We finally know why some people got COVID while others didn’t

By Marko Nikolic, Kaylee Worlock, UCL

Throughout the pandemic, one of the key questions 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 in the UK, we set out to answer this question using the world’s first controlled “challenge trial” for COVID – where volunteers were deliberately exposed to SARS-CoV-2, the virus that causes COVID, so that it could be studied in great detail.

Unvaccinated healthy volunteers with no prior history of COVID were exposed – via a nasal spray – to an extremely low dose of the original strain of SARS-CoV-2. The volunteers were then closely monitored in a quarantine unit, with regular tests and samples taken to study their response to the virus in a highly controlled and safe environment.

For our recent study, published in Nature, we collected samples from tissue located midway between the nose and the throat as well as blood samples from 16 volunteers. These samples were taken before the participants were exposed to the virus, to give us a baseline measurement, and afterwards at regular intervals.

The samples were then processed and analysed using single-cell sequencing technology, which allowed us to extract and sequence the genetic material of individual cells. Using this cutting-edge technology, we could track the evolution of the disease in unprecedented detail, from pre-infection to recovery.

To our surprise, we found that, despite all the volunteers being carefully exposed to the exact same dose of the virus in the same manner, not everyone ended up testing positive for COVID.

In fact, we were able to divide the volunteers into three distinct infection groups (see illustration). Six out of the 16 volunteers developed typical mild COVID, testing positive for several days with cold-like symptoms. We referred to this group as the “sustained infection group”.

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