Study population and setting
The study used 12 three-month old New Zealand White rabbits (Oryctolagus cuniculus) sourced from a pathogen-free farm to test the susceptibility of this species to SARS-CoV-2. Animals were confirmed to be seronegative for SARS-CoV-2 prior to the study and then split into four groups of three animals. Three groups were inoculated intranasally with either 10^4, 10^5, or 10^6 50% tissue culture infective dose (TCID50) of SARS-CoV-2 and then monitored for 4 days post-infection (DPI). Monitoring included daily observations of clinical signs, changes in body weight, and collection of swabs from the nose, throat, and rectum. Animals were then sacrificed at 4 DPI for histopathology and to test for SARS-CoV-2 RNA in nose and lung tissues. The fourth group of three animals were inoculated with 10^6 TCID50 and monitored for 21 days. Nose, throat, and rectal swabs were collected at 0, 7, 9, 11, 14, and 21 DPI and blood serum was collected at 21 DPI to test for neutralizing antibodies against SARS-CoV-2. In addition to in vivo experiments, the authors also evaluated the entry of live SARS-CoV-2 virus and pseudotyped vesicular stomatitis virus (VSV) expressing the SARS-CoV-2 spike protein into human cells expressing the ACE2 receptor from humans, rabbits, and two bat species.
Summary of Main Findings
Cell culture experiments showed that pseudotyped VSV expressing the SARS-CoV-2 spike protein and live SARS-CoV-2 virus successfully entered human cells expressing the domestic rabbit ACE2 receptor. Animals inoculated with 10^6 TCID50 and monitored for 4 DPI shed viral RNA in the nose and throat from 1-4 DPI; only one animal had a positive rectal swab at 3 DPI. After rabbits were sacrificed at 4 DPI, SARS-CoV-2 RNA was detected in nasal turbinates but not lung tissues collected during necropsy, although there were signs of pathology in some lung cells. Animals inoculated with 10^5 TCID50 shed viral RNA in the nose from 1-4 DPI and in the throat from 2-4 DPI; no viral RNA was detected in rectal swabs. No viral RNA was detected in any swabs collected from animals inoculated with 10^4 TCID50. For the animals inoculated with 10^6 TCID50 and monitored for 21 DPI, viral RNA was shed in the nose until 21 DPI, in the throat until 14 DPI, and in the rectum until 9 DPI. Infectious SARS-COV-2 virus was detected via tissue culture from nasal swabs until 7 DPI, from throat swabs only at 1 DPI, and was not detected from rectal swabs. All 3 animals with this treatment produced detectable neutralizing antibodies 21 days after inoculation. None of the inoculated animals showed any clinical signs of infection.
This study included a separate analysis of elderly populations, which is important as this is a high risk population in which immune responses are often decreased compared to younger populations.
The study only examined the susceptibility of a single breed, age, and population of domesticated rabbits. The experiment did not assess the potential of inoculated rabbits to transmit the virus to naïve rabbits. The animals were also not tested for concurrent or past infection with other coronaviruses that might affect susceptibility to infection or serological tests.
Rabbits are farmed in many countries for food and fur, so there has been concern that SARS-CoV-2 could infect farmed rabbits and spread widely, as has been seen in farmed mink. This is the first study to demonstrate the susceptibility of rabbits to SARS-CoV-2 infection.
This review was posted on: 19 February 2021