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Event: 1939

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Viral infection and host-to-host transmission, proliferated

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Viral infection, proliferated
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Individual

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
viral release from host cell increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
SARS-CoV-2 leads to infection proliferation AdverseOutcome Sally Mayasich (send email) Under development: Not open for comment. Do not cite Under Development

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
human Homo sapiens High NCBI
cat Felis catus High NCBI
rhesus macaque Macaca mulatta High NCBI
Nyctereutes procyonoides Nyctereutes procyonoides High NCBI
Odocoileus virginianus texanus Odocoileus virginianus texanus High NCBI
mink Mustela lutreola High NCBI
Vulpes vulpes Vulpes vulpes Moderate NCBI
Golden hamsters Mesocricetus auratus High NCBI
ferret Mustela putorius furo Moderate NCBI
Tupaia belangeri chinensis Tupaia chinensis High NCBI
Peromyscus maniculatus bairdii Peromyscus maniculatus bairdii High NCBI
Mephitis mephitis Mephitis mephitis High NCBI
Neotoma cinerea Neotoma cinerea High NCBI
Oryctolagus cuniculus Oryctolagus cuniculus High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
All life stages High

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Unspecific High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Much is now understood in terms of human-to-human COVID-19 transmission. Coronaviruses, as with many other respiratory viruses, are transmitted primarily through respiratory droplets, but can also spread through aerosols, fecal-oral transmission, or contact with contaminated surfaces (Harrison et al. 2020). Respiratory droplets and aerosols containing the virus are generated through an infected person coughing, sneezing or talking, and enter the secondary host system through upper and lower respiratory tissues, with the lung being the primary tropism. Barriers to transmission in place worldwide include social distancing, face shields, cloth masks, frequent hand washing, and surface disinfection (Harrison et al. 2020). 

Widespread testing and contact tracing were later instituted, and more effective (medical-grade) masks also became available (Fritz et al., 2023). Fritz et al. (2023) determined that the most effective control measure in reducing COVID-19 spread is a comprehensive testing strategy, until vaccination levels can establish herd immunity.

Vaccination is the standard strategy for reducing or eliminating viral disease transmission, symptoms, and mortality in humans, and in some cases domesticated animals. COVID-19 vaccines were developed using mRNA technology to deliver the viral spike protein sequence against which the host would develop antibodies. The first to gain Emergency Use Authorization from the U.S. Food and Drug Administration (FDA) were the Pfizer-BioNTech (BNT162b2) and Moderna vaccines in December 2020 (Katella, 2023). The effectiveness of the vaccines is monitored by the U.S. Centers for Disease Control (CDC, 2023) with criteria as follows:

  • Hospitalization for COVID-19 or medically attended COVID-19 (e.g., emergency department visits)
  • Death due to COVID-19
  • Post-COVID Conditions and multisystem inflammatory syndrome (MIS)
  • Symptomatic SARS-CoV-2 infection

Prevention of transmission is not part of this monitoring program, however, recent studies have estimated vaccination effect on transmission of the SARS-CoV-2 alpha and delta variants. Vaccines BNT162b2 and ChAdOx1 nCoV-19 (a vaccine developed at Oxford University, England, using an adenoviral vector) were found to be less effective in preventing transmission than preventing serious disease outcomes. Variation in polymerase chain reaction (PCR) cycle-threshold (Ct) values in index patients, which indicate viral load, explained 7 to 23% of vaccine-associated reductions in index-to-secondary patient transmission for the two variants (Eyre et al., 2022). This means viral load was not the only factor in transmission, and other factors associated with positive PCR tests in contacts included the type of exposure between patients and contacts and the age of the index patient. The highest rates of PCR positivity were seen after household exposures of index patients at least 40 years old compared with exposures at the workplace, educational facilities, or events (Eyre et al., 2022). Braeye et al. (2023) in a 2020-21 Belgian contact tracing study showed vaccine effectiveness against transmission (VET) for BNT162b2 for primary vaccination at 96% against Alpha, 87% against Delta and 31% against Omicron. A booster elevated protection against Omicron to 68%, but 150–200 days after booster-vaccination protection waned somewhat for Delta to 71% and for Omicron to 55% (Braeye et al., 2023).

Different control measures will be required to prevent future spillover from the reservoir species (bats in the case of betacoronaviruses) and potential intermediate host species. Indeed, the original intermediate host of the SARS-CoV-2 virus has yet to be identified (Delahay et al. 2021). However, Wuhan, China, was the epicenter of the SARS-CoV-2 pandemic, and Worobey et al. (2022) reported that live animals, many of which proved to be susceptible to the virus, were sold at the Huanan Wholesale Market in Wuhan in late 2019. Worobey et al. (2022) found SARS-CoV-2-positive environmental samples associated with the spaces where the live animals were housed. These animals included raccoon dogs and red foxes (species shown to transmit the virus; Table 1), and other species related to known transmitters like the mink (members of the Mustelidae family including the Asian badger and hog badger).

