SARS-CoV-2 Secondary Spillover: From Doubt to Evidence

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the culprit behind the coronavirus disease 2019 (COVID-19) and it is believed that bats may have been the source. SARS-CoV-2 can naturally infect humans and various animal species, including pets, farm animals, zoo animals, and wild animals that might serve as potential reservoirs for the viral transmission to humans. Most infected animals with SARS-CoV-2 are associated with exposure to infected humans; therefore, SARS-CoV-2 is characterized by zoonosis and reverse zoonosis. It is critical to quickly detect and classify variants of concern of SARS-CoV-2 in both domestic and wild animals. In addition, it’s possible that novel variants emerging due to viral mutation, making the infection of incidental animal hosts worrying. Here, we discuss the most recent information on the spreading of SARS-CoV-2 among animals and humans, the importance of genomic research, and active surveillance of these animals that may help us to understand the spread of viruses and the emergence of variants.

1. Introduction

In 1937, coronavirus (CoV) was discovered to be the cause of the first respiratory infection; the virus had a terrible impact on poultry. In 1965, it was established that CoV was to blame for 15–30% of human common colds [1]. Three novel, highly pathogenic human respiratory coronaviruses (HCoVs) that have caused global infections in the last twenty years, are the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle-East respiratory syndrome coronavirus (MERS-CoV) in 2012, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 [2]. They are all assumed to have evolved from an animal reservoir through viral spillover into humans via an intermediate host [3], highlighting the role of animals as reservoirs. (CoVs) have the propensity for rapid adaptation to various geographic settings and to transmit consistently to new species [4]. SARS-CoV-2 has been detected in Wuhan’s Huanan food market, China following its jumping from animals into humans (spill-over).

CoVs cause respiratory, gastrointestinal, neurological, and other widespread disorders in various hosts, such as birds, companion animals, livestock, zoo animals, and wild animals. CoVs are the most extensive diverse group of positive-sense, single-stranded RNA-enveloped viruses. CoV has “crown”-shaped spikes that project from its envelope, giving the appearance of a stellar corona and that’s why is termed “coronavirus.” The spikes, the large type 1 transmembrane spike (S) glycoprotein, enable viral adherence, host entrance, and subsequent infections. The Coronaviridae family of the Nidovirales order includes the Orthocoronavirinae subfamily. According to the International Committee on the Taxonomy of Viruses (ICTV), the Orthocoronavirinae subfamily is further divided into four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. Gamma and delta CoVs predominantly infect birds and some mammals, while alpha and beta CoVs most commonly infect mammals such as bats, rats, domestic animals, and humans.

SARS-CoV-2, the etiological agent of the COVID-19 pandemic, is a member of the Coronaviridae family, Betacoronavirus genus, and Sarbecovirus subgenus [5]. As of 16 July 2023, 6.9 million deaths have been reported out of over 768 million confirmed cases worldwide by the WHO [6].

This virus is very infectious and spreads very quickly with a high rate of genome mutation. Since the outbreak started in late 2019, the virus has continued to affect many populations in wide geographic areas to reach everywhere mostly [7, 8]. Since then, there have been claims about the contribution of animals to the viral transmission from animals to humans. Even though this disease is zoonotic, both the public and many researchers pay less attention to this point in the pandemic. The fact that SARS-CoV-2 causes primarily human-to-human transmission, causing a devastating pandemic; however, it also results in severe respiratory infections of animals (spillback), which cause illness in animals [9]. Many different exotic animal species have the potential to transmit the CoVs to people, especially in locations where these animals are kept for food [10, 11, 12].

The COVID-19 outbreak shows that specific risk factors, such as sufficient contact between infected individuals and recipient animals, the availability of animal hosts for multiplying viral infection, and the capacity of animal host populations to ensure viral survival, maybe the primary factors in the emergence of newly emerging contagious zoonotic diseases [13, 14]. The main problem is that the virus spreads to animal species that are vulnerable to it, as SARS-CoV-2 has shown remarkable host adaptability.

At least 31 different animal species, such as domestic cats (Felis catus domesticus), mink (Neovison vison), white-tailed deer (Odocoileus virginianus), domestic dogs (Canis lupus familiaris), non-domestic felid species, gorillas (Gorilla gorilla), black-tailed marmoset (Mico melanurus), mule deer (Odocoileus hemionus), hyena (crocuta crocuta), Asian small-clawed otter (Aonyx cinereus), manatee (Trichechus manatus), giant anteater (Myrmecophaga tridactyla), and golden hamsters (Mesocricetus auratus), are recognized to be vulnerable to SARS-CoV-2. SARS-CoV-2 has been observed to spread rapidly among animal groups, including mink and white-tailed deer, raising worry that viral variants may accumulate among these animals.

