A colourised scanning electron micrograph of a cell (purple) infected with SARS-CoV-2 (pink), isolated from a patient sample. Image: NIAID/Flickr, CC BY 2.0
- The results of three studies indicate that the first human-to-human transmission of the novel coronavirus occurred in the Huanan Seafood Market in Wuhan
- While a species of bats is known to have been the virus’s primary host, none of the three studies have identified the intermediate host that introduced the virus to humans.
- The studies’ authors have said that their efforts eliminate the possibility that the virus leaked from a lab – but independent experts aren’t yet convinced.
- In parallel, the studies could help us improve what we know about the family of coronaviruses, and in future developed vaccines that can counter all of them.
New Delhi: Today is the second anniversary of the day the WHO declared the COVID-19 outbreak to be a ‘pandemic’. We have learnt a lot about the causative virus, with the deceptively simple name of novel coronavirus, since, as well as have developed vaccines against its effects in record-breaking duration.
Yet in all this time, one significant and fundamental detail has remained elusive: how did the virus evolve?
In the early half of the pandemic thus far, former US president Donald Trump squarely blamed China for the virus’s rise. He even alleged that the virus had leaked from a lab in Wuhan, the city from which the first human cases of the virus’s infection were reported. Such trickles of misinformation – given that it was speculation founded on zero evidence – have today avalanched into a problem paralleling the pandemic, which the WHO has called the “infodemic”.
At the same time, many scientists have countered such misinformation with a vehemence of their own, contending that the virus could only have evolved naturally. But just like the conspiracists and trolls, this group hasn’t been able to conclusive evidence of their being right.
Then there have been yet other scientists urging everyone to keep an open mind instead of jumping to conclusions, to collect empirical evidence, and to not rule out the possibility of a lab leak just because it sounds outlandish.
Today, knowing the virus’s provenance remains important to solve a deep scientific mystery – one that is likely to become only more unsolvable with time.
Recently, three groups of researchers uploaded the results of their studies online, all of which take aim at the origin question. One group is from China, primarily from the China Centre for Disease Control and Prevention and the Chinese Academy of Sciences, and led by George Gao, a virologist affiliated with the latter.
The other two have been coauthored by scientists from European and North American research institutes, some of whom are authors on both papers.
One is about the origin of the virus in the now-infamous Huanan Seafood Market in Wuhan. It was led by Michael Worobey, an evolutionary biologist at the University of Arizona. The other is an extended explanation of how the virus could have spilled over at the market from animals to humans. It was led by Jonathan E. Pekar, a PhD student at the University of California, San Diego.