This key event is therefore focused primarily on the species of potential concern, exposure and transmission routes across species, and the conditions indicative of or conducive toward cross-species spillover of zoonoses or infectious viral diseases of animal origin.

Species of Potential Concern

The reservoir host for SARS-CoV-2-like viruses is believed to be the bat. See Table 1 below for species known to transmit SARS-CoV-2.

Exposure and Transmission Routes

SARS-CoV-2-infected media (respiratory droplets, bodily fluids, tissues, feces): Exposure routes are the pathway into the body of the virus shed from an infected reservoir host animal to the intermediate host, or either type of host animal to humans. These routes may include inhalation, oral, or through broken skin or mucosal membranes (e.g., eyes, nostrils) after touching contaminated media or surfaces and then touching the face (Harrison et al. 2020). Animals may transfer saliva or nasal discharge directly through facial contact, licking or biting. Transmission occurs through these routes when the virus reaches a tissue with cells that allow entry and replication.

Spillover Conditions

Conditions that allow for exposure and transmission across species:

  • Close proximity of animal communities (bats to potential intermediate hosts; wildlife to domestic animal farms).
  • Direct human contact with wildlife (Kreuder Johnson et al. 2015), including:
    • Zoos, wildlife farms, domesticated animal farms, feeding and animal care;
    • Hunting and dressing wild game;
    • Cleaning of storage buildings, barns, or other structures that may be used by wildlife for shelter, breeding, or feeding, with potential for feces or other contamination (CDC, 2021);
    • Wet markets where live animals or bush meat are traded;
    • Research facilities that express viruses from wild samples in cell culture, that house potential host species, or that collect and store bodily fluid or tissue samples.
  • Virus isolated from animal species shows genomic similarity to the human virus, but also high host plasticity to be capable of cross-species viral immune evasion and replication (Kreuder Johnson et al. 2015).
  • Spillover species and new host species share genetic similarity in the components of the cell entry, immune system and replication machinery (Warren et al. 2019). That is, the virus can enter the cell and evade the virus detection and immediate systemic type I interferon (IFN) response to allow replication and generation of viral load in both species. The viral proteins must be capable of interacting with the appropriate cellular proteins in either species. The most studied and considered indicative of infectability is the ACE2 and other cell entry proteins.

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Either the virus or antibodies can be detected with available tests. Active infection can be detected through PCR tests from nasal swab, oropharyngeal swab, rectal swab or saliva samples that indicate the quantity and/or presence of the virus. Antibodies can be detected in blood using various assays including immunofluorescence.

ELISA, Indirect immunofluorescence assay (IIFA) for antibodies (Schlottau et al. 2020; Freuling et al. 2020)

Virus neutralization test (VNT) for antibodies (Schlottau et al. 2020; Freuling et al. 2020)

Quantitative reverse transcription PCR (qRT-PCR) for viral load (log10 genome copies) (Freuling et al. 2020)

Titration (Tissue culture infectious dose where 50% of infected cells display cytopathic effect [TCID50 assay]: levels of infectious virus, or viral titre) (Freuling et al. 2020)

Virus-specific immunoglobulin characterization (Freuling et al. 2020)

SARS-CoV-2 spike protein neutralizing antibodies in saliva from animals that developed serum antibodies (Freuling et al. 2020)

Serum sample, autopsy, histopathology for tissue lesions (Schlottau et al. 2020; Freuling et al. 2020)

Viral whole genome sequencing (Kuchipudi et al., 2022)

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Life Stage and Sex. Viral load was not influenced by age or sex according to Challenger et al. (2022), however more recently Hughes et al. (2023) found wild-type- or Alpha-infected children 5–11-years old had lower viral loads than adults based on PCR cycles, so might transmit less than adults, but smaller differences in viral loads with age were observed in Delta infections. In terms of sex, infection rate and viral load were found not to differ (Arnold et al., 2022; Qi et al., 2021; Cheemarla et al., 2021).

Taxonomic. No non-mammalian vertebrates have been found to become infected with SARS-CoV-2. Many mammals have tested positive according to PCR tests for viral RNA and antibody test evidence (see compilation by EFSA/Nielson et al, 2023). However, some that have tested positive for RNA or antibodies were determined not to transmit or shed the virus. These include Cattle (Bos taurus; Ulrich et al., 2020), bank vole (Myodes glareolus; Ulrich et al., 2021), and domestic dogs (Canis lupus familiaris; Bosco-Lauth, Hartwig et al., 2021). Several experimentally exposed species did not become infected and hence, did not shed the virus, including coyote (Canis latrans; Porter et al., 2022), pig (Sus scrofa; Schlottau et al., 2020), and in one study by Bosco-Lauth, Root et al. (2021) the house mouse (Mus musculus), Wyoming ground squirrel (Urocitellus elegans), fox squirrel (Sciurus niger), black-tailed prairie dog (Cynomys ludovicianus), raccoon (Procyon lotor), and cottontail rabbits (Sylvilagus sp.).