The group habitation and interaction network structure in these sensitive animal species may contain another virus library that can be reintroduced into humans [15]. Now, after three years, studies have revealed SARS-CoV-2’s spreading from animal to human. More interestingly, different kinds of animals can do this kind of viral transmission (White-tailed deer [16, 17, 18], Cat [19], Pet hamsters [20, 21], African lion [22], and Contaminated hair of Dog [23]), and one of them helped in the SARS-CoV-2 variant’s transmission that is highly transmissible among humans (Mink [24, 25]) (Figure 1).

Figure 1.

SARS-CoV-2 transmission among humans and animals.

Wild animals that can adapt effectively to an environment where humans predominate, such as rats, bats, and primates, will spread more viruses to humans as the human population rises [26]. Because of population growth, humans now occupy most of the living area traditionally allotted for animals, resulting in frequent interactions between people and animals. These animals are at significant risk of transferring the virus to humans since they reside near human homes, farms, and crops. Restricting human contact with wild animals is essential to reduce the possibility of SARS-CoV-2 transmitting from wild animals to humans and to protect wild animals [27].

The initial victims of the COVID-19 outbreak in Wuhan, Hubei Province, China, were workers or consumers who had previously had a lot of contact with animals, raising the possibility that SARS-CoV-2 can be spread from animals to people [28, 29, 30]. Also, it was recorded that numerous coronaviruses have been found in Cameroon, some of which are closely related to human coronavirus 229E [31].

SARS-CoV-2 may have evolved further in new hosts due to interspecies transmission, which would have led to new spread, such as the SARS-CoV-2 mutation in minks and human exposure to minks [32, 33], which enforced the Netherlands and Denmark to substantial mink culling late 2020. In a previous similar scenario, several months after SARS-CoV was under control within the impacted nations, similar outbreaks occurred in animals at the end of 2003. A restaurant serving civet cats reared on a farm was related to fresh human infections with SARS-CoV [34], which prompted China’s mass culling of civet cats.

Human-to-animal spreading of SARS-CoV-2 may occur when wildlife is handled or eaten [35]. Additionally, despite being a respiratory virus, SARS-CoV-2 is excreted in the feces and connected with certain cases of diarrhea in people [36]. Additionally, some animal food sources have a reputation for raising concerns that diseases could spread through direct contact with or consumption of wild animals and/or animals used for farming [37]. It is crucial to keep monitoring the animal-source of SARS-CoV-2 and adapt control and preventative methods to prevent a large-scale communal transmission brought on by the virus moving from animals to humans in the future. Relying solely on the development of vaccines while neglecting this approach could result in the loss of many lives [38].

1.1 Bats

Since the first identification and early outbreak at the end of 2019 of the COVID-19 pandemic, epidemiological investigations have revealed that the infectious agent is of animal origin, likely from bats [39], through an unidentified intermediary animal host [40]. SARS-CoV-2 was first found in bats and later transmitted to pangolins or other wild species, where it interacted with viruses that were already present in these animals to become able to infect people [7]. SARS-CoV and MERS-CoV are just two of the coronaviruses that have spread from bats to other animals. There have been discovered a large number of bat-originating coronaviruses (Bat-CoV), including Bat-CoV-RaTG13 (RaTG13), RpYN06, PrC31, RmYN02, Bat-SL-CoVZC45, and Bat-SL-CoVZXC 21 [7, 41, 42].

The RTG13 identified in the Chinese chrysanthemum-headed bat (Rhinolophus sinicus) shared 96.2%, 97.5%, and 89.2% nucleotide and amino acid sequence similarities with SARS-CoV-2 for the spike (S) protein and the receptor-binding domain (RBD), respectively [41]. Because SARS-CoV-2’s mutation spectrum resembles that of coronavirus RaTG13, it is likely that the SARS-CoV-2 emerged from RaTG13 in a bat-like host cell environment before being transmitted to humans. This research confirms SARS-CoV-2’s natural origins and suggests that it started in bats [43].

