The coronavirus began in the horseshoe bat genus, Rhinolophus. The bats are natural reservoirs for coronaviruses, and the bats aren't affected by the viruses. GETTY IMAGES/ATTILA BARSAN
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 fled the bat to begin its devastating flight across the globe remain open questions.
In just one year, SARS-CoV-2, the virus that causes COVID-19, has infected 100 million people and killed 2 million, 400,000 of them in the U.S. Answers could stop such a calamity from happening again.
Researchers in China, under government scrutiny, have been investigating since January. This week, a World Health Organization delegation of scientists from 10 different nations finally was allowed in the country to explore the virus' origins.
"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 just after the team left for China.
It's not clear how much evidence will remain a year later, and what the team will be able to learn. The Wuhan fish market, seen as a likely breeding ground for the virus, has been scrubbed and shuttered.
But the effort is worth it, infectious disease experts say. 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 flu.
"These are emerging diseases that breach the barrier between animals and humans and cause devastation in human populations," the WHO's Mike Ryan said at a Monday news conference. "It is an absolute requirement that we understand that interface and what is driving that dynamic and what specific 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 Programme. 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 find 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 global pandemic in a century started with a tiny, insect-eating mammal with the mundane name, 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 how well they 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.
Humans are one of those animals.
This happens all the time – a virus harmlessly infects one creature then finds its way to another, mutates and becomes something new. The newly mutated virus can be insignificant but annoying (think common colds, some of which are caused by coronaviruses) or devastating and deadly (think smallpox.)
SARS-CoV-2 is a little of both.
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 Americans older than 85. Among those infected, some percentage — we don't yet know how many — 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 likely 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 now 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," said Boni. "Over the last 20 years we haven't been doing enough sampling."
There's really not a clear tree where we have forensic evidence to point to exactly where it came from. It looks like it's a bat-derived virus, and there's a big question mark after that.
Boni is among those who think 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, identified 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, while SARS-CoV-2 has changed a lot more, Connor said.
With SARS-CoV-2, a suspect is the frequently trafficked 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 persistent conspiracy theory that SARS-CoV-2 was developed in a lab, perhaps an infectious disease lab in Wuhan, there’s no evidence to support the claim and plenty to counter it.
In March, a group of researchers found the virus most closely resembled existing 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 prestigious journal Nature.
No new details have emerged since to change the author 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 through some sort of gain-of-function experiments."
Connor said he's also 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, who is also an investigator at Boston University's National Emerging Infectious Disease Laboratories.
Viruses, especially RNA viruses like coronaviruses, make tiny mistakes as they reproduce. One person's nose might contain 10 to a 100,000 copies of the virus, and with so many replications and so many mistakes, it's plausible chance 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."
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. 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 pre-existing virus as the template. The virus that’s now killing millions has novel mutations, many of them, said Chiu.
“We barely know how to manipulate even a few base pairs in a single viral gene," he said. "The difference between Chinese bat coronaviruses and SARS-CoV-2 is more than 3,000 base pairs."
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 we deal with the current situation, which is at a crisis state in the United States.
"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 flu instead of a coronavirus, the world would have been alerted within days of the first 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 influenza 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 a year globally, said Boni. "It's not expensive for the benefit we'd get."
To track SARS-COV-2 as it transferred 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. He's been trying for months to do so, and when he attempted to send his own sampling tools into the country the U.S wouldn't allow it.
"We now have obstruction on both sides," said Lipkin, who's been working to get into China himself since early in the outbreak. "I don't know when that's going to let up. I'm hoping the Biden administration will feel differently."
Lipkin's March paper explored key features of the new virus but nothing more has been learned since about SARS-CoV-2's earliest days, he said.
"We still haven't had a full post-mortem on what went wrong in China," said Lipkin, who caught COVID-19 in March in New York and was recently vaccinated.
The U.S. has a very good system of reporting outbreaks, and rapidly publishes information in the CDC's journal, Morbidity and Mortality Weekly. 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.
And the world needs to have the ability to respond faster to novel viruses like 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 influenzas.
"These drugs might not be ideal but we should think of them as a finger in the dike," Lipkin said, so outbreaks won't get out of hand, the way this one did.
Connor, at Boston University, agrees that effective and transparent public health systems around the world are essential for detecting and preventing outbreaks like COVID-19.
While Wuhan may have had a good health care system, that was not the case in West Africa, where a 2014-2016 epidemic of Ebola infected more than 28,000, killed over 11,000 and terrified 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, five 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 now infecting animals could make the leap to humans. A much better approach, he said, is to focus on the viruses that do emerge.
"What matters is how good we are at responding quickly," he said.
The race is now between the speed of mutations and the speed of vaccination, said Chiu.
Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, says 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 roll out.
In the meantime, public health measures to stop the spread – masking, social distancing and handwashing – are essential, experts repeat.
“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," said Chiu. "That’s what keeps me up at night.”
Contact Elizabeth Weise at eweise@usatoday.com and Karen Weintraub at kweintraub@usatoday.com.
Health and patient safety coverage at USA TODAY is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation and Competition in Healthcare. The Masimo Foundation does not provide editorial input.
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