Next week, U.S. intelligence agencies are expected to release a report on the origins of COVID-19. The report is meant to address a heated public debate on whether the SARS-CoV-2 virus behind the pandemic was released from a lab or through natural spillover from an animal host.
So far, nothing definitive clinches either scenario, but two separate analyses put out this week lay out the evidence to date on the virus coming from nature. The first, published in Science Magazine on Tuesday, involves a handful of collaborators based in the U.K. and China. The second, released by Cell, involves more than 20 researchers located around the world, a cohort of preeminent virologists, epidemiologists, bat ecologists and immunologists. Both teams assert that a zoonotic spillover, which happens when a germ jumps from an animal host to humans, was the most likely scenario.
The latter study sketches out the geographic relationship of the first known cases of SARS-CoV-2 infections in Wuhan and shows that they occurred in people who were in close proximity to the Huanan wet market, the original place cases were noticed. The authors point out that two out of the three earliest known cases had direct links to the market and over half of all the cases in December of 2019 had exposures to Huanan or other wet markets in the city. This area also reported the highest rates of excess pneumonia deaths in January 2020. Scientists say this is the best evidence that the virus originated in the market rather than the Wuhan Institute of Virology. This happenstance would be one in a long line of such events.
New York Spillovers
History shows that zoonotic spillovers occur all the time. In fact, the Centers for Disease Control and Prevention claim that three out of every four new infectious diseases come from animals. According to Joel Wertheim, a biologist at UC San Diego and co-author of the Cell paper, “outbreaks and pandemics are just the tip of the iceberg,” and many spillovers are happening without our knowledge.
New York, for example, has long-standing issues with zoonotic spillover, including Lyme disease, leptospirosis, and food-borne E. coli illnesses. Foodborne outbreaks date back to the state’s slaughterhouse days that started in the mid-1800s.
Even today, slaughterhouses exist in all five boroughs of New York City and have repeatedly received citations for deficiencies, such as lack of cleanliness and sterilization of equipment. Many worry that these live animal markets are a pandemic threat to this densely populated city of over eight million residents.
In the early days of the COVID pandemic, some borough residents clamored for them to be shut down, and in August 2020, Governor Andrew Cuomo extended a moratorium on issuing licenses to live markets near New York City residential buildings. Under it, such markets are supposed to be closed within 1,500 feet of residences. A state bill that would fully prohibit these markets is currently making its way through both chambers.
The urine of rodents is one route for zoonotic spillovers in New York, According to Albert Ko, an epidemiologist at the Yale School of Public Health. He says the excrement has been tied to the transmission of leptospirosis, a bacterial infection. Worldwide, it tends to strike tropical regions more often and kills 60,000 people a year, but outbreaks occasionally pop up in New York, too. In 2017, a leptospirosis outbreak in the Bronx sickened three people and killed one.
So given the frequency of animal-to-human spillover events, how likely is there to be a large-scale outbreak in New York? Ko says this is difficult to predict. A virus often has to jump into more than one animal to become adept at infecting humans. It then needs to be in the right place at the right time, like a crowded city market, to infect enough people to start an outbreak. Animal spillover likely happens frequently, but the perfect storm of events hasn’t occurred lately to spark a large outbreak stateside—as far as anyone knows.
The most likely scenario is the SARS-CoV-2 coronavirus originated in a bat and then jumped into another species, like ones sold at the wet market, said Susan Weiss, a virologist at the University of Pennsylvania and co-author on the Cell study. There, it may have evolved enough to become better at infecting humans.
Weiss says the early epidemiological data supports this, although proof that it jumped into a second species is still lacking. But the markets in Wuhan traded thousands of wild animals throughout 2019, including high-risk species like civets and raccoon dogs. And although no animals that were tested for the virus came up positive for infection, SARS-Cov-2 was detected in environmental samples and in associated drainage areas.
Weiss says scientists will have definitive proof when they can find an intermediate species infected with a coronavirus that more closely resembles SARS-CoV-2. Until then, we can’t know for sure.
Long Road To Origins
But just because we don’t have the evidence yet doesn’t mean we will never find it. The exact animal origins of many human outbreaks like Ebola, Hepatitis C and polio have never been identified. It took over 15 years to find the bat origins of the original SARS outbreak that started in 2002.
Wertheim from UC San Diego reminds us that viruses like HIV and Ebola had been infecting people for decades in small clusters before they blossomed into large-scale epidemics. Based on the amount of genetic diversity of HIV observed worldwide, scientists estimate that it had been circulating among human populations for years before it was officially recognized. And small Ebola outbreaks have been happening since the 1970s, but it wasn’t until 2014 that there was a major outbreak.
But Ko thinks the probability of wet markets in New York sparking a global pandemic is low. For one, they are much smaller in volume than those in Asia. Maciej Boni, an epidemiologist at Penn State and co-author of the Cell study, agrees.
He says the scale at which wet markets exist in Asia are orders of magnitude larger than in New York. Boni lived in southeast Asia for several years and says that grocery shopping there often involves interacting with live animals and that millions of customers interact with live animals on a daily basis.
“I lived in Ho Chi Minh city for eight years, and the numbers of roadside stands and individual sellers at the side of the road and markets numbered in the thousands,” said Boni, adding that on his street alone, there were dozens of bird sellers with live goose and duck. “They were right there on the side of the road, five feet away from me if I was driving past on my motorbike,” he says.
Additionally, New York wet markets are unlikely to be selling high-risk wild animals like the one in Wuhan. Domestic animals are frequently in contact with each other and pose less of a risk. But animals taken from the wild that don’t typically come into contact and are suddenly stacked next to each other in cages pose a more serious threat. According to Rachel Abbott, a veterinary pathologist at Cornell University, “That's where the bigger risk is.”
Ko also stresses that the types of viruses found in Asia, like bat coronaviruses that are transmitted through respiratory droplets, are not common here.
“But we have other problems to worry about,” says Ko. He is increasingly concerned about antibiotic-resistant strains of E. coli that have been detected in New York. A study from 2018 sampled mice throughout the state and found strains of salmonella and E. coli that can cause gastrointestinal illness, sometimes life-threatening. They also found genes in the bacteria that could confer antibiotic resistance.
One thing that might affect New Yorkers, however, is if SARS-CoV-2 reservoirs get established in wild animal populations and are then able to spread back to humans. Abbott works at the Wildlife Health Lab at Cornell University that samples hundreds of wild animals a year. The lab partners with the New York Department of Environmental Conservation to surveil diseases in wild animal populations.
Abbott is concerned about SARS-CoV-2 infecting local wildlife. Earlier this month, a study was published showing one-third of the white-tailed deer population in the U.S. tested positive for SARS-CoV-2 antibodies, a sign of a past infection. That included deer in New York. More studies are needed to determine whether deer can infect each other and humans.
Abbots says the lab at Cornell is not currently planning to test deer for the virus, but the opportunity to do so would be during hunting season in the fall. Deer are routinely brought to the lab to test for Chronic Wasting Disease, a prion-borne illness, and it is possible they might be able to test for the coronavirus through those samples, too.