Studies in which animals experimentally inoculated or naturally infected were tested for viral shedding and found to transmit the original Wuhan virus include Primates and species in Table 1.

Table 1. Species that transmit or shed infectious SARS-CoV-2 virus.

 

Common name

Species

References

White-tailed deer

Odocoileus virginianus texanus

Cool, 2022; Palmer, 2021; Martins, 2022; Chandler, 2021; Kuchipudi, 2022; Pickering, 2022; McBride, 2023

Cat

Felis catus

Bosco-Lauth, Hartwig, et al. 2021

European (NZ white) rabbit

Oryctolagus cuniculus

Myktykyn, 2021

Golden (Syrian) hamster

Mesocricetus auratus

Sia, 2020; Hoagland, 2021

Raccoon dog

Nyctereutes procyonoides

Freuling 2020

European mink

Mustela lutreola

Oude Munnink, 2020; Mastutik, 2022; Fenollar, 2021; Molenaar 2022

American mink

Neovison vison

Ip, 2021; Harrington, 2021

Striped skunk

Mephitis mephitis

Bosco-Lauth, Root, et al. 2021

Deer mouse

Peromyscus maniculatus bairdii

Bosco-Lauth, Root, et al. 2021

Bushy-tailed wood rat

Neotoma cinerea

Bosco-Lauth, Root, et al. 2021

Tree shrew

Tupaia belangeris

Zhao 2020

Ferret

Mustela putorius furo

Schlottau 2020; Kim, 2020

Red fox

Vulpes vulpes

Porter, 2022, Yes/Jemersic, 2021, No

       

An example of a study of infection and transmission was conducted among raccoon dogs (Freuling et al., 2020). Nine naive animals received intranasal inoculations with 105 50% tissue culture infectious dose (TCID50) SARS-CoV-2 2019_nCoV Muc-IMB-1, and 3 naive animals were introduced in cages separated from the inoculated animals by meshed wire 24 hours after inoculation. Six inoculated and two contact animals became infected; none showed clinical symptoms. Viral RNA was measured by qPCR in nasal, oropharyngeal, and rectal swab samples collected on days 2, 4, 8, 12, 16, 21, and 28, and the levels of infectious virus was determined by titration on Vero E6 cells. The inoculated animals shed virus in nasal and oropharyngeal swab samples on days 2–4. The mean viral genome load was highest for nasal swab samples at 3.2 (range 1.0–6.45) log10 genome copies/mL, and nasal swab viral titers peaked at 4.125 log10 TCID50/mL on day 2. Viral RNA was first detected in a contact animal 7 days after contact (Freuling et al., 2020).

Early in the pandemic, mink farms were found to be hotspots of non-human COVID-19 spread in both Europe and North America (Fenollar et al., 2021). In the Netherlands, Oude Munnink et al., (2020) showed that the virus was initially introduced from humans working or living at the farms and mutated through widespread circulation among mink. They also documented the first transmission from the mink back to humans (Oude Munnink et al., 2020). Ip et al. (2021) surveyed coronavirus-infected animals in Utah, USA, near mink farms affected by a SARS-CoV-2 outbreak. They suggest that mink farms could be potential hot spots for coronavirus spillover. According to Harrington et al., (2020), wild American minks (Neovison vison) are also a concern for the spread and mutation of SARS-CoV-2, considering their broad native range in North America and introduced range (via escape from farms) across Eurasia and southern South America.

Several researchers have reported wide-spread infection and transmission among wild and captive white-tailed deer:

