Distribution of the new coronavirus

On December 30, 2019 (^{Chowdhury & Oommen, 2020}; ^{Rothan & Byrareddy, 2020}) an outbreak of pneumonia of unknown etiology was reported in the city of Wuhan (Fig. 1). On January 7, 2020, the isolation and identification of the genome of a new coronavirus was performed (^{Bulut & Kato, 2020}). On January 13, 2020, an increase in the propagation of the virus associated with nosocomial infections and direct contact with infected relatives was detected. On the same day, the first case of the novel coronavirus was confirmed in Thailand, and on January 19, the first cases were reported in Beijing, which indicated the spread of the virus within China and across the surrounding region (^{Sun et al., 2020}). By January 22, the National Health Commission of China reported 17 deaths and 571 infected people in 25 provinces of China (Rothan & Byrareddy, 2020), which is why the government of Wuhan implemented a total closure of activities inside and outside the city. Unfortunately, these measures coincided with the beginning of the Chinese New Year, which meant that more than five million people left the city to return to their homes. This caused an increase in the number of confirmed cases; therefore, on January 30, 2020, the WHO declared the disease caused by SARS-CoV-2 a “Public Health Emergency of International Concern” (WHO, 2020).

Source: Own elaboration with data from: (^{OIE-WAHIS, 2021}; WHO, 2021).

Figure 1 Timeline of the epidemiological spread of SARS-CoV-2 in humans and animals.  

During the first week of February in Wuhan, a turning point in the epidemic was observed, where the daily number of confirmed cases began to decrease; however, it is not known whether the reduction in virus transmission was due to the established blockade, the public health measures implemented or other factors (^{Sun et al., 2020}). Since its onset in China, the disease spread rapidly. The number of cases increased exponentially worldwide, and in a couple of months, it extended to all continents except Antarctica (^{Bulut & Kato, 2020}; ^{Chowdhury & Oommen, 2020}; ^{Rothan & Byrareddy, 2020}; ^{Sun et al., 2020}; WHO, 2021).

Although there is extensive documentation on the progress of COVID-19 in humans, there are few studies related to the epidemiological distribution of SARS-CoV-2 in animals. In outbreaks in animals, the presence of clinical respiratory signs has been reported, in addition to low mortality and morbidity. It should be noted that contact with previously infected owners or workers has been identified as a source of infection for animals (^{OIEWAHIS, 2021}).

Epidemiological information worldwide indicates a greater number of outbreaks in domestic animals, with morbidity and mortality rates of 52.5% and 2.6%, respectively. Cats are the species with the most reported outbreaks (^{OIE-WAHIS, 2021}). In zoo animals, the disease has been identified in gorillas, cougars, lions, leopards, and tigers, with a presence of respiratory signs in 83.7% of the outbreaks (^{OIE-WAHIS, 2021}).

One year after the beginning of the pandemic, on December 8, 2020, the first person worldwide was vaccinated against SARS-CoV-2, and a new viral variant was identified in the United Kingdom. By January 2021, two million deaths and more than 100 million infected people were counted worldwide; the OIE established a risk manual for farm animals due to the great losses in the production of minks (^{OIE-WAHIS, 2021}). By April, the number of deaths in humans increased to three million, and the application of the first vaccines against COVID-19 in animals began. In August and October, the first reports of COVID-19 in wild deer, otters, and binturong were presented, reporting a total of 1,850 confirmed cases in animals and 267 million in humans. A possible animal-to-human transmission of SARS-CoV-2 was documented on January 31, 2022, in Hong Kong, where the Delta variant was detected in hamsters as well as in a pet store employee (^{OIEWAHIS, 2021}) .

Possible hosts of the virus

In China, there are established farms dedicated to the breeding of exotic animals for human consumption (civets, bats, pangolins, snakes), which distribute their products to various restaurants. Consequently, it has been assumed that farms, restaurants, and wet markets were probably responsible for the zoonotic origin of the new coronavirus (^{Tiwari et al., 2020}). Different authors point to four possible animal species as the initial hostsbats, pangolins, civets, and snakes (Fig. 2) due to the high similarity in their genome and in some surface proteins that the coronaviruses of these animal species have in relation to SARS-CoV-2 (^{Anand et al., 2020}; ^{Ji & Li, 2020}; ^{Lau et al., 2020}; ^{Zheng, 2020}).

