Here’s a question: given everything we’ve heard about the COVID-19 death tolls across the world, would you volunteer to get infected?

For 34 healthy young men and women, the answer was “yes” – and thanks to them, a landmark new study, currently available as a preprint, has now been produced. While it’s yet to be peer-reviewed, it’s already making waves thanks to the startling new insights into the coronavirus pandemic it offers.

“The … results have provided useful insights which could be used to inform public health decisions on COVID-19 symptoms and virus detection going forward, including isolation periods for infectious individuals, the use of LFTs, and establishing the human challenge platform to investigate further aspects of COVID-19,” said Dr Andrew Catchpole, study co-author and Chief Scientific Officer at hVIVO – a company that specializes in this kind of “human challenge trial.”

What is a human challenge trial?

The Human Challenge Programme – a partnership between Imperial College London, the UK’s Vaccine Taskforce and Department of Health and Social Care (DHSC), hVIVO (part of Open Orphan plc.), and the Royal Free London NHS Foundation Trust – is, in simple terms, a scheme that purposefully infects volunteers with a virus. Researchers are then able to monitor the development of the disease – how many people get sick, how long it takes, what symptoms they get, and other things of that nature – in a clinical setting.

“Scientifically these studies offer real advantage,” explained Professor Sir Jonathan Van-Tam, Deputy Chief Medical Officer for England and study co-author in a statement from Imperial. “[The] timing of exposure to the virus is always known exactly, therefore things like the interval between exposure and the profile of virus shedding can be accurately described.”

And if you’re thinking that purposefully making people sick with a new and potentially deadly virus sounds ethically murky, don’t worry – you’re not alone. That’s why human challenge studies are subject to rigorous ethical review before they go ahead.

“Human challenge studies have been performed using other pathogens for decades, including flu and Respiratory Syncytial Virus (RSV),” Prof. Van-Tam said. “They need full independent ethical review and very careful planning – as has been the case this time. Every precaution is taken to minimize risk.”

Good news: infections were mild, antigen tests are reliable

So what were the results of this seminal study? Well, first of all, it’s good news – among healthy young adults, “there were no severe symptoms or clinical concerns in our challenge infection model,” explained trial chief investigator Professor Christopher Chiu from the Department of Infectious Disease and the Institute of Infection at Imperial College London.

“People in this age group are believed to be major drivers of the pandemic and these studies, which are representative of mild infection, allow detailed investigation of the factors responsible for infection and pandemic spread,” Chiu added.

Also on the good news pile is the finding that lateral flow tests – the same “rapid” at-home tests available from the recently-launched free COVID tests website in the US – are a reliable tool for controlling the pandemic.

“We found that overall, lateral flow tests correlate very well with the presence of infectious virus,” said Chiu. “Even though in the first day or two they may be less sensitive, if you use them correctly and repeatedly, and act on them if they read positive, this will have a major impact on interrupting viral spread.”

Clinical results

One of the main benefits of a human challenge trial is that the progress of the infection and resulting illness can be measured precisely – the researchers knew exactly when the volunteers were exposed to the virus, when they first tested positive, and so on.

“Our study reveals some very interesting clinical insights,” said Chiu, listing in particular the “short incubation period of the virus, extremely high viral shedding from the nose, as well as the utility of lateral flow tests.”

Specifically, the researchers discovered that symptoms start very quickly after exposure to the virus – about two days later, on average, which is less than half of the commonly accepted five- or six-day COVID incubation period. The infection starts in the throat, but by about five days into the infection, when symptoms are at their worst and people are most infectious, there is a much higher viral load in the nose.

Reassuringly, none of the study participants suffered any serious adverse effects, including any changes to their lungs. Out of the 18 who became sick, 16 experienced mild-to-moderate cold-like symptoms like a stuffy or runny nose, sneezing, and a sore throat. Some experienced headaches, muscle and joint aches, tiredness and fever.

And despite being a latecomer to the official COVID-symptom party, the telltale loss of smell associated with COVID-19 was experienced by 13 of the volunteers – that’s nearly three out of four cases (all the volunteers who lost their sense of smell were either recovered or recovering within 90 days of infection).

Study limitations

As with all scientific studies, it’s important to be aware of any limitations that may reduce the applicability of the results. This human challenge study, while important, had two major drawbacks: firstly, the small and non-diverse volunteer pool, and secondly, the COVID variant used in the study.

Despite the rise of several variants since the start of the pandemic – including the Omicron variant, which has a huge number of mutations compared with the original virus – the study volunteers were infected with viral particles collected very early in the pandemic, before even Alpha made its debut.

Nevertheless, said Professor Peter Openshaw, co-investigator on the study and Professor of Experimental Medicine at Imperial College London, the findings should be applicable for other strains.

“While the characterisation 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,” he said. “These data provide a clear platform to now utilise the human challenge model to expedite product efficacy testing for new vaccines or antivirals.”

Future developments

With the results finally available to the public, the researchers are hopeful that they will provide valuable insights for public health measures.

“This important study has provided further key data on COVID-19 and how it spreads, which is invaluable in learning more about this novel virus, so we can fine-tune our response,” said Van-Tam. “Challenge studies could still prove to be important in the future to speed the development of ‘next-generation’ COVID-19 vaccines and antiviral drugs.”

“These data underline just how useful a tool lateral flow tests can be to pick up people when infectious and the importance of wearing a face covering in crowded, enclosed spaces,” he added.

Another mystery the researchers want to solve is what was different for those 16 participants who didn’t get sick. And with the COVID challenge study now tested and found to be safe, there’s also hope this study could form the basis of a slew of future projects testing COVID variants and therapies – including new vaccines.

“It is exciting to see the results of this study published,” commented Dr Doug Brown, Chief Executive of the British Society for Immunology, who was not involved in the study. “These studies are not easy to carry out and require a lot of resources. However, they provide us with hugely valuable insights into minutiae of disease progression that cannot be obtained through other types of research.”

“While the main aim of this study was to establish a safe and successful protocol to build on in the future, the significance of it should not be underestimated,” he added. “This study has already generated intriguing insights into the timeline of infection, particularly in the early phase. In the longer-term, the hope is that these findings will now open up a new research avenue to develop a platform that will allow us to speed up the development of new vaccines, antivirals and diagnostics against COVID-19.”