COVID-19 Pandemic: Perception and Contributions of Veterinarians

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Introduction

Corona Virus Disease-19 (Covid-19) is a viral infection caused by a novel strain of corona virus (SARS-CoV-2) which was not known to exist anywhere in the world  before it was first reported from Wuhan city in Hubei province of China on December 26th 2019. It is third corona virus after SARS-Cov and MERS-Cov which crossed species barrier to human but only it assumed pandemic status. It spread to all continents except Antarctica attaining dangerous proportions. Eventually, Covid-19 outbreak was first declared a Global Public Health Emergency on 30 January 2020 and later on 11 March 2020 a pandemic by World Health Organization (WHO). Origin of this virus and a possible animal reservoir is still under investigation. This pandemic is still haunting the world in 219 countries through human to human transfer and being maintained by natural and by antigenic mutant strains such as British, South African, Brazilian and double mutant variants. Global count of Covid-19 as on 3April 2021 is 130,820,485 infected cases and 2,850,523 deaths.

COVID-19 Pandemic Indian Scenario

Corona virus causing COVID-19 pandemic in India began in January 2020 and soon increased in March and reached to record first peak which subsided after quick preventive measures viz. lockdown, quick diagnosis to detect infected person followed by their complete isolation and appropriate treatment, quarantine of infected persons coming from abroad, adoption of sanitary measures and follow measures (use of mask, hand washing and use of sanitizer, keeping distance of 2-feet) to prevent person to person transfer of virus. However, currently the rise in infected cases has been witnessed and it appears the second wave of COVID-19 due to SARS-CoV-2 virus and its Variants Of Concern (VOC) viz British (B.1.1.7), South African (B.1.351) and Brazilian (P.1). Recently, a new double mutant variant (E484Q, L452R) has also been detected in India, which allows the virus to escape immune response posing difficulty in the mission to control COVID-19 pandemic. Prediction is that, witnessing the rise of corona meter of infected cases and dead cases, second peak will be in mid April to May 2021.

As of 3rd April 20121, there have been 12,392,260 confirmed cases and 164,110 deceased across India . Two indigenously produced vaccines viz. ‘Covishield’ (Oxford-AstraZeneca) and ‘Covaxin’ (Bharat Biotech, NIV) are being used for vaccinating population in priority groups made by the government. A third generation vaccine ,  3-dose needle-free DNA plasmid platform Covid19 vaccine ‘ZycoV-D’ ( ZydusCadila) is also under phase-3 clinical trial and is expected soon; efforts to make it 2-dose is also in progress. Meanwhile, a mRNA vaccine (Gennova Pharmaceutic als) is also in pieline. Current rate of vaccination in India is far greater than the spread of corona virus. Rate of reproduction of corona virus called R factor (= RO pronounced as R-naught), let’s know how many healthy persons an infected patient can infect. R-factor in second wave is currently 1.32 meaning that one infected person on an average can infect 1.32 healthy persons.

Origin of Covid-19 and its Veterinary Linkage

WHO in collaboration with China is still investigating to find a source of Covid-19 infection which will determine how virus crossed to human population? Possibility of an animal reservoir spreading this deadly infection is yet to be established though the genetic sequencing has indicated that SARS-CoV-2 is closely related to a corona virus circulating in Rhinolophus bat (Chinese Horseshoe Bat) population. However, the route of transmission to human is yet to be established. Most likely, virus originated in bats and transferred to human through an intermediate host viz. pangolin as evident by investigations done so far.

Many animal species are found infected with Covid-19 virus; both experimentally as well as naturally through contact with infected human. However, so far poultry and cattle are not found susceptible to experimental infection. Some dogs and domestic cats as well as mink, lion and tiger, which were in contact with infected humans showing signs of illness, have tested positive. Possibly, the infected animal is capable to transfer the Covid-19 infection to other animal as well as to in-contact human.

Covishield vaccine has a veterinary linkage in its development. This vaccine used a replication-deficient chimpanzee adenovirus as vector modified genetically encoding SARS-CoV2 spike(s) glycoprotein.

Is Covid-19 Zoonotic??

The pandemic Covid-19 has been classified as a zoonotic disease. It seems premature as no animal reservoir has been found so far. It is a fact that about more than 70% human- disease causing pathogens came from animals resulting to a large list of zoonotic diseases. Though the circumstantial evidence   suggests the possibility of initial zoonotic emergence of COVID-19. The first case in human was linked to Hunan South Seafood Market which sells exotic live animals. Snake, pangolin or even mink or dog or any other wild animal are suspected to serve as a possible reservoir to spread the virus causing COVID-19 virus. This needs to be established by proving Koch’s postulates.