Source: Own elaboration with data from: (^{Anand et al., 2020};^{Ji & Li, 2020};^{Lau et al., 2020};^{Zheng, 2020}).

Figure 2 There is a possible origin, transmission, and infection of SARS-CoV-2. The natural reservoir is bats, and the possible intermediate hosts are pangolins, civets, and snakes. Species infected with SARSCoV-2 include humans, domestic animals (dogs and cats); animals with experimental infections (ferrets, pigs, macaques, ducks, and chickens), zoo animals (lions, tigers, and gorilla), and farm animals (minks).  

It has been described those bats are reservoirs for different species of coronavirus due to because when the carry the virus, it remains latent and asymptomatic. As well, the great distances they must travel to obtain food allows them to infect other animal species (^{Tiwari et al., 2020}). Laboratory findings reported that SARS-CoV-2 has a genetic identity of 87.6%, 87.8%, and 96.1% with SARSr-Rp-BatCoV-ZXC21, SARSr-Rp-BatCoV-ZC45, and SARSr-Ra-BatCoV-RaTG13, respectively, which are viruses identified in bats (Rhinolophus pusillus, R affinis) captured in China (^{Lau et al., 2020}).

Although SARS-CoV-2 appears to have originated initially in bats, it is probably that it used pangolins as intermediate hosts. Analysis of pangolin samples revealed several viral sub-lineages related to SARS-CoV-2 (Table 1) (^{Hu et al., 2021}; ^{Zheng, 2020}). Several studies point to the Malayan pangolin (Manis javanica) as a possible natural reservoir or intermediate host of COVID-19 (^{Zhang et al., 2020}). Genomic analyses suggest that GD Pangolin CoV has a nucleotide sequence similarity of 90.32% and 90.24% with SARSCoV-2 and Bat-CoV-RaTG13, respectively. However, the similarity in some viral protein sequences could be 100% (^{Liu et al., 2020}). These results could consider pangolins as an intermediate host of SARS-CoV-2 (^{Xiao et al., 2020}), referring that it probably could have originated from a genetic recombination between bat and pangolin coronaviruses (^{Wong et al., 2020}).

However, other researchers consider civets as a possible intermediate host and transmitter of the new coronavirus due to seroepidemiological results that identified antibodies against SARS-CoV-2 in people previously exposed to contact with these animals (^{Salata et al., 2019}). Phylogenetic analysis of SARS-CoV-2 showed a genome similarity of 78.6% with Civet-SARSr-CoVs. The ability of SARS-CoV-2 to emerge and infect humans could be caused by the genetic similarity between SARSr-BatCoV and Civet-SARSr-CoV from Yunnan, China (^{Lau et al., 2020}).

Similarly, there is a theory that the snake can serve as a natural reservoir of SARS-CoV2 and participate in its transmission between animals and humans (^{Ji & Li, 2020}), due to the similarity of the codons of SARS-CoV-2, bat-SL-CoVZC45, and snake coronavirus. However, SARS-CoV-2 has not been isolated in snakes so far (^{Zheng, 2020}). These investigations suggest that COVID-19 possesses similar genetic information to bat and snake coronaviruses, and thus, recombination in its viral binding proteins could be responsible for cross-species transmission (^{Ji et al., 2020a}).

Infected animal species

The identification of reservoir animals as infectious agents with zoonotic potential is essential for the establishment of sanitary measures to mitigate the adverse effects of the disease. However, this type of infectious agent can infect a wide variety of domestic or wild animals (^{OIE-WAHIS, 2021}). Because coronaviruses have a wide diversity of animal species they can infect, there is the possibility they can cross the barrier between species by means of genetic recombination mechanisms that allow them to infect other animal species and even humans (^{Abdel-Moneim & Abdelwhab, 2020}).

This process has been previously identified in SARS and MERS outbreaks. Like SARSCoV-2, these were caused by a coronavirus that jumped the species barrier. Although the true origin of SARS-CoV-2 is currently unknown, the phylogenetic identity has served as a basis for suspicions that it was initially transmitted by bats, where this virus, in addition to infecting humans, has infected other animal species (^{Tiwari et al., 2020}). Other research detected probable SARS-CoV-2 deer-to-deer transmission that demonstrates the possibility of opening new evolutionary pathways (^{Hale et al., 2022}).

