key: cord-326736-jd6fvaop authors: Bosco-Lauth, Angela M.; Hartwig, Airn E.; Porter, Stephanie M.; Gordy, Paul W.; Nehring, Mary; Byas, Alex D.; VandeWoude, Sue; Ragan, Izabela K.; Maison, Rachel M.; Bowen, Richard A. title: Pathogenesis, transmission and response to re-exposure of SARS-CoV-2 in domestic cats date: 2020-05-29 journal: bioRxiv DOI: 10.1101/2020.05.28.120998 sha: doc_id: 326736 cord_uid: jd6fvaop The pandemic caused by SARS-CoV-2 has reached nearly every country in the world with extraordinary person-to-person transmission. The most likely original source of the virus was spillover from an animal reservoir and subsequent adaptation to humans sometime during the winter of 2019 in Wuhan Province, China. Because of its genetic similarity to SARS-CoV-1, it is likely that this novel virus has a similar host range and receptor specificity. Due to concern for human-pet transmission, we investigated the susceptibility of domestic cats and dogs to infection and potential for infected cats to transmit to naïve cats. We report that cats are highly susceptible to subclinical infection, with a prolonged period of oral and nasal viral shedding that is not accompanied by clinical signs, and are capable of direct contact transmission to other cats. These studies confirm that cats are susceptible to productive SARS-CoV-2 infection, but are unlikely to develop clinical disease. Further, we document that cats develop a robust neutralizing antibody response that prevented re-infection to a second viral challenge. Conversely, we found that dogs do not shed virus following infection, but do mount an anti-viral neutralizing antibody response. There is currently no evidence that cats or dogs play a significant role in human exposure; however, reverse zoonosis is possible if infected owners expose their domestic pets during acute infection. Resistance to re-exposure holds promise that a vaccine strategy may protect cats, and by extension humans, to disease susceptibility. The first report of reverse zoonosis, or transmission from human to animal, was reported 46 from Hong Kong, where a COVID patient's dog tested PCR positive for SARS2 multiple times 47 (Sit et al. 2020 ). In following weeks, other reports of domestic pets becoming infected following Cat cohort 2 (n=4) Two of the four cats were lightly anesthetized, and challenged with SARS2 as for Cohort 1. Forty-eight hours post-infection, two naïve cats were introduced into the room with the infected 120 cats and sampled on the same schedule as before. The two directly challenge cats were 121 euthanized on 5 DPI and the following tissues collected for virus isolation and histopathology: 122 nasal turbinates, trachea, esophagus, mediastinal lymph node, lung, liver, spleen, kidney, small 123 intestine, uterus, and olfactory bulb. Tissues were collected into BA-1 frozen at -80C and 124 homogenized prior to plaque assay. Additional tissues collected for histopathology included 125 heart, colon, pancreas, hemi-lung lobe, and mesenteric lymph nodes. Thoracic radiographs were 126 also obtained for these two cats pre-challenge and just prior to euthanasia. The remaining two 127 cats were euthanized at 30 DPI and necropsied; these cats will be referred to as contact cats Step qRT-PCR system (Invitrogen), with the following modification; the initial reverse Tissues from cats were fixed in 10% buffered formalin for 12 days and transferred to 70% with their pets, there is minimal risk of a potentially exposed cat infecting another human. 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