COVID Content Catch-Up

Introduction

According to LitCovid, an open-resource literature hub developed with the support of the US National Institute of Health, over 14,000 relevant articles have been posted to PubMed on the 2019 novel coronavirus.³ Thousands more articles are available as pre-prints. Obviously this explosion of information can be intimidating for the busy veterinarian, but you can use the resources listed in Table 1  to stay current on the latest information. Then turn to this review article and our supplemental LafeberVet Literature Search as well as LafeberVet’s Coronavirus in Animals and Determinants of Viral Infection, published in early April 2020, to dive a bit deeper.

Coronavirus 

Coronaviruses (CoVs) are enveloped, nonsegmented positive-sense RNA viruses. Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an emerging zoonotic virus that has achieved extensive community spread among humans.^5,7 Large droplet transmission and contact transmission are the two main routes of human-to-human transmission, however SARS-CoV-2 can also persist on inanimate surfaces for up to 9 days.⁹ Coronavirus disease 2019 first emerged as the cause of severe pneumonia in Wuhan City, Hubei Province, China in December 2019 and it was declared a pandemic in March 2020.^7,10,15,21

Likely sources of infection

During the past two decades, three novel coronaviruses have emerged to cause serious outbreaks of human infectious diseases:  SARS-CoV, MERS-CoV, and now SARS-CoV-2.^{16, 23, 24,}  Although it is unusual for a virus to make the jump from animals to people, MERS and SARS originated from bats.¹⁶ The bat is also widely believed to be the original host of SARS‐CoV‐2^15,16,21. Analysis has shown that SARS-CoV-2 shares 96.2% nucleotide homology with a coronavirus isolated from the horseshoe bat (Rhinolophus spp.) (Bat-CoV-RaTG13).^13,21,23  This suggests that SARS-CoV-2 could be of bat origin ¹³, however the spike protein of the bat coronavirus does not bind well to the human receptor. Therefore it seems likely that spillover of SARS-CoV-2 to humans occurred through an intermediate host, as with SARS-CoV and MERS-CoV.^11,13

The intermediate hosts for SARS-CoV and MERS-CoV are the masked palm civet (Paguma larvata) and the dromedary camel (Camelus dromedaries) respectively.¹⁶The intermediate hosts of SARS-CoV-2 are completely unknown.^16,21

Since angiotensin‐converting enzyme 2 (ACE2) is the receptor for SARS‐CoV‐2, the specificity of the interaction between SARS‐CoV‐2 and the receptor determines the host range for the virus.¹⁵  The spike protein (S) of SARS‐CoV‐2 has attracted great attention because of its role in receptor binding. Angiotensin‐converting enzyme 2 (ACE2) binds to the receptor‐binding domain (RBD) of SARS‐CoV‐2 S protein and functions as a receptor for SARS‐CoV‐2.¹⁵

Visit LafeberVet’s Determinants of Viral Infection for more information about the spike protein, angiotensin-converting enzyme 2, and the receptor-binding domain.

PANGOLIN

The RBD region on the S protein of pangolin coronavirus is similar to that of SARS‐CoV‐2. This suggests the involvement of pangolin virus in the recombination of SARS‐CoV‐2 ¹⁵, however pangolin ACE2 was predicted to recognize SARS‐CoV‐2 RBD less efficiently because it only preserved 14 of 20 critical amino acids.^15,16

Evaluation of Pangolin-CoV-2020, identified in three Malayan pangolins (Manis javanica) with severe respiratory disease, was found to be genetically associated with both SARS-CoV-2 and a group of bat coronaviruses.¹³Phylogenetic analyses and amino acid sequencing of the S protein of SARS-CoV-2 does not support the hypothesis of SARS-CoV-2 arising directly from the pangolin-CoV-2020. It is unclear whether this coronavirus is a common virus flora in the respiratory tract of pangolins.¹³

HAMSTER

A study by Luan et al suggested that Bovidae and Cricetidae  (true hamsters, voles, lemmings, New World rats and mice) should be included in the screening of intermediate hosts for SARS‐CoV-2.^15,16

REPTILE

Based on analysis of codon usage of SARS‐CoV‐2, the snake has been suggested as a potential host.^8,15 Another study evaluating the key amino acids in ACE2 used to interact with the SARS‐CoV RBD indicated that the turtle could be a potential intermediate host for SARS‐CoV‐2.^14,15 However all known hosts for coronaviruses are endothermic animals, therefore it is unlikely that reptiles will be infected with SARS‐CoV‐2.¹⁵ Additionally, a recent investigation into potential interaction between S protein and ACE2, concluded that SARS‐CoV‐could not infect the snake or turtle.¹⁵