  • Palmer et al. (2021) conducted intranasal inoculations of deer fawns with SARS-CoV-2, resulting in infection and shedding of infectious virus in nasal secretions. The infected animals were found to transmit the virus to contact deer.
  • Chandler et al., (2021) conducted SARS-CoV-2 tests on 624 serum samples taken before and during the pandemic from wild deer in the US states of Michigan, Illinois, Pennsylvania, and New York. Antibodies were detected in 152 samples (40%) from 2021, 3 samples from 2020, and one sample from 2019, but all 2011-2018 samples were negative.
  • Martins, et al., 2022 found that white-tailed deer fawns shed infectious virus in nasal and oral secretions up to 5 days after intranasal inoculation with SARS-CoV-2 B.1 lineage, with deer-to-deer transmission occurring on day 3 post-inoculation. Contact animals added on days 6 and 9 did not become infected. Multiple sites of virus replication were revealed in adults, as infectious virus was detected up to 6 days after inoculation in nasal secretions, and respiratory-, lymphoid-, and central nervous system tissues.
  • Cool, et al., 2022 investigated transmission in adult white-tailed deer co-infected with both the SARS-CoV-2 ancestral lineage A and the alpha variant of concern (VOC) B.1.1.7. Presence and transmission of each strain was determined using next-generation sequencing, with the finding that the alpha VOC B.1.1.7 isolate outcompeted ancestral lineage A. They found direct contact transmission and also vertical transmission from doe to fetus.
  • Kuchipudi et al., 2022 tested for the presence of SARS-CoV-2 RNA by RT-PCR in 283 retropharyngeal lymph node (RPLN) samples from 151 free-living and 132 captive deer in Iowa from April 2020 through January of 2021, with positive results in 94 (33.2%) of the 283 samples. Over a 7-wk period during the peak deer hunting season, SARS-CoV-2 RNA was detected in 80 of 97 (82.5%) RPLN samples. Whole genome sequencing revealed presence of 12 SARS-CoV-2 lineages with two B lineages accounting for 75% of samples. The results suggest multiple human-to-deer transmission events followed by deer-to-deer spread.
  • Pickering et al. (2022) identified a new and highly divergent lineage of SARS-CoV-2 with 76 consensus mutations including 37 previously associated with non-human animal hosts, and evidence of host adaptation under neutral selection. They also provide the first evidence of a SARS-CoV-2 deer-to-human transmission, indicating that a high divergent mutated strain can be generated in deer and transmitted back to humans.
  • McBride et al., (2023) found that SARS-CoV-2 was introduced from humans into white-tailed deer more than 30 times in Ohio, USA November 2021-March 2022. Transmission within deer populations continued for 2–8 months and over an area covering hundreds of kilometers. They also found SARS-CoV-2 evolution to be three-times faster in white-tailed deer, with different mutational biases and selection pressures compared to humans.

The deer’s susceptibility is in contrast to more resistant species in the Order Artiodactyla including pigs, cattle, and horses. More than 600 race horses in California were tested through 2020 for viral presence in nasal secretions (qPCR) and serum antibodies (ELISA), with 0% positive qPCR tests and 5.9% positive for serum antibodies to SARS-CoV-2  (Lawton et al., 2022). Also note that in the Family Canidae, raccoon dogs and red foxes may transmit the original Wuhan SARS-CoV-2 strain while domestic dogs and coyotes do not, therefore taxonomic relatedness is not necessarily a predictor of infection and transmission. Early in the pandemic, cross-species similarity in the viral entry receptor angiotensin converting enzyme 2 (ACE2) protein sequence to the human ACE2 sequence was studied as a predictor of potential infectability (Damas et al., 2020). However, empirical evidence has shown that some species with low ACE2 similarity, such as the mink, are highly susceptible. While other factors including the type I interferon (IFN-I) pathway proteins are being studied for predictive potential, empirical testing is currently the most reliable method of determining species susceptibility to infection, and more studies are needed to determine which species may be capable of transmitting the virus.

Regulatory Significance of the Adverse Outcome

An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help

There is currently no regulatory guidance for host-to-host transmission of SARS-CoV-2, however mask mandates and institutional controls have been used during the pandemic, and in most countries vaccination is voluntary. The information in this AOP could aid in identification of effective control strategies. With regard to SARS-CoV-2 and other zoonotic disease threats, this AOP points out that more cross-species studies on immune systems are needed to guide which species should be monitored, and need to regulate domestic animal and wildlife trade to avoid future pandemics.

References

List of the literature that was cited for this KE description. More help

Arnold, C. G., Libby, A., Vest, A., Hopkinson, A., & Monte, A. A. (2022). Immune mechanisms associated with sex-based differences in severe COVID-19 clinical outcomes. Biology of Sex Differences, 13(1), 7. https://doi.org/10.1186/s13293-022-00417-3

Bosco-Lauth, A. M., Hartwig, A. E., Porter, S. M., Gordy, P. W., Nehring, M., Byas, A. D., VandeWoude, S., Ragan, I. K., Maison, R. M., & Bowen, R. A. (2020). Experimental infection of domestic dogs and cats with SARS-CoV-2: Pathogenesis, transmission, and response to reexposure in cats. Proceedings of the National Academy of Sciences, 117(42), 26382–26388. https://doi.org/10.1073/pnas.2013102117

Bosco-Lauth, A. M., Root, J. J., Porter, S. M., Walker, A. E., Guilbert, L., Hawvermale, D., Pepper, A., Maison, R. M., Hartwig, A. E., Gordy, P., Bielefeldt-Ohmann, H., & Bowen, R. A. (2021). Peridomestic Mammal Susceptibility to Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Emerging Infectious Diseases, 27(8), 2073–2080. https://doi.org/10.3201/eid2708.210180

Braeye, T., Catteau, L., Brondeel, R., Van Loenhout, J. A. F., Proesmans, K., Cornelissen, L., Van Oyen, H., Stouten, V., Hubin, P., Billuart, M., Djiena, A., Mahieu, R., Hammami, N., Van Cauteren, D., & Wyndham-Thomas, C. (2023). Vaccine effectiveness against transmission of alpha, delta and omicron SARS-COV-2-infection, Belgian contact tracing, 2021–2022. Vaccine, 41(20), 3292–3300. https://doi.org/10.1016/j.vaccine.2023.03.069

