Potential zoonotic sources of SARS-CoV-2 infections

Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing coronavirus disease-2019 (COVID-19) likely has evolutionary origins in other animals than humans based on genetically related viruses existing in rhinolophid bats and pangolins. Similar to other animal coronaviruses, SARS-CoV-2 contains a functional furin cleavage site in its spike protein, which may broaden the SARS-CoV-2 host range and affect pathogenesis. Whether ongoing zoonotic infections are possible in addition to efficient human-to-human transmission remains unclear. In contrast, human-to-animal transmission can occur based on evidence provided from natural and experimental settings. Carnivores, including domestic cats, ferrets and minks, appear to be particularly susceptible to SARS-CoV-2 in contrast to poultry and other animals reared as livestock such as cattle and swine. Epidemiologic evidence supported by genomic sequencing corroborated mink-to-human transmission events in farm settings. Airborne transmission of SARS-CoV-2 between experimentally infected cats additionally substantiates the possibility of cat-to-human transmission. To evaluate the COVID-19 risk represented by domestic and farmed carnivores, experimental assessments should include surveillance and health assessment of domestic and farmed carnivores, characterization of the immune interplay between SARS-CoV-2 and carnivore coronaviruses, determination of the SARS-CoV-2 host range beyond carnivores and identification of human risk groups such as veterinarians and farm workers. Strategies to mitigate the risk of zoonotic SARS-CoV-2 infections may have to be developed in a One Health framework and non-pharmaceutical interventions may have to consider free-roaming animals and the animal farming industry.

Keywords: COVID-19; SARS-CoV-2; carnivore; coronavirus; domestic animal; farmed animal.

Figure 1

Mammals as reservoirs and intermediary hosts of endemic and emerging human coronaviruses. (a) Animal reservoirs and intermediary hosts of human coronaviruses. (b) Cladogram of mammalian orders adapted from (Foley et al., 2016). Hosts of coronaviruses are depicted by pictograms (teal). Squares depict families susceptible to SARS‐CoV (orange), SARS‐CoV‐2 (purple) and other SARS‐related CoVs (grey) [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 2

Mammalian hosts of coronaviruses. (a) Large diversity of bat‐associated SARS‐related CoVs in comparison to other hosts. The phylogeny was constructed with 77 SARS‐related CoV full‐length genomes using a neighbour‐joining method with 1,000 bootstrap replicates. Circles at nodes indicate bootstrap values ≥75%. Scale bar indicates nucleotide substitutions per site. (b) High divergence of bat SARS‐related CoVs in comparison with viruses infecting pangolin, civet and human hosts. P‐distance within SARS‐related CoVs in each host. The human SARS‐CoV‐2 and SARS‐CoV genomes included all sequences found in GenBank as of 16.04.2020, excluding identical genomes. GenBank accession numbers of all other genomes used in panel A and B: Bat SARS‐related CoVs: MN996532, MG772934, MG772933, KY938558, KU182964, KJ473811, KY770860, KJ473813, KJ473812, DQ412042, KY770859, KY770858, BKJ473816, KY417145, KF294455, DQ071615, KY417152, KY417151, KF367457, KC881006, KC881005, KY417144, KY417150, KT444582, KY417146, KY417149, KY417143, FJ588686, KY417148, KY417147, KP886809, KP886808, KJ473815, KU973692, KF569996, KJ473814, DQ648857, DQ412043, JX993987, KF294457, GQ153548, GQ153546, GQ153545, GQ153544, GQ153541, GQ153539, GQ153540, DQ084199, DQ084200, DQ022305, GQ153547, GQ153543, GQ153542, KY352407, GU190215; Human SARS‐CoV‐2: MN908947; Human SARS‐CoV: AY568539, AY390556; Civet SARS‐CoV: AY572034, AY572035, AY686863, AY686864, AY304486, AY304488, AY572038, AY686864, AY613948, AY613949, AY613950; and Pangolin SARS‐related CoVs: MT121216, MT040335, MT072865, MT072864, MT040336, MT040334, MT040333 [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 3

Susceptibility of carnivore hosts to coronaviruses (a) Carnivores susceptible to SARS‐related CoVs are dispersed across the family tree. Cladogram of carnivore families adapted from (Foley et al., 2016). (b) Furin cleavage site between the spike subunits S1 and S2 is predominantly present in betacoronaviruses. Scheme of SARS‐CoV‐2 genome organization with a magnified S1/S2 furin cleavage site within carnivore and human coronaviruses . Functional cleavage sites are highlighted with coloured ‘R S’ (orange and teal). Maximum‐likelihood tree of human and carnivore coronaviruses showing grouping of cat (green), dog (purple) and mustelid (grey) CoVs with human CoVs based on translated spike amino acid sequences. WAG + G + I was used as a substitution model and a complete deletion option was chosen. Scale bar indicates amino acid substitutions per site. Circle at nodes indicate bootstrap values ≥75% (1,000 bootstrap replicates). GenBank accession numbers: YP_004070194, AFG19726, AKZ66476, YP009256197, ADI80513, ACT10854, AEQ61968, YP_003767, NP_073551, AAR01015, AQT26498, YP_173238, YP_009047204, QHU36864, ACB69905 [Colour figure can be viewed at wileyonlinelibrary.com]