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

SARS-CoV-2感染在人类中通过严重的临床表现而导致无症状。围绕感染和传播动力学的参数已经在动物模型中进行了研究。然而，越来越多的报告称，SARS-CoV-2病毒在“康复”几个月后“重新激活”并再次感染。在继发性种内和种间感染后，传染性病毒脱落和继续传播方面的频率、时间、临床和病毒学后果尚不清楚。这些感染背后的潜在免疫学机制也尚不清楚。此外，水貂感染SARS-CoV-2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，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(人和动物适应病毒)的雪貂模型，在六个月的时间内研究两种基因不同的病毒感染呼吸道飞沫的纵向结果。我们将监测SARS-CoV-2纵向感染的病毒学和免疫学进展；调查SARS-CoV-2同源和异种毒株再次感染的后果；以及在这些感染过程中适应和免疫对SARS-CoV-2进化的影响。我们假设，SARS-CoV-2变种的有效再感染可以导致感染和感染两个阶段，后者能够传播疾病，而无论先前的暴露和免疫状态如何。这些研究将提供与飞沫避免、群体免疫、疫苗接种和病毒进化等缓解策略相关的详细而有力的新信息。它还将解决动物水库中可能威胁到COVID根除和长期管理的SARS-CoV-2的出现和维持问题

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