key: cord-0862222-1uzy39bm
authors: Zhu, Lin; Chen, Honglin; Cai, Zongwei
title: Zoonotic attack: An underestimated threat of SARS-CoV-2?
date: 2022-04-15
journal: Innovation (N Y)
DOI: 10.1016/j.xinn.2022.100242
sha: 47702091b1ef76095f94bb200aa819693625870f
doc_id: 862222
cord_uid: 1uzy39bm

nan

As the first coronavirus pandemic is walking into its third year, it is likely that the pandemic will transform to an endemic disease soon. With global efforts and measures on mass immunization, non-pharmaceutical interventions and therapeutics advancements, the scales of death, illness or social isolation have been relieved. However, endemic does not mean harmless, rather, it could be widespread and deadly. 1 Ever since its emergence in 2019, SARS-CoV-2 has been mutating and evolving, leading to recent variants Omicron with significant transmissibility and immune-escaping capacities. Current vaccines could alleviate severe diseases but might not prevent infection and block the transmission. Growing genetic diversity of SARS-CoV-2 and large population of infection have increased the frequency of coinfection by distinct viral lineages, consequently leading to meaningful recombination events, and generating novel recombinants with potential impact. In fact, multiple recombinant strains were reported worldwide in the past few days. XE, a recombinant of Omicron sublineages BA.1 and BA.2, was reported to have 9.8% relative growth advantage over the current major variant BA.2. 2 It is likely that new variants will continue to generate, leading to challenges in public health measurements.

A recent study reported multiple zoonotic transmission events from pet hamster to human, revealing a worrying loophole in current pandemic control and surveillance systems. 2 A delta variant of concern (VOC) circulated among pet hamsters and transmitted to human, causing a local outbreak in Hong Kong. Phylogenetic and epidemiological analyses indicated that the virus had infected and persisted among hamsters prior to importation, which later became the source of local transmission of delta. 3 It is believed that SARS-CoV-2 might have originated from bat and acquired its ability to infect human via mutations on Spike protein. 4 Prior to the reported hamster-to-human transmission, mammals in wild or farm, or as pets have been reported to be infected by different SARS-CoV-2 lineages via human contact. Continuous evolution of human SARS-CoV-2 was observed in mink during the mink farm outbreak and in wild white-tailed deer, which were caused by selection pressure in the new hosts. A phylogenetic tree was plotted using 69 whole viral genome sequences isolated from different animal hosts deposited in NCBI SARS-CoV-2 Data Hub ( Figure 1A) . A great variety of PANGOLIN lineages was found, suggesting spillovers from human to animal was relatively easy and frequent.

However, these spillover events, except the one in mink farms, were only one-way transmission but could not occur from animals to human. The reason might either be a mutation that disabled the infectivity of the virus to human under selection pressure of animal hosts, or an unfavourable environment in the new host to generate enough infectious virions. In the case of mink farm, the transmission probably occurred due to high-dose environmental exposure of virus with high density of animals. 4 Therefore, the reported transmission of pet hamster to human was particularly worrisome: it showed how easy it would be for the virus to be transferred across international borders via pet commerce, while international travel for human is still in tight control. Given the pet animals including dog, cat, hamster, etc. have been reported to be infected by SARS-CoV-2, the lack of surveillance in pet industry would be a potential loophole for prevention and control of COVID-19. This incident also confirmed the abilities of virus to circulate, persist, and mutate among hamsters, yet remain its competency to infect human. It not only meant the virus could continue to evolve and spillover back to humans, but also indicated an emerging bigger issue. The possibility of coronavirus to acquire a key host adaptation mutation to enable it to jump back-and-forth between humans and animals might increase ( Figure 1A ).

The host tropism of SARS-CoV-2 has continuously expanded by acquiring different host adaptation mutations. N501Y mutation existing in multiple VOCs enables the virus to infect and reproduce in wild murine. 5 Considering the widespread of VOCs carrying N501Y that has been detected in both human and environments, an undiscovered circulation of SARS-CoV-2 among murine and even other zoonotic species may exist, constituting a serious challenge to public health.

What's more, reported incidents of SARS-CoV-2 infection in animals and related zoonotic transmissions may just be a tip of iceberg due to limited surveillance. It is known that the virus may circulate among wild white-tailed deer. New variants carrying host adaptation mutations may appear and transmit to other wild animals. The expansion of host tropism of coronavirus may bring novel variants with unknown threats to human, including significant immune-escaping property, the increased transmissibility and the varied pathogenesis.

Another threat in formation but rarely being brought up is the establishment of SARS-CoV-2 reservoir in wild animals. Influenza A virus, for example, primarily relies on wild birds as its natural reservoir and continuously serves as gene pools to influenza viruses in domestic poultry and swine. Cross-species transmission from animals to human caused by host adaptation mutations was believed to lead to the 1918 Spanish flu pandemic and a number of pandemics later on, including the 2009 swine flu pandemic. Similar scenario might also happen for SARS-CoV-2 if the coronavirus could persist and circulate in wild animals globally, which would increase the difficulty for monitoring. Given the frequent recombination of coronaviruses, novel recombinant viruses might appear by recombination between SARS-CoV-2 and other coronaviruses that already circulated among wild animals ( Figure 1B ). Potential threats of recombination between distinct lineages were already suggested by the appearance of recombinant XD, XF and XE. 2 However, very few efforts were made currently to monitor possible recombination events in animal population. Therefore, even COVID-19 pandemic may end in the near future, there are still much to do for public health managements. Systemic surveillance and monitoring for SARS-CoV-2 existing in wild, farmed and pet animals are of crucial importance. Preparation for investigation and production of vaccine based on newly detected variants may be considered. Additional measures for regulating and monitoring pet trade seem to be necessary, while the policy makers should take extra care when making decisions and adopting guideline regarding the management of susceptible pet animals due to the unique and emotional bond between pets and their owners.

Is Omicron variant of SARS-CoV-2 coming to an end

UKHSA Immunisations Team, UKHSA Surveillance Team, UKHSA Public Health Incident Directors, UKHSA Data Analytics and Surveillance

Transmission of SARS-CoV-2 delta variant (AY.127) from pet hamsters to humans, leading to onward human-to-human transmission: a case study

SARS-CoV-2 spillover events

Emerging SARS-CoV-2 variants expand species tropism to murines

The authors acknowledge the funding support from Theme-Based Research Scheme (T11-709/21-N) of Research Grants Council, Hong Kong SAR, China.

The authors declare no competing interests.J o u r n a l P r e -p r o o f