Severe acute respiratory syndrome coronavirus-2 natural animal reservoirs and experimental models: systematic review

Abstract

The current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak has been rapidly spreading worldwide, causing serious global concern. The role that animal hosts play in disease transmission is still understudied and researchers wish to find suitable animal models for fundamental research and drug discovery. In this systematic review, we aimed to compile and discuss all articles that describe experimental or natural infections with SARS-CoV-2, from the initial discovery of the virus in December 2019 through to October 2020. We systematically searched four databases (Scopus, PubMed, Science Direct and Web of Science). The following data were extracted from the included studies: type of infection (natural or experimental), age, sample numbers, dose, route of inoculation, viral replication, detection method, clinical symptoms and transmission. Fifty-four studies were included, of which 34 were conducted on animal reservoirs (naturally or experimentally infected), and 20 involved models for testing vaccines and therapeutics. Our search revealed that Rousettus aegyptiacus (fruit bats), pangolins, felines, mink, ferrets and rabbits were all susceptible to SARS-CoV-2, while dogs were weakly susceptible and pigs, poultry, and tree shrews were not. In addition, virus replication in mice, mink, hamsters and ferrets resembled subclinical human infection, so these animals might serve as useful models for future studies to evaluate vaccines or antiviral agents and to study host-pathogen interactions. Our review comprehensively summarized current evidence on SARS-CoV-2 infection in animals and their usefulness as models for studying vaccines and antiviral drugs. Our findings may direct future studies for vaccine development, antiviral drugs and therapeutic agents to manage SARS-CoV-2-caused diseases.

Keywords: Covid-19; SARS-CoV-2; animal hosts; animal models; therapeutic agents; vaccines.

FIGURE 1

Prisma flow diagram of the systematic review study selection process. The search strategy yielded 19,012 studies. A total of 54 studies were included in the systematic review. SARS‐CoV‐2, severe acute respiratory syndrome coronavirus‐2

FIGURE 2

Characteristics of the included studies. Articles obtained from the systematic search were categorized based on the animal used in each study. Most of the studies were conducted on mice and NHPs. Fewer studies were conducted on felines, poultry, dogs, ferrets, fruit bats, minks, hamsters, pigs, rabbits, and tree shrews. Some studies included more than one animal; NHPs, non‐human primates

FIGURE 3

Representative figure of potential intermediate hosts. Bats are the natural reservoir origin of SARS‐CoV‐2. Pangolins are natural hosts of Betacoronaviruses. Metagenomic sequencing identified pangolin‐associated coronaviruses that belong to two sub‐lineages of SARS‐CoV‐2‐related coronaviruses; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus‐2

FIGURE 4

Animal host classification according to susceptibility. NHPs, hamsters, transgenic mice, felines, ferrets, minks, pangolins, and rabbits have high susceptibility, dogs have low susceptibility, while pigs, poultry, and tree shrews have no susceptibility to SARS‐CoV‐2 infection; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus‐2