CDC, 2021. https://www.cdc.gov/hantavirus/hps/transmission.html

CDC, 2023. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/effectiveness/how-they-work.html

Challenger, J. D., Foo, C. Y., Wu, Y., Yan, A. W. C., Marjaneh, M. M., Liew, F., Thwaites, R. S., Okell, L. C., & Cunnington, A. J. (2022). Modelling upper respiratory viral load dynamics of SARS-CoV-2. BMC Medicine, 20(1), 25. https://doi.org/10.1186/s12916-021-02220-0

Chandler, J. C., Bevins, S. N., Ellis, J. W., Linder, T. J., Tell, R. M., Jenkins-Moore, M., Root, J. J., Lenoch, J. B., Robbe-Austerman, S., DeLiberto, T. J., Gidlewski, T., Kim Torchetti, M., & Shriner, S. A. (2021). SARS-CoV-2 exposure in wild white-tailed deer ( Odocoileus virginianus ). Proceedings of the National Academy of Sciences, 118(47), e2114828118. https://doi.org/10.1073/pnas.2114828118

Cheemarla, N. R., Watkins, T. A., Mihaylova, V. T., Wang, B., Zhao, D., Wang, G., Landry, M. L., & Foxman, E. F. (2021). Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics. Journal of Experimental Medicine, 218(8), e20210583. https://doi.org/10.1084/jem.20210583

Conceicao, C., Thakur, N., Human, S., Kelly, J. T., Logan, L., Bialy, D., Bhat, S., Stevenson-Leggett, P., Zagrajek, A. K., Hollinghurst, P., Varga, M., Tsirigoti, C., Tully, M., Chiu, C., Moffat, K., Silesian, A. P., Hammond, J. A., Maier, H. J., Bickerton, E., … Bailey, D. (2020). The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins. PLOS Biology, 18(12), e3001016. https://doi.org/10.1371/journal.pbio.3001016

Cool, K., Gaudreault, N. N., Morozov, I., Trujillo, J. D., Meekins, D. A., McDowell, C., Carossino, M., Bold, D., Mitzel, D., Kwon, T., Balaraman, V., Madden, D. W., Artiaga, B. L., Pogranichniy, R. M., Roman-Sosa, G., Henningson, J., Wilson, W. C., Balasuriya, U. B. R., García-Sastre, A., & Richt, J. A. (2022). Infection and transmission of ancestral SARS-CoV-2 and its alpha variant in pregnant white-tailed deer. Emerging Microbes & Infections, 11(1), 95–112. https://doi.org/10.1080/22221751.2021.2012528

Damas, J., Hughes, G. M., Keough, K. C., Painter, C. A., Persky, N. S., Corbo, M., Hiller, M., Koepfli, K.-P., Pfenning, A. R., Zhao, H., Genereux, D. P., Swofford, R., Pollard, K. S., Ryder, O. A., Nweeia, M. T., Lindblad-Toh, K., Teeling, E. C., Karlsson, E. K., & Lewin, H. A. (2020). Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates. Proceedings of the National Academy of Sciences, 117(36), 22311–22322. https://doi.org/10.1073/pnas.2010146117

Delahay, R. J., De La Fuente, J., Smith, G. C., Sharun, K., Snary, E. L., Flores Girón, L., Nziza, J., Fooks, A. R., Brookes, S. M., Lean, F. Z. X., Breed, A. C., & Gortazar, C. (2021). Assessing the risks of SARS-CoV-2 in wildlife. One Health Outlook, 3(1), 7. https://doi.org/10.1186/s42522-021-00039-6

EFSA Panel on Animal Health and Welfare (AHAW), Nielsen, S. S., Alvarez, J., Bicout, D. J., Calistri, P., Canali, E., Drewe, J. A., Garin‐Bastuji, B., Gonzales Rojas, J. L., Gortázar, C., Herskin, M., Michel, V., Miranda Chueca, M. Á., Padalino, B., Pasquali, P., Roberts, H. C., Spoolder, H., Velarde, A., Viltrop, A., … Ståhl, K. (2023). SARS‐CoV‐2 in animals: Susceptibility of animal species, risk for animal and public health, monitoring, prevention and control. EFSA Journal, 21(2). https://doi.org/10.2903/j.efsa.2023.7822

Eyre, D. W., Taylor, D., Purver, M., Chapman, D., Fowler, T., Pouwels, K. B., Walker, A. S., & Peto, T. E. A. (2022). Effect of Covid-19 Vaccination on Transmission of Alpha and Delta Variants. New England Journal of Medicine, 386(8), 744–756. https://doi.org/10.1056/NEJMoa2116597

Fenollar, F., Mediannikov, O., Maurin, M., Devaux, C., Colson, P., Levasseur, A., Fournier, P.-E., & Raoult, D. (2021). Mink, SARS-CoV-2, and the Human-Animal Interface. Frontiers in Microbiology, 12, 663815. https://doi.org/10.3389/fmicb.2021.663815