Pet animals

The first reported case was identified in Hong Kong on February 29, 2020, in a domestic dog belonging to a family infected with coronavirus, whereas in domestic and zoo felids, the first outbreaks of this disease were reported on March 28 and April 6, 2020 (^{OIEWAHIS, 2021}), respectively. The first reports of COVID-19 in dogs and cats in China were diagnosed by using polymerase chain reaction (PCR) for the isolation and sequencing of the viral genome (^{Ruiz-Arrondo et al., 2020}; ^{Sit et al., 2020}). Studies showed that after a local outbreak in humans, antibodies to SARS-CoV-2 were detected in dogs and cats (^{Abdel-Moneim & Abdelwhab, 2020}). After the outbreak in China, cases of COVID-19 were reported in domestic animals in different countries of the world (^{OIE-WAHIS, 2021}). In all the outbreaks, the animals belonged to people previously ill with COVID-19. This evidence suggests a possible origin of the infection: the transmission from human to animal as well as the transmission from infected animals to humans, which has not been identified until now (^{Sit et al., 2020}).

Farm animals

The first official report on SARS-CoV-2 in farm animals comes from mink farms located in the Netherlands. On April 19, 2020, some animals began to manifest clinical respiratory signs ranging from a slight nasal discharge to severe respiratory distress. Subsequently, outbreaks have occurred in other mink farms, affecting a population of 736,257 animals. The possible cause of infection was contact with sick workers with COVID-19. Due to the growing number of infected animals and the discovery of a new mutation of SARS-CoV2, several countries of the European Union proceeded to slaughter more than 17 million minks, thus preventing the propagation and dispersion of a new viral variant (^{OIE-WAHIS, 2021}; ^{Oreshkova et al., 2020}).

Zoo animals

There have been reports of lions, tigers, cougars, leopards, lynx, otters, coati, binturong and gorillas diagnosed by PCR and genetic sequencing as SARS-CoV-2-positive. Most of these animals presented respiratory clinical signs where the possible cause of infection was previously infected zookeepers (^{OIE-WAHIS, 2021}).

Experimental infections

Experimental infections in various animal species have been developed in the laboratory to understand the pathogenesis and development of the disease. For this reason, species such as hamsters, ferrets, macaques, shrews, and mice have been inoculated by different routes (intratracheal, intranasal, ocular, and oral), where the immunopathology, transmission and development of COVID-19 treatments have been established (^{Abdel-Moneim & Abdelwhab, 2020}; ^{Shi et al., 2020}). Experimentally infected swine and poultry (quails, geese, ducks, turkeys, and chickens) showed no clinical signs or pathological lesions, and it was not possible to identify the presence of viral RNA or antibodies. These results indicate that none of these animal species are susceptible to SARS-CoV-2, and they do not play an important role in its transmission (^{Shi et al., 2020}; ^{Suarez et al., 2020}).

Characteristics of SARS-CoV-2

Until recently, coronaviruses in humans were not considered to cause anything more serious than the common cold. However, before advent of the COVID-19 pandemic, these viruses have had a higher profile in veterinary medicine (Table 2). SARS-CoV-2 is a βcoronavirus of the subgenus Sarbecovirus, subfamily Orthocoronavirinae, whose members primarily infect bats (^{Wrobel et al., 2020}). The Coronaviridae family consists of four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus (^{Chen et al., 2021}).

As a member of the Betacoronavirus genus, SARS-CoV-2 shares a genomic similarity of 50% and 79% with MERS-CoV2 and SARS-CoV, respectively, and SARS-CoV-2 encoded proteins have a similar length to those corresponding to SARS-CoV (^{Hu et al., 2021}). Several authors point out the degree of molecular divergence between SARS-CoV-2 and other coronaviruses. The phylogenetic analysis of SARS-CoV-2 shows a relationship with SARS-CoV, and other SARS-related coronaviruses found in bats (^{Tang et al., 2020}).

SARS- CoV-2 clusters in a distinct lineage along with four bat coronaviruses, RaTG13, RmYN02, ZC45, and ZXC21, as well as new coronaviruses recently identified in pangolins, which cluster similarly to SARS coronavirus (^{Hu et al., 2021}).

