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Researchers have made a significant breakthrough in understanding why some individuals manage to avoid contracting COVID-19 despite exposure to the virus.

This new insight comes from a collaborative study involving the Wellcome Sanger Institute, University College London (UCL), Imperial College London, the Netherlands Cancer Institute, and other partners.

The findings were recently published in the journal Nature as part of a groundbreaking COVID-19 human challenge study.

The study focused on the body’s response to the initial exposure to the SARS-CoV-2 virus, which causes COVID-19. A group of 36 healthy adult volunteers, who had no prior history of the disease, were deliberately exposed to the virus through nasal administration as part of the research.

The aim was to monitor and capture their immune responses from the very beginning of exposure.

Using advanced techniques like single-cell sequencing, researchers analyzed over 600,000 individual cells from these volunteers to observe how their immune systems reacted.

This method allowed them to track changes in the blood and the nasal lining, providing a detailed view of how the body attempts to fend off the virus.

The study revealed some critical findings. While all participants were exposed to the virus, not everyone went on to develop COVID-19. This difference in susceptibility was linked to specific immune responses observed in those who avoided infection.

These individuals displayed unique, previously undocumented immune reactions that involved the activation of specialized mucosal immune cells and a decrease in certain inflammatory white blood cells. These cells typically help in engulfing and destroying pathogens.

Interestingly, the researchers noted that individuals who effectively cleared the virus did not exhibit a typical, robust immune response.

Instead, they had subtle innate immune responses that were highly effective in combating the virus before it could establish an infection. This included heightened activity of a gene known as HLA-DQA2, which seemed to play a pivotal role in preventing a sustained viral infection.

Conversely, the volunteers who developed a sustained infection showed different patterns in their immune responses. They had a rapid immune response in the blood but a delayed response in the nasal area, which allowed the virus more time to embed itself and proliferate.

The study also identified common patterns among the activated T cell receptors, which play a crucial role in recognizing and attacking virus-infected cells. This finding could lead to new ways of developing targeted therapies, not only against COVID-19 but potentially other diseases as well.

Dr. Rik Lindeboom, co-first author of the study and now at the Netherlands Cancer Institute, emphasized the unique nature of the research setting, which allowed for precise control over factors like the timing of infection and lack of prior disease exposure.

Dr. Marko Nikolić, senior author from UCL, highlighted that these insights are crucial for understanding the early immune responses that either allow the virus to take hold or help clear it before the onset of symptoms.

Additionally, Dr. Sarah Teichmann, a senior author and co-founder of the Human Cell Atlas, pointed out that this research contributes significantly to the Human Cell Atlas initiative.

The initiative aims to map every cell type in the human body to better understand cellular functions and disease responses.

Shobana Balasingam from the Wellcome’s Infectious Disease team remarked on the value of human challenge models in enhancing our understanding of infectious diseases.

She noted the importance of expanding such studies to low-resource settings to develop effective tools and treatments that are relevant globally.

This research not only offers new insights into how the immune system can prevent COVID-19 but also opens up possibilities for developing treatments that mimic these natural protective responses.

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The research findings can be found in The Lancet.

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