Freuling, C. M., Breithaupt, A., Müller, T., Sehl, J., Balkema-Buschmann, A., Rissmann, M., Klein, A., Wylezich, C., Höper, D., Wernike, K., Aebischer, A., Hoffmann, D., Friedrichs, V., Dorhoi, A., Groschup, M. H., Beer, M., & Mettenleiter, T. C. (2020). Susceptibility of Raccoon Dogs for Experimental SARS-CoV-2 Infection. Emerging Infectious Diseases, 26(12), 2982–2985. https://doi.org/10.3201/eid2612.203733

Fritz, M., Gries, T., & Redlin, M. (2023). The effectiveness of vaccination, testing, and lockdown strategies against COVID-19. International Journal of Health Economics and Management, 23(4), 585–607. https://doi.org/10.1007/s10754-023-09352-1

Harrington, L. A., Díez‐León, M., Gómez, A., Harrington, A., Macdonald, D. W., Maran, T., Põdra, M., & Roy, S. (2021). Wild American mink ( Neovison vison ) may pose a COVID‐19 threat. Frontiers in Ecology and the Environment, 19(5), 266–267. https://doi.org/10.1002/fee.2344

Harrison, A. G., Lin, T., & Wang, P. (2020). Mechanisms of SARS-CoV-2 Transmission and Pathogenesis. Trends in Immunology, 41(12), 1100–1115. https://doi.org/10.1016/j.it.2020.10.004

Hoagland, D. A., Møller, R., Uhl, S. A., Oishi, K., Frere, J., Golynker, I., Horiuchi, S., Panis, M., Blanco-Melo, D., Sachs, D., Arkun, K., Lim, J. K., & tenOever, B. R. (2021). Leveraging the antiviral type I interferon system as a first line of defense against SARS-CoV-2 pathogenicity. Immunity, 54(3), 557-570.e5. https://doi.org/10.1016/j.immuni.2021.01.017

Hughes, D. M., Cheyne, C. P., Ashton, M., Coffey, E., Crozier, A., Semple, M. G., Buchan, I., & García-Fiñana, M. (2023). Association of SARS-CoV-2 viral load distributions with individual demographics and suspected variant type: Results from the Liverpool community testing pilot, England, 6 November 2020 to 8 September 2021. Eurosurveillance, 28(4). https://doi.org/10.2807/1560-7917.ES.2023.28.4.2200129

Ip, H. S., Griffin, K. M., Messer, J. D., Winzeler, M. E., Shriner, S. A., Killian, M. L., K. Torchetti, M., DeLiberto, T. J., Amman, B. R., Cossaboom, C. M., Harvey, R. R., Wendling, N. M., Rettler, H., Taylor, D., Towner, J. S., Barton Behravesh, C., & Blehert, D. S. (2021). An Opportunistic Survey Reveals an Unexpected Coronavirus Diversity Hotspot in North America. Viruses, 13(10), p2016. https://doi.org/10.3390/v13102016

Jemeršić, L., Lojkić, I., Krešić, N., Keros, T., Zelenika, T. A., Jurinović, L., Skok, D., Bata, I., Boras, J., Habrun, B., & Brnić, D. (2021). Investigating the Presence of SARS CoV-2 in Free-Living and Captive Animals. Pathogens, 10(6), 635. https://doi.org/10.3390/pathogens10060635

Katella, K., (2023). Comparing the COVID-19 Vaccines: How Are They Different? Website: YaleMedicine.org, October 5, 2023 (https://www.yalemedicine.org/news/covid-19-vaccine-comparison)

Kim, Y.-I., Kim, S.-G., Kim, S.-M., Kim, E.-H., Park, S.-J., Yu, K.-M., Chang, J.-H., Kim, E. J., Lee, S., Casel, M. A. B., Um, J., Song, M.-S., Jeong, H. W., Lai, V. D., Kim, Y., Chin, B. S., Park, J.-S., Chung, K.-H., Foo, S.-S., … Choi, Y. K. (2020). Infection and Rapid Transmission of SARS-CoV-2 in Ferrets. Cell Host & Microbe, 27(5), 704-709.e2. https://doi.org/10.1016/j.chom.2020.03.023

Kreuder Johnson, C., Hitchens, P. L., Smiley Evans, T., Goldstein, T., Thomas, K., Clements, A., Joly, D. O., Wolfe, N. D., Daszak, P., Karesh, W. B., & Mazet, J. K. (2015). Spillover and pandemic properties of zoonotic viruses with high host plasticity. Scientific Reports, 5(1), 14830. https://doi.org/10.1038/srep14830

