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A Review of COVID-19 and its implication on animal health

 What role do animals play in the coronavirus pandemic?

As the death toll of COVID-19 keeps rising, scientists now are still uncertain about the origin of the novel SARS-CoV-2 virus. This virus is the youngest in the family of coronaviruses known to infect humans and animals alike. It is believed that the pangolins and bats [Rhinolophus] that were sold in the wet market of china are the most likely candidates. One study indicated that a coronavirus [BetaCoV/RaTG13/2013] found in bats [bed reservoir] shared 96% of its genetic material with the virus [SARS-CoV-2] responsible for the current pandemic, COVID-19. But this particular bat virus is unlikely to have infected human cells directly, suggesting that the virus jumped to humans via another animal, the pangolin. Due to mutations, the same virus developed the ability to infect humans. All coronaviruses are lethal but there are always the ones that are more harmful because of how easily they can be transmitted. When a virus jumps from animal to humans it is called a zoonotic virus. But the infection is not just limited to humans as there are reports of it spreading to other animals. 

SARS-CoV-2 Infection in pets.

Studies and risk factors:

A tiger at the Bronx Zoo, New York City has tested positive for COVID-19 after developing a dry cough. A small number of lions at the same zoo also showed signs of infection.

There are several reports from countries like Hong Kong where dogs have tested positive without manifesting any of the usual symptoms. Scientists also believe that cats are very susceptible to the SARS-CoV-2 virus. Such circumstances have caused panic among pet owners as they wonder what this means for them and their pets. 

Caretakers and their vets are curious about how the virus can affect the livestock. Although, pigs, chicken and ducks are not likely to get infected according to the research papers released from china and the Republic of Korea. There are clear hints that pets can contract the infection from their SARS-CoV-2 infected owners, but the claims are more obscure due to lack of research. 

Precautions and quarantine:

The current events are shocking enough to rattle pet owners. Following the statistics, it will not be surprising to see many reports of such cases shortly. Studies have hinted that the transmission is of a reverse zoonosis type, where pets are at the risk of getting infected from positive SARS-CoV-2 owners and not the other way around. It is thus safe to conclude that both human and animal species are facing a greater risk. Therefore, during the quarantine phase, you should consider the needs of your pets and prepare accordingly. 

Exposure and care

The first symptoms that appear after a possible SARS-CoV-2 infection are dry cough and fever. If your pet develops the following symptoms or seems more lethargic than usual it is important to take the advice of your veterinarian. The period for which the virus can survive on the surface of your pet’s body depends on factors such as humidity, temperature, and nature of the surface. But the current understanding denies the possibility of transmission of the infection from pets to their owners. Comparing the larger number of cases of positive COVID-19 humans and the small number of pet infection. It is improbable that your pet will be infected or can transmit the disease to others. 

Should your pet exhibit symptoms of SARS-CoV-2 infection, contact your veterinarian immediately for further advice. According to the data gathered from the few animal cases, it is seen that the symptoms are mild. Therefore, all COVID-19 positive animals need is rest and recovery. In case of a more severe incident, your veterinarian will consult with the animal and public health officials on the course of action. 

SARS-CoV-2 infection in farm animals.

Studies and risk factors:

The SARS-CoV-2 has shown an adequate ability to evolve and adapt in an intermediate host before reaching humans. The receptor sequence binding to SARS-CoV-2 in animals and humans is remarkably similar, suggesting that there is a weak species barrier for the virus to transmit to farm animals. The members of Coronaviridae cause respiratory and intestinal infections in animals. Introductory data shows that the spike protein of SARS-CoV-2 is cleaved by the enzyme Furin during its biosynthesis. This is similar to the avian influenza viruses, which acquire a polybasic structure if introduces in poultry farms and yet again cause a deadly outbreak of a highly pathogenic virus. 

ANGIOTENSIN CONVERTING ENZYME-2 commonly known as ACE-2 is a single-pass type 1, an integral membrane protein that covers the entirety of a cellular membrane [transmembrane protein]. It has a key expression in vascular endothelial cells, renal cells and Leydig cells of the testis. Analysis via Polymerase chain reaction [PCR] revealed it is also expressed in cells of the lung and gastrointestinal tract. Angiotensin II is the major substrate of ACE-2, meaning it negatively regulates the Renin-Angiotensin System.

ACE-2 and SARS-CoV-2 

Evidence reveals that the SARS-CoV-2 virus also uses ACE-2 as a receptor for entering the cells. There are similarities between the mechanism of viral entry into different cells between humans and animals. This creates a better foundation to the factorize a higher probability of the same virus infecting humans due to contact residues that have been found between Spike protein and ACE-2. 

The ACE-2 in humans is glycosylated at following binding sites – N53, N90, N322N53 did not give similarities in any animal species. N90 was not the site for glycosylation in ACE-2 in the following animals – mouse, pig, racoon, civet, fox, and chicken. N322 was not the site in mouse, rat, cattle, sheep, and pangolin.

But the big risk arises after it was found that some species have additional glycosylation sites in the same region. In chicken residue, L79 is a potential site with M82 being the sites in pangolin and rat. Drawing from the results, the most interesting is the ACE-2 proteins in farm animals and pet cats, as they are the next plausible reservoirs of SARS-CoV-2. Until now, there are chances of minimal exchange and therefore does not pose an intermediate threat of infection.

