The hunt for the origin of the COVID-19 pandemic has new leads. Researchers have identified half a dozen animal species that could have passed SARS-CoV-2, the coronavirus that causes COVID-19, to people, by reanalysing genomes collected from an animal market in Wuhan, China1. The study establishes the presence of animals and the virus at the market, although it does not confirm whether the animals themselves were infected with the virus.
Many of the earliest cases of COVID-19 were linked to the city’s Huanan Seafood Wholesale Market, and so it became a focus in the search for the pandemic’s origin. The study, published in Cell today, is the latest in a series of analyses of the market samples. The researchers argue that their reanalysis adds more weight to the market being the site of the first spillover events, in which animals with the virus infected people, sparking the pandemic. This expands on a preliminary analysis on a subset of the China CDC data, which the same team published in March 2023.
However, the team’s conclusion differs from the first peer-reviewed analysis of the data, published in Nature2 in April last year, in which a separate team also identified several animals and the virus but concluded the role of the market in the pandemic’s origin was unclear.
The search for how the pandemic began has been hugely controversial. Most researchers say the virus originated in bats who infected people, most probably through an intermediate animal, as has happened with other pathogens that have emerged in humans. But a lack of strong evidence for an intermediate host has led some researchers to argue that the virus could have escaped — deliberately or accidentally — from the Wuhan Institute of Virology.
Market stalls
The genomic data used in the Cell, Nature and other analyses were collected by researchers at the Chinese Center for Disease Control and Prevention (China CDC) shortly after the market was shut down on 1 January 2020. Over several weeks, China CDC staff visited the market many times to swab stalls, rubbish bins, toilets, sewage, stray animals and abandoned frozen animal products. The samples contained lots of DNA and RNA from multiple sources that researchers had to sequence and sift through.
“It’s one of the most important data sets on the early pandemic and on the origin of SARS-CoV-2,” says Florence Débarre, an evolutionary biologist at the the French national research agency CNRS, and co-author of the Cell analysis.
When researchers at the China CDC published their analysis in Nature last April, they reported samples that contained SARS-CoV-2 and came from wild animals in the market, most noteably raccoon dogs (Nyctereutes procyonoides), which are susceptible to SARS-CoV-2 and can spread the virus to other animals. But the team noted that there was no way to establish that the animals were infected with SARS-CoV-2. Even if they were infected, they could have caught the infection from a person who brought the virus to the market, which leaves open the possibility that the market was not the site of the pandemic’s emergence.
New techniques
The latest study used more-sophisticated genomic techniques to identify species represented in the samples, including half a dozen animals the team say are possible intermediate hosts of SARS-Cov-2. The most likely hosts include raccoon dogs and masked palm civet (Paguma larvata), which also might be susceptible to the virus. Other possible hosts include hoary bamboo rats (Rhizomys pruinosus), Amur hedgehog (Erinaceus amurensis) and the Malayan porcupine (Hystrix brachyura), but it is unclear whether these animals can catch SARS-CoV-2 and spread the infection. The team say the Reeves’s muntjac (Muntiacus reevesi) and the Himalayan marmot (Marmota himalayana) could also be carriers, but are less likely than the other species.
The co-location of viral and animal genetic material is “strongly suggestive” that the animals were infected, says Gigi Gronvall, a biosecurity specialist at Johns Hopkins University in Baltimore, Maryland. “I was quite amazed by how many animals were there,” she says.
Bats, from which the progenitor of SARS-CoV-2 probably originated, were not detected in the genetic data. The lack of bat DNA is unsurprising, says Alice Hughes, a conservation biologist at the University of Hong Kong who studies bats and the wildlife trade. Although bats are commonly eaten in southern China, they are not typically sold in the country’s markets.
The authors of the Cell study also argue that the viral diversity present in the market suggests it was the site of the pandemic’s emergence. In particular, they say the presence of two SARS-CoV-2 lineages — known as A and B — circulating in the market suggests that the virus jumped twice from animals to people. The researchers conclude that, although it is possible that infected humans brought the virus to the market on two separate occasions, that is a much less likely scenario than the virus jumping twice from animals, especially since their analysis suggests that very few people would have been infected at that point and it is unlikely that one person seeded both lineages. “It really just fits this ongoing infection in animal populations that spilled over multiple times to people,” says Gronvall.
