A study reveals unique immune responses that help some individuals resist COVID-19 infection.

RT’s Three Key Takeaways:

  1. Novel Immune Responses Identified: Researchers discovered unique immune responses in individuals who resisted sustained SARS-CoV-2 infection, including activation of specialized mucosal immune cells and a reduction in inflammatory white blood cells, offering new insights into how some people avoid getting COVID-19.
  2. Importance of the HLA-DQA2 Gene: High levels of activity of the HLA-DQA2 gene before exposure were associated with preventing sustained infection, highlighting the gene’s potential role in immune protection against COVID-19 and possibly other infectious diseases.
  3. Implications for Future Treatments and Vaccines: The study’s findings on immune responses and T cell receptor patterns provide a basis for developing targeted therapies and vaccines that mimic these natural protective responses, which could be crucial for combating COVID-19 and other diseases, according to researchers.

Scientists have discovered novel immune responses that help explain how some individuals avoid getting COVID-19.

Using single-cell sequencing, researchers from the Wellcome Sanger Institute, University College London (UCL), Imperial College London, the Netherlands Cancer Institute, and their collaborators, studied immune responses against SARS-CoV-2 infection in healthy adult volunteers, as part of a COVID-19 human challenge study. 

Not all exposed participants went on to develop a COVID-19 infection, allowing the team to uncover unique immune responses associated with resisting sustained viral infection and disease.

Novel Immune Responses Identified

The findings, published in Nature, provide the a timeline of how the body responds to SARS-CoV-2 exposure, or any infectious disease. The work is part of the Human Cell Atlas initiative to map every cell type in the human body.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions across the globe with Coronavirus disease 2019 (COVID-19). While it is potentially fatal, many will have come into contact with someone who has tested positive for COVID-19, but have managed to avoid getting ill themselves, whether remaining negative on PCR testing or having an asymptomatic case of the disease.

While previous studies have examined COVID-19 patients after symptom onset, in this new study researchers set out to capture immune responses right from exposure, in an immunologically naïve cohort.

Study Methodology and Key Findings

As part of the UK COVID-19 Human Challenge study, led by Imperial College London, 36 healthy adult volunteers without previous history of COVID-19 were administered SARS-CoV-2 virus through the nose. Researchers performed detailed monitoring in the blood and lining of their noses, tracking the entire infection as well as the immune cell activity prior to the infection event itself for 16 volunteers. The teams at the Wellcome Sanger Institute and UCL then used single-cell sequencing to generate a dataset of over 600,000 individual cells.

Across all participants, the team discovered previously unreported responses involved in immediate virus detection. This included activation of specialized mucosal immune cells in the blood and a reduction in inflammatory white blood cells that normally engulf and destroy pathogens.

Individuals who immediately cleared the virus did not show a typical widespread immune response but instead mounted subtle, never-seen-before innate immune responses. 

Insights and Implications for Future Treatments

Researchers suggest high levels of activity of a gene called HLA-DQA2 before exposure also helped people prevent a sustained infection from taking hold. In contrast, the six individuals 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 recognize and bind to virus-infected cells. This offers insights into immune cell communication and the potential for developing targeted T-cell therapies against not just COVID-19 but other diseases.

“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,” says Rik Lindeboom, PhD, co-first author of the study, now at the Netherlands Cancer Institute, in a release.

Marko Nikolić, PhD, senior author of the study at UCL and honorary consultant in respiratory medicine, adds in a release, “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.”

Human Challenge Models and Future Research

Shobana Balasingam, research lead in Wellcome’s Infectious Disease team, says in a release, “Human challenge models are an invaluable way to build our understanding of how the body responds to infectious disease. These studies enable us to closely monitor what happens from the moment of infection by allowing us to follow the immune response through to the development and severity of symptoms. These results are an exciting addition to our evidence-base of how different people might respond to, or be protected against, COVID-19 infections. 

“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 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.”

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