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Hot spot for exposure of initially infected an elderly infirm person found was Wet Seafood wholesale Market of Wuhan (Hubei Province) China. None of his family member became infected and thus source of his virus remained unknown. Also first 41 and 7 cases had no contact with seafood market. Therefore, it was opined that virus was not amplified in the market and may neither be site of origin nor the only source of the outbreak. It was also suggested that virus might have been circulating unnoticed and might be imported there from elsewhere and later amplified. There are some cases of COVID-19   in animals viz. cat dogs and ferrets as also captive-managed mink, lions, tigers, deer, mice confirming reverse zoonosis (zooanthroonosis). Almost all human infections all over the globe are of human to human transfer (community transfer)

Contributions of Vets in Covid-19 Pandemic

Experimental Animal Models

A promising animal model which closely mimics the clinical picture is required for evaluation of potential drugs and clinical trials of developed vaccines for Covid-19. This is achieved through One Health Approach inclusive of human, veterinary and environmental sciences. Various animal models have been suggested with its own merits and demerits. Presently mouse, ferrets, golden Syrian hamsters, monkeys are preferred for researches on COVID-19 infection. Others viz. bats, cats are also suitable but pig, dog, chicken and tree shrew are minimally infected, so are of limited use as experimental animal for COVID-19 virus research. Several cell-lines derived from human and animal, stem cells, organ explants and organoids are usable in covid-researches to understand drug/viral efficacy, immune-resposne, pathogenicity mechanism and histopathology etc.

Veterinarians of the world are all discharging their responsibility of providing clean: germ –free (gnotobiotic), SPF experimental animals to covid researchers. Genetically modified mouse expressing (h) ACE2 receptor is model of choice to for SARs-CoV researches.

Reliable, Quick and Accurate diagnosis

3-T (test, track, treat) is being adopted through out the globe for wiping COVID-19 pandemic. Testing of COVID-19 is being done by two diagnostic tests: (i) Antigen Test, (ii) Polymerase Chain Reaction (PCR); recommended by Food & Drug Administration (FDA) of USA.

Real-Time Reverse Transcriptase (RT)-PCR detects SAR-COV-2 virus’s genetic material whereas Antigen Test detects specific protein of the virus.  A third, Serum Antibody Test, is also being used to know the level of antibodies after SAR-COV-2 infection and to do sero- survey in the population. A CRISPER-Cas12a and Cas13a-based assay has been developed which provide results faster with 95% positive predictive and 100% negative predictive agreement with real-time RT-PCR.  All the state and national Animal Diagnostic Laboratories are well – equipped and scientists are proficient and experienced to perform these tests. Several animal disease testing laboratories (NISHAD, Bhopal; IVRI, Izatnagar; NRCE, Hisar, Int.Centre for FMD, Khardha; Vety. College, Mathura) are providing COVID-19 test services hand-in hand with human-disease testing labs.

A novel 20-second Virolens Covid (iAbra, TT electronics) screening test has been innovated. This test uses a brand new device which combines microscopic holographic  imaging and artificial intelligence (AI) software technology. It has 98.1% sensitivity and 99.7% specificity. Test is usable at airports. Railways, schools, sport arena, cinema halls etc. Similarly, an AcuVid Covid-19, a rapid antigen saliva test has also been developed but pending for clinical trial before releasing for use in the field.

Prevention, Control and Treatment

“Prevention is better than cure” principle is adapted to control animal diseases and this principle is also in place as well to control COVID-19 pandemic.  Rapid identification of Covid-19 infected cases as done to contain animal epidemic by reliable diagnostic tests, namely Ag-detection and RT-PCR followed by complete isolation and treatment is done. Also the areas where such cases occur are declared as containment zone to prevent spread the virus. Incoming positive and suspects cases from outside of Indian Territory are quarantined till proved negative. As no specific and effective treatment for cure of COVID-19 is available, infected cases are given supportive care which includes: symptomatic treatment, fluid therapy, oxygen support and medicines, device support to affected vital organs. Helpful antiviral drugs such as Remdesivir, Chloroquine or hydroxychloroquine with or without Azithromycin, Ivermectin, Lopinavir/Ritonavir/Tocilzumab, blood thinners, corticosteroids  and other HIV Protease inhibitors

Convalescent Plasma therapy and monoclonal antibody therapy to  severe COVID-19 patients is significant method of cure. Anti-Covid-19 serum is proposed to be produced at CRI, Kasauli (Himachal Pradesh) most possibly in horses. It is likely to replace plasma therapy and anti-serum will also be useful in developing new diagnostic tools.

