Experimental re-infected cats do not transmit SARS-CoV-2

Gaudreault, Natasha N.; Carossino, Mariano; Morozov, Igor; Trujillo, Jessie D.; Meekins, David A.; Madden, Daniel W.; Cool, Konner; Artiaga, Bianca Libanori; McDowell, Chester; Bold, Dashzeveg; Balaraman, Velmurugan; Kwon, Taehyun; Ma, Wenjun; Henningson, Jamie; Wilson, Dennis W; Wilson, William C.; Balasuriya, Udeni B. R.; Garcı́a-Sastre, Adolfo; Richt, Jüergen A.

doi:10.1080/22221751.2021.1902753

Cited by 49 publications

(57 citation statements)

References 43 publications

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“…The case described here presents striking similarities (clinical, virological and pathological) with severe cases of COVID-19 in humans [ 33 , 35 ]. Clinically the animal presented severe progressive respiratory distress for 5–6 days and was non-responsive to supportive therapy.…”

Section: Discussionmentioning

confidence: 99%

Severe SARS-CoV-2 Infection in a Cat with Hypertrophic Cardiomyopathy

Carvallo

Martins

Joshi

et al. 2021

Viruses

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Coronavirus disease 19 (COVID-19), has claimed millions of human lives worldwide since the emergence of the zoonotic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China in December 2019. Notably, most severe and fatal SARS-CoV-2 infections in humans have been associated with underlying clinical conditions, including diabetes, hypertension and heart diseases. Here, we describe a case of severe SARS-CoV-2 infection in a domestic cat (Felis catus) that presented with hypertrophic cardiomyopathy (HCM), a chronic heart condition that has been described as a comorbidity of COVID-19 in humans and that is prevalent in domestic cats. The lung and heart of the affected cat presented clear evidence of SARS-CoV-2 replication, with histological lesions similar to those observed in humans with COVID-19 with high infectious viral loads being recovered from these organs. The study highlights the potential impact of comorbidities on the outcome of SARS-CoV-2 infection in animals and provides important information that may contribute to the development of a feline model with the potential to recapitulate the clinical outcomes of severe COVID-19 in humans.

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Section: Discussionmentioning

confidence: 99%

Severe SARS-CoV-2 Infection in a Cat with Hypertrophic Cardiomyopathy

Carvallo

Martins

Joshi

et al. 2021

Viruses

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“…The full set of signature mutations on and around the RBD of the S protein, as well as mutations in other genomic regions of SARS-CoV-2 VOC, contribute to the characteristics of each variant, and particular attention has been directed towards the roles of amino acid residues located on the S protein's RBD, due to its direct interaction with ACE2. To understand the effects of key mutations of the Alpha, Beta, and Delta VOC, we tested respective pseudotyped viruses in virus neutralization assays with convalescent human and cat (from a challenge study with the SARS-CoV-2 USA-WA1/2020 strain [72]) sera, and hyperimmune rabbit sera (immunized with baculovirus-expressed prototype parental S protein). Substitution N501Y is found in Alpha, Beta and Gamma VOC and reported to have an increased binding efficacy to human ACE2 [73].…”

Section: Discussionmentioning

confidence: 99%

Effects of Spike Mutations in SARS-CoV-2 Variants of Concern on Human or Animal ACE2-Mediated Virus Entry and Neutralization

