The zoonotic origin of SARS-CoV-2 and its eventual establishment as an endemic virus

In December 2019, the world first become aware of a novel virus outbreak in a Wuhan Seafood Market. Within this market various live animals were being traded, a breeding ground for inter-species transmission. The SARS-CoV-2 virus (COVID-19) sequenced was a Betacoronavirus and found to be most similar to SARS-related coronaviruses from bats. There are currently seven coronaviruses that infect humans and most of these are thought to originate from bats. Many related coronaviruses are enzootic, meaning they are present in animals, as well as zoonotic, meaning they regularly spill over into humans. To pinpoint a specific animal as the source of a virus is quite difficult as we would need to identify a virus that is highly similar (>99%). For example, palm civets have been identified as the most likely animal source of the 2002-2003 SARS outbreak, as they carry a SARS-CoV related virus that is 99.8% identical to SARS-CoV.

Phylogeny of the SARS-CoV-2 strain
Phylogeny of the SARS-CoV-2 strain

Where could they originate from?

Pangolins are victims of the animal trade and have been found to harbor SARS-related CoVs that possess unusually similar genomic regions to SARS-CoV-2 that are known to be important for binding the human angiotensin-converting enzyme 2 (ACE2) receptors which are required for infection. There is evidence suggesting that particular species of pangolin and bat may co-habitat in certain environments which could facilitate the exchange of different CoVs. However, this adaptation could also be the result of independent convergent evolution.

There are many potential scenarios for the evolution of the SARS-CoV-2 virus in animals and eventual spillover into humans, although the exact details remain a mystery. Bats are great reservoirs for disease as they roost in large colonies and travel long distances, interacting with many animal species. A bat coronavirus could have evolved into SARS-CoV-2 before spilling over into humans. Or through infection of another as of yet undetermined intermediate animal, where it underwent adaptive evolution before spreading to humans. It is also possible that a SARS-related-CoV evolved into SARS-CoV-2 in humans shortly after spilling over from an animal source through rapid transmission.

Reservoirs of the SARS-CoV-2 strain
Reservoirs of the SARS-CoV-2 strain

Zoonotic consequences of the pandemic

Despite control measures, SARS-CoV-2 has continued to spread globally infecting not just humans but jumping to different animals. In particular, cats living in the same household with COVID‐19 patients are highly susceptible to infection. Lions and tigers have incidentally been infected while held captive in zoos. While infection studies have shown ferrets, cats, raccoon dogs, bats, hamsters, rabbits to be susceptible to infection.

Alarmingly, SARS-CoV-2 has spread through farmed mink in Denmark and the Netherlands, with more than 200 farms infected by November 2020. Genome analysis was undertaken in the mink and humans, revealing that the virus had not only gained significant mutations, including the emergence of 5 different variants but that it had jumped back to humans. 8 out of 24 stray cats surrounding two of the farms also showed evidence of infection. On Nov 5, the Ministry of Environment and Food of Denmark announced the culling of 17 million animals. However, the spillover of SARS-CoV-2 from humans to mink and minks to humans is not a new finding as it was first reported in the Netherlands in April, and since then has been found in numerous countries.

Minks (Source: Mads Claus Rasussen, Ritzau Scanpix, Getty Images)

Mink belong to the Mustelidae family, which includes ferrets. Ferrets are exceptional animals for modeling respiratory virus disease such as SARS-CoV-2. Ferrets can pass the virus to each other not only through direct contact but readily through the airborne spread. Mink farms place thousands of animals together in small cages which allows the virus to spread unhindered. Some of the mutations observed in the viral genome sequences taken from mink farms are suggestive of adaptation. The concern is now that it will be difficult to eradicate the virus from human populations, especially if we are not the only reservoir the virus uses for maintenance. Dutch mink fur farms are to be permanently closed by March 2021 and it is hoped that other countries will follow suit.

How is the virus passed on?
How is the virus passed on?

There are other Mustelidae species related to mink that we also have to worry about, not just in farms, but transmission to wild species. If we have a reservoir in wildlife, it becomes almost impossible to control and we may never be free of re-introductions into human populations. Animals have been at the center of this pandemic from the beginning. A team from the World Health Organization (WHO) is now conducting their much-anticipated investigation into the origins of this virus and it is hope we can uncover evidence that can help us to prevent future emergencies.

We are responsible for the health of all species, as our health and theirs are interlinked. Public health agencies with an interest in human health need to now expand their visions to include the health and surveillance of both domestic and wild animals, including the development of vaccines and therapeutics for animals to prevent potential disease and zoonotic transmission. In the case of SARS-CoV-2, humans are currently the largest reservoir of the virus on Earth, and the threat of spillover from human hosts to farmed animals and wildlife species is now evident. If we don’t address the origin of the virus and ignore the signs of its eventual establishment as an endemic virus, we will fail to protect both human and animal health.

About the author

Morgan Freney, University of Queensland
Morgan is a second year PhD student at the University of Queensland and is currently undertaking studies in translational RNA Virology. Her project focuses on pathogenic mosquito-borne flaviviruses including emerging zoonotic viruses and aims to develop broad-spectrum antibody therapeutics as well as a cross-protective vaccine to fight these infectious diseases. She avidly shares her life in the lab and passion for Virology through her Instagram profile @virus.vs.labcoat. Do follow her Instagram for a detailed insight into the life of a virologist and for in-depth information on the nuances of virology!
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