Covid-19: Study sheds light on how some people avoid the disease
BMJ 2024; 385 doi: https://doi.org/10.1136/bmj.q1382 (Published 21 June 2024) Cite this as: BMJ 2024;385:q1382
Scientists say that they have discovered novel immune responses that help explain how some people avoid getting covid-19.
High levels of a key gene in volunteers who managed to quickly fight off infection suggest that this has a protective effect against SARS-CoV-2.
Researchers from the Wellcome Sanger Institute, University College London (UCL), Imperial College London, and the Netherlands Cancer Institute set out to capture immune responses from immediately after exposure, in an immunologically naive cohort, for the first time.
The findings, published in Nature on 19 June,1 showed that high expression of a gene called HLA-DQA2 before exposure was associated with preventing sustained infection. The authors said that better understanding of the full range of immune responses could help in developing potential treatments and vaccines that mimic natural protective responses.
Kaylee Worlock, the study’s co-first author from UCL Division of Medicine, said, “Studies so far have only offered a snapshot of what is going on during covid-19, whereas our approach allowed us to study the evolution of infection in three distinct infection groups prior to and during infection, right through to the resolution, in unprecedented detail.”
The research, which is part of the UK Covid-19 Human Challenge study led by Imperial College London, involved 36 healthy adult volunteers without previous history of covid-19. They were administered SARS-CoV-2 virus through the nose.
Researchers performed detailed monitoring in the blood and lining of the participants’ noses, tracking the entire infection as well as immune cell activity before the infection event itself, in 16 volunteers. Six participants developed a sustained SARS-CoV-2 infection.
Subtle immune responses
The teams at the Wellcome Sanger Institute and UCL used single cell sequencing to generate a dataset of more than 600 000 individual cells.
Across all participants the team discovered “previously unreported responses involved in immediate virus detection.” This included activation of specialised mucosal immune cells in the blood and a reduction in the inflammatory white blood cells that normally engulf and destroy pathogens.
Participants who immediately cleared the virus did not show a typical widespread immune response but instead “mounted subtle, never-seen-before innate immune responses.”
The researchers said that high levels of the HLA-DQA2 gene before exposure also helped people to prevent a sustained infection from taking hold. People with high levels of this gene cleared the virus so effectively that they did not return a positive PCR test at all and had no symptoms, while another group tested positive intermittently and had very mild symptoms.
In contrast, the six participants who developed a sustained SARS-CoV-2 infection exhibited a rapid immune response in the blood but a slower immune response in the nose, allowing the virus to establish itself there.
The researchers further identified common patterns among activated T cell receptors, which recognise and bind to virus infected cells. They said that this held potential for developing targeted T cell treatments against not just covid-19 but other diseases.
Shobana Balasingam, research lead in Wellcome’s infectious disease team, said, “We need to understand how factors like natural exposure to the disease affect the body’s response to the virus or a vaccine. Therefore, it is crucial [that] studies like this expand to low resource settings where diseases are endemic, to ensure we are developing context specific tools and therapeutics that work for those most vulnerable.”
The research was supported by Wellcome, Action Medical Research, and the Medical Research Council.
This article is made freely available for personal use in accordance with BMJ's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.
https://bmj.com/coronavirus/usage