COVID 19: LESSONS FROM FATAL CORONAVIRUS INFECTIONS IN COMPANION ANIMALS

同伴动物容易感染冠状病毒，包括SARS-CoV-2。这项建议解决了3个重要的未得到满足的需求：1：我们不确切地知道为什么某些个人或种族更容易感染新冠肺炎，以及这种易感性的差异是否有遗传基础。2：SARS-Cov2是一种新病毒，所以我们没有准备好识别或管理无法预见的慢性或晚期出现的COVID-19.3：狗和猫可能是未来人畜共患病冠状病毒的宿主，但这些物种对冠状病毒的反应还不清楚。我们假设，在对兽用冠状病毒的极端反应中进行切片和全基因组测序分析，将揭示与新冠肺炎相关的新的遗传易感基因和治疗靶点。这些数据还将增加对新冠肺炎延迟并发症和未来新型人畜共患冠状病毒的准备。冠状病毒是一种高度传染性的呼吸道贝塔冠状病毒，与SARS-CoV-2有许多相似之处。在受影响的狗舍中，几乎100%的狗在暴露后21天内血清转换。许多狗没有任何症状，有些会出现“犬咳”，少数会因严重的支气管炎而被安乐死。CRCoV代表了一种自发的贝塔冠状病毒模型，它与SARS-CoV-2有许多相似之处，可以提高我们对与轻度和严重冠状病毒感染相关的遗传风险因素的理解。猫传染性腹膜炎(FIP)是一种致命的多系统炎症性疾病，发生在冠状病毒感染后数月至数年。FIP与新冠肺炎相关的儿童川崎样综合征有共同的特征。FIP是由一种常见的猫科肠道α-冠状病毒的罕见宿主内突变引起的，该病毒将其嗜性从上皮细胞改变为巨噬细胞。值得注意的是，SARS-CoV-1 S基因是一个含有FIP衍生序列的马赛克。FIP为检验冠状病毒感染的严重长期后果提供了一个极好的模型研究建议：利用来自自发性冠状病毒感染的狗和猫的独特的兽医组织档案，我们将使用全基因组测序(WGS)和RNA测序(RNA-Seq)来识别与狗和猫的兽医冠状病毒严重并发症相关的宿主遗传因素和转录事件。翻译潜力：这是一个在兽医和人类医学的界面上合作的‘同一健康’建议，所以我们理想地准备迅速翻译研究结果。

Companion animals are susceptible to coronaviruses, including SARS-CoV-2. This proposal addresses 3 important unmet needs:1: We do not know precisely why certain individuals or ethnic groups are more susceptible to COVID-19, and whether this difference in susceptiblity has a genetic basis.2: SARS-Cov2 is a novel virus, so we are poorly prepared to recognise or manage unforeseen chronic or late-presenting medical complications of COVID-19.3: Dogs and cats may act as a reservoir for future zoonotic coronaviruses, but the responses of these species to coronaviruses are poorly understood.We hypothesise that transcriptomic and whole genome sequencing analysis in extreme responses to veterinary coronaviruses will reveal reveal new genetic susceptibilty loci and treatment targets relevant to COVID-19. These data will also increase preparedness for delayed COVID-19 complications and novel future zoonotic coronaviruses.CANINE RESPIRATORY CORONAVIRUS (CRCoV) is a highly contagious respiratory beta-coronavirus sharing many parallels with SARS-CoV-2. Almost 100% of dogs sero-convert within 21 days of exposure in affected kennels. Many dogs are asymptomatic, some develop 'kennel cough' and a small number are euthanased with severe bronchopneumonia. CRCoV represents a spontaneous beta-coronavirus model which shares many parallels with SARS-CoV-2 and can improve our understanding of genetic risk factors associated with mild and severe coronavirus infections. FELINE INFECTIOUS PERITONITIS (FIP) is a fatal multi-systemic inflammatory disease, occurring months to years after coronavirus infection. FIP shares features with COVID-19 associated Kawasaki-like syndrome in children. FIP is caused by a rare, in-host, mutation of a common feline enteric alpha-coronavirus, changing its tropism from epithelial cells to macrophages. Notably, the SARS-CoV-1 S gene is a mosaic containing FIP-derived sequence. FIP offers an excellent model to examine serious long-term consequences of coronavirus infectionRESEARCH PROPOSAL: Utilising unique veterinary tissue archives from dogs and cats with spontanous coronavirus infections, we will use Whole Genome Sequencing (WGS) and RNA-Sequencing (RNA-Seq) to identify host genetic factors and transcriptomic events associated with severe complications of veterinary coronaviruses in dogs and cats. TRANSLATIONAL POTENTIAL: This is a collaborative 'One Health' proposal at the interface of veterinary and human medicine, so we are ideally poised to translate findings promptly.