Why are some people's immune systems better able to fight off SARS-CoV-2?
Theme Lead: Professor Tracy Hussell, Professor of Inflammatory Disease at the University of Manchester
It is estimated that millions of people within the UK have been infected with SARS-CoV-2, the virus that causes COVID-19. It has proven to be highly contagious and difficult to control, however it is clear that there is a lot of variability in how the virus affects each person – some catch it without ever knowing, remaining asymptomatic as their immune system successfully fights off the infection, whereas others are unable to do so, becoming seriously unwell or possibly dying as a result.
Over the last few months, many research centres around the world and in the UK have been collecting data on COVID-19 patients, largely during the primary wave of infection in the first half of the year. After looking into this data, it quickly became clear that we need to learn more about the specific ways that the immune system responds to the virus. For example, researchers saw low counts of one type of white blood cell but high activation levels of others, and very high levels of inflammation.
By working collaboratively, across research centres, scientists that are a part of UK-CIC will be able to pool their data and look at how differences in immune response relate to how well a patient copes with infection. This will also include differences across subgroups, such as BAME patients or those with comorbidities like obesity or cardiovascular disease, to see how pre-existing health differences can affect patient outcomes.
Thanks to the consortium’s collaborative nature, the researchers have access to a wealth of resources to answer these questions. This includes tissue samples collected over the course of the outbreak, including from patients in high risk groups or BAME backgrounds. The researchers also plan to recruit new patients, through local hospital admissions (linked to sister project ISARIC-4C), community sampling, and a ‘track and study’ system.
Within this theme, the consortium has identified three outstanding questions:
1. How does the function of the immune system in the blood affect the likelihood of severe infection?
The aim is to bring together all of the information collected that identifies the types of immune cells present in severe COVID-19 patients. Researchers will use a specialised computer programme and machine learning to combine this data, which will come from six different research centres. The hope is to establish a clear example of the immune response and the specific cells present during a SARS-CoV-2 infection, that other researchers can compare their work to in further study.
2. How has the immune system responded in someone who presents asymptomatically or with only mild symptoms?
Most people infected with SARS-CoV-2 do not suffer serious infection, in fact many are asymptomatic and may be completely unaware that they ever came into contact with it. Understandably, many of the research efforts so far have focused on those with severe COVID-19, in an effort to quickly help those hospitalised with the virus. As a consequence, we know relatively little about the immune response of those who successfully fight off the infection.
UK-CIC has identified more than 250 asymptomatic or mild cases within healthcare workers or the community, and continues to recruit more patients as they are identified. The aim of this study is to compare the immune responses of these patients with those who experience severe symptoms, and identify what specific aspects of their immune systems meant they could fight off the virus.
3. What does the immune response to the virus look like on a detailed, cellular level?
Some early studies have found a range of unique features of how the immune system responds to SARS-CoV-2. Researchers answering this question will use a number of techniques to look at these in further detail, and combine the skills and resources of many different centres across the UK.
Research into this first theme will deliver the largest meta-analysis of the immune system and its response to SARS-CoV-2 in the world. The results will be crucial and inform our understanding of disease severity, how infection develops in the body, and what types of treatment might be useful as a result. The immune system understanding achieved could also be used in treatment analysis and vaccine trials.
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