COVID-19 pandemic puzzle: tracing the origins of SARS-CoV-2

Dr Lekshmy Sreekumar, Science writer
Tracing the origins of SARS-CoV-2 virus

It was by pure chance that bat expert Wang Linfa found himself in the Chinese city of Wuhan in January 2020. Wang was attending the annual scientific retreat at the Wuhan Institute of Virology (WIV), where he once served as chairman of the scientific advisory board. While the first reports of a SARS-like virus outbreak in Wuhan were making headlines around the world, the virus still felt like a distant threat, even to people in Wuhan. No one had any inkling to what degree this new virus was going to penetrate the population and how it was going to change the world.

“My friends from WIV and I went for dinner to a local restaurant three nights in a row. We discussed this new virus. But my discussion was limited to the Wuhan institute as I didn’t have access to the hospitals to study the situation more closely,” recalled Wang, who is a professor with Duke-NUS’ Emerging Infectious Diseases (EID) Programme, about his time in Wuhan.

While he went about his business as usual, he declined to visit the Wuhan Huanan Seafood market, which had become associated with the outbreak, and took the necessary safety precautions, like washing and sanitising hands and maintaining social distancing, which Wang said come naturally to a researcher.

Wang only realised the seriousness of the situation when he left Wuhan four days later, on 18 January 2020. He could board the flight to Singapore only after going through temperature screening three times at the airport.

“At the airport, I felt the urgency. The government implemented stringent screening measures at the airport and railway stations,” said Wang, observing that no one seemed to be particularly alarmed yet despite the increased screening.

Five days after he left, Wuhan, a city of 11 million people, went into lockdown as the presumed epicentre of a global pandemic. But a year on, experts are still hunting for the spot where SARS-CoV-2 first jumped into humans, a quest that has turned the focus of attention some 2,000 kilometres further south to the bat caves of Yunnan and beyond to Southeast Asia.


Why puzzling out the origin is key to solving the mystery

From the very beginning of the pandemic, the World Health Organisation (WHO) has stressed the need to find the origin of the virus in order to better understand the emergence of new pathogens, identify possible exposures earlier and guide future prevention strategies. For this, a team of international experts was assigned to conduct field visits in China from 14 January to 10 February 2021.

The WHO team’s report, published on 30 March 2021, determined that the virus jumping from bats to humans via an intermediate animal was the most probable scenario, while it dismissed a theory involving the virus leaking from a laboratory as ‘extremely unlikely’.

Most scientists working in this field, including Wang, agree with the consensus conclusion from the report. But like 17 years earlier after the first SARS outbreak, the report is not the end but rather the beginning of years of work to come as scientists try to address the many unanswered questions. Virus trackers like Wang are now hunting for conclusive evidence of the first transmission events.

While the WHO report pointed Yunnan as a likely site for the jump, it could also be that the first transmission started much further afield beyond China’s borders. The best example for this is HIV. The initial human outbreaks were detected in the USA in the early 1980s, but retrospective research later discovered that the virus had jumped from animal to human in Africa in 1950s.

“That’s why cross-border surveillance is also needed to unearth the original host of the virus,” said Dr Tan Chee Wah, Senior Research Fellow from Wang’s lab.

And Tan and Wang are already working with scientists in the ASEAN region on that, as horseshoe bats, which carrying SARS-related viruses, are widely present in this region.

As likely intermediaries, the WHO report listed pangolins, mink, rabbits, raccoon dogs and domesticated cats. And in concurrence with this finding, Wang’s team discovered that SARS-CoV-2-related coronaviruses are circulating in both bats and pangolins found in Thailand. Wang’s team, in collaboration with a Thai team, made the discovery using cPassTM, an invention his team had developed after he’d returned from Wuhan in January 2020. cPassTM is the world’s first SARS-CoV-2 serological test, which can rapidly detect neutralising antibodies (NAbs) without the need for containment facilities or live biological materials, is FDA approved.

