Original study reveals novel immune response that confers resistance to COVID-19

People who resist COVID-19 have “An unprecedented immune response and possibly high levels of HLA-DQA2These findings Researchers and collaborators from the Wellcome Sanger Institute, University College London (UCL), Imperial College London and the Netherlands Cancer Institute used data from their own 'challenge study'.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a The world's first COVID-19 human challenge study. This study:“Controlled investigations into etiology, correlates of prevention, and efficacy testing of future interventions.” Using nasopharyngeal swabs and blood samples, the researchers used single-cell sequencing technology to create a comprehensive timeline of the body's response to exposure to SARS-CoV-2.

Their Work Published in Nature This week's featured author Rik GH Lindeboom, of the Wellcome Sanger Institute, now at the Netherlands Cancer Institute;

SARS-CoV-2 has infected millions of people worldwide with COVID-19, a potentially fatal infection. However, many people avoid becoming ill themselves, despite having been in contact with COVID-19 positive individuals. While previous studies have investigated COVID-19 patients after the onset of symptoms, in this new study, for the first time, researchers aimed to capture the immune response immediately after exposure in an immunologically immature cohort.

As part of the UK COVID-19 Human Challenge Study, led by Imperial College London, 36 healthy adult volunteers with no prior history of COVID-19 were given the SARS-CoV-2 virus via their nose. The researchers closely monitored the blood and nasal mucosa of 16 volunteers, tracking immune cell activity throughout infection and before the infection event itself. The Wellcome Sanger Institute and UCL team then used single-cell sequencing to generate a dataset of more than 600,000 individual cells.

Although not all infected participants developed COVID-19 infection, the research team was able to discover unique immune responses associated with resistance to persistent viral infection and disease.

The team discovered a “previously undescribed” response to the immediate detection of the virus, including the activation of specialized mucosal immune cells in the blood and a reduction in inflammatory white blood cells that normally engulf and destroy pathogens.

Those who quickly cleared the virus didn't mount the typical broad-based immune response, but instead mounted a subtle innate immune response never seen before, which the researchers say suggests is due to high levels of gene activity. HLA-DQA2 Vaccinating before infection also helped prevent persistent infection from taking hold. In contrast, the six people who developed persistent SARS-CoV-2 infections had a rapid immune response in the blood but a slower one in the nasal passages, allowing the virus to take hold there.

The researchers further identified a common pattern of activated T cell receptors that recognize and bind to virus-infected cells, providing insight into immune cell communication and the possibility of developing targeted T cell therapies for not only COVID-19 but also other diseases.

“This was a really unique opportunity to see what the immune response is like when adults with no prior history of COVID-19 encounter a new pathogen in an environment where we can control for factors like timing of infection and comorbidities,” Lindeboom said.

“By building the Human Cell Atlas, we can better identify which cells are important for fighting infection and understand why different people respond differently to coronaviruses,” said Sarah Teichmann, lead author of the study, co-founder of the Human Cell Atlas and director of the Cambridge Stem Cell Institute.