The human immune system is extremely complex but understanding how it reacts during and after infection with SARS-CoV-2 is critical to our ability to control the pandemic. Immune system responses dictate not only how quickly patients can clear the virus, but also how sick they will get and how long any immunity generated to the virus might last.
However, the world has had little time to make rapid and effective progress in our understanding of how the body’s defence mechanisms interact with SARS-CoV-2. A new approach is required if our scientists are to fight COVID-19 by developing better diagnostics, treatments and vaccines.
Led by immunology experts at the University of Birmingham, and backed by funding from UKRI and NIHR, the new UK Coronavirus Immunology Consortium (UK-CIC) is examining what happens on a cellular and molecular level when someone becomes infected with SARS-CoV-2 by finding out exactly what the patient’s immune system is doing.
UK-CIC embodies an unprecedented ‘collegiate’ approach to tackling the issue with immunologists around the country working together to build understanding of how different people react to COVID-19. The 20 UK centres are co-ordinating coronavirus immunology research and rapidly addressing five critical questions:
- Why is there so much variation in the severity of COVID-19?
- How long does immunity from the virus last?
- Why does the immune system damage the body?
- Does previous infection with seasonal coronaviruses help the body fight COVID-19?
- How does the virus ‘hide’ from’ the immune system?
“Our knowledge of SARS-CoV-2 infection is increasing all the time,” comments Professor Paul Moss, UK-CIC Principal Investigator from the University of Birmingham.
"Findings established by reviewing serum and blood samples (bioRxiv, November 2020) from a cohort of more than 2,000 clinical and non-clinical healthcare workers including 100 individuals who tested sero-positive for SARS-CoV-2 cause us to be cautiously optimistic about the strength and length of immunity generated after SARS-CoV-2 infection.
"However, this is just one piece of the puzzle. There is still a lot for us learn before we have a full understanding of how immunity to COVID-19 works. While we increase our understanding, whether we think we have previously had COVID-19 or not, we all should still follow Government guidelines on social distancing to ensure we play our part in minimising the spread of COVID-19 within our communities.”
UK-CIC is supported by the British Society for Immunology (BSI) and the consortium’s aims were developed from research priorities on immunology and COVID-19 set out in May 2020 by the Academy of Medical Sciences and BSI expert taskforce. It unites top immunologists at Birmingham with their counterparts at other leading research institutions including Bradford Institute for Health Research; Imperial College London; King’s College London; University College London; the Crick and Sanger Centres, and the Universities of Bristol, Cambridge, Cardiff, Dundee Edinburgh, Glasgow, Liverpool, Manchester, Newcastle, Oxford, Sheffield, Ulster and York.
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Researchers are also working closely with ISARIC-4C, an internationally-leading project to examine the immune profile of hospitalised patients with COVID-19. In addition, the project interacts with data from major UK coronavirus projects, including the COVID-19 Genomics UK Consortium (COG-UK) and GenOMICC. “It is important for us to make best use of the wealth of samples and data provided by existing projects and COG-UK is fascinating as it is checking the rate of new mutations in the virus. At the moment, indications are that whilst SARS-CoV-2 is mutating, it is not doing so rapidly, and cases of re-infection have been rare.”
A major focus of UK-CIC is cellular immunity. “We know that the immune response develops after infection and is robust, but there are concerns that antibody responses decline,” explains Professor Moss. “However cellular immune responses appear to remain and the key to unlocking longer-term immunity to COVID-19 may lie in the way that white blood cells respond to the virus.”
A report produced by immunology experts for the UK Government’s Scientific Advisory Group for Emergencies (SAGE) highlighted that the lack of a co-ordinated approach was limiting depth of understanding with no UK platform existing to evaluate immunity and immunopathology.
Establishing UK-CIC has helped to address this issue and is providing insights to inform COVID-19 patient management, developing new therapies and diagnostic tools to support vaccine development.
“The UK has one of the strongest immunology communities in the world and UK-CIC is an excellent example of how we have rapidly come together to address crucial issues,” adds Professor Moss. “We have a clear direction of travel – discovering new treatments, developing new diagnostic tests and helping to inform vaccine studies. For example, dexamethasone has been found useful in helping to control the immune response to SARS-CoV-2, but we want to find more targeted ways of damping down the immune system.
“Key to rapid progress will be the innovation and new ways of working that the consortium introduces. For example, we’ve worked hard on optimising the cellular assays and the process for measuring cellular immunity – taking a blood sample, we separate out the white cells and stimulate these using viral protein. If ‘immunity’ is present in the sample there will be a response which we can measure.”
Establishing UK-CIC has helped to develop co-ordinated infrastructure and oversight across the UK immunology community –reaping the benefits of prior investments in life sciences and accommodating new research questions around SARS-CoV-2 as they emerge. As well as supporting global diagnostic, vaccine and drug development, insights emerging from the consortium are helping to inform critical public health policy.
“The UK is a world leader in immunology research and it’s an honour to lead this consortium as we work together to build our knowledge of this disease and create meaningful benefit for patients. There is so much that we still need to learn about how SARS-CoV-2 interacts with our immune systems and UK-CIC gives us a unique opportunity to answer these key questions and speed the introduction of effective pandemic control,” comments Professor Moss.
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