Kuchipudi, S. V., Surendran-Nair, M., Ruden, R. M., Yon, M., Nissly, R. H., Vandegrift, K. J., Nelli, R. K., Li, L., Jayarao, B. M., Maranas, C. D., Levine, N., Willgert, K., Conlan, A. J. K., Olsen, R. J., Davis, J. J., Musser, J. M., Hudson, P. J., & Kapur, V. (2022). Multiple spillovers from humans and onward transmission of SARS-CoV-2 in white-tailed deer. Proceedings of the National Academy of Sciences, 119(6), e2121644119. https://doi.org/10.1073/pnas.2121644119

Lawton, K. O. Y., Arthur, R. M., Moeller, B. C., Barnum, S., & Pusterla, N. (2022). Investigation of the Role of Healthy and Sick Equids in the COVID-19 Pandemic through Serological and Molecular Testing. Animals, 12(5), 614. https://doi.org/10.3390/ani12050614

Martins, M., Boggiatto, P. M., Buckley, A., Cassmann, E. D., Falkenberg, S., Caserta, L. C., Fernandes, M. H. V., Kanipe, C., Lager, K., Palmer, M. V., & Diel, D. G. (2022). From Deer-to-Deer: SARS-CoV-2 is efficiently transmitted and presents broad tissue tropism and replication sites in white-tailed deer. PLOS Pathogens, 18(3), e1010197. https://doi.org/10.1371/journal.ppat.1010197

McBride, D. S., Garushyants, S. K., Franks, J., Magee, A. F., Overend, S. H., Huey, D., Williams, A. M., Faith, S. A., Kandeil, A., Trifkovic, S., Miller, L., Jeevan, T., Patel, A., Nolting, J. M., Tonkovich, M. J., Genders, J. T., Montoney, A. J., Kasnyik, K., Linder, T. J., … Bowman, A. S. (2023). Accelerated evolution of SARS-CoV-2 in free-ranging white-tailed deer. Nature Communications, 14(1), 5105. https://doi.org/10.1038/s41467-023-40706-y

Molenaar, R. J., Vreman, S., Hakze-van Der Honing, R. W., Zwart, R., De Rond, J., Weesendorp, E., Smit, L. A. M., Koopmans, M., Bouwstra, R., Stegeman, A., & Van Der Poel, W. H. M. (2020). Clinical and Pathological Findings in SARS-CoV-2 Disease Outbreaks in Farmed Mink ( Neovison vison ). Veterinary Pathology, 57(5), 653–657. https://doi.org/10.1177/0300985820943535

Moustaqil, M., Ollivier, E., Chiu, H.-P., Van Tol, S., Rudolffi-Soto, P., Stevens, C., Bhumkar, A., Hunter, D. J. B., Freiberg, A. N., Jacques, D., Lee, B., Sierecki, E., & Gambin, Y. (2021). SARS-CoV-2 proteases PLpro and 3CLpro cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): Implications for disease presentation across species. Emerging Microbes & Infections, 10(1), 178–195. https://doi.org/10.1080/22221751.2020.1870414

Mykytyn, A. Z., Lamers, M. M., Okba, N. M. A., Breugem, T. I., Schipper, D., Van Den Doel, P. B., Van Run, P., Van Amerongen, G., De Waal, L., Koopmans, M. P. G., Stittelaar, K. J., Van Den Brand, J. M. A., & Haagmans, B. L. (2021). Susceptibility of rabbits to SARS-CoV-2. Emerging Microbes & Infections, 10(1), 1–7. https://doi.org/10.1080/22221751.2020.1868951

Oude Munnink, B. B., Sikkema, R. S., Nieuwenhuijse, D. F., Molenaar, R. J., Munger, E., Molenkamp, R., Van Der Spek, A., Tolsma, P., Rietveld, A., Brouwer, M., Bouwmeester-Vincken, N., Harders, F., Der Honing, R. H., Wegdam-Blans, M. C. A., Bouwstra, R. J., GeurtsvanKessel, C., Van Der Eijk, A. A., Velkers, F. C., Smit, L. A. M., … Koopmans, M. P. G. (2020). Jumping back and forth: Anthropozoonotic and zoonotic transmission of SARS-CoV-2 on mink farms [Preprint]. Genomics. https://doi.org/10.1101/2020.09.01.277152

Palmer, M. V., Martins, M., Falkenberg, S., Buckley, A., Caserta, L. C., Mitchell, P. K., Cassmann, E. D., Rollins, A., Zylich, N. C., Renshaw, R. W., Guarino, C., Wagner, B., Lager, K., & Diel, D. G. (2021). Susceptibility of White-Tailed Deer (Odocoileus virginianus) to SARS-CoV-2. Journal of Virology, 95(11), e00083-21. https://doi.org/10.1128/JVI.00083-21

Pickering, B., Lung, O., Maguire, F., Kruczkiewicz, P., Kotwa, J. D., Buchanan, T., Gagnier, M., Guthrie, J. L., Jardine, C. M., Marchand-Austin, A., Massé, A., McClinchey, H., Nirmalarajah, K., Aftanas, P., Blais-Savoie, J., Chee, H.-Y., Chien, E., Yim, W., Banete, A., … Bowman, J. (2022). Divergent SARS-CoV-2 variant emerges in white-tailed deer with deer-to-human transmission. Nature Microbiology, 7(12), 2011–2024. https://doi.org/10.1038/s41564-022-01268-9