1.2 Hamsters

In Hong Kong, China, the earliest documented instance of naturally occurring SARS-CoV-2 infection in hamsters [44]. An epidemiological investigation determined that the SARS-CoV-2 variant AY.127 was transmitted from pet hamsters to customers and workers at pet shops, which was connected to the origin of this case in Hong Kong [20, 21, 45]. The human patient in this case had a SARS-CoV-2 strain that shared substantial sequence similarity with the positive Syrian hamster (Mesocricetus auratus) sample, both of which belonged to the AY.127 lineage [20], whereas the possibility that a dog serving as a passive mechanical carrier of the SARS-CoV-2 transmitted the Omicron BA.2 subvariant to Chinese people [23].

1.3 Minks

COVID-19 has been found in farmed mink, and transmission from among mink and human (mink to mink, human to mink, and mink to human) has been established [46]. Over one million minks have been exterminated due to reports like these in countries like Spain and the Netherlands [47]. Other than the Netherlands and Denmark, reports of SARS-CoV-2-infected minks have also been recorded in Spain and the US. Denmark’s discovery of mink-associated variant and its human transmission, even those who do not interact with mink [25], where the spike protein in this strain underwent mutations. Additionally, the variant associated with minks had enhanced binding to the mink angiotensin-converting enzyme 2 (ACE2) receptor, potentially indicating host adaptability [48]. SARS-CoV-2 has been detected in 11 wild minks in Utah, USA, which are thought to have escaped from a farm nearby where they were captured [49]. The SARS-CoV-2 infection in two wild minks in Spain has been confirmed to be phylogenetically identical to the Wuhan variant [50], thus demonstrating the power of SARS-CoV-2 to spread to wild populations of species that have a high vulnerability to the virus, such as mink.

It’s possible that the evolution of a variant that has enhanced adherence to the cat ACE2 receptor might have an impact on transmission from cat to cat and raise the possibility that cats could act as virus reservoirs [51]. Interestingly, feline coronaviruses showed a mutation of feline enteric coronavirus into feline infectious peritonitis virus [52].

In 474 farms across 12 different countries as of August 2022, SARS-CoV-2 was being studied in farm-raised mink [53]. Farmed minks have drawn attention from all around the world because of their extremely high SARS-CoV-2 vulnerability, an infection that is both symptomatic and subclinical, high mortality, and capability to spread the virus to other mink and animal species [54, 55, 56, 57]. Denmark discovered SARS-CoV-2-positive mink between June 2020 and November 2020 on 290 farms and 4000 human sequences with suspected mink-related mutations [53, 58].

There have been reports of SARS-CoV-2-infected minks (Neovison vision) in the Netherlands, Denmark, the USA, Canada, Spain, France, Italy, and other countries. [59]. In the Netherlands, it was recorded that SARS-CoV-2 may have been transmitted from animal-to-human among mink farms. Whole-genome sequencing revealed that 68% of people who lived in mink farms, worked there, or had contact with them had SARS-CoV-2 infection [46]. It was reported that, SARS-CoV-2 animal-to-human transmission in the Netherlands from infected farm minks to farmworkers [46].

Naturally, the caretaker’s infection spread to the minks. Infections of SARS-CoV-2 were identified in two-thirds of the mink farm inhabitants and employees who were screened [46]. Munnink et al. sequenced the whole genomes of the SARS-CoV-2 strains from 16 mink farms in the Netherlands that were of mink and human origin. They also disclosed the first evidence of human-to-animal transmission, raising the possibility that minks could serve as the SARS-CoV-2 virus’ possible intermediate host . The most likely way for minks to infect humans with SARS-CoV-2 is through the dust or aerosols of infected bedding from mink farms [60].

Closeness of people to animals, including dogs, cats, minks, and captive wild animals, is often a contributing element in COVID-19 natural events. One cat that tested positive for RNA and seven stray cats that were seropositive for SARS-CoV-2 indicate that there is a possibility of mink-to-cat transmission [61]. Human-to-mink transmission of SARS-COV-2 then mink-to-human transmission poses the greatest public health risk besides mink-to-feline transmission and among minks [46].

