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

SARS-CoV-2感染通过严重的临床表现在人类中引起无症状。在动物模型中研究了感染和传播动力学的参数。然而，越来越多的报告称，在“康复”数月后，变异的SARS-CoV-2病毒“重新激活”和重新感染。在继发性种内和种间感染后的感染性病毒脱落和向前传播方面，频率、时间、临床和病毒学后果仍未知。这些感染背后的潜在免疫机制也尚未探索。此外，水貂的SARS-CoV-2感染产生了新的病毒变体，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雪貂模型的SARS-CoV-2（人类和动物适应病毒），研究纵向结果的呼吸道飞沫感染两种遗传不同的病毒在六个月的时间。我们将监测纵向SARS-CoV-2感染的病毒学和免疫学进展;研究同源和异源菌株再次感染SARS-CoV-2的后果;并研究适应和免疫对这些感染期间SARS-CoV-2进化的影响。我们假设SARS-CoV-2变异体的生产性再感染可以导致感染和传染阶段，后者能够传播疾病，而不管先前的暴露和免疫状态如何，这些调查将提供详细可靠的新信息，与缓解策略相关，如液滴避免，群体免疫，疫苗接种和病毒进化。它还将解决有关SARS-CoV-2在动物宿主中的出现和维持的问题，这些问题可能威胁到COVID的根除和长期管理

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