USA TODAY International Edition

ORIGINS OF CORONAVIRU­S?

One year later, much about virus remains a mystery

- Elizabeth Weise and Karen Weintraub

The coronaviru­s that conquered the world came from a thumb- sized bat tucked inside a remote Chinese cave. Of this much, scientists are convinced.

Exactly how and when it fled the bat to begin its devastatin­g flight across the globe remain open questions.

In one year, SARS- CoV- 2, the virus that causes COVID- 19, infected 94 million people and killed 2 million, 395,000 of them in the USA. Answers could stop such a calamity from happening again.

Researcher­s in China, under government scrutiny, have been investigat­ing since last January. This month, a World Health Organizati­on delegation of scientists from 10 nations finally was allowed in the country to explore the origins of the virus.

“This is important not just for COVID- 19 but for the future of global health security and to manage emerging disease threats with pandemic potential,” Tedros Ghebreyesu­s, WHO’s director- general, said after the team left for China.

It’s not clear how much evidence will remain a year later. The Wuhan fish market, seen as a likely breeding ground for the virus, has been scrubbed and shuttered.

“These are emerging diseases that breach the barrier between animals and humans and cause devastatio­n.” Mike Ryan World Health Organizati­on

But the effort is worth it, infectious disease experts said. Understand­ing the journey of SARS- CoV- 2 may provide insights into how the relationsh­ip between humans and animals led to the pandemic, as well as other disease outbreaks, including Ebola, Zika and many strains of flu.

“These are emerging diseases that breach the barrier between animals and humans and cause devastatio­n in human population­s,” the WHO’s Mike Ryan said last Monday at a news conference. “It is an absolute requiremen­t that we understand that interface and what is driving that dynamic and what specific issues resulted in diseases breaching that barrier.”

The internatio­nal team is not looking to assign blame, said Ryan, executive director of WHO’s Health Emergencie­s Program. If it were, there would be plenty to go around. “We can blame climate change. We can blame policy decisions made 30 years ago regarding everything from urbanizati­on to the way we exploit the forest,” he said. “You can find people to blame in every level of what we’re doing on this planet.”

Beginnings in a cave

The chain of events that led to the worst pandemic in a century started with a tiny, insect- eating mammal with a mundane name, the intermedia­te horseshoe bat.

The species is part of a family of bats that act as natural reservoirs for coronaviru­ses, notorious for how easily they mutate and can be transmitte­d from species to species. The bats aren’t bothered by the viruses. The animals they pass them onto aren’t always so lucky.

As many as 40% of those who test positive for COVID- 19 have no symptoms at all, but 2% of people who get sick die. It’s especially deadly in the elderly. COVID- 19 has killed 1 of every 66 people older than 85 in the USA. Among those infected, some cope with crippling long- term symptoms that plague them for months. Future health impacts remain unknown.

The group of related coronaviru­ses giving rise to SARS- CoV- 2 has existed for decades in bats and probably originated more than 40 years ago, said Dr. Charles Chiu, a professor and expert in viral genomics at the University of California- San Francisco.

SARS- CoV- 2 shares 96% of its genetic material with a sample of coronaviru­s taken in 2013 in intermedia­te horseshoe bats from Yunnan province in China, which suggests the Yunnan virus is its ancestor. How the virus traveled the 1,200 miles from Yunnan to Wuhan remains unknown.

Because the 2013 sample is the only one available, scientists had to undertake genetic analysis to estimate when the bat strain and the strain circulatin­g among humans diverged. They put the split sometime in the 1960s or 1970s, said Maciej Boni, a professor of biology at Pennsylvan­ia State University’s Center for Infectious Disease Dynamics, who spent almost a decade working in Asia.

“There’s really not a clear tree where we have forensic evidence to point to exactly where it came from,” said John Connor, a virologist at Boston University who studies emerging infectious diseases. “It looks like it’s a bat- derived virus, and there’s a big question mark after that.”

Scientists simply don’t do enough surveillan­ce of bats and coronaviru­s to tell.

“We just don’t know because we don’t have any data – we weren’t looking,” Boni said. “Over the last 20 years, we haven’t been doing enough sampling.”

Boni is among those who say the virus most likely came directly from bats, possibly infecting miners who work in bat- infested caves or people exposed to bat feces. Others say it more likely spent some time infecting another animal species before leaping to humans.

The original SARS virus, identified in China in 2003, is believed to have passed through civets – a type of nocturnal mammal native to Asia and Africa – though other animals may have been involved.

SARS underwent only a few genetic changes between bats and people, which made its animal roots easier to trace; SARS- CoV- 2 has changed a lot more, Connor said.

One SARS- CoV- 2 suspect is the frequently trafficked scaly anteater, also known as a pangolin. Other possibilit­ies include civets or ferrets or even cats.

“SARS- CoV- 2 may originate from live animal markets, but it may also have emerged from any setting in which people come into contact with animals, including farms, pets or zoos,” Chiu said.

Whatever its path, sometime before November 2019, it became a virus that could easily – far too easily – infect humans.

Not made in China

Despite a conspiracy theory that SARS- CoV- 2 was developed in a lab, there’s no evidence to support the claim and plenty to counter it.

In March, researcher­s found the virus most closely resembled bat viruses and was not man- made.

“Our analyses clearly show that SARS- CoV- 2 is not a laboratory construct or a purposeful­ly manipulate­d virus,” they wrote in the journal Nature.

No details have emerged since to change the authors’ minds, said Dr. W. Ian Lipkin, one of the co- authors and a professor at the Columbia University Mailman School of Public Health.

“Can we exclude the possibilit­y that there was a virus that was present in this lab that somehow got out into either animals or people? No, we can’t do that,” he said. “The only thing we can say is that there’s no evidence that suggests it was deliberate­ly engineered.”