The earliest known minks’ infection with SARS-CoV-2 was found to have occurred spontaneously on a mink farm in the Dutch proven of North Brabant. After that, numerous mink farms in the Netherlands had an outbreak of the SARS-CoV-2 virus [54, 62, 63]. The disease was shown to have been introduced by humans and subsequently spread among mink, according to a detailed outbreak analysis at Dutch mink farms. After that, the virus changed within the minks, creating a mink SARS-CoV-2 strain. According to whole-genome sequencing, several mink farm workers were infected with the mink strain, proving that minks can also spread SARS-CoV-2 to people [46, 62].

Given the high sensitivity of minks to SARS-CoV-2 and the viral development in minks, it is plausible to expect that variants might regularly be transmitted from minks to people or other species, potentially enhancing viral transmission [56, 62]. Additionally, mink and 12 human specimens from affected Danish farms and nearby settlements have the Cluster 5 variant, which has been shown to be less susceptible to neutralizing antibodies [64, 65]. The spike protein alone contained 35 changes and four deletions in the Cluster 5 version [58].

The Danish government authorized roughly 17 million minks depopulation in November 2020; Cluster 5 has yet to be discovered in humans since September 2020 [58, 64, 65]. These findings have emphasized the significance of comprehensive epidemiologic studies to assess the effects of SARS-CoV-2 epidemics in farmed mink on human and animal health [66], as well as indications of anthropogenic and zoonotic transmission [25, 46] and the possibility for species-wide spillover transmission [54, 56, 67], including susceptible free-roaming wildlife [53, 68].

1.4 Pets

With the early discovery of SARS-CoV-2 in pets, worries about zoonotic transmission from animals in close contact with people have grown [69]. There are 370 million pet cats and 470 million pet dogs who reside with their human owners, according to some estimates. The SARS-CoV-2 virus has been found in a few pets and wild animals, including cats [70, 71], which are more susceptible than dogs to this virus [72, 73], and susceptibility studies have revealed that the virus can replicate in cats as well [74]. Neutralizing antibodies in pets against SARS-CoV-2 were reported and correlated to COVID-19 incidence in humans [75]. The same scenario was reported in SARS-CoV, which can replicate with disease signs in cats [76]. Domestic cats in Hong Kong’s Amoy Gardens apartment block with SARS-infected residents were infected with the virus [76]. Since late March 2020, natural infections in domestic cats contracted from COVID-19-positive owners have been documented in the United States [77], Italy [78, 79], Spain [80, 81, 82], Netherlands [83], France [84], Brazil [72], Belgium, and Hong Kong. Also, large non-domestic cats were reported to have naturally contracted SARS-CoV-2, probably by reverse zoonosis [85]. According to some scientists, the severity of the COVID outbreak in northern Italy was exacerbated by the high rates of dog ownership in this area [86]. Others stated that serious consideration is needed in light of the minimal evidence of SARS-CoV-2 infection in domestic animals like dogs and cats and the recognized similarities in ACE2 receptor binding sites between humans and some domesticated species [87].

Viral transmissibility has been attenuated via serial passages with SARS-CoV-2 strain in cats, which may be due to weaker interactions of SARS-CoV-2 with feline ACE2 compared to human receptors [51]. The infection rate within the domestic cat population is low, and reports are describing the relatively short duration of shedding and resistance to reinfection in cats [88, 89], speculating that SARS-CoV-2 occurs in domestic cats with a narrow transmission bottleneck [90, 91]. Lu et al. [92] suggested there are 5 variations that exist at feline ACE2 receptor than human ACE2. Additionally, Wu et al. [93] recognized that the feline ACE2 receptor’s binding affinity to the SARS-CoV-2 RBD was 3 to 4 times weaker due to mutated amino acids at sites 24 and 34. This finding explains why the SARS-CoV-2 transmission from cat-to-cat is less persistent over time than the sustained transmission from human-to-human. However, it is unknown if domestic and wild cat populations could act as SARS-CoV-2 reservoirs for human exposure [51]. Previous research was constrained by the tiny sample size and laboratory tests of young, healthy, and adult cats. We need a larger population, more elderly cats, cats with comorbid conditions, and cats with coinfections to better understand the typical course of infection and immunity in community populations of cats [51, 94, 95]. During the outbreak in Thailand, a domestic cat was infected with another critical respiratory virus, H5N1 virus, after eating a pigeon carcass infected with H5N1 virus [96, 97]. Pigeons can contract SARS-CoV-2 as well [98] due to the existence of angiotensin-converting enzyme 2 (ACE2) receptor in their body that is utilized by SARS-CoV-2, suggesting that feral cats can catch the infection from infected pigeons [99]; however, this hypothesis needs to be investigated. Household cats (Felis domesticus) can catch SARS-CoV and SARS-CoV-2 infections from infected owners, and they can easily spread the virus to previously uninfected animals that share their room [76]. Because cats are frequent indoor pets, there is worry about disease transfer to humans [97].

