New discovery about Covid: they find out why there are people who do not get infected

Not all exposed participants developed Covid-19 infection, allowing the researchers to detect immune responses associated with resistance to infection.

Scientists have discovered new immune responses that help explain how some people avoid contracting COVID-19. Using single-cell sequencing, researchers from the Wellcome Sanger Institute, University College London (UCL), Imperial College London (all in the United Kingdom) and the Netherlands Cancer Institute (Netherlands) and their collaborators studied immune responses against SARS infection. -CoV-2 in healthy adult volunteers in the world’s first human exposure study of COVID-19.

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

The most complete chronology of the body’s response to SARS-CoV-2
The findings, published in the journal Nature, provide the most comprehensive timeline to date of how the body responds to exposure to SARS-CoV-2 or any infectious disease. This work is part of the Human Cell Atlas initiative, which aims to map every cell type in the human body.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people worldwide with coronavirus disease 2019 (COVID-19). Although it is potentially fatal, many have been exposed to someone who has tested positive for COVID-19 but have avoided getting sick either due to a negative PCR result or being an asymptomatic case.

While previous studies have studied COVID-19 patients after the onset of symptoms, this new study is the first time researchers have chosen to capture immune responses directly as a result of exposure in an immunologically naive cohort.

High levels of the HLA-DQA2 gene
As part of the study, the virus was administered through the nose to 36 healthy adult volunteers with no history of COVID-19. The researchers carried out detailed monitoring of the blood and nasal mucosa, tracking the entire infection, as well as the activity of immune cells, until the infection occurred in 16 volunteers. Teams from the Wellcome Sanger Institute and UCL then used single-cell sequencing to create a dataset 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.

The ten people who cleared the virus immediately did not have 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 persistent 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-19 but other diseases as well.

Basis for the development of possible treatments and vaccines
Dr Rik Lindeboom, one of the study’s first authors and now at the Netherlands Cancer Institute, said: “This was an incredibly unique opportunity to see what immune responses look like when faced with a new pathogen in adults without a history of COVID. -19, in an environment where factors such as timing of infection and comorbidities can be controlled.

For his part, Marko Nikolic, lead author of the study at UCL and honorary consultant in respiratory medicine, added: “These results shed new light on the important early events that allow the virus to gain a foothold or quickly eliminate it before it can develop. symptoms. “We now have a much better understanding of the full spectrum of immune responses, which could inform the development of potential treatments and vaccines that mimic these natural protective responses.”

In this spirit, Sarah Teichmann, lead author of the study and co-founder of the Human Cell Atlas, formerly of the Wellcome Sanger Institute and now based at the Cambridge Stem Cell Institute at the University of Cambridge, states: “As we build the Human Cell Atlas, With the help of the Atlas cells, we can better determine which of our cells are critical to fighting infections and understand why different people react differently to the coronavirus. “Future studies could be compared with our reference dataset to understand how the normal immune response to a new pathogen compares to the immune response induced by a vaccine.”

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