Human-to-animal transmission

The coronavirus that caused the 2003 SARS outbreak in China, Singapore, Taiwan, Hong Kong, and Toronto was shown to result in household pets testing positive for SARS.⁷ This triggered panic abandonment of such pets, however, no dog-to-human transmission was shown, and SARS was successfully contained by focusing on interruption of human-to-human transmission.⁷

The issue of the need to evaluate companion animals and their status with regards to SARS-CoV-2 was first raised on January 29 when a member of the senior expert team from China’s National Health Commission stated on Chinese state television that pet owners should take extra care of their animals because (1) the virus “moves between mammals”; (2) if your animals “come into contact with the outbreak or people infected with the virus, then your pets should be put in quarantine”; and (3) “because the epidemic spreads between mammals, therefore we should take precaution against other mammals”. No scientific data were presented to support this statement but, nonetheless, it prompted a severe public response that resulted in many pet dogs and cats being killed and thousands being abandoned.

This prompted the World Health Organization to state that “there is no evidence dogs and cats can be infected with the virus”. No scientific data were provided to support this statement about a novel zoonotic threat either. Despite this appeal, the culling of pets continued in China through February 21…

…on March 13, the IDEXX veterinary diagnostic laboratory announced that it had tested >3,500 dog, cat, and equine specimens from across the United States and South Korea with their COVID-19 RT-qPCR and that they had no positives. What the press release did not make clear, however, is the fact that although animals tested were from affected areas, it is “unknown if any of the animals lived in homes with people that had COVID-19”.— McNamara et al ¹⁷

The reader is encouraged to read the complete Vector-Borne and Zoonotic Diseases review article: “A critical needs assessment for research in companion animals and livestock following the pandemic of COVID-19 in humans”.¹⁷ This is a chronological and comprehensive review on COVID-19 in companion and captive animals that begins with the SARS-CoV-2-positive dog reported in Hong Kong and continues through April 19, 2020.¹⁷

A Nature News Round-Up¹⁹ provides useful insight:  The first two dogs reported to have coronavirus probably caught the infection from their owners, say researchers who studied the animals and members of the infected households in Hong Kong. An analysis of viral genetic sequences from the dogs showed them to be identical to those in the infected people.

Researchers suspected that the infection had been passed from the owners to the dogs, and the direct genomic link strongly supports that, says Malik Peiris, a virologist at the University of Hong Kong who led the study, which was published in Nature (Sit et al 2020).²³

The study showed no evidence that dogs can pass the infection to other dogs or to people, but it is impossible to be certain in which direction the virus travelled “so we have to keep an open mind”, says Peiris.

Although the analysis confirms that people with COVID-19 can infect dogs, the probability of this happening is low, says Arjan Stegeman, a veterinary epidemiologist at Utrecht University in the Netherlands. In the study, only 2 of the 15 dogs who lived with infected people got the disease.

The diversity of species susceptible to SARS-CoV and SARS-Cov-2 strongly suggests a propensity of these viruses to cross the species barrier.^5,11 Interspecies transmission is most likely to be facilitated when there is close contact close between humans with high infectious virus loads and companion or captive mammals.^5,11

Animal-to-animal transmission

As efforts are made to develop vaccines and antiviral drugs for humans, what animals can best be used to model the efficacy of medical countermeasures?^18,7 The ideal animal model would mimic high human-to-human transmission rates so that we can better understand the rapid spreading characteristics of SARS-CoV-2.^10,18

FERRET

Ferrets are frequently used as an animal model for respiratory viruses that infected humans and ferret ACE2 has been shown to contain critical SARS-CoV binding residues.^10,21 Kim et al performed infection and direct and indirect contact transmission studies using a ferret model previously developed for influenza virus infections.¹⁰ SARS-CoV-2 is effectively transmitted to naive ferrets by direct contact and virus is detected in naive direct contact ferrets 2 days post-contact.¹⁰ A few naïve indirect contact ferrets were also positive for viral RNA, suggesting airborne transmission. Infected ferrets shed SARS-CoV-2 in nasal washes, saliva, urine, and feces up to 8 days post-infection.^10,21