SARS-CoV was discovered in domestic cats in 2003 [100], and recombinant events of Betacoronavirus were recorded in cats [101]. Domestic dogs, cats, and mustelids in China, Hong Kong, Europe, and the United States were all found to have natural SARS-CoV-2 infections [102, 103] as a result of a reverse zoonotic transmission route [46, 104]. Additionally, it was noted that ACE2 is highly homologous in both humans and cats [105].

However, owners who tested positive for COVID-19 were responsible for the majority of SARS-CoV-2 infections in animals [106, 107], and there was some indication of human-to-animal transfer, although it was minimal. As a result, several researchers hypothesized that even if dogs were carriers of the SARS-CoV-2 virus, they would not have a major epidemiological role in human SARS-CoV-2 transmission [69]. Songkhla Province in southern Thailand announced the first confirmed incidence of cat-to-human transmission [19, 108]. A recent study suggested that a cat may have transmitted the zoonotic SARS-CoV-2 virus to a human in Thailand [19]. Because of this, petting or kissing infected pets can cause owners to contract the virus through intimate contact with their hair, paws, or pads; therefore, there is a possibility that domestic pets could spread SARS-CoV-2 [83].

Following contact with an infected cat belonging to an infected patient, a Thai veterinarian was discovered to have COVID-19. Genetic studies supported the idea that SARS-CoV-2 was transmitted from the owner to the cat, and then from the cat to the veterinarian. It is assumed that this brief, but extremely close, interaction led to transmission from the cat’s sneeze. Bangkok was most likely the origin of the SARS-CoV-2 infection chain in this cluster. It is generally known that cats can contract the SARS-CoV-2 virus from people, especially when they are in close proximity to those who are already showing symptoms of the infection. This cat likely only had a week before becoming infected with SARS-CoV-2 and perhaps passing the infection on to patient A, the veterinarian who examined the infected cat and caught the infection from it, because infected cats have relatively short incubation and infectious periods.

Investigation revealed that the purported dog-to-human transmission of variant was passive and mechanical because the dog’s nasopharyngeal swab samples for SARS-CoV-2 were negative despite the dog’s hair and kennel being positive [23]. By having intimate contact with the pet dog, the owners could mechanically contract SARS-CoV-2 [23]. These results may confirm the critical hypothesis for outbreak investigations that SARS-CoV-2 transmitters can spread the virus through intimate contact with infected dogs. Furthermore, Chan et al. assert that human-to-human transmission of the SARS-CoV-2 Delta variant AY.127 caused a COVID-19 outbreak at a pet store in Hong Kong [45]. Therefore, veterinarians and owners should be cautious when dealing with cat environments and flea-infested cats. Canine Coronavirus-Human Pneumonia-2018 (CCoV-HuPn-2018), a unique canine-feline recombinant alphacoronavirus, was recently discovered. It was initially found in a case of human pneumonia in Sarawak, Malaysia [109]. CCoV-HuPn-2018 might be the eighth coronavirus to infect humans, following SARS-CoV-2 [109, 110]. Despite the fact that the influenza A (H7N2) virus of avian origin only sporadically passes from human to human [111], it’s notable that Lee et al. [112] confirmed the first instance of H7N2 cat-to-human transmission occurred following an outbreak among cats in New York City animal shelters. Even though this danger is minimal, the fact that it exists and the possibility of it returning pose a health concern [113]. We urgently want a One Health surveillance effort since there is no clear evidence for this scenario with SARS-CoV-2 in cats.

1.5 Deer

Since just one study has identified the white-tailed deer (WTD; Odocoileus virginianus) variant version of SARS-CoV-2 that has been isolated from humans in Canada, it raises the prospect that the virus could spread from deer to humans [114]. The results are significant because they demonstrate that handling and processing WTD corpses may expose workers to infected SARS-CoV-2, which could cause the virus to spread from deer to humans. This is accurate even if few samples contained the live virus [115].