Nature’s news team reached out to the authors of the Nature paper, asking them about the results and conclusions of the latest study, but did not receive a reply before deadline.
Southern China
The latest study also suggests that the raccoon dogs at the Huanan market were probably more closely related to wild raccoon dogs collected at other markets in the same province, and not as closely related to farmed animals found in northern Chinese provinces, suggesting they could have originated from central or southern China. The closest-known relatives of SARS-CoV-2 have been isolated from bats in southern China, Laos and other countries in southeast Asia.
The next step would be to follow some of these leads by studying animals in the wildlife trade, says study co-author Joshua Levy, an applied mathematician at the Scripps Research Institute in La Jolla, California. The paper provides actionable information about how to prevent future spillovers, he says, such as by tracking down stallholders and testing animals for viruses closely related to SARS-CoV-2, as well as conducting studies on the susceptibility of the wild mammals found at the market to SARS-CoV-2, and whether these animals can readily transmit the virus.
For Hughes, the findings demonstrate that the wildlife trade needs to be better regulated to minimize the risk of pathogen spread.
Crits-Christoph, A. et al. Cell 187, 5468–5482 (2024).
". Don't add the title at the beginning of the created content. Write it as if you want to inform the readers about who, what, when, where, why and how. Dont exceed 120 characters. Style: Maintain a professional level of formality suitable for a newspaper, but avoid overly complex language to ensure the content is accessible to a wide audience. Include keywords related to the news event and phrases likely to be used by readers searching for information on the topic. Tone: While keeping the tone professional, use engaging language to capture the reader's interest without sensationalizing. Reply in plain Text without putting the meta-description into any quotes. Excerpt:">
The hunt for the origin of the COVID-19 pandemic has new leads. Researchers have identified half a dozen animal species that could have passed SARS-CoV-2, the coronavirus that causes COVID-19, to people, by reanalysing genomes collected from an animal market in Wuhan, China1. The study establishes the presence of animals and the virus at the market, although it does not confirm whether the animals themselves were infected with the virus.
Many of the earliest cases of COVID-19 were linked to the city’s Huanan Seafood Wholesale Market, and so it became a focus in the search for the pandemic’s origin. The study, published in Cell today, is the latest in a series of analyses of the market samples. The researchers argue that their reanalysis adds more weight to the market being the site of the first spillover events, in which animals with the virus infected people, sparking the pandemic. This expands on a preliminary analysis on a subset of the China CDC data, which the same team published in March 2023.
However, the team’s conclusion differs from the first peer-reviewed analysis of the data, published in Nature2 in April last year, in which a separate team also identified several animals and the virus but concluded the role of the market in the pandemic’s origin was unclear.
The search for how the pandemic began has been hugely controversial. Most researchers say the virus originated in bats who infected people, most probably through an intermediate animal, as has happened with other pathogens that have emerged in humans. But a lack of strong evidence for an intermediate host has led some researchers to argue that the virus could have escaped — deliberately or accidentally — from the Wuhan Institute of Virology.
Market stalls
The genomic data used in the Cell, Nature and other analyses were collected by researchers at the Chinese Center for Disease Control and Prevention (China CDC) shortly after the market was shut down on 1 January 2020. Over several weeks, China CDC staff visited the market many times to swab stalls, rubbish bins, toilets, sewage, stray animals and abandoned frozen animal products. The samples contained lots of DNA and RNA from multiple sources that researchers had to sequence and sift through.
“It’s one of the most important data sets on the early pandemic and on the origin of SARS-CoV-2,” says Florence Débarre, an evolutionary biologist at the the French national research agency CNRS, and co-author of the Cell analysis.
When researchers at the China CDC published their analysis in Nature last April, they reported samples that contained SARS-CoV-2 and came from wild animals in the market, most noteably raccoon dogs (Nyctereutes procyonoides), which are susceptible to SARS-CoV-2 and can spread the virus to other animals. But the team noted that there was no way to establish that the animals were infected with SARS-CoV-2. Even if they were infected, they could have caught the infection from a person who brought the virus to the market, which leaves open the possibility that the market was not the site of the pandemic’s emergence.
