Human Challenge Studies with Coronaviruses Old and New.
Human Challenge Studies with Coronaviruses Old and New.
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DOI：
10.1007/82_2021_247
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发表时间：
2022-02
影响因子：
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通讯作者：
Richard T. McKendry;Nana-Marie Lemm;L. Papargyris;C. Chiu
中科院分区：
文献类型：
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作者：
Richard T. McKendry;Nana-Marie Lemm;L. Papargyris;C. Chiu
早在20世纪20年代，人们就知道冠状病毒感染会导致动物疾病。然而，到目前为止，只发现了七种能够引起人类疾病的冠状病毒。这些人类冠状病毒（hcov）包括引起普通感冒的原因，但最近出现的冠状病毒（即SARS-CoV、MERS-CoV和SARS-CoV-2）的发病率和死亡率要高得多。与其他常见呼吸道感染相比，hcov的研究相对不足，因为从历史上看，它们的症状较轻。这导致对其动物宿主、传播和免疫保护决定因素的了解相对有限。为了解决这一问题，已经开展了hcov人类感染挑战研究，能够在控制条件下使用标准化病毒接种在特定时间点对宿主反应进行详细的临床和免疫学分析。直到最近，所有这类人体挑战研究都是针对普通感冒hcov进行的，SARS-CoV和MERS-CoV的研究由于致病性更强而不可接受。然而，随着SARS-CoV-2的出现和COVID-19大流行（在年轻健康成年人中很少出现严重后果），目前正在开展SARS-CoV-2的人体挑战研究。英国正在进行两项SARS-CoV-2人类挑战研究，研究有和没有预先免疫的个体。除了提供抗病毒药物和疫苗测试平台外，这类研究对于了解与SARS-CoV-2感染易感性相关的因素，从而制定改进的战略，以应对当前和未来的HCoV大流行至关重要。在这里，我们总结了人类感染挑战研究在历史上试图回答的关于HCoV感染的保护和发病机制的主要问题，以及旨在通过当代模型解决的知识空白。
Coronavirus infections have been known to cause disease in animals since as early as the 1920s. However, only seven coronaviruses capable of causing human disease have been identified thus far. These Human Coronaviruses (HCoVs) include the causes of the common cold, but more recent coronaviruses that have emerged (i.e. SARS-CoV, MERS-CoV and SARS-CoV-2) are associated with much greater morbidity and mortality. HCoVs have been relatively under-studied compared to other common respiratory infections, as historically they have presented with mild symptoms. This has led to a relatively limited understanding of their animal reservoirs, transmission and determinants of immune protection. To address this, human infection challenge studies with HCoVs have been performed that enable a detailed clinical and immunological analysis of the host response at specific time points under controlled conditions with standardised viral inocula. Until recently, all such human challenge studies were conducted with common cold HCoVs, with the study of SARS-CoV and MERS-CoV unacceptable due to their greater pathogenicity. However, with the emergence of SARS-CoV-2 and the COVID-19 pandemic during which severe outcomes in young healthy adults have been rare, human challenge studies with SARS-CoV-2 are now being developed. Two SARS-CoV-2 human challenge studies in the UK studying individuals with and without pre-existing immunity are underway. As well as providing a platform for testing of antivirals and vaccines, such studies will be critical for understanding the factors associated with susceptibility to SARS-CoV-2 infection and thus developing improved strategies to tackle the current as well as future HCoV pandemics. Here, we summarise the major questions about protection and pathogenesis in HCoV infection that human infection challenge studies have attempted to answer historically, as well as the knowledge gaps that aim to be addressed with contemporary models.