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UK immunologists joint search for answers on COVID-19

Three new UK-wide research studies, including one led by the University of Edinburgh, to help understand immune responses to the novel coronavirus have been awarded £8.4 million from the NIHR and UK Research and Innovation (UKRI).

The researchers 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 UK universities. 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 if they’re infected 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 20,000 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, 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.

“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 groups of people: NHS workers – in collaboration with the SIREN study and hospitalised patients.

The study will look in detail at the role of antibodies in immunity to SARS-CoV-2 and characterise the antibody response in people who have mild or asymptomatic 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 harm. This will help to determine why 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 consortium is a collaboration led by Professors Wilhelm Schwaeble and Jonathan Heeney, University of Cambridge, and Dr Helen Baxendale, Royal Papworth Hospital NHS Trust, who said: “ Understanding the role of antibody responses to SARS-CoV-2 and the critical role that overshooting immune system activation plays in driving the disease processes associated with COVID-19 is critical to optimising management of severe acute COVID-19 disease and developing the most effective vaccination strategies.

“In critical care, we know most patients have high levels of antibodies to SARS-CoV-2; however, we don’t know whether these antibodies are helpful. Pilot data has shown that many of our NHS staff have been exposed to SARS-CoV-2, but we don’t know 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 types of antibody responses will allow us to determine beneficial antibodies from bad ones.”

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 effect of the disease on the whole body.

By 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.”

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.”

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.