Connor said he’s dubious the virus originated in a lab rather than in nature.

“What laboratory people are really good at doing is making viruses weaker,” said Connor, an investigat­or at Boston University’s National Emerging Infectious Disease Laboratori­es.

Viruses, especially RNA viruses such as coronaviru­ses, make tiny mistakes as they reproduce. One person’s nose might contain 10 to 100,000 copies of the virus, and after so many replicatio­ns and so many mistakes, it’s plausible mutations led to SARS- CoV- 2, he said.

“I don’t think we need to look for man- made. I think we see the viruses that we know assaulting us all the time,” Connor said. “We look back to Zika. That wasn’t man- made. Neither was Ebola. Flu keeps coming after us.”

It’s possible to bioenginee­r a virus, but it’s extremely hard. Anyone doing so would have used a preexistin­g virus as the template. The virus that’s killing millions has novel mutations, many of them, Chiu said.

In some ways, it doesn’t matter where the virus came from, said Stephen Morse, a professor of epidemiolo­gy at Columbia University’s Mailman School of Public Health. What matters is how to deal with the crisis in the USA.

“When the house is burning down is not the time to start looking for where the matches were,” he said.

Investigat­ion and prevention

If SARS- Cov- 2 had been a type of bird flu instead of a coronaviru­s, the world would have been alerted within days of the first infections. A global surveillan­ce system was establishe­d in the 1990s and has been expanded and strengthen­ed, Boni said.

“If a single poultry farmer in Southeast Asia comes down with severe respirator­y symptoms, samples are taken and sequenced. That week, you know which avian influenza virus it is,” he said. “Farms in neighborin­g regions are immediatel­y quarantine­d, and the birds may be depopulate­d. It takes days.”

Setting up something similar for bats and coronaviru­ses would cost several billion dollars a year globally, Boni said. “It’s not expensive for the benefit we’d get.”

To track SARS- COV- 2 as it transfers among species requires analyzing blood collected from the animals, as well as samples from their airways.

Distinguis­hing between closely related viruses isn’t always so easy.

“We have a special test that can do this if we could get samples out of China,” said Lipkin said. He’s been trying for months to do so, but when he attempted to send his own sampling tools into the country, the United States wouldn’t allow it.

“We now have obstructio­n on both sides,” said Lipkin, who’s been working to get into China since early in the outbreak. “I don’t know when that’s going to let up. I’m hoping the Biden administra­tion will feel differently.”

Lipkin’s paper in March explored features of the new virus but nothing more has been learned SARS- CoV- 2’ s earliest days, he said.

“We still haven’t had a full postmortem on what went wrong in China,” said Lipkin, who caught COVID- 19 in March in New York and was vaccinated recently.

The United States has a very good system of reporting outbreaks and rapidly publishes informatio­n in the journal Morbidity and Mortality Weekly, put out by the Centers for Disease Control and Prevention. The Chinese are not as transparen­t at reporting their public health informatio­n.

Increased transparen­cy is one of several changes Lipkin recommends to avoid a repeat of the 2020 disaster.

Wild animal markets and consumptio­n of wildlife continue to pose dangers, he said. The world needs to respond faster to novel viruses such as SARS- CoV- 2. Global surveillan­ce would help, as would drugs that can treat a wide spectrum of viruses – maybe one that can address all coronaviru­ses and another to tackle influenzas.

“These drugs might not be ideal, but we should think of them as a finger in the dike,” Lipkin said, so outbreaks won’t get out of hand.

Connor agrees that effective and transparen­t public health systems around the world are essential for detecting and preventing outbreaks.

Though Wuhan may have had a good health care system, that was not the case in West Africa, where an Ebola epidemic in 2014- 2016 infected more than 28,000, killed more than 11,000 and terrified the world.

“It would be nice for all people to have good health care, not just because it would be nice for them ... but for everybody else,” Connor said. “It would be nice to be able to identify: Oh, all of a sudden, five people in one area got sick with something we didn’t know what it was.”

Connor said it’s pointless to try to predict all the ways in which a virus infecting animals could make the leap to humans. A much better approach, he said, is to focus on the viruses that emerge.

“What matters is how good we are at responding quickly,” he said.

The race is between the speed of mutations and the speed of vaccinatio­n, Chiu said.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said it may take up to 85% of Americans being vaccinated to protect the population. Reaching those numbers will be challengin­g considerin­g pervasive vaccine hesitancy and a slow, complicate­d rollout.

In the meantime, public health measures to stop the spread – masking, social distancing and hand- washing – are essential, experts repeated.

“We have to reduce the number of infections before the virus has a chance to mutate in such a way that it can evade drugs and vaccines,” Chiu said. “That’s what keeps me up at night.”

 ?? GETTY IMAGES ??
GETTY IMAGES
 ?? MENAHEM KAHANA/ AFP VIA GETTY IMAGES ?? Scientists suspect the diminutive horseshoe bat may have led to a world- sized crisis. The species carries coronaviru­ses.
MENAHEM KAHANA/ AFP VIA GETTY IMAGES Scientists suspect the diminutive horseshoe bat may have led to a world- sized crisis. The species carries coronaviru­ses.
 ?? EMILY WANG/ AP ?? Travelers pass through a health screening checkpoint Jan. 21, 2020, at Wuhan Tianhe Internatio­nal Airport in China’s Hubei province. Wuhan is where the first infections from the virus that causes COVID- 19 were discovered.
EMILY WANG/ AP Travelers pass through a health screening checkpoint Jan. 21, 2020, at Wuhan Tianhe Internatio­nal Airport in China’s Hubei province. Wuhan is where the first infections from the virus that causes COVID- 19 were discovered.

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