Porter, S. M., Hartwig, A. E., Bielefeldt-Ohmann, H., Bosco-Lauth, A. M., & Root, J. J. (2022). Susceptibility of Wild Canids to SARS-CoV-2. Emerging Infectious Diseases, 28(9), 1852–1855. https://doi.org/10.3201/eid2809.220223

Qi, S., Ngwa, C., Morales Scheihing, D. A., Al Mamun, A., Ahnstedt, H. W., Finger, C. E., Colpo, G. D., Sharmeen, R., Kim, Y., Choi, H. A., McCullough, L. D., & Liu, F. (2021). Sex differences in the immune response to acute COVID-19 respiratory tract infection. Biology of Sex Differences, 12(1), 66. https://doi.org/10.1186/s13293-021-00410-2

Rui, Y., Su, J., Shen, S., Hu, Y., Huang, D., Zheng, W., Lou, M., Shi, Y., Wang, M., Chen, S., Zhao, N., Dong, Q., Cai, Y., Xu, R., Zheng, S., & Yu, X.-F. (2021). Unique and complementary suppression of cGAS-STING and RNA sensing- triggered innate immune responses by SARS-CoV-2 proteins. Signal Transduction and Targeted Therapy, 6(1), 123. https://doi.org/10.1038/s41392-021-00515-5

Schlottau, K., Rissmann, M., Graaf, A., Schön, J., Sehl, J., Wylezich, C., Höper, D., Mettenleiter, T. C., Balkema-Buschmann, A., Harder, T., Grund, C., Hoffmann, D., Breithaupt, A., & Beer, M. (2020). SARS-CoV-2 in fruit bats, ferrets, pigs, and chickens: An experimental transmission study. The Lancet Microbe, 1(5), e218–e225. https://doi.org/10.1016/S2666-5247(20)30089-6

Sia, S. F., Yan, L.-M., Chin, A. W. H., Fung, K., Choy, K.-T., Wong, A. Y. L., Kaewpreedee, P., Perera, R. A. P. M., Poon, L. L. M., Nicholls, J. M., Peiris, M., & Yen, H.-L. (2020). Pathogenesis and transmission of SARS-CoV-2 in golden hamsters. Nature, 583(7818), 834–838. https://doi.org/10.1038/s41586-020-2342-5

Ulrich, L., Michelitsch, A., Halwe, N., Wernike, K., Hoffmann, D., & Beer, M. (2021). Experimental SARS-CoV-2 Infection of Bank Voles. Emerging Infectious Diseases, 27(4), 1193–1195. https://doi.org/10.3201/eid2704.204945

Ulrich, L., Wernike, K., Hoffmann, D., Mettenleiter, T. C., & Beer, M. (2020). Experimental Infection of Cattle with SARS-CoV-2. Emerging Infectious Diseases, 26(12), 2979–2981. https://doi.org/10.3201/eid2612.203799

Warren, C. J., & Sawyer, S. L. (2019). How host genetics dictates successful viral zoonosis. PLOS Biology, 17(4), e3000217. https://doi.org/10.1371/journal.pbio.3000217

Worobey, M., Levy, J. I., Malpica Serrano, L., Crits-Christoph, A., Pekar, J. E., Goldstein, S. A., Rasmussen, A. L., Kraemer, M. U. G., Newman, C., Koopmans, M. P. G., Suchard, M. A., Wertheim, J. O., Lemey, P., Robertson, D. L., Garry, R. F., Holmes, E. C., Rambaut, A., & Andersen, K. G. (2022). The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic. Science, 377(6609), 951–959. https://doi.org/10.1126/science.abp8715

Wu, L., Chen, Q., Liu, K., Wang, J., Han, P., Zhang, Y., Hu, Y., Meng, Y., Pan, X., Qiao, C., Tian, S., Du, P., Song, H., Shi, W., Qi, J., Wang, H.-W., Yan, J., Gao, G. F., & Wang, Q. (2020). Broad host range of SARS-CoV-2 and the molecular basis for SARS-CoV-2 binding to cat ACE2. Cell Discovery, 6(1), 68. https://doi.org/10.1038/s41421-020-00210-9

Zhou, P., Yang, X.-L., Wang, X.-G., Hu, B., Zhang, L., Zhang, W., Si, H.-R., Zhu, Y., Li, B., Huang, C.-L., Chen, H.-D., Chen, J., Luo, Y., Guo, H., Jiang, R.-D., Liu, M.-Q., Chen, Y., Shen, X.-R., Wang, X., … Shi, Z.-L. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579(7798), 270–273. https://doi.org/10.1038/s41586-020-2012-7