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Some people have unique immune responses that block Covid

A team of scientists has identified previously unrecognized immune responses that explain why some individuals do not contract COVID-19

The experts utilized single-cell sequencing to investigate immune reactions to SARS-CoV-2 in healthy volunteers as part of the world’s first COVID-19 human challenge study. 

The research was led by researchers from Wellcome Sanger Institute, University College London (UCL), Imperial College London, and the Netherlands Cancer Institute.

Unique immune responses to COVID-19

The study involved 36 volunteers exposed to the virus, with detailed monitoring revealing unique immune responses associated with resisting infection.

“This was an incredibly unique opportunity to see what immune responses look like when encountering a new pathogen – in adults with no prior history of COVID-19, in a setting where factors such as time of infection and comorbidities could be controlled,” said co-first author Rik Lindeboom, a researcher at the Netherlands Cancer Institute.

Basis for new treatments 

“These findings shed new light on the crucial early events that either allow the virus to take hold or rapidly clear it before symptoms develop,” noted study senior author Marko Nikolić, a clinical scientist fellow at UCL.

“We now have a much greater understanding of the full range of immune responses, which could provide a basis for developing potential treatments and vaccines that mimic these natural protective responses.”

Activation of protective immune cells

Using single-cell sequencing, the researchers generated a dataset of over 600,000 cells. They discovered immediate virus detection responses, including activation of specialized mucosal immune cells and a reduction in inflammatory white blood cells. 

Individuals who cleared the virus immediately showed unique innate immune responses, influenced by high pre-exposure activity of the gene HLA-DQA2. Those who developed sustained infections had a rapid blood immune response but a slower nasal response.

“As we’re building the Human Cell Atlas we can better identify which of our cells are critical for fighting infections and understand why different people respond to coronavirus in varied ways,” said Sarah Teichmann, co-founder of the Human Cell Atlas.

“Future studies can compare with our reference dataset to understand how a normal immune response to a new pathogen compares to a vaccine-induced immune response.”

Critical insights into immune responses 

The study also identified patterns in T cell receptors, offering insights for targeted T cell therapies.

Shobana Balasingam from Wellcome emphasized the value of human challenge models in understanding the body’s response to infectious diseases, highlighting the need for such studies in low-resource settings to develop effective tools and treatments.

This research provides critical insights into immune mechanisms that allow some individuals to avoid COVID-19, offering potential pathways for improved therapeutic strategies and vaccine designs. 

By understanding these natural protective responses, scientists can better inform the development of treatments and preventive measures for COVID-19 and other infectious diseases.

How does Covid invade the body?

COVID-19, caused by the SARS-CoV-2 virus, invades the body through a multi-step process. 

Point of entry 

Initially, the virus enters the body primarily through the respiratory system, as people inhale droplets containing the virus from an infected person’s coughs, sneezes, or speech. The virus can also enter through the eyes, nose, and mouth. 

Attachment to cells

Once inside, the virus targets specific cells in the respiratory tract by using its spike protein to bind to ACE2 receptors on the surface of these cells, which are abundant in areas such as the lungs, heart, kidneys, and intestines.

Fusion and cell entry

Upon binding to the ACE2 receptor, the virus’s membrane fuses with the host cell membrane, allowing the viral RNA to penetrate the host cell. 

Virus replication and assembly

Inside the host cell, the viral RNA takes control of the cell’s machinery, directing it to replicate the viral RNA and produce viral proteins necessary for creating new virus particles. These new viral particles are then assembled within the host cell.

Once assembled, the new viral particles are released from the host cell and proceed to infect neighboring cells, thereby spreading the infection throughout the body. 

Immune response 

The body’s immune system responds to this invasion, often leading to inflammation and symptoms associated with COVID-19, such as fever, cough, and difficulty breathing. 

In severe cases, this can result in complications like pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure, as the immune system’s response can cause significant tissue damage.

The study is published in the journal Nature.


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