New techniques
The latest study used more-sophisticated genomic techniques to identify species represented in the samples, including half a dozen animals the team say are possible intermediate hosts of SARS-Cov-2. The most likely hosts include raccoon dogs and masked palm civet (Paguma larvata), which also might be susceptible to the virus. Other possible hosts include hoary bamboo rats (Rhizomys pruinosus), Amur hedgehog (Erinaceus amurensis) and the Malayan porcupine (Hystrix brachyura), but it is unclear whether these animals can catch SARS-CoV-2 and spread the infection. The team say the Reeves’s muntjac (Muntiacus reevesi) and the Himalayan marmot (Marmota himalayana) could also be carriers, but are less likely than the other species.
The co-location of viral and animal genetic material is “strongly suggestive” that the animals were infected, says Gigi Gronvall, a biosecurity specialist at Johns Hopkins University in Baltimore, Maryland. “I was quite amazed by how many animals were there,” she says.
Bats, from which the progenitor of SARS-CoV-2 probably originated, were not detected in the genetic data. The lack of bat DNA is unsurprising, says Alice Hughes, a conservation biologist at the University of Hong Kong who studies bats and the wildlife trade. Although bats are commonly eaten in southern China, they are not typically sold in the country’s markets.
The authors of the Cell study also argue that the viral diversity present in the market suggests it was the site of the pandemic’s emergence. In particular, they say the presence of two SARS-CoV-2 lineages — known as A and B — circulating in the market suggests that the virus jumped twice from animals to people. The researchers conclude that, although it is possible that infected humans brought the virus to the market on two separate occasions, that is a much less likely scenario than the virus jumping twice from animals, especially since their analysis suggests that very few people would have been infected at that point and it is unlikely that one person seeded both lineages. “It really just fits this ongoing infection in animal populations that spilled over multiple times to people,” says Gronvall.
Nature’s news team reached out to the authors of the Nature paper, asking them about the results and conclusions of the latest study, but did not receive a reply before deadline.
Southern China
The latest study also suggests that the raccoon dogs at the Huanan market were probably more closely related to wild raccoon dogs collected at other markets in the same province, and not as closely related to farmed animals found in northern Chinese provinces, suggesting they could have originated from central or southern China. The closest-known relatives of SARS-CoV-2 have been isolated from bats in southern China, Laos and other countries in southeast Asia.
The next step would be to follow some of these leads by studying animals in the wildlife trade, says study co-author Joshua Levy, an applied mathematician at the Scripps Research Institute in La Jolla, California. The paper provides actionable information about how to prevent future spillovers, he says, such as by tracking down stallholders and testing animals for viruses closely related to SARS-CoV-2, as well as conducting studies on the susceptibility of the wild mammals found at the market to SARS-CoV-2, and whether these animals can readily transmit the virus.
For Hughes, the findings demonstrate that the wildlife trade needs to be better regulated to minimize the risk of pathogen spread.
Crits-Christoph, A. et al. Cell 187, 5468–5482 (2024).
". Don't add the title at the beginning of the created content. Write it as if you want to inform the readers about who, what, when, where, why and how. Dont exceed 120 characters. Style: Maintain a professional level of formality suitable for a newspaper, but avoid overly complex language to ensure the content is accessible to a wide audience. Include keywords related to the news event and phrases likely to be used by readers searching for information on the topic. Tone: While keeping the tone professional, use engaging language to capture the reader's interest without sensationalizing. Reply in plain Text without putting the meta-description into any quotes. Excerpt:">
Neue Studie legt nahe, dass COVID-Pandemie ihren Ursprung im Tiermarkt von Wuhan hatte
Die Suche nach dem Ursprung der COVID-19-Pandemie hat neue Hinweise ergeben. Forscher haben eine Handvoll Tierarten identifiziert, die SARS-CoV-2, das Coronavirus, das COVID-19 verursacht, an Menschen übermittelt haben könnten. Dies geschah durch die erneute Analyse von Genomen, die von einem Tiermarkt in Wuhan, China, gesammelt wurden1. Die Studie belegt das Vorhandensein von Tieren und dem Virus auf dem Markt, auch wenn sie nicht bestätigt, ob die Tiere selbst mit dem Virus infiziert waren.
