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New research suggests that the Wuhan coronavirus, which has killed at least 100 people, may not have originated in the Huanan Wholesale Seafood Market in Wuhan, Hubei, China.

The virus is zoonotic, meaning it can be passed from animals to humans. So experts thought people in Wuhan likely caught the virus from snakes in a wet market, where meat is sold alongside live animals, often in poorly regulated conditions.

However, a new report – “Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China” – by Prof Chaolin Huang, MD, Yeming Wang, MD, Prof Xingwang Li, MD, Prof Lili Ren, PhD, Prof Jianping Zhao, MD, Yi Hu, MD, et al. (DOI: https://doi.org/10.1016/S0140-6736(20)30183-5) a group of Chinese scientists, published in the medical journal The Lancet on January 24, 2020, challenges that idea, suggesting that the virus could have originated elsewhere before entering the Wholesale Seafood Market.

Looking in detail at the cases of the first 41 people hospitalized with the coronavirus, the scientists found that 13 cases had no link to the marketplace, including the first case of the virus on December 1, Science magazine reported.

“That’s a big number, 13, with no link,” Daniel Lucey, an infectious-diseases specialist at Georgetown University, told Science.

Lucey told the magazine it was possible that the first cases occurred in November and that the virus could have spread undetected among people before it was found in the first group of cases from the wet market.

One way to establish for certain whether the virus outbreak originated at the market would be to take samples from the animals in the market as well as local animal populations, but the market has been cleared and disinfected, a group of microbiology professors wrote in The Conversation.

In The Lancet, the scientists write:

All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analyzed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardized data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not.

The study has been funded by China’s Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

Health officials in Wuhan closed the market on January 1 and have banned the sale of live animals at wet markets.

The virus has spread to at least 12 other countries, including the U.S., Australia, Japan, and Thailand.

The paper, written by a large group of Chinese researchers from several institutions, offers details about the first 41 hospitalized patients who had confirmed infections with what has been dubbed 2019 novel coronavirus (2019-nCoV).

In the earliest case, the patient became ill on December 1, 2019 and had no reported link to the seafood market, the authors report.

“No epidemiological link was found between the first patient and later cases,” they state. Their data also show that, in total, 13 of the 41 cases had no link to the marketplace.

Earlier reports from Chinese health authorities and the World Health Organization (WHO) had said the first patient had onset of symptoms on December 8, 2019, and those reports simply said “most” cases had links to the seafood market, which was closed on January 1.

Lucey says if the new data are accurate, the first human infections must have occurred in November 2019 – if not earlier – because there is an incubation time between infection and symptoms surfacing. If so, the virus possibly spread silently between people in Wuhan – and perhaps elsewhere – before the cluster of cases from the city’s now-infamous Huanan Seafood Wholesale Market was discovered in late December. “The virus came into that marketplace before it came out of that marketplace,” Lucey asserts.

The Lancet paper’s data also raise questions about the accuracy of the initial information China provided, Lucey says. At the beginning of the outbreak, the main official source of public information were notices from the Wuhan Municipal Health Commission. Its notices on January 11 started to refer to the 41 patients as the only confirmed cases and the count remained the same until January 18. The notices did not state that the seafood market was the source, but they repeatedly noted that there was no evidence of human-to-human transmission and that most cases linked to the market. Because the Wuhan Municipal Health Commission noted that diagnostic tests had confirmed these 41 cases by January 10 and officials presumably knew the case histories of each patient, “China must have realized the epidemic did not originate in that Wuhan Hunan seafood market,” Lucey tells Science Insider. (Lucey also spoke about his concerns in an interview published online yesterday by Science Speaks, a project of the Infectious Disease Society of America.)

Kristian Andersen, an evolutionary biologist at the Scripps Research Institute who has analyzed sequences of 2019-nCoV to try to clarify its origin, says the December 1 timing of the first confirmed case was “an interesting tidbit” in The Lancet paper. “The scenario of somebody being infected outside the market and then later bringing it to the market is one of the three scenarios we have considered that is still consistent with the data,” he says. “It’s entirely plausible given our current data and knowledge.” The other two scenarios are that the origin was a group of infected animals or a single animal that came into that marketplace.

