Why did some folks never get covid, and others *always* got it?

The Conversation finds a scientific reason for an often-observed phenomenon – that some people seemed strangely immune to COVID-19, while others would come down with it more than once:

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.

Out of the ten volunteers who did not develop a sustained infection, suggesting that they were able to fight off the virus early on, three went on to develop an “intermediate” infection with intermittent single positive viral tests and limited symptoms. We called them the “transient infection group”.

The final seven volunteers remained negative on testing and did not develop any symptoms. This was the “abortive infection group”. This is the first confirmation of abortive infections, which were previously unproven.

…[W]e were able to identify cells stimulated by a key antiviral defence response in both the nose and the blood. This response, called the “interferon” response, is one of the ways our bodies signal to our immune system to help fight off viruses and other infections. We were surprised to find that this response was detected in the blood before it was detected in the nose, suggesting that the immune response spreads from the nose very quickly.

Lastly, we identified a specific gene called HLA-DQA2, which was expressed (activated to produce a protein) at a much higher level in the volunteers who did not go on to develop a sustained infection and could hence be used as a marker of protection. Therefore, we might be able to use this information and identify those who are probably going to be protected from severe COVID.


You can read more of the research here, in Nature.