Viele der frühesten COVID-19-Fälle waren mit dem Huanan-Seafood-Großmarkt in der Stadt verbunden, weshalb er ein Fokus in der Suche nach dem Ursprung der Pandemie wurde. Die heute in der Zeitschrift Cell veröffentlichte Studie ist die neueste in einer Reihe von Analysen der Marktproben. Die Forscher argumentieren, dass ihre erneute Analyse das Gewicht der Hypothese verstärkt, dass der Markt der Ort der ersten Übertragungsereignisse war, bei denen Tiere mit dem Virus Menschen infizierten und die Pandemie auslösten. Dies erweitert eine vorläufige Analyse eines Teils der Daten des CDC China, die dasselbe Team im März 2023 veröffentlicht hatte.
Die Schlussfolgerung des Teams unterscheidet sich jedoch von der ersten peer-reviewed Analyse der Daten, die im letzten Jahr im Fachblatt Nature2 veröffentlicht wurde, bei der ein separates Team ebenfalls mehrere Tiere und das Virus identifizierte, jedoch zu dem Schluss kam, dass die Rolle des Marktes im Ursprung der Pandemie unklar sei.
Die Suche danach, wie die Pandemie begann, ist stark umstritten. Die meisten Forscher sagen, dass das Virus wahrscheinlich von Fledermäusen stammt, die Menschen infizierten, wahrscheinlich durch ein Zwischenwirt-Tier, wie es bei anderen Krankheitserregern, die beim Menschen aufgetreten sind, der Fall war. Doch ein Mangel an starken Beweisen für einen Zwischenwirt hat einige Forscher dazu veranlasst zu argumentieren, dass das Virus entweder absichtlich oder versehentlich aus dem Wuhan Institute of Virology entwichen sein könnte.
Die genomischen Daten, die in den Analysen von Cell, Nature und anderen verwendet wurden, wurden von Forschern des chinesischen Zentrums für Seuchenkontrolle und -prävention (China CDC) kurz nach der Schließung des Marktes am 1. Januar 2020 gesammelt. Über mehrere Wochen besuchten Mitarbeiter des China CDC den Markt häufig, um Stände, Müllbehälter, Toiletten, Abwässer, streunende Tiere und verlassene gefrorene Tierprodukte abzupicken. Die Proben enthielten viel DNA und RNA aus verschiedenen Quellen, die von den Forschern sequenziert und durchforstet werden mussten.
„Es ist eines der wichtigsten Datensätze zur frühen Pandemie und zum Ursprung von SARS-CoV-2“, sagt Florence Débarre, Evolutionsbiologin beim französischen Forschungsdienst CNRS und Mitautorin der Analyse in Cell.
Als die Forscher des China CDC ihre Analyse im letzten April in Nature veröffentlichten, berichteten sie über Proben, die SARS-CoV-2 enthielten und von Wildtieren auf dem Markt stammten, insbesondere von Marderhunden (Nyctereutes procyonoides), die anfällig für SARS-CoV-2 sind und das Virus auf andere Tiere übertragen können. Das Team bemerkte jedoch, dass es keine Möglichkeit gab festzustellen, ob die Tiere mit SARS-CoV-2 infiziert waren. Selbst wenn sie infiziert waren, könnten sie die Infektion von einer Person erworben haben, die das Virus zum Markt brachte, was die Möglichkeit offen lässt, dass der Markt nicht der Ort des Pandemienbeginns war.
Die neueste Studie verwendete fortschrittlichere genomische Techniken, um die in den Proben vertretenen Arten zu identifizieren, einschließlich einer Handvoll Tiere, von denen das Team sagt, dass sie mögliche Zwischenwirte von SARS-CoV-2 sind. Zu den wahrscheinlichsten Wirten gehören Marderhunde und der Maskenpalmenzibet (Paguma larvata), die ebenfalls anfällig für das Virus sein könnten. Weitere mögliche Wirte sind staubige Bambusratten (Rhizomys pruinosus), Amur-Igel (Erinaceus amurensis) und der malaysische Stachelschwein (Hystrix brachyura), aber es ist unklar, ob diese Tiere SARS-CoV-2 fangen und die Infektion übertragen können. Das Team sagt, dass das Reeves-Muntjak (Muntiacus reevesi) und das Himalaya-Murmeltier (Marmota himalayana) ebenfalls Überträger sein könnten, jedoch weniger wahrscheinlich als die anderen Arten.