Pathogenesis

The routes of transmission identified in animals for infection caused by COVID-19 have been reported as the main cause of contact with infected persons as well as the inhalation of aerosol particles (^{OIE-WAHIS, 2021}), which have the capacity to lodge in the respiratory tract (^{Rothan & Byrareddy, 2020}; ^{Woodby et al., 2020}). In animals, a incubation period has been described in experimental and natural SARS-CoV-2 infections (2 to 14 days; Fig. 3) (^{Munster et al., 2020}; ^{Shi et al., 2020}; ^{Tiwari et al., 2020}). It has been observed in most outbreaks that the onset of clinical manifestations and recovery is earlier, with the first clinical signs being observed as early as 0-10 days postexposure (dpe) and ceasing between 9 or 17 dpe. However, the presence of viral RNA can be detected from 3-13 dpe, whereas the formation of antibodies is generated at 10 dpe or more. Furthermore, the presence of radiographic changes in the lungs and pathological lesions in various organs (1-3 dpe) has been described, which may persist after the end of the disease (^{Abdel-Moneim & Abdelwhab, 2020}; ^{Chan et al., 2020}; ^{Lu et al., 2020}). Outbreaks with clinical manifestations have occurred mainly in animals with a history of cardiovascular, respiratory, neurological diseases, neoplasms, and obesity (^{OIE-WAHIS, 2021}; ^{Ruiz-Arrondo et al., 2020}).

Source: Own elaboration with data from: (^{Abdel-Moneim & Abdelwhab, 2020}; ^{Chan et al., 2020}; ^{Lu et al., 2020})

Figure 3 Natural history of SARS-CoV-2 in animals.  

Nasal epithelial cells have been identified as the site of initiation of SARS-CoV-2 infection, where an increase in ACE2 levels has been observed due to a high binding affinity for the SARS-CoV-2 spike glycoprotein. Subsequently, through inspiration, the virus manages to colonize the respiratory tract, where it invades type II pneumocytes and initiates a phase of rapid viral replication, producing localized inflammation, increased vascular permeability, increased chemotaxis, and pulmonary edema (^{Chan et al., 2020}; ^{Munster et al., 2020}).

The presence of edema in the lungs hinders them from filling with air, causing low oxygen saturation, pneumonia, lung damage, and death. Lung damage allows the virus to enter the bloodstream and initiate the activation of the coagulation cascade, thrombus formation, and damage to other organs such as the heart, kidney, brain, stomach, and intestine (^{Lotfi & Rezaei, 2020}; ^{Shi et al., 2020}).

In animals, reports of natural and laboratory infections have described the presence of histopathological lesions in the liver, heart, kidney, and intestine; respiratory failure; arrhythmias; and complication with opportunistic bacterial infections (^{Lu et al., 2020}; ^{OIEWAHIS, 2021}). These reports demonstrate that if the organism is unable to control the early stages of viral replication, it can give rise to severe disease and cause death as a result of an impaired or delayed immune response (^{Woodby et al., 2020}).

Clinical manifestations in animals

During the development of this pandemic, the clinical symptomatology in humans has been described in detail; however, in animals, there are currently few reports of outbreaks describing the clinical manifestations, lesions, and pathological alterations associated with SARS-CoV-2 infection (^{OIE-WAHIS, 2021}). It has been observed that the presentation of the disease in animals (Table 3, 4) is very similar to its presentation in humans. In animals, respiratory clinical signs include cough, dyspnea, nasal secretion, sneezing, fever, and inflammation in the anterior and posterior respiratory tract (^{Abdel-Moneim & Abdelwhab, 2020}; ^{OIE-WAHIS, 2021}; ^{Shi et al., 2020}).

In addition to anorexia, fatigue, depression, and stooped posture (^{Chan et al., 2020}; ^{Munster et al., 2020}), in farm animals, alterations in reproductive parameters, increased mortality, and development of secondary infections have been reported (^{Oreshkova et al., 2020}).

The principal postmortem lesions described in animals (Table 4) show acute interstitial pneumonia with the presence of edema, hemorrhages, and areas of pulmonary consolidation; epithelial necrosis in the anterior airways; decrease in the alveolar lumen; infiltration of inflammatory and immune cells; and hematological alterations and radiographic changes in the pulmonary pattern (^{Boudewijns et al., 2020}; ^{Pruijssers et al., 2020}; ^{Schlottau et al., 2020}).