Kim

Gaudreault

Meekins

et al. 2021

Preprint

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SARS-CoV-2 is a zoonotic agent capable of infecting humans and a wide range of animal species. Over the duration of the pandemic, mutations in the SARS-CoV-2 Spike protein (S) have arisen in circulating viral populations, culminating in the spread of several variants of concern (VOC) with varying degrees of altered virulence, transmissibility, and neutralizing antibody escape. In this study, we employed lentivirus-based pseudotyped viruses that express specific SARS-CoV-2 S protein substitutions and cell lines that stably express ACE2 from nine different animal species to gain insights into the effects of VOC mutations on viral entry and antibody neutralization capability. All animal ACE2 receptors tested, except mink, support viral cell entry for pseudoviruses expressing the parental (prototype Wuhan-1) S at levels comparable to human ACE2. Most single S substitutions (e.g., 452R, 478K, 501Y) did not significantly change virus entry, although 614G and 484K resulted in a decreased efficiency in viral entry. Conversely, combinatorial VOC substitutions in the S protein were associated with significantly increased entry capacity of pseudotyped viruses compared to that of the parental Wuhan-1 pseudotyped virus. Similarly, infection studies using live ancestral (USA-WA1/2020), Alpha, and Beta SARS-CoV-2 viruses in hamsters revealed a higher replication potential for the Beta variant compared to the ancestral prototype virus. Moreover, neutralizing titers in sera from various animal species, including humans, were significantly reduced by single substitutions of 484K or 452R, double substitutions of 501Y-484K, 452R-484K and 452R-478K and the triple substitution of 501Y-484K-417N, suggesting that 484K and 452R are particularly important for evading neutralizing antibodies in human, cat, and rabbit sera. Cumulatively, this study reveals important insights into the host range of SARS-CoV-2 and the effect of recently emergent S protein substitutions on viral entry, virus replication and antibody-mediated viral neutralization.

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“…Previous studies have shown successful infection of cats with SARS-CoV-2 via intranasal (1–3.05 × 10 5 PFU) and/or intra-oral routes (5 × 10 5 TCID 50 / mL ) and have confirmed cat-to-cat transmission through both respiratory droplets and aerosolization [ 16 , 26 , 27 , 28 ]. However, these studies failed to produce clinical signs in infected cats, and evidence of lower respiratory pathology mirroring severe COVID-19 in humans was not observed [ 16 , 26 , 27 , 28 ], potentially due to concentration of the viral inoculum and/or inoculation route. Interestingly, pulmonary disease with diffuse alveolar damage was previously documented in cats intratracheally infected with 1 × 10 6 TCID 50 SARS-CoV-1, which also resulted in efficient transmission of virus to uninfected animals [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical and Histopathologic Features of a Feline SARS-CoV-2 Infection Model Are Analogous to Acute COVID-19 in Humans

Rudd

Selvan

Cowan

et al. 2021

Viruses

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The emergence and ensuing dominance of COVID-19 on the world stage has emphasized the urgency of efficient animal models for the development of therapeutics for and assessment of immune responses to SARS-CoV-2 infection. Shortcomings of current animal models for SARS-CoV-2 include limited lower respiratory disease, divergence from clinical COVID-19 disease, and requirements for host genetic modifications to permit infection. In this study, n = 12 specific-pathogen-free domestic cats were infected intratracheally with SARS-CoV-2 to evaluate clinical disease, histopathologic lesions, and viral infection kinetics at 4 and 8 days post-inoculation; n = 6 sham-inoculated cats served as controls. Intratracheal inoculation of SARS-CoV-2 produced a significant degree of clinical disease (lethargy, fever, dyspnea, and dry cough) consistent with that observed in the early exudative phase of COVID-19. Pulmonary lesions such as diffuse alveolar damage, hyaline membrane formation, fibrin deposition, and proteinaceous exudates were also observed with SARS-CoV-2 infection, replicating lesions identified in people hospitalized with ARDS from COVID-19. A significant correlation was observed between the degree of clinical disease identified in infected cats and pulmonary lesions. Viral loads and ACE2 expression were also quantified in nasal turbinates, distal trachea, lungs, and other organs. Results of this study validate a feline model for SARS-CoV-2 infection that results in clinical disease and histopathologic lesions consistent with acute COVID-19 in humans, thus encouraging its use for future translational studies.

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Experimental re-infected cats do not transmit SARS-CoV-2

Cited by 49 publications

References 43 publications

Severe SARS-CoV-2 Infection in a Cat with Hypertrophic Cardiomyopathy

Severe SARS-CoV-2 Infection in a Cat with Hypertrophic Cardiomyopathy

Effects of Spike Mutations in SARS-CoV-2 Variants of Concern on Human or Animal ACE2-Mediated Virus Entry and Neutralization

Clinical and Histopathologic Features of a Feline SARS-CoV-2 Infection Model Are Analogous to Acute COVID-19 in Humans

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