“The most likely origin of the pandemic is what we’ve always been concerned about in this field, which is taking these sorts of wild animals that harbor exotic viruses and placing them in the middle of the tinderbox of a big city.” Michael Worobey, professor and head, Ecology and Environmental Biology, University of Arizona
“[T]he findings demonstrate that the wildlife trade needs to be better regulated to minimize the risk of pathogen spread.”
Smriti Mallapty, Nature News reporter, September 20, 2024
The COVID-19 pandemic has killed more than 7 million people worldwide since it emerged in Wuhan, China in December, 2019. Yet, to the chagrin of a large number of epidemiologists, virologists, and other scientists from human and veterinary medicine, no consensus has been reached regarding the origin of COVID-19.
In this week’s Germ Gems post, I discuss a recent study published in Cell that supports the so-called “zoonosis hypothesis.” (See “Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic,” Cell, September 19, 2024). While the whole story is still not known, I highlight what I believe are key lessons we’ve learned.
Prevailing views about COVID-19’s origin. “The zoonosis hypothesis” and the “lab leak hypothesis” are two major schools of thought regarding the origin of COVID-19. The “zoonosis hypothesis” supports a natural origin of SARS-CoV-2, the novel coronavirus that causes COVID-19, whereas the “lab leak hypothesis” purports that SARS-CoV-2 was crafted in a laboratory. Both hypotheses emerged in the first year of the pandemic.
Zoonosis hypothesis update. The crux of the zoonosis hypothesis is that some time toward the end of 2019, SARS-CoV-2 jumped (or spilled over) from an infected bat into an intermediary animal reservoir in an animal market—specifically, the Hunan Seafood Market in Wuhan, China. From there SARS-CoV-2 acquired naturally the ability to jump or be transmitted by respiratory aerosols from human to human. This hypothesis fits well with the established importance of zoonoses in the majority of infectious diseases that emerged over the past half century, the best example of which is the 2002 SARS pandemic.
The 2002 SARS pandemic was caused by another coronavirus, SARS-CoV-1. Researchers initially found SARS-CoV-1 in the masked palm civet which appeared to be the most likely reservoir of the virus residing in Chinese wild animal markets. (In 2005, researchers subsequently identified SARS-CoV-1 in the Chinese horseshoe bat.) Culling of palm civets from these markets appeared to play a pivotal role in the eradication of the SARS pandemic by the end of 2003.
Since the beginning of the COVID-19 pandemic, the zoonosis hypothesis has been extensively tested. The most recent study of samples collected from various sites in the Hunan Seafood Market before and immediately after it was shuttered in January, 2020, used new genomic techniques to determine what animal species would have been the most likely intermediate (reservoir) host for the virus. Of particular interest were raccoon dogs, which are known to be susceptible to SARS-CoV-2 infection. But other possible animal reservoirs, none of which are known to be susceptible to SARS-CoV-2, were also tested. These included masked palm civets, hoary bamboo rats, Amur hedgehogs, and the Malayan porcupine.
When the researchers parsed the genetic sequences of thousands of organisms picked up from a stall in the southwest corner of the market, they found a “hot spot” in Stall A. Samples taken from Stall A contained genetic footprints of a host of exotic animals, including raccoon dogs, as well as the viral RNA of SARS-CoV-2. (Researchers at the Chinese Center for Disease Control and Prevention had published their genomic analysis of samples from the Wuhan market in Nature in April 2024, and they too found evidence suggesting raccoon dogs can spread SARS-CoV-2 to other animals.)
This is all circumstantial evidence. It doesn’t prove that raccoon dogs, for example, were the intermediary host of SARS-CoV-2. Nor does it shed light on the putative progenitor animal of the pandemic, that is bats. (Bats are eaten in China but they’re not among the animals for sale in animal markets.)
Lab leak hypothesis of COVID-19. This hypothesis purports that the SARS-CoV-2 virus that causes COVID-19 got its start in the Wuhan Institute for Virology in Wuhan, China, where scientists were hypothetically carrying out “gain of function” experiments—experiments designed to enhance a virus’s ability to be passed from person-to-person. This hypothesis goes on to suggest that an infected researcher from the Wuhan Institute of Virology brought the manipulated SARS-CoV-2 virus to the Wuhan Seafood Market either on purpose or, more likely, by accident.
There is no credible evidence to support the lab leak hypothesis. But given the absence of definitive evidence of the zoonosis hypothesis, the lab leak hypothesis is still very much alive in certain circles. It has garnered the favor of political conservatives who lack trust in the American government and has become a “conspiracy theory” by others. It is important to emphasize the detrimental effects to science (and to the researchers who’ve been singled out) of promoting this hypothesis without any credible evidence. (See “The harms of promoting the lab leak hypothesis for SARS-CoV-2 origins without evidence,” Journal of Virology, August, 2024).
What’s been learned so far? Perhaps the most important lesson to be learned so far from the intense study and debate about the origin of COVID-19 is the potential role of live wild animal markets as a source of emerging infectious diseases. In the September 27, 2024 Medscape article, “Species Possibly Responsible for COVID Pandemic Identified,” Florence Debarre, research director at the French National Center for Scientific Research at the Institute of Ecology and Environmental Sciences in Paris, France, and her colleagues reported that while their team was searching live animal markets for the species responsible for the COVID pandemic, it found other zoonotic viruses, such as avian flu. They concluded, “This study confirms that live animal markets pose a high health risk, especially when they are at the heart of urban centers.”
At the beginning of the pandemic, the Chinese government was slow to shut down food markets that sold wild animals. And some experts remain concerned that they haven’t gone far enough to ensure that this type of spillover can’t happen again.
The search for the origin of COVID-19 is far from over and may never be established with certainty. Nonetheless, as the zoonosis hypothesis seems the most tenable, it may be time for governments to curb people from going wild in urbanfood markets worldwide. It’s worth a try.
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