The first results from a UK trial that deliberately exposed people to the coronavirus are finally here. Among other things, the research found that people who caught the infection became symptomatic within two days and remained infectious for longer than a week. None of the volunteers became severely sick, though a few did continue to have trouble smelling things months later.
The research is an example of a human challenge trial. Human challenge trials have been used in the past for other infectious diseases, often in areas where these diseases have become rare or difficult to track in their natural environment. But there was no shortage of controversy about using them to study the SARS-CoV-2 coronavirus and COVID-19, as some researchers had wanted to do early on into the pandemic.
Criticisms included the fact that COVID-19 was and remains widespread in the world, including in the UK. Until recently, there had also been no reliable early treatments available for COVID-19, only treatments for severe illness. Advocates have argued that human challenge trials for COVID-19 could be run safely and would provide invaluable information about the natural history of infection as well as how effective vaccines are at preventing infection.
By early 2021, the UK government finally permitted researchers to start the first human challenge trial. This trial was spearheaded by scientists at the Imperial College London, but it also involved collaboration from the research organisation Open Orphan and its clinical subsidiary, hVIVO. And this week, researchers released preliminary data from the trial on a preprint server.
The trial involved 36 healthy male and female volunteers between the ages of 18 to 30. They were all exposed to a low dose of the original strain of the coronavirus, and were then monitored at a quarantine facility for two weeks.
Overall, half of the volunteers successfully contracted an infection, the researchers found. On average, symptoms began to start two days into exposure, which is shorter than the median four to five days currently estimated by many authorities as the incubation period of the virus. Volunteers tended to carry the highest amount of infectious virus on day 5, meaning they were most able to infect people at that time. But on average, people still carried infectious virus up to nine days after exposure, and some still appeared infectious by day 12.
All of the infected volunteers experienced no more than mild to moderate illness, with common symptoms such as runny nose, sneezing, and a sore throat. None developed lung complications or other serious adverse events. Thirteen participants did temporarily lose their sense of smell, another common COVID-19 symptom. Three months later, three volunteers still experienced some loss of smell, though they continued to show improvement as time went on. Lateral flow tests, used to rapidly detect when people are actively infectious, appeared to work well with these volunteers as well.
The findings do add some possible wrinkles to our understanding of the risks posed by COVID-19. Currently, for instance, U.S. health agencies recommend that many people can stop isolating at home five days after testing positive and without the need for added testing — a time frame some experts have criticised as too early. The UK, however, recommends ten days of isolation for people who don’t get tested again. More recently, the country has recommended five days of isolation, but only for people who test negative on a rapid test two days in a row.
That said, these results are based on a small sample of volunteers, with a strain of the coronavirus that is no longer circulating in the world. So it is possible that its implications aren’t quite as relevant today as they would have been when the pandemic first began. But the researchers say that there aren’t likely to be huge differences between how the variants infect people. And they argue that their success here shows that human challenge research for COVID-19 can be safely conducted, which should speed along the progress of similar trials in the future.
“While the characterization study was focused on the original SARS-CoV-2 strain, and there are differences in transmissibility between it and the other variants, the same factors will be responsible for protection against it, meaning the findings remain valuable for variants such as Delta or Omicron,” lead investigator Christopher Chiu said in a statement from Imperial. “These data provide a clear platform to now utilise the human challenge model to expedite product efficacy testing for new vaccines or antivirals.”
Last April, Oxford University researchers announced they would start a challenge trial to test the limits of natural immunity by trying to reinfect volunteers. And the Imperial researchers plan to continue running their own trials, including one that will infect people with the Delta variant.