Andersen posted his analysis of 27 available genomes of 2019-nCoV on January 25 on a virology research website. It suggests they had a “most recent common ancestor” – meaning a common source – as early as October 1, 2019.

Bin Cao of Capital Medical University, the corresponding author of The Lancet article and a pulmonary specialist, wrote in an email to Science Insider that he and his co-authors “appreciate the criticism” from Lucey.

“Now it seems clear that [the] seafood market is not the only origin of the virus,” he wrote. “But to be honest, we still do not know where the virus came from now.”

Lucey notes that the discovery of the coronavirus that causes Middle East respiratory syndrome, a sometimes-fatal disease that occurs sporadically, came from a patient in Saudi Arabia in June 2012, although later studies traced it back to an earlier hospital outbreak of unexplained pneumonia in Jordan in April 2012. Stored samples from two people who died in Jordan confirmed they had been infected with the virus. Retrospective analyses of blood samples in China from people and animals – including vendors from other animal markets – may reveal a clear picture of where the 2019-nCoV originated, he suggests. “There might be a clear signal among the noise,” he says.

Snake

Another new study provides insights on the potential origins of the most recent outbreak of viral pneumonia in China, which started in the middle of December and now is spreading to Hong Kong, Singapore, Thailand, and Japan.

Findings of the study – “Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross‐species transmission from snake to human” – by Wei Ji, Wei Wang, Xiaofang Zhao, Junjie Zai, Xingguang Li have been published online in Journal of Medical Virology, 2020 (DOI: 10.1002/jmv.25682).

Emerging viral infections – from bird flu to Ebola to Zika infections – pose major threats to global public health. Understanding origins of these can help scientists design defensive strategies against future outbreaks.

The study notes that patients who became infected with the virus, which is a type of virus called a novel coronavirus as determined by sequencing the viral RNA genome, and has been named 2019-nCoV by the WHO, were exposed to wildlife animals at a wholesale market, where seafood, poultry, snake, bats, and farm animals were sold.

The study report said: The current outbreak of viral pneumonia in the city of Wuhan, China, has been caused by the 2019‐nCoV. Many patients were potentially exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold.

To determine the possible virus reservoir, the scientists have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on existing sequences of the 2019‐nCoV.

The study report said: Results obtained from analyses suggest that the 2019‐nCoV appears to be a recombinant virus between the bat coronavirus and an origin‐unknown coronavirus. The recombination occurred within the viral spike glycoprotein, which recognizes cell surface receptor. Additionally, the findings suggest that snake is the most probable wildlife animal reservoir for the 2019‐nCoV based on its RSCU bias resembling snake compared to other animals. Taken together, the study results suggest that homologous recombination within the spike glycoprotein may contribute to cross‐species transmission from snake to humans.

By conducting a detailed genetic analysis of the virus and comparing it with available genetic information on different viruses from various geographic locations and host species, the investigators concluded that the 2019-nCoV appears to be a virus that formed from a combination of a coronavirus found in bats and another coronavirus of unknown origin. The resulting virus developed a mix or “recombination” of a viral protein that recognizes and binds to receptors on host cells. Such recognition is the key to allowing viruses to enter host cells, which can lead to infection and disease.

The scientists found evidence that the 2019-nCoV likely resided in snakes before transmitted to humans.

“Results derived from our evolutionary analysis suggest for the first time that snake is the most probable wildlife animal reservoir for the 2019-nCoV,” the authors wrote. “New information obtained from our evolutionary analysis is highly significant for effective control of the outbreak caused by the 2019-nCoV-induced pneumonia.”

An accompanying editorial notes that although the ultimate control of emerging viral infections requires the discovery and development of effective vaccines and/or antiviral drugs, currently licensed antiviral drugs should be tested against the 2019-nCoV.


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