We finally know why some people get COVID and others don't.

During the pandemic, a key query on everyone's mind was why some people avoided getting COVID, while others caught the virus multiple times.

Through a collaboration between University College London, the Wellcome Sanger Institute and Imperial College London within the UK, we have now created the world's first controlled “Challenge Trial” for COVID – where volunteers were deliberately exposed to SARS-CoV-2, the virus that causes COVID, to check it in great detail.

Unvaccinated healthy volunteers with no previous history of COVID were exposed – via nasal spray – to very low doses of the unique strain of SARS-CoV-2. The volunteers were then closely monitored in a quarantine unit, with regular tests and samples taken to check their response to the virus in a highly controlled and secure environment.

For us A recent studyPublished in Nature, we collected samples from tissue situated between the nose and throat and blood samples from 16 volunteers. These samples were taken before participants were infected with the virus, to offer us a baseline measurement, and at regular intervals thereafter.

The sample was then processed and analyzed using single-cell sequencing technology, which allowed us to extract and sequence the genetic material of individual cells. Using this advanced technology, we will track the evolution of disease from pre-infection to recovery, in unprecedented detail.

To our surprise, despite all volunteers being fastidiously exposed to the identical dose of virus in the identical manner, not everyone tested positive for COVID.

Indeed, we were capable of divide the volunteers into three distinct infection groups (see illustration). Six of the 16 volunteers developed typical mild COVID, testing positive for several days with cold-like symptoms. We termed this group the “persistent infection group”.

Of the ten volunteers who didn't develop a persistent infection, suggesting that they were capable of fight off the virus early on, three developed intermittent “intermediate” infections with a positive viral test and limited symptoms. We called them the “temporary infection group.”

The final seven volunteers tested negative and didn't develop symptoms. This was the “Abortive Infection Group”. This is the primary confirmation of abortion infection, which was earlier. Unproven. Despite differences within the final result of the infection, participants in all groups shared some specific recent immune responses, including those whose immune systems prevented the infection.

When we compared the cellular response times between the three infection groups, we observed distinct patterns. For example, in transiently infected volunteers where the virus was only briefly detected, we observed a robust and rapid accumulation of immune cells within the nose in the future after infection.

This is in contrast to the persistent infection group, where a more delayed response was observed, starting five days after infection and possibly enabling the virus to take hold in these volunteers.

In these people, we were capable of discover cells activated by a key antiviral defense response in each the nose and blood. This response, called the “interferon” response, is one in every of the ways our bodies help our immune system fight viruses and other infections. We were surprised to seek out that this response was detected within the blood before it was detected within the nose, suggesting that the immune response spreads rapidly through the nose.

Protective genes

Finally, we identified a particular gene, HLA-DQA2, that was expressed (lively to provide a protein) at high levels in volunteers who didn't develop persistent infection and due to this fact protected. Can be used as an indication. . Therefore, we may have the ability to make use of this information and discover people who find themselves more likely to be protected against severe COVID.

These findings help us fill in among the gaps in our knowledge, painting a far more detailed picture of how our bodies react to a brand new virus, especially in the primary two days of infection. Which could be very vital.

We may use this information to check our data with other data we're currently generating, particularly where we're “challenging” volunteers to other viruses and up to date strains of COVID. Unlike our current study, these will mostly include volunteers who've been vaccinated or naturally infected – that's, individuals who have already got immunity.

Our study has vital implications for future treatment and vaccine development. By comparing our data from volunteers who've never been exposed to the virus with those that are already immune, we may have the ability to discover recent ways to induce protection, in addition to future treatments. It may also help develop simpler vaccines for pandemics. In summary, our research is a step toward higher preparedness for the subsequent pandemic.