Experimental infection of domestic dogs and cats with SARS-CoV-2: Pathogenesis, transmission, and response to reexposure in cats

Abstract

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (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 probable 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 naive cats. We report that cats are highly susceptible to 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 developed a robust neutralizing antibody response that prevented reinfection following a second viral challenge. Conversely, we found that dogs do not shed virus following infection but do seroconvert and mount an antiviral neutralizing antibody response. There is currently no evidence that cats or dogs play a significant role in human infection; however, reverse zoonosis is possible if infected owners expose their domestic pets to the virus during acute infection. Resistance to reinfection holds promise that a vaccine strategy may protect cats and, by extension, humans.

Keywords: SARS-CoV-2; cats; experimental infection; transmission.

Fig. 1.

Inoculation and exposure with SARS-CoV-2 leads to nasal and oropharnygeal shedding in cats. SARS-CoV-2 virus is detected by plaque assay from (A) nasal and (B) oropharyngeal secretions of cats 1–5 DPI. Viral titers expressed as log₁₀ pfu/mL. Cats 1, 2, and 3 represent cohort 1. Cats 4, 5, 6, and 7 represent cohort 2. Cats 4 and 5 were euthanized on 5 DPI. Cats 6 and 7 were introduced to the infected cats in cohort 2 on 2 DPI.

Fig. 2.

SARS-CoV-2 exposure results in acute upper respiratory inflammation and mild lung infiltrates during later courses of infection. (A) Cat 4, cohort 2, trachea 5 DPI. The submucosa is expanded by edema (arrows) and abundant lymphocytic inflammatory infiltrates (asterisks) which dissect and disrupt submucosal glands. H&E stain, 100× magnification. (B) Cat 5, cohort 2, nasal turbinates, 5 DPI. Normal thickness respiratory mucosa is present in the section (open arrow). Nasal respiratory epithelium ranges from hyperplastic (filled black arrow) to ulcerated (arrowhead). The submucosa in regions of ulceration is edematous and infiltrated by scattered neutrophils and mononuclear cells. H&E stain, 40× magnification. (C) Cat 5, cohort 2, nasal turbinates, 5 DPI. Nasal respiratory epithelium ranges from attenuated (arrow) to ulcerated (arrowhead) with overlying remnant cellular debris. The submucosa (asterisk) in regions of ulceration is edematous and infiltrated by scattered neutrophils and mononuclear cells. H&E stain, 100× magnification. (D) Cat 1, cohort 1, lung, 42 DPI. Alveolar spaces (“A”) contain scattered mononuclear cells (arrows). The alveolar wall is expanded by mixtures of mononuclear cells and occasional neutrophils (asterisk). H&E stain, 400× magnification.

Fig. 3.

Cats and dogs infected with SARS-CoV-2 rapidly develop antibodies against viral antigens. (A) Sera from cats with intranasal inoculation of SARS-CoV-2 (n = 3, ‘EI’) or exposed to inoculated cats (n = 2, ‘C’) were evaluated for seroreactivity to RBD, Spike, or NP for 30–42 d post exposure. IgG reactivity to Spike and RBD was evident at day 7, and all animals had clearly seroconverted by day 14. (B) IgM against RBD was transiently detected at low levels relative to IgG on days 7 and 14 post exposure in cats (experimentally inoculated animals, n = 3). Bars represent 1 SE of the mean. Dogs infected with SARS-CoV-2 seroconvert versus Spike and RBD antigen with lower reactivity than cats (C). Sera tested on days indicated. IgG reactivity was evident by day 14 but plateaued and/or waned by day 42. Dashed lines indicate cut off values for seropositive diagnosis. Colors correspond to RBD (red), Spike (blue), or Nucleocapsid (green) ELISAs.