COVID 19: LESSONS FROM FATAL CORONAVIRUS INFECTIONS IN COMPANION ANIMALS

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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.