A UK underpinning platform to study immunology and immunopathology of COVID-19:The UK Coronavirus Immunology Consortium

The immune response to SARS-CoV-2 infection is the critical determinant of clinical outcome for patients but although this can suppress virus replication (immunity) it can also cause damage to tissues such as the lung (immunopathology). It is unclear how effective immunity is established or why it damages tissues. Many UK research groups have initiated research and UK-CIC will bring together a consortium of 17 UK centres to coordinate coronavirus immunology research. We will work on 5 questions: -the features of immunity during initial infection and how this relates to clinical outcome of individual patients. SARS-CoV-2 infection triggers an immediate (innate: interferon and white cell) and delayed (adaptive: antibody and cellular) immune response. How these develop and interact is currently unclear but will determine how quickly the infection is cleared. We will study this in patients with mild and severe infection. A number of risk factors for severe Covid-19 infection have been identified including age, gender, obesity and ethnicity. These will be studied in relation to the features of the initial immune response. -how effective immunity is established and maintained to prevent re-infection After infection the immune response develops some 'memory' of the infection and this helps to prevent reinfection. For some infections (e.g. measles) this protection is virtually complete; for others (such as the common cold) this protection is brief. We do not know what the situation will be for SARS-CoV-2. This work will take samples from people in the first year after infection and measure the virus-specific immune response. We will examine the fine details of how the immune system kills the virus and the longevity of this response. We will examine a broad representation of population groups to do this work effectively and compare groups of different ages and backgrounds. -the mechanisms by which the immune system can damage tissue and how this can be stopped In severe or fatal infection the problems arise due to two mechanisms: (1) The virus infects and damages tissue (2) The immune response to the virus can itself damage tissue In this research theme we will investigate the relative importance of these two problems and try to find ways to prevent them. This will involve taking blood and tissue samples from patients with severe disease and also using post mortem tissue. -if immunity to mild 'seasonal' coronaviruses alters the outcome of SARS-CoV-2 infection The term coronavirus was first used in 1965 to describe identification of a common cold virus and these viruses circulate widely in the community. It is thought that the immune response to these viruses may potentially 'cross-react' with the new SARS-CoV-2 coronavirus, perhaps giving some people relative protection against infection. We will investigate this possibility and assess how it might happen. Here we will use blood samples in the laboratory to assess their recognition of both viruses and also see if blood samples frozen down before the Covid-19 pandemic make any response to the new virus. -the details by which the virus 'evades' the immune system and how this could be targeted by new treatments. Viruses can only grow, spread and cause disease if they are able to evade being killed by the immune system. If we can understand how this happens we might be able to develop new drugs that can block this response and allow the virus to take control and eliminate the virus. This work takes place in the laboratory using viral infection studies of cells. UK-CIC will work with other major recent UK investments in Covid-19 biology and represents an essential additional pillar of UK research infrastructure to hasten the control of the pandemic.