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Unprecedented national effort by UK immunologists to search for answers on COVID-19

28/08/2020

Unprecedented national effort by UK immunologists to search for answers on COVID-19

Three new UK-wide studies, bringing together scientists from 17 research institutions, will receive £8.4 million from UK Research and Innovation (UKRI) and the National Institute for Health Research (NIHR) to understand immune responses to the novel coronavirus.

The scientists aim to develop better tests to define immunity, to study the body’s immune response to SARS-CoV-2 and to understand why some people suffer from severe life-threatening COVID-19 while others have mild or asymptomatic infections but can still transmit the virus. Importantly these studies will determine when and how immunity persists or whether people can become re-infected.

Together, it is hoped these studies will improve the treatment of patients and inform the development of vaccines and therapies.

The UK Coronavirus Immunology Consortium (UK-CIC) will receive £6.5 million to bring together leading immunologists from 17 research institutions*. The consortium will investigate key questions including:

  • How long does immunity from COVID-19 last?
  • Why are some people’s immune systems better able to fight off the virus?
  • Why do some people’s immune responses cause damage, especially to the lungs?
  • How does the virus ‘hide from’ the immune system and how can this be tackled?
  • Does immunity to previous infection with seasonal coronaviruses (which cause the common cold) alter a person’s outcome with SARS-CoV-2?

Better understanding of these immune responses, particularly the T cell response, could provide targets for new therapies to treat COVID-19 and inform the efforts to develop a vaccine.

The project will use samples and data from major UK COVID-19 projects already underway, and funded by UKRI and NIHR, including ISARIC-4C (characterizing and following more than 75,000 hospitalized patients with COVID-19) and the genomic studies COG-UK (sequencing the SARS-CoV-2 virus genomes) and GenOMICC (sequencing the genomes of people with COVID-19).

The consortium is led by Professor Paul Moss at the University of Birmingham, who said: “Understanding the complexities of the immune response to SARS-CoV-2 is key to successfully developing new diagnostics, treatments and vaccines against COVID-19. The UK Coronavirus Immunology Consortium will see the UK immunology community come together in an unprecedented way to answer questions that are crucial in helping us control this pandemic, such as how effective immunity is developed and why individuals respond differently to the disease.

“The UK is a world leader in immunology research and it’s an honour to lead this consortium to deliver a co-ordinated and agile national research programme to build our knowledge of this disease, which will translate into meaningful benefit for patients. There is so much that we still need to learn about how the novel coronavirus interacts with our immune systems and, with this investment, we have a unique opportunity to answer these key questions and hasten effective pandemic control.”

The Humoral Immune Correlates of COVID-19 (HICC) consortium will receive £1.5m to study the humoral immune response - molecules produced by the immune system to fight infection, including antibodies – by focusing on two cohorts: NHS workers - in collaboration with SIREN - to track immunity over 12 months, and hospitalised patients.

The study will look in detail at the role of antibodies in immunity to SARS-CoV-2 and characterize the antibody response in people who have mild or asymptomatic SARS-CoV-2 infection versus those who develop moderate or severe COVID-19 disease. The researchers want to better understand the differences between beneficial - or protective - antibody responses versus those that cause disease. This will help to determine why early indications suggest that people with stronger antibody responses may have had more life-threatening disease and what types of antibody responses are more effective in preventing severe infection.

The results from the study will help to develop better tests to diagnose protective immunity as well as determine how long protective antibodies persist after exposure to the virus. The researchers also hope the study will inform treatments for COVID-19 patients at different stages and with different severities of the disease, including whether targeting the overactivation of the innate humoral immune response – known as the ‘complement system’ – to SARS-CoV-2, could provide a unique approach to reducing severe COVID-19 related disease and death.

The consortium is a collaboration led by Professor Wilhelm Schwaeble and Professor Jonathan Heeney at the University of Cambridge, and Dr Helen Baxendale at Royal Papworth Hospital NHS Foundation Trust who said: “Understanding the role of antibody responses to SARS-CoV-2, and the role that the overactivation of the immediate innate immune response to the virus plays through complement activation in the initiation and maintenance of inflammatory disease, is critical to improve the clinical management of life-threatening cases of COVID-19.”

 “In critical care, we know most patients have high levels of antibody to SARS-CoV-2 however what we don’t know is whether these antibodies are helpful. Pilot data has shown that many of our NHS staff have been exposed to SARS-CoV-2, but we need to find out whether this means they are protected from further infection either in the short or the long term, or may be at risk of disease in the future. Understanding the different types of antibody responses will allow us to determine beneficial antibodies from dangerous ones.

“Collaborating nationally with other UK COVID-19 projects and supported by clinical research networks and scientists across the country, we are delighted to receive this investment to answer these fundamentally important questions.”

Both the UK-CIC and HICC have been given urgent public health research status by the Department of Health and Social Care, to prioritise their delivery by the health and care system.

The third study will specifically focus on the key features of fatal COVID-19 and the impact the virus has upon the lungs and other vital organs. The project, titled ‘Inflammation in Covid-19: Exploration of Critical Aspects of Pathogenesis’, or ICECAP, will receive £394k.

Using authorised hospital post-mortem examinations of patients who have died from COVID-19, this study will provide a unique opportunity for expert clinicians and scientists to study the whole body in a level of detail that is not possible during life.

By collecting and analysing tissue samples collected during these examinations, researchers will be able to collect crucial information on the presence of COVID-19 in multiple organs across the body and gain a more in-depth understanding of how the body’s immune system is responding to the virus.

The study is led by Dr Christopher Lucas at the University of Edinburgh, who said: “We have learned so much from Covid-19 patients during the past six months. However, there is only so much that we can learn from clinical examinations and blood tests. By having a deeper look at those who have died from Covid-19 through post-mortem examination, we will increase our understanding of what is happening to the body in the most severe cases of this disease. Critically, this will allow us to rapidly answer key clinical questions and help inform the care of patients and the development of new treatments.”

Medical Research Council, part of UKRI, Executive Chair Fiona Watt said: “The UK is funding a collaboration of world-leading immunologists to investigate the major unanswered questions related to coronavirus immunity. Finding out more about the immune response to COVID-19 will be key to developing better treatments and vaccines and improving public health strategies.”

Chief Medical Officer for England and Head of the NIHR Professor Chris Whitty said: “Understanding how our immune systems respond to COVID-19 is key to solving some of the important questions about this new disease, including whether those who have had the disease develop immunity and how long this lasts, and why some are more severely affected.

“This investment by the NIHR and UKRI will help immunology experts to discover how our immune systems respond to SARS-CoV-2, including our T cell response. This is vital information to help prevent and treat the disease.”

Science Minister Amanda Solloway said:

“Thanks to the brilliant work of our world-leading scientists and researchers, we continue to gain greater knowledge and understanding of coronavirus, enabling us to rapidly develop new treatments, as well as potential new vaccines.

“These three studies will help further improve our understanding of people’s immune responses to coronavirus, ensuring that the UK continues to play a critical role in the global effort to treat and defeat it.”

These studies build on the UK’s world-class expertise and capability in global heath and infectious disease that has already shaped our understanding of the pandemic and is informing measures to tackle it.

*The full list of research institutions include the University of Birmingham, University of Bristol, University of Cambridge and Wellcome Sanger Institute, UCL, King’s College London, Imperial College London, University of Liverpool, University of Manchester, Newcastle University, University of Oxford, University of Sheffield, University of York, Cardiff University, University of Dundee, University of Edinburgh, University of Glasgow and the Bradford Institute for Health Research.


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