Why is COVID-19 life threatening for some, but not others?

patient on oxygen

With the SARS-CoV-2 pandemic still holding the world in its grip, identifying how our immune system responds to the virus is critical to understanding the unknowns surrounding COVID-19.

The human immune system is extremely complex but understanding of 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 19 UK centres will co-ordinate coronavirus immunology research and rapidly address 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?

"The body’s immune response to SARS-CoV-2 infection can suppress virus replication, but may also cause significant damage to tissue such as the lungs. Also, it is still unclear how effective immunity is established or how long it lasts"

Professor Paul Moss, UK-CIC Principal Investigator from the University of Birmingham

Professor Moss continued: “Immunology in the UK is strong but research so far has been somewhat fragmented, which has limited progress. Putting together a consortium of expertise on this scale is unprecedented and will undoubtedly help us to address the challenges ahead in answering these critical questions relating to SARS-CoV-2.”

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.

illustration of virus with DNA strand
Genomic data suggests that, to date, SARS-CoV-2 is not mutating too rapidly and cases of re-infection have been rare

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 already underway, 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 project and COG-UK is fascinating as it is checking the rate of new mutations in the virus. At the moment, indications are that SARS-CoV-2 is not mutating too rapidly and cases of re-infection have been rare. Another major focus of UK-CIC will be cellular immunity.

“We know that the immune response develops after infection and is robust, but there are concerns that antibody responses decline” – 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 helps to address this issue and will provide insights to inform COVID-19 patient management, develop 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 can rapidly bring together this 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 will help to develop co-ordinated infrastructure and oversight across the UK immunology community – potentially 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 will help 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.