Zooanthroponotic potential of SARS-CoV-2 and implications of reintroduction into human populations

Abstract

The emergence of alternate variants of SARS-CoV-2 due to ongoing adaptations in humans and following human-to-animal transmission has raised concern over the efficacy of vaccines against new variants. We describe human-to-animal transmission (zooanthroponosis) of SARS-CoV-2 and its implications for faunal virus persistence and vaccine-mediated immunity.

Keywords: SARS-CoV-2; immunity; persistence; re-emergence; zooanthroponosis.

Figure 1

Zooanthroponotic transmission of SARS-CoV-2 Bidirectional transmission of SARS-CoV-2 between humans and animals raises important questions about surveillance of susceptible animal species and virus persistence in alternate animal reservoirs. (A) Proposed hierarchical system to prioritize selected animal species for SARS-CoV-2 surveillance based on receptor homology, detection of virus infection, likelihood of animal-human interaction, and risk of animal-to-human transmission of the virus. A hypothetical phylogenetic tree is used to indicate mammalian species. Degree of ACE2 homology with human ACE2 sequence was extracted from recent data (Banerjee et al., 2020), and the heatmap indicates the range of percentages that constitute low, medium, and high ACE2 amino acid homology with the human ortholog. High-contact scenarios represent anthropogenic behavior that facilitates animal-human contact such as domestication and farming. High-risk species represent selected animal species, such as domestic cats, that are likely to be over-represented in high-contact scenarios. High-risk areas constitute environmental settings that would facilitate increased human-animal contact, such as zoos and wildlife conservation areas. (B) SARS-CoV-2 can infect and replicate in cats, non-human primates, hamsters, ferrets, minks, and monkeys. There are likely other susceptible mammals that have not been discovered yet (indicated by ?). Thus, the risk of animal-to-human transmission of SARS-CoV-2 exists from all susceptible animal species. Virus-host interaction in susceptible species will dictate the long-term infection status of these animals, which could play out in three different ways. Scenario I: limiting short-term infection with long-term protective immunity and low chances of virus persistence. In this scenario, infected animals would pose a short-term risk of infecting humans when viremic. Scenario II: short-term viremia followed by a short period of immunity, which would allow the virus to infect members of an animal species in “waves” as immunity wanes in individuals. This would allow the virus to persist in susceptible animal species at the population level, thus creating long-term risks of virus evolution and re-emergence. Scenario III: latent SARS-CoV-2 infection in susceptible animal species. The virus may emerge from these animals when immunity wanes. This scenario would enable SARS-CoV-2 to evolve and persist at both individual and population levels in susceptible animals, posing a high risk of re-emergence to infect humans.

Figure 2

Implications of back and forth human-to-animal and animal-to-human transmission of SARS-CoV-2 As SARS-CoV-2 spreads from humans to susceptible animals via zooanthroponosis, the virus may undergo adaptive evolution in the animal host. Mutations within the spike protein of SARS-CoV-2 will determine the likelihood of animal-to-human transmission followed by human-to-human transmission of the animal-adapted variant of SARS-CoV-2. The animal-adapted SARS-CoV-2 will pose no health risk to humans if the altered spike protein can no longer interact with the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) (A). Similarly, if SARS-CoV-2 spike antibodies, either from natural infection or vaccination, can bind to the animal-adapted SARS-CoV-2 spike, there would be no risk of significant disease in an exposed individual and low chances of human-to-human spread of the new virus (C). If the animal-adapted SARS-CoV-2 spike protein is able to bind to human ACE2 (B), the outcome could include enhanced virus transmission and pathogenicity. Alternately, the virus could enter human cells but cause mild to no disease, depending on the overall changes within the genome of the animal-adapted virus. Changes within the spike protein of the animal-adapted SARS-CoV-2 could also affect antibody binding, resulting in the loss of antibody-mediated immunity from vaccination or a previous exposure to SARS-CoV-2 (D).