SARS-CoV-2 samples from WTD have substantially higher mutations than those found in samples from humans, which shows that SARS-CoV-2 has been circulating and evolving in the deer population. Some of the changes that have been noticed could be the result of host adaptation. For instance, the ORF1a: L4111F mutation has been identified in WTD-derived samples from various geographical locations and is present throughout all human sequences in the GISAID database at a low frequency (0.5%). This shows that this mutation originated independently in deer following human spills. The lack of or extremely low frequency of fixed mutations in the S gene, which shows that host-specific adaptation was not required for spillover from humans to deer, supports SARS-CoV-2’s designation as a “generalist” virus [116].

2. Conclusions

All pathogenic human coronaviruses originate in animals; therefore, concerns about the possibility of interspecies transmission between people and animals have arisen as a result of SARS-CoV-2 emerging after cross-species jumping in animals; as a result, a vaccine strategy for companion animals is conceivable and plausible (Table 1) [118].

Animal vaccine	Description	Target animals
Carnivac-Cov (inactivated vaccine)	The first COVID-19 vaccine for animals developed by Russia have been shown to elicit robust responses in animals vulnerable to SARS-CoV-2 infection such as dogs, cats, foxes, and minks. It contains an inactivated SARS-CoV-2 virus strain.; Vaccination with Carnivac-Cov induced immunity that lasted for at least six months after the vaccination	Dogs, cats, foxes, and minks
LinearDNA™ COVID-19 vaccine	LinearDNA™ (“linDNA”) vaccine encoding the RBD domain of SARS-CoV-2. linDNA developed through a joint effort between Applied DNA Sciences (United States) and EvviVax (Italy). Clinical trials showed that the vaccine is safe and immunogenic and support the development of vaccines for preventing viral spread in susceptible species, especially those in close contact with humans. Recently, a linearDNA vaccine was successfully elicited neutralizing antibodies and cellular immunity against SARS-CoV-2.; LineaRx announced the successful expression in vitro of its linDNA SARS-CoV-2 vaccine candidate encapsulated within lipid nanoparticles (LNP). The linDNA-LNP vaccine will be used in upcoming in vivo animal studies to assess the performance of linDNA-LNP vaccines and will inform the final design of the Company’s lead veterinary asset, a linDNA-LNP canine lymphoma vaccine candidate.	Domestic cats (Now is reported to be focused on inoculating mink instead)
Zoetis vaccine	The captive orangutans and bonobos at the San Diego Zoo in the United States of America became the first non-human primates to receive an experimental COVID-19 vaccine developed specifically for animals by the veterinary pharmaceutical company Zoetis.; It has been authorized for experimental use on a case-by-case basis by the United States Department of Agriculture (USDA).	Dogs, cats, and minks
Ancovax	India’s first COVID-19 vaccine for animals. It contains an inactivated SARS-CoV-2 (Delta) antigen capable of neutralizing both Delta and Omicron variants	Dogs, lions, leopards, mice, and rabbits

Table 1.

Examples of animal COVID-19 vaccines used in domestic and wild animals [117].

The SARS-CoV-2 virus has been naturally acquired by domestic animals (dogs, cats, and ferrets), captive species (tiger, lion, snow leopard, puma, otter, and gorilla), and wild and farmed minks, according to the OIE database. It is possible that the transmission of SARS-CoV-2 in populations of wild animals is periodically to blame for the reappearance of COVID-19 in people at the human-animal interface (Figure 2) [119].

Figure 2.

Spillover and spillback of SARS-CoV-2 among domestic and wild animals, and humans.

FAO, OIE, and WHO released a joint statement on March 7, 2022, encouraging all nations to cooperate to lessen the danger of SARS-CoV-2 transmission between humans and animals to decrease the risk of variant emergence and safeguard both people and wildlife [120]. It is crucial to carry out viral surveillance and sequencing in animals, especially those who have frequent interaction with people.

Finally, the One Health strategy must be used urgently to adequately track the virus in animal populations by observation of livestock, pets, and trading networks. Although the idea of One Health is not new, effective public health initiatives necessitate cooperation between the human, veterinary, and environmental health sectors since humans interact with both wild and domestic animals regularly. Despite the minimal number of reported cases of animal-to-human SARS-CoV-2 transmission [121], it is critical to recognize the significant risks associated with zoonotic transmissions or spillover of the SARS-CoV-2 virus from animals to humans and motivate us to conduct genomic research on these animals as they are under active observation to learn more about viral circulation and how variants emerge.