicator of whether infected people are likely to transmit the virus to others.
Another important finding was that high levels of viral shedding occurred irrespective of how severe people’s symptoms were, helping to explain why COVID-19 is so difficult to contain.
Why are challenge trials needed?
Although contact tracing and large observational studies that rely on natural infection provide a lot of useful information about the nature of a disease like COVID-19, they are less good at elucidating such details as the quantity of a virus needed to trigger an infection, detailed characteristics of the immunity people build in response to different doses, and whether people can transmit the virus if they don’t have symptoms.
Challenge trials, which involve deliberately infecting healthy people and closely monitoring them in a laboratory, can help to establish such details, and have previously been used to study, e.g., influenza and malaria. They could also be used to compare the real-world effectiveness of different COVID-19 vaccines, and provide a faster means of testing next-generation vaccines.
The current study provides reassurance that challenge trials can be conducted safely in the context of COVID-19, and paves the way for future ones.
Have you read?
What did the study do?
Thirty-six healthy 18- to 30-year-olds, who had never been infected with, or vaccinated against, COVID-19 were given a low dose of virus from very early in the pandemic (before the emergence of the Alpha variant), introduced through drops up the nose. The amount they were exposed to was the lowest possible dose found to cause infection – roughly equivalent to the amount found in a single droplet of nasal fluid when someone is at their most infectious. The volunteers were then carefully monitored at a contained medical laboratory in London, UK, for the next two weeks, and will continue to be monitored for a year after infection for any long-term effects.
What did it find?
Half of those exposed to the virus became infected, 16 of whom went on to develop mild-to-moderate cold-like symptoms, including a stuffy or runny nose, sneezing, and a sore throat. Some experienced headaches, muscle or joint aches, tiredness and fever, and 13 participants temporarily lost their sense of smell – although this returned to normal within 90 days in all but three of them. No-one developed serious symptoms.
The study, which has not yet been peer-reviewed, also provided some surprises: Whereas previous studies have estimated that the average time it takes to develop symptoms after exposure to the virus is five to six days, among challenge study participants, the average incubation period was 42 hours. Five days best aligned with a peak in participants’ symptoms, the researchers said.
Following the development of symptoms, there was a steep rise in the amount of virus detected in people’s noses and throats, reaching peak levels in the throat 4.7 days after the initial infection, and peaking at even higher levels in the nose after 6.2 days – highlighting the importance of covering both orifices to reduce transmission.
However, PCR tests could detect virus in the throat after 40 hours (1.7 days), and in the nose after 58 hours (2.4 days), while high levels of infectious virus were detectable for up to nine days after infection on average, and up to 12 days for some participants.
Another important finding was that high levels of viral shedding occurred irrespective of how severe people’s symptoms were, helping to explain why COVID-19 is so difficult to contain.
Next-steps
Now that the relative safety of this infection challenge platform has been established, the team is planning further studies to investigate why some people became infected and others did not, and to develop a challenge platform involving the Delta variant (including working out the lowest infectious dose), meaning it could be used in future studies.