“As this test can measure NAbs from different animals in a species-independent manner, it can act as a powerful tool to investigate the role of animals in the transmission of COVID-19,” said Tan.

cpass team

Wang (centre) and team worked on developing the world’s first SARS-CoV-2 neutralising antibody test that can be used in animals as well as humans.

Genetic changes in the virus and its implications on the pandemic

One of the closest known relatives of SARS-CoV-2 is a coronavirus strain found in a bat sample from Yunnan province, China, in 2013. It is 96 per cent genetically identical to SARS-CoV-2. A recent study showed that most of the adaptations that were necessary for SARS-CoV-2 to jump from bats to humans and spread across the world arose in bats decades ago.

“Viruses evolve quickly and we can use the rate at which these mutations accumulate as a ‘molecular clock’. For example, if one mutation arises per month, six mutations difference between two viruses means they shared a common ancestor six months ago”, said Gavin Smith, professor and interim director of Duke-NUS’ EID Programme.

Using this molecular clock, scientists estimated that the mutations known to allow human infection by a coronavirus were present in bat viruses found many years ago.

“This does not mean that there were sporadic human infections, but that is possible. Virus populations are so diverse that there is a good chance that the right combination of mutations arose at random,” added Smith.

Examining a plate of virus

Researchers are closely monitoring the changes in the virus over time

Solutions to prevent the next pandemic

With an estimated 1.6 million different viruses circulating in the animal kingdom, knowing which ones are just a few mutations away from spreading to humans is much like following a raindrop once it lands in the ocean. But the current wait-and-respond approach is not sufficient, experts agree.

“We have a whack-a-mole policy right now. We wait for a pathogen to cause a lot of morbidity, and then we respond. We have to figure out a better way to predict these and mitigate them before they cause a lot of harm,” said Gregory Gray, a professor of medicine, global health and environmental health at Duke University. He also holds appointments at Duke-NUS Medical School in Singapore and Duke Kunshan University in China. 

To achieve that, experts urge greater investment in identifying and tracking the viruses in animals that are most capable of infecting humans. While this is a long-term project, a more immediate viral firebreak can be established by taking steps to reduce human exposure to wild animals, particularly farmed wildlife.

Smith highlights that while the solution is just two-pronged, its implementation is far more complex.

Everything sounds simple in practice but these are complicated issues, often with major economic consequences,” said Smith.

Surveillance at the human-animal interface is key. Instances where humans are infected by animal viruses are relatively common, however, in most cases they result in dead-end infections that don’t spread beyond the initial infected individual. But it is these little blips that could become sentinel events.

“If we can conduct surveillance in key animal species such as bats, birds and pigs and the people who are exposed to them, we can detect virus ‘spillover’ events that could become the first step in an emerging pandemic. Then we can change some of the practices that have the highest risk of producing spillover, such as keeping wild animals in markets,” added Smith.
So long as humans continue to encroach on wildlife habitats, spillover events remain a clear and present danger

So long as humans continue to encroach on wildlife habitats, spillover events remain a clear and present danger

More than anything, then, humans should avoid disturbing wildlife habitats as the emergence of zoonotic diseases is often associated with environmental changes or ecological disturbances, such as agricultural intensification and human settlement, or encroachments into forests and other habitats.

“There are a lot of very cost-effective things we can do to prevent that kind of abuse of the world’s natural ecosystems. Limiting wildlife trade, limiting the number of species we use as bushmeat,” said Stuart Pimm, a professor of conservation ecology at Duke University’s Nicholas School of the Environment. 

Amidst all the unanswered questions and speculation, one thing is certain that the coronavirus outbreak comes from the animal world.

“It is human activity that enabled the virus to jump to people, and if nothing changes, many other pandemics of this nature will follow,” said Wang, who is working with the WHO and other international agencies such as FAO and OIE in many areas of COVID-19 management “The COVID-19 outbreak is a wake-up call for us to rethink our daily choices and actions.”