UCL study reveals nasal immune response key to COVID-19 defense

British media describe an experiment in which 36 healthy, unvaccinated volunteers who had not previously contracted COVID-19 were given a small dose of the coronavirus nasally. The experiment took place in 2021, at the peak of the pandemic. Today, we know its results. What do they tell us?

Scientists monitored the activity of immune cells in the blood and nasal mucosa of 16 participants, allowing them to create a detailed picture of the immune response before, during, and after exposure to SARS-CoV-2. The volunteers were divided into three distinct groups: six people developed a persistent infection and got sick; three people temporarily tested positive but did not develop a full infection; and seven people experienced a so-called incomplete infection—they never tested positive, but studies showed their immune system responded to contact with the virus.

In the groups with incomplete and temporarily positive infection, samples taken before exposure to COVID-19 showed high activity of a gene called HLA-DQA2. This gene was present in antigen-presenting cells, which signal a threat to the immune system. Dr. Kaylee Worlock from UCL, the study's lead author, explains that these cells take up a small amount of the virus and present it to immune cells, signaling that a foreign agent needs to be fought.

The findings, published in Nature, suggest that people who have high levels of activity in this gene (HLA-DQA2) may have a more efficient immune response to Covid, meaning the infection never gets beyond the body’s first line of defence. However, they were not completely immune – the volunteers were followed after the study and some later caught Covid in the community, reports The Guardian.

In people who temporarily tested positive, scientists observed a rapid immune response in nasal cells within a day of exposure and a slower response in the blood. In contrast, in those who developed a full infection, the reaction in the nose was much slower, beginning on average five days after contact with the virus, allowing SARS-CoV-2 to take hold in the body.

According to the research team, the obtained results could form the basis for developing more effective therapies and vaccines that mimic the body's optimal defense responses. Dr. Marko Nikolić, senior author of the study from University College London, emphasizes that these discoveries greatly enhance our understanding of the full range of immune responses, which could help create potential treatments and vaccines that mimic these natural protective mechanisms.

The study sheds new light on the early stages of SARS-CoV-2 infection, determining whether the virus will take root or be quickly eliminated before a full-blown disease develops. Understanding these processes could be crucial for developing more effective strategies to combat the Covid-19 pandemic.

Although the results are promising, scientists stress that further research on a larger group of volunteers is necessary to confirm the observed relationships and better understand the immunity mechanisms to SARS-CoV-2. This does not change the fact that these findings represent an essential step toward more effectively dealing with current and potential future pandemics.

The UK COVID-19 Human Challenge study is the first in the world in which healthy volunteers were intentionally infected with the SARS-CoV-2 virus. Although controversial from an ethical standpoint, controlled exposure to pathogens has long been used to better understand infectious diseases and develop more effective ways to combat them.