Die gemeinsame Lokalisation von viraler und tiergenetischer Materie ist „stark suggestiv“, dass die Tiere infiziert waren, sagt Gigi Gronvall, Biosecurityspezialistin an der Johns Hopkins University in Baltimore, Maryland. „Ich war wirklich überrascht, wie viele Tiere dort waren“, sagt sie.
Fledermäuse, von denen wahrscheinlich der Vorläufer von SARS-CoV-2 stammt, wurden in den genetischen Daten nicht gefunden. Das Fehlen von Fledermaus-DNA ist nicht überraschend, sagt Alice Hughes, eine Naturschutzbiologin an der Universität Hongkong, die Fledermäuse und den Wildhandel untersucht. Obwohl Fledermäuse in Südkorea häufig gegessen werden, werden sie normalerweise nicht auf den Märkten des Landes verkauft.
Die Autoren der Cell-Studie argumentieren außerdem, dass die virale Diversität, die auf dem Markt vorhanden ist, darauf hindeutet, dass es der Ort des Ausbruchs der Pandemie war. Insbesondere sagen sie, dass die Anwesenheit zweier SARS-CoV-2-Linien — bekannt als A und B —, die auf dem Markt zirkulierten, darauf hindeutet, dass das Virus zweimal von Tieren auf Menschen sprang. Die Forscher kommen zu dem Schluss, dass, obwohl es möglich ist, dass infizierte Menschen das Virus an zwei verschiedenen Gelegenheiten zum Markt brachten, dies ein viel unwahrscheinlicheres Szenario ist als ein zweimaliger Sprung des Virus von Tieren, insbesondere da ihre Analyse darauf hindeutet, dass zu diesem Zeitpunkt nur sehr wenige Menschen infiziert gewesen wären und es unwahrscheinlich ist, dass eine Person beide Linien hervorgebracht hat. „Es passt wirklich zu dieser fortdauernden Infektion in Tierpopulationen, die sich mehrfach auf Menschen übertrugen“, sagt Gronvall.
Das Nachrichtenteam von Nature kontaktierte die Autoren des Nature-Artikels und fragte sie nach den Ergebnissen und Schlussfolgerungen der neuesten Studie, erhielt jedoch vor Frist keinen Antwort.
Die neueste Studie deutet auch darauf hin, dass die Marderhunde auf dem Huanan-Markt wahrscheinlich enger mit wilden Marderhunden verwandt sind, die auf anderen Märkten in derselben Provinz gesammelt wurden, und nicht so eng mit gezüchteten Tieren, die in nordchinesischen Provinzen gefunden wurden, was darauf hindeutet, dass sie aus Zentral- oder Südchina stammen könnten. Die nächsten bekannten Verwandten von SARS-CoV-2 wurden von Fledermäusen in Südchina isoliert, Laos und anderen Ländern in Südostasien isoliert worden.
Der nächste Schritt bestünde darin, einige dieser Hinweise zu verfolgen, indem man Tiere im Wildhandel untersucht, sagt Joshua Levy, Mitautor der Studie und angewandter Mathematiker am Scripps Research Institute in La Jolla, Kalifornien. Die Studie liefert umsetzbare Informationen darüber, wie man zukünftige Übertragungen verhindern kann, indem man Stallinhaber verfolgt und Tiere auf Viren testet, die eng mit SARS-CoV-2 verwandt sind, sowie Studien zur Anfälligkeit der im Markt gefundenen Wildsäugetiere gegenüber SARS-CoV-2 durchführt und ob diese Tiere das Virus leicht übertragen können.
Für Hughes zeigen die Ergebnisse, dass der Wildhandels besser reguliert werden muss, um das Risiko der Verbreitung von Krankheitserregern zu minimieren.
Crits-Christoph, A. et al. Cell 187, 5468–5482 (2024).
