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

对SARS-CoV-2感染的免疫反应是患者临床结果的关键决定因素，但尽管这可以抑制病毒复制（免疫），但也可能对肺等组织造成损害（免疫病理）。目前尚不清楚免疫是如何有效建立的，也不清楚它为什么会损害组织。许多英国研究小组已经启动了研究，UK- cic将召集一个由17个英国中心组成的联盟，协调冠状病毒免疫学研究。我们将研究5个问题：-初始感染期间的免疫特征及其与个体患者临床结果的关系。SARS-CoV-2感染触发即时（先天性：干扰素和白细胞）和延迟（适应性：抗体和细胞）免疫反应。目前尚不清楚这些病毒是如何发展和相互作用的，但将决定这种感染被清除的速度。我们将在轻度和重度感染患者中进行研究。已经确定了一些Covid-19严重感染的风险因素，包括年龄、性别、肥胖和种族。这些将与初始免疫反应的特征相联系进行研究。-如何有效地建立和维持免疫系统，以防止再次感染感染后，免疫反应形成一些“记忆”的感染，这有助于防止再次感染。对于某些感染（如麻疹），这种保护几乎是完全的；对于其他疾病（如普通感冒），这种保护作用是短暂的。我们不知道SARS-CoV-2的情况会如何。这项工作将在感染后的第一年从人们身上采集样本，并测量病毒特异性免疫反应。我们将研究免疫系统如何杀死病毒的细节以及这种反应的持续时间。为了有效地开展这项工作，我们将对具有广泛代表性的人群进行调查，并对不同年龄和背景的人群进行比较。在严重或致命的感染中，由于两种机制而出现的问题：(1)病毒感染和损害组织(2)对病毒的免疫反应本身可以损害组织在本研究主题中，我们将调查这两个问题的相对重要性，并试图找到预防它们的方法。这将包括从患有严重疾病的患者身上采集血液和组织样本，以及使用死后组织。冠状病毒一词于1965年首次被用于描述一种普通感冒病毒的鉴定，这些病毒在社区中广泛传播。据认为，对这些病毒的免疫反应可能会与新的SARS-CoV-2冠状病毒“交叉反应”，可能会给一些人提供相对的感染保护。我们将调查这种可能性，并评估它是如何发生的。在这里，我们将使用实验室中的血液样本来评估它们对这两种病毒的识别能力，并观察在Covid-19大流行之前冷冻的血液样本是否对新病毒有任何反应。-病毒如何“逃避”免疫系统的细节，以及新的治疗方法如何针对这一点。病毒只有在能够避免被免疫系统杀死的情况下才能生长、传播并引发疾病。如果我们能理解这是如何发生的，我们就能开发出新的药物来阻止这种反应，让病毒控制并消灭病毒。这项工作在实验室进行，利用细胞的病毒感染研究。UK- cic将与英国最近在Covid-19生物学方面的其他主要投资合作，并代表英国研究基础设施的重要支柱，以加速控制大流行。

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-infectionAfter 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 stoppedIn 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 tissueIn 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.