Is COVID-19 Testing Of Animals Necessary??

It should be clearly understood that human zoonotic epidemic and pandemic can not be controlled unless these are controlled in animals. Covid-19’s effect in animals is not known as yet. After, a tiger tested positive for covid-19 in New York’s Bronx Zoo in April 2020, zoos in India were on high alert and monitor animals. Three institutions were permitted to test animals:  Indian Veterinary Research Institute (IVRI), Izatnagar (Bareilly); National Institute of High Security Animal Diseases (NIHSAD) Bhopal; National Research Centre on Equines (NRCE) Hisar. None of the samples from tigers, leopards, monkeys, bats, elephant and boar proved positive. So far there is no evidence to suggest that an infected animal can transfer covid-19 to human or vice-versa but no chances can be taken for pandemic of this magnitude. So testing of wild and even domesticated animals must continue in order to contain the pandemic.

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Innovative Vaccine Approach

Scientists have designed a vaccine candidate that induces protection in mice against a wide range of related corona viruses. This innovation may help protect against future pandemic-potential viruses crossing from animals to humans. Further, a novel ‘Mosaic Nanoparticle’ vaccine is also likely to be prepared having shape like a cage  made of 60 small protein tag representing identical proteins  which function like a piece of Velcro. Viral pieces tag on the cage resulting nano-particle having spikes representing different virus strains.

An Artificial Intelligence (AI) framework has been invented to create COVID vaccine candidate within seconds at a time when Covid-mutations are emerging; bringing existing vaccines effectiveness questionable.  AI assisted method predicted 26 COVID vaccine candidates, out of which 11 best to construct a multi-epitope vaccine. A Genomic Consortium (G2P-UK) has been formed which will look solely into mutation occurring places. Designed proposed vaccine  framework can tackle 3 existing mutants and potential unknown mutations.

Animal Trade Safety

Surveillance of  domesticated food animal- and wild animal -population for COVID-19 is essential for preventing SARS-COV-2 from establishing in another animal species especially companion and food animals. Zoonotic epidemic or pandemic are inevitable unless governments establish legislation  for wildlife trade,, protection of habitat and for minimization of wildlife-livestock-human interaction. WHO and OIE recommend that COVlID-19 related sanitary measures should be applied along with risk assessment for international movement of live animals and their products

Response of OIE & WHO

Two international organizations, Office International des Epizooties (OIE) and World Health Organization (WHO) are responsible to contain and control the Covid-19 pandemic affecting animal and human population of the world. One-health approach recommends that veterinarians, medical doctors and human and animal health scientists should be involved in the fight against COVID-19 pandemi

Prospects of COVID-19 Pandemic

Covid-19 pandemic has shaken the global health system and economy of the world. It is still with us with no sign of leaving us. Fact is that in every decade of 21st century, there is a new major corona-virus epidemic; Severe Acute Respiratory Syndrome (SARS) in 2002, Middle East Respiratory Syndrome (MERS) in 2012 and now Corona Virus Disease-19 (Covid-19) pandemic in 2019.Currently pandemic COVID-19 continues to evolve, we are simply moving to new phase of pandemic. SARS-CoV-2 probably can never be eradicated because of its probable presence in many animal species, incomplete vaccine coverage of population and variable immunological protection as also vaccine efficacy against variants. If immunity to virus is less than a year, covid-19 will continue to surge through 2025. WHO has warned that pandemics far deadlier than Covid-19 are likely in future as more countries detected new variant strains of deadly corona virus.

It is certainly clear that SARS-CoV-2 virus originated from bats which are considered as probable natural reservoir. However, its evolution and path of spill-over to humans is not yet clearly understood. Pangolins, scaly mammal, possibly acted as intermediate host for transmission to humans. SARS-Cov-2 from human shares about 96% of genome sequence with corona virus from bats whereas match between pangolin corona virus with human SARS-Cov-2 is 90.3%. But, researchers have found that bat corona virus (RaTG13) could not bind with receptors in human or pangolin whereas pangolin corona virus could bind to pangolin and human receptors. So it is still not confirm that pangolin virus was part of SARS-CoV-2’s evolution to human. All it means that possibly RaTG13 or a similar bat corona virus merged with a corona virus in a species other than a pangolin or there may be an unknown bat corona virus that could infect pangolin and then moved to humans. Searches are still on to find and establish an intermediate host to facilitate transfer to human. It is essential as only then it will be possible to control COVID-19 pandemic by blocking the path of transmission to humans.

