Unique immune responses reveal why some people never get COVID-19 by Dr Semyon B

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Unique immune responses of those who avoid developing COVID-19 have been uncovered in a new study.

The study wanted to understand how some people had never developed COVID-19 despite encountering others infected with the SARS-CoV-2 virus, which causes COVID-19. The research, published in Nature, examined the immune responses in clinical trial volunteers before and immediately after infection with the SARS-CoV-2 virus. Previous studies have investigated the immune response from the first appearance of symptoms of COVID-19 rather than from the moment of 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 Dr Rik Lindeboom, study co-author and researcher at the Netherlands Cancer Institute.

This work was a collaboration between Imperial College London, the Wellcome Sanger Trust, University College London (UCL), and the Netherlands Cancer Institute. The research was part of the Human Cell Atlas, which seeks to identify each cell type within the human body (see BioNews 946).

Researchers from Imperial College London injected 36 volunteers with a SARS-Cov-2 viral load into their nasal cavities. All volunteers had never sustained a COVID-19 infection or been vaccinated with a COVID-19 vaccine. The immune activity of 16 of the volunteers was examined before infection.

Biological samples of the volunteers' nasal cavities lining and their blood were taken and sequenced by researchers at the Wellcome Sanger Institute and UCL, producing a dataset of over 600,000 single cells. The results revealed the different responses of the mucosal cells within the nasal lining compared to the white blood cells.

A heightened immune response was observed in the mucosal cells of the volunteers who recorded no symptoms of infection or a positive PCR test. This activity prevented an infection from developing in the nose and was associated with the upregulation of the gene HLA-DQA2. In addition, a decrease in the number of white blood cells responsible for identifying and engulfing pathogens was measured.

In contrast, six volunteers developed a sustained infection, displaying disease symptoms and testing positive on a PCR test. Results from these individuals showed a faster immune response in the blood compared to the nasal lining, suggesting that the infection could develop more in the nose, leading to a more sustained infection.

'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. 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,' said Dr Marko Nikolić, study senior author and researcher at UCL.

It is hoped that a greater understanding of the different immune responses to COVID-19 infection, particularly the activity of T cells (a type of white blood cell), could aid in more potent treatments for COVID-19.