They have discovered new immune responses that explain how some people avoid Covid.

A scientific team has discovered new immune responses that help explain how some people, despite being exposed to the coronavirus, avoid contracting and developing Covid-19.

Using single-cell sequencing, researchers from the Wellcome Trust Sanger Institute, University College (UCL) and Imperial College London studied immune responses against SARS-CoV-2 infection in healthy adult volunteers.

Not all exposed participants developed Covid-19 infection, allowing the team to discover unique immune responses associated with resistance to persistent viral infections and diseases.

The findings, published this Wednesday in the journal Nature, represent “the most comprehensive timeline to date” of how the body responds to exposure to SARS-CoV-2 or any infectious disease, the authors say.

This work is part of the international Human Cell Atlas initiative, which maps every cell type in the human body to transform the understanding of health and disease.

The researchers set out to capture immune responses directly from exposure, the Wellcome Trust Sanger Institute said in a statement.

To do this, 36 healthy adult volunteers with no history of Covid were injected with the SARS-CoV-2 virus through the nose. The researchers closely monitored the blood and nasal mucosa, tracking the entire infection as well as immune cell activity prior to infection in 16 volunteers.

The teams then used single-cell sequencing to create a data set of more than 600,000 individual cells. In all participants, the team found previously unreported reactions that led to immediate detection of the virus. This involved activating specialized mucosal immune cells in the blood and reducing the number of inflammatory white blood cells that normally engulf and destroy pathogens.

People who cleared the virus immediately did not exhibit the typical generalized immune response, but instead developed subtle innate immune responses never seen before.

The researchers suggest that high levels of HLA-DQA2 gene activity before infection also helped people prevent long-term infection. In contrast, the six people who developed persistent SARS-CoV-2 infection had a rapid immune response in the blood but a slower immune response in the nose, allowing the virus to establish itself there.

The researchers also identified common patterns among activated T cell receptors that recognize and bind to virus-infected cells. This provides insight into immune cell interactions and the potential to develop T cell-targeted therapies not only against Covid but also against other diseases.

Rik Lindeboom, now at the Netherlands Cancer Institute, notes that it was an “incredibly unique opportunity” to see what immune responses are like when encountering a new pathogen in an environment where factors such as timing of infection and comorbidities are at play.

UCL’s Marco Nicoli now has a much better understanding of the full range of immune responses, which could inform the development of potential treatments and vaccines that mimic these natural protective responses.

Sarah Teichmann, lead author of the study and co-founder of the Human Cell Atlas, adds that as this map is created, it will be possible to better identify which cells are needed to fight infections and understand why different people respond differently to the coronavirus. ways.