Think Beyond COVID-19 Pandemic

There are more than 1.67 million unknown viruses infecting animals on earth and veterinary scientists want to find them. Approximately, 631,000 to 827,000 unknown animal viruses could potentially infect humans.  A 10-year Global Virome Project comprising international scientists is scheduled to launch late this year. It aims to identify hundreds of thousands of unknown animal-borne viruses  in a hope to prevent them from causing next great pandemic.

Bats are viral reservoir host for several emerging viral epidemics and now pandemic. There exist about 1400 species of bats which are a source of high viral diversity and they directly or indirectly (following genomic recombination, gene mutation, gene duplication loss/gain) cause a new outbreak. More than 5717 animal viruses have been associated with bats and almost all RNA viruses have the ability to adapt to changing environment through high genetic variability. Virome diversity of   bats and bat- human interaction is under extensive investigation in order to designs new control measures in future. Likewise, veterinarians and other researchers are busy continuously to monitor new human pathogen in bats and impact of bats in their diffusion to humans. Needless to say that bats span of life is approximately 300 years and as such they perpetuate pathogens like SARS-Cov2 virus for extremely long time in the environment and to other hosts including humans.

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Latest of the Latests

Two New corona virus mutants (N440, E484K), which are cause of concern, has been detected in India; being prevalent in Maharashtra, Kerala, Telegana and Andhra Pradesh states so far . These have been found during second wave of COVID-19 and N440K mutant can escape the immune system and can cause reinfection in patients already recovered from Covid-19. This N440 mutant has high prevalence of over 33% in Andhra Pradesh.

Twenty Global leaders along side WHO on 30.3.21 have called for an urgent International Pandemic Treaty to help prepare for future pandemics, in consideration that Covid Pandemic is greatest challenge for global community since late 1940s. ‘No one is safe until all are safe’ is bottom line of propsed Treaty and is expected by the end of 2021.

Russia  on 31.3.21 announced registering of world’s first corona virus vaccine  ‘Carni-vac-cov’ for animals; production will start in April 2021 Vaccinated animals(dog, cat, mink, fox etc.) developed antibodies to corona virus in 100% cases. It will prevent Covid-19 in animals.

In San Diego Zoo Safari Park, where first great apes Gorilla tested Covid-19 positive, later other 8 become positive; all vaccinated with experimental vaccine developed by Zoetis- pharmaceutical company.

A four week WHO-China Joint Mission , comprised of 10 international experts, was aimed to find clues as to how the COVID-19 virus originally jumped from animals to humans (?) but it remained uncertain in establishing origin of the pandemic and only could put-forward hypotheses for the origin of virus. Mission concluded to recommend further researches to find firmly the origin of virus and establish link  intermediate animal host for spill- over to human.

Thoughts and Actions at Last

SARS-Cov2 virus causing deadly COVID-19 pandemic has shown to have an ecological origin in bat population and thus is of natural origin and is not a manipulated or constructed virus. This pandemic has disrupted trade, employment, travel and governments are taking measures to control the spread of virus and minimize mortality and morbidity. Nobody knows how long this pandemic will continue? Future pandemic of zoonotic origin are likely to occur and, therefore, protection of human-health on this planet should be ensured on top priority. One health approach needs integrated public health, animal health and environmental efforts to stop jumping pandemic-potential pathogens from animal/wild animals to human population.

List of zoonotic pathogens (>70% human pathogens) as also list of pandemic is lengthening. Global efforts are in progress to prevent future occurrence of such pandemic. Two actions are mention worthy:  launching of PREZODE (PREventing ZOonotic Disease Emergence), a new French-led international research coalition at the One Planet Summit and a US Congress Bill S37 in pipe-line ‘Preventing Future Pandemic Act of 2021’. A leading Abbott pharma formed a “Pandemic Defense Coalition” which will establish a global network to monitor emerging and re-emerging threats and help track evolution of new viruses and their surveillance. All these programmes will have expert veterinarians specialized in microbiology, molecular technology, biotechnology, veterinary public health epizootiology etc.

India also emphasized to come up with long term strategies and road maps systems to deal future pandemics. UN general assembly proclaimed December 27 as the ‘International Day of Epidemic Preparedness’ and UN ‘Decade of Healthy Ageing 2021-2030’

Time has come to mobilize resources and accelerate mission oriented projects and policies to safeguard human-life at ‘Earth’ rather than searching life at other planet ‘Moon’

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