Diagnostic techniques

Several diagnostic methods have been developed for clinical use or research. Their rationale is based mainly on the detection of nucleic acids or immunological and pathological changes. The WHO has established the importance of the use of SARS-CoV2 diagnostic tests that allow surveillance of the disease, limit its spread, assess the epidemiological risk, trace positive cases, local control of outbreaks, and determine previously infected individuals. COVID-19 tests are divided into two groups based on their diagnostic foundation (Table 5): tests for the detection of viral nucleic acid and tests for the detection of antigens or antibodies (^{Jarrom et al., 2020}).

Molecular tests are based on the presence of nucleic acids in a sample to make a diagnosis. These tests can detect nucleic acids prior transcription and are therefore considered essential for the diagnosis of diseases of viral origin. Some of these tests use procedures to identify and amplify viral nucleic acid, such as real-time reverse transcriptase PCR, reverse transcriptase loop-mediated isothermal amplification and reverse transcriptase recombinase polymerase amplification (^{Jarrom et al., 2020}). These techniques have high sensitivity, specificity, and performance and are reliable and easy to implement. However, they have a disadvantage in their complex design of primers and alteration in sensitivity due to an insufficient viral load, in addition to not indicating whether the disease has been present previously (^{Gao & Quan, 2020}; ^{Jarrom et al., 2020}; ^{Li et al., 2020}).

Serological tests focus on the detection of antigens or antibodies against SARS-CoV-2. These tests are easy to perform, have a high yield, and allow working many samples in a short time. However, they are less accurate and are likely to give false positives and negatives. Some of the techniques used on this basis are enzyme-linked immunosorbent assay (ELISA), enzyme immunoassay, lateral flow immunoassay, serum virus neutralization assay, immunofluorescence test, dot blot/western blot, and virus neutralization test. These techniques allow a diagnosis to be made in the laboratory or in an environment close to the patient, allowing the identification of sick, healthy, convalescent, reinfected, or previously infected animals (^{Gao & Quan, 2020}; ^{Jarrom et al., 2020}).

ELISA detects the presence and concentration of immunoglobulin G or immunoglobulin M antibodies in the blood but have low specificity and cannot detect viral variables because the antibodies produced are very stable between species (^{Li et al., 2020}; ^{Michel et al., 2020}; ^{Sidiq et al., 2020}). The western blot technique is based on the presence of viral or immune proteins in blood serum, and it can identify the molecular weight of unknown proteins other than a virus. However, it is a very laborious and time-consuming technique and is recommended more for research than for diagnosis (^{Sidiq et al., 2020}). Techniques such as immunohistochemistry make it possible to demonstrate the damage caused by the virus in the various affected tissues and is used as a support for other diagnostic techniques. This technique provides physical evidence of the lesions caused by the virus in addition to being able to reveal its presence through high resolution microscopes (^{Gao & Quan, 2020}; ^{Nguyen et al., 2021}).

Treatment

Therapeutic strategies to combat SARS-CoV-2 infection focus on reducing the severity of the disease because there are no specific drugs for treatment in animals. Even some of the most used drugs in humans (paracetamol and naproxen) are not recommended for use in dogs and cats (^{Papich, 2015}); however, it has been recommended that the therapeutic protocol used in humans be adapted for animals according to the drugs approved for veterinary use (^{Ahn et al., 2020}; ^{Guo et al., 2020}; ^{Izda et al., 2020}). Therapeutic indications have been established in dogs and cats with acute respiratory problems applicable to the alterations induced by SARS-CoV-2 (^{Nelson & Couto, 2019}; ^{Papich, 2015}; ^{Plumb, 2018}). These are aimed at controlling each of the different clinical manifestations present in this disease (Table 6), reducing inflammation, edema and lack of pulmonary oxygenation through the use of drugs such as ibuprofen, acepromazine and oxygen administration respectively, as well as cough control (dextromethorphan, butorphanol) and bronchoconstriction (terbutaline, aminophylline). The use of antiviral drugs that inhibit viral replication processes (acyclovir, oseltamivir, ribavirin) is also suggested, as well as the administration of antibiotics that prevent the development of secondary infections of the respiratory tract that could be originated as a consequence of the alterations and lesions caused by SARS-CoV-2 (^{Ahn et al., 2020}; ^{Das et al., 2021}; ^{Nelson & Couto, 2019}; ^{Papich, 2015}; ^{Plumb, 2018}).