A study in ferrets also demonstrated evidence of robust transmission of SARS-CoV-2 via the air:  Richard, M., Kok, A., de Meulder, D. et al. SARS-CoV-2 is transmitted via contact and via the air between ferrets. Nat Commun 11, 3496 (2020). ²¹

CAT

Preliminary studies have demonstrated direct cat-to-cat spread of SARS-CoV-2 through nasal shedding and limited airborne transmission, as well as the production of specific neutralizing antibodies against SARS-CoV-2 in this species.^6,21

RHESUS MACAQUE

In a study evaluating SARS-CoV-2-infected macaques, virus was excreted from the nose and throat in the absence of clinical signs. Virus was also detected in type I and II pneumocytes in foci of diffuse alveolar damage and in ciliated epithelial cells of nasal, bronchial, and bronchiolar mucosae.^18,19 More severe interstitial pneumonia was seen in older monkeys when compared to young animals.²⁵

HAMSTER

The ACE2 proteins from Cricetidae are able to recognize SARS-CoV-2 RBD (Table 1), and the golden Syrian hamster (Mesocricetus auratus ) has been established as a model to study the pathogenesis and transmission of COVID‐19.^2,15

MOUSE

Mice cannot typically be used as an animal model of SARS-CoV-2 directly because the ACE2 of mice cannot interact with SARS-CoV-2¹⁶, however some studies have used mice transfected with human ACE2 to serve as animal models for SARS-CoV-2 infection.^1,10

Clinical disease

The SARS-CoV-2 infection has a wide clinical spectrum in humans, from mild infection to death, but how does the virus behave in other animals? ²²

• The dogs that tested positive did not develop clinical signs.
• One domestic cat naturally infected by her owner in Belgium presented with respiratory difficulty, vomiting, and diarrhea.^2,12
• All of the cats in one small, preliminary study were asymptomatic.⁶
• The four Siberian tigers (Panthera tigris) and three African lions (Panthera leo) at the Bronx Zoo in New York developed a dry cough, some wheezing, and loss of appetite. None of the animals were in respiratory distress.^5,11
• Ferrets exhibited elevated body temperature and acute bronchiolitis was present within infected lungs. Fatalities were not observed.^10,21
• SARS-CoV-2 causes respiratory disease in infected rhesus macaques, with illness lasting 8-16 days. Pulmonary infiltrates were visible on survey radiographs.¹⁸
• Bao et al reported weight loss in transgenic mice following SARS-CoV-2 infection however, no other clinical signs were observed.^1,10

Animal-to-human transmission

The close association between humans and their pets has led to an examination of the potential risks of transmission.^1,17 Currently, there is no evidence that household pets have transmitted disease to humans, and the World Organisation for Animal Health has stated, ‘there is no justification in taking measures against companion animals which may compromise their welfare.⁷ Nevertheless in a recent letter to parliament, Agricultural Minister of the Netherlands reported that a Dutch farm worker contracted coronavirus from mink.²² Outbreaks on mink farms were first reported in April, when keepers noticed some animals with respiratory difficulty.²²

Just as with the 2003 SARS outbreak, animal welfare is again seriously threatened during the SARS-CoV-2 pandemic. Panic abandonment of household pets is neither justified nor morally supported.⁷ Animal health professionals must be proactive to stop or prevent panic abandonment or killing of household pets in response to social media panic and misinformation during the COVID-19 outbreak.⁷

One Health management strategies

The zoonotic origin of SARS-CoV-2 is indicative of its ability to cross the species barrier.⁹ There is a critical need for One Health surveillance, intervention, and management strategies to lessen the effects on wild, captive, and companion animal populations and to address many important questions:⁴

• What are the risks of SARS-CoV-2 contamination of pets by their owners? ⁹
• What is the potential for domesticated (companion) animals to serve as a reservoir of infection contributing to continued human-to-human disease, infectivity, and community spread? ^4,14
• What are the ramifications for food security, economy, and trade issues should coronavirus establish itself within livestock and poultry? ¹⁴
• Is there a risk for multiple spillover episodes in animal populations that could result in SARS-CoV-2 becoming endemic in multiple animal species and populations? ⁴

As a precautionary measure, US Centers for Disease Control recommends that people with COVID-19 have someone else care for their companion animals while they are sick. Frequent handwashing before and after contact with animals, and avoiding intimate contact, is also strongly recommended.⁷

Infected animals should also be quarantined.⁵

References