It should be reflected that for generations cattle producers have been dealing with infections in farm animals from different strains of coronaviruses. Animals caretakers and veterinarians have come across coronavirus infections in swine – porcine epidemic diarrhoea [PED] virus and Transmissible Gastroenteritis [TGE] virus and in companion animals – Feline INFECTIOUS peritonitis [FIP] virus. As discussed above, the difference in protein structure and varying sites, show that there is a lack of consistency in the types of vaccines used in animals, which means the evidence of its usefulness in humans is even more variable. 

Precautions and quarantine:

Practising precautionary measures during the pandemic will guarantee that there is a secure, safe, and stable food supply. Preparing well in advance for plausible viral interactions in livestock should include maintaining a proper source for feeding and medications. In case, any abnormal behaviour is detected, or if any unit of the livestock shows the usual symptoms of COVID-19 disease, it is best to inform your veterinarian as a better effort towards disaster management. 

Drugs and SARS-CoV-2 VIRUS

The present fight against the pandemic caused by the SARS-CoV-2 virus has been solely dependent on prevention and containment. But there is hope as more and more existing drugs are showing positive results towards inhibition of the SARS-CoV-2 virus. One such drug that surfaced quite recently is Ivermectin. It is an FDA- approved drug used for parasitic infections. It was originally known to be an inhibitor of the interaction between the HIV-1[Human Immunodeficiency Virus-1] protein and the importer protein [IMP ɑ? 1]. Its inclusion on the WHO model list of essential medicines makes Ivermectin widely available across the globe. 

Ivermectin is responsible for opening the glutamate sensitive chloride channel currents in helminths, which is believed to be the reason why it shows such anti-parasitic activity. It is the drug of choice for the treatment of Onchocerciasis and Strongyloidiasis, both of which are parasitic infections. It is also effective against several intestinal nematodes including Ascariasis, Trichuriasis, Cutaneous Larva Migrans, Wucheria bancrofti, Brugia malayi, Masonella ozzardi and Loa loa. It is also used for the treatment of scabies and head lice. 

The reason why ivermectin might be effective against the SARS-CoV-2 infection.

Once the SARs-CoV-2 virus enters the cells of a body using the H2 receptor, it releases its messenger RNA into the same cells. The infected cell then starts to translate the messenger RNA from the virus which leads to the production of viral proteins responsible for the formation of new viral cells. New viral proteins then enter the nucleus, impairing the ability of the host cell to fight the infection. Scientists believe that the viral proteins enter the nucleus of a cell through specific channels made up of Importin [Protein]. There are various forms of Importin proteins namely, Importin Type alpha [imp alpha] and Type beta [Imp Beta]. It is in this process of nuclear entry of the virus where Ivermectin has an inhibitory role. It inhibits the passage of the viral protein into the nucleus. It does so by binding to the protein channels, effectively blocking the passage of the SARS-CoV-2 viral proteins from the cytoplasm into the nucleus of the cells, in vitro. Scientist at Monash University, Melbourne, were able to demonstrate that Ivermectin killed COVID-19 virus growing in cells of primates in a culture dish. A single dose of ivermectin had a 5000-fold reduction in virus levels at 48 hours in cell cultures. Justifying that this drug has a significant impact on SARS-CoV-2, in vitro. 

The drug Ivermectin, therefore, shows ample basis for further investigation for use to cure COVID-19 patients. Other drugs that have been investigated in clinical trials against SARS-CoV-2 virus are Remdesivir, Chloroquine and Hydroxychloroquine

Although, Ivermectin is shown to be effective in a laboratory environment, is still cannot be used in humans who have tested positive for COVID-19. The potential operation of the drug to combat COVID-19 needs funding to conduct clinical trials to confirm the effectiveness of the drugs at levels that are safe for human dosing. 

Based on what is already known, the most common adverse reaction of ivermectin is the Mazzoti reaction. The compromise takes place only when ivermectin is used for the treatment of Onchocerciasis, a parasitic infection.

 The Mazzoti reaction was first described in 1948, it is a symptoms complex seen in patients after the treatment of Nematode infestation. This was seen to occur particularly with the medication diethylcarbamazine [DEC] and the same symptoms occurred with Ivermectin. Mazzoti reactions are known to be life-threatening, characterized by symptoms such as fever, hives, generalized swelling, swollen lymph nodes, tachycardia [fast heart rate], hypertension [low blood pressure], joint pain and abdominal pain. Whilst using Ivermectin to treat onchocerciasis particularly, there is a 25% chance of Mazzoti reactions and 2% chance of diarrhoea. Treating COVID-19 with the same drug it is unlikely that Mazzoti reaction should surface. Ivermectin should not be administered to pregnant or lactating women and to children weighing less than 15 kilograms. 

Conclusion

The emergence of SARS-CoV-2 is definitive of the firm relationship existing between animal and human health, conditions in the ecosystem and human habits. It is strongly agreed that many viruses have existed in their natural reservoirs for a great deal of time. The constant jumping of the same viruses from their natural hosts to human species and other animals is mainly due to factors such as modern agricultural practices and urbanizations. Therefore, it is safe to say that the most constructive method of preventing viral zoonosis and reverse zoonosis is to maintain these barriers between human society and natural reservoirs. Despite the probable animal origin, the SARS-CoV-2 virus causing COVID-19 has not yet infected many animals including companion animals and farm animals, although human cases are now quite common. But there is a need to observe and investigate all animal species that are in close contact with humans for signs of infection. The current situation is saturated with vulnerabilities if new evidence emerges in terms of the virus behaving differently than what is expected.