Scientists have discovered differences in the immune response that could explain why some people seem to reliably escape Covid infection.
The study, in which healthy adults were deliberately given a small nasal dose of the Covid virus, suggested that specialized immune cells in the nose could ward off the virus at its earliest stages before full infection manifested. Those who did not succumb to infection also had high levels of activity in a gene that is thought to help signal the presence of viruses in the immune system.
“These findings shed new light on the crucial early events that allow the virus to take hold or rapidly disappear before symptoms develop,” said Dr. Marko Nikolić, senior author of the study at University College London and honorary consultant in respiratory medicine. “We now have a much better understanding of the full range of immune responses, which could provide a basis for the development of potential treatments and vaccines that mimic these natural protective responses.”
As part of the UK Covid-19 Human Challenge study, 36 healthy adult volunteers with no history of Covid-19 and who had not been vaccinated were given a low dose of the virus through the nose. The survey was conducted in 2021, at the height of the pandemic.
In 16 volunteers, the researchers monitored activity in immune cells in the blood and the lining of the nose to obtain the most detailed timeline of immune activity before, during and after infection. These participants appeared to fall into three different groups: six people developed a persistent infection and became ill; three people became temporarily positive, but without developing full-blown infection; and seven experienced an “abortive infection.” This subgroup never tested positive, but the tests showed that they had mounted an immune response.
In the failed and transient groups, samples from before Covid exposure showed that these volunteers had high background levels of activity in a gene called HLA-DQA2. This was seen in ‘antigen presenting’ cells, which signal danger to the immune system. “These cells pick up a little bit of the virus, show it to immune cells and say, ‘This is strange: you need to go and find out’,” said Dr Kaylee Worlock from UCL, first author of the study.
The findings, published in Nature, suggest that people with high levels of activity in this gene may have a more efficient immune response to Covid, meaning the infection never gets past the body’s first line of defense. However, they were not completely immune – the volunteers were monitored after the study and some later discovered Covid in the community.
In the people who tested positive briefly, the scientists also recorded a rapid immune response in the nose cells, within a day of exposure, and a slower immune response in the blood cells. In contrast, those who developed full-blown infection showed a much slower nasal response, starting on average five days after exposure, allowing the virus to become established.
The team said the findings could provide a basis for developing more effective treatments and vaccines that mimic optimal protective responses.