SARS-Cov-2 infection at the animal-human interface: longevity and re-infection dynamics with virus evolution

动物与人界面上的 SARS-Cov-2 感染：病毒进化过程中的寿命和再感染动态

• 批准号: BB/W006839/1
• 负责人: Sharon Brookes
• 金额: $ 60.9万
• 依托单位: ANIMAL AND PLANT HEALTH AGENCY
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW006839%2F1
• 关键词: SARS; Cov; infection; animal; human

SARS-CoV-2 infection causes asymptomatic through severe clinical presentations in humans. Parameters around infection and transmission dynamics have been studied in animal models. However, there are growing reports of 'reactivation' and re-infection with variant SARS-CoV-2 viruses, months after 'recovery'. The frequency, timing, clinical and virological consequence, in terms of infectious virus shedding and onward transmission following secondary intra- and inter-species infections, remain unknown. The underlying immunological mechanisms behind these infections also remain unexplored. Additionally, SARS-CoV-2 infection in mink has generated novel virus variants, capable of infecting and partially evading existing immunity in humans, increasing the threats of re-infection. Here, we propose to use our established ferret model of SARS-CoV-2 (human and animal adapted viruses), to study longitudinal outcomes of respiratory droplet infection for two genetically different viruses over a six-month period. We will monitor virological and immunological progression of longitudinal SARS-CoV-2 infection; investigate the consequences of SARS-CoV-2 re-infection with homologous and heterologous strains; and investigate the effect of adaptation and immunity on the evolution of SARS-CoV-2 during these infections. We hypothesise that productive re-infection with SARS-CoV-2 variants can result in both infected and infectious stages, the latter being able to transmit disease irrespective of prior exposure and immune status.These investigations will provide detailed robust novel information relevant to mitigation strategies such as droplet avoidance, herd immunity, vaccination and virus evolution. It will also address questions regarding the emergence and maintenance of SARS-CoV-2 in animal reservoirs which may threaten eradication and long-term management of COVID

SARS-CoV-2 感染导致人类出现严重临床表现但无症状。已经在动物模型中研究了有关感染和传播动力学的参数。然而，越来越多的报告称，在“恢复”几个月后，变异 SARS-CoV-2 病毒“重新激活”和再次感染。继发性种内和种间感染后传染性病毒脱落和继续传播的频率、时间、临床和病毒学后果仍然未知。这些感染背后的潜在免疫机制也尚未被探索。此外，水貂中的 SARS-CoV-2 感染产生了新的病毒变种，能够感染并部分逃避人类现有的免疫力，增加了再次感染的威胁。在这里，我们建议使用我们建立的 SARS-CoV-2（人类和动物适应性病毒）雪貂模型来研究两种遗传不同的病毒在六个月内呼吸道飞沫感染的纵向结果。我们将监测纵向 SARS-CoV-2 感染的病毒学和免疫学进展；研究同源和异源毒株再次感染 SARS-CoV-2 的后果；并研究这些感染期间适应和免疫对 SARS-CoV-2 进化的影响。我们假设，SARS-CoV-2 变体的有效再感染可导致感染阶段和感染阶段，后者无论先前的暴露和免疫状态如何都能够传播疾病。这些研究将提供与避免飞沫、群体免疫、疫苗接种和病毒进化等缓解策略相关的详细、可靠的新信息。它还将解决有关动物宿主中 SARS-CoV-2 的出现和维持的问题，这可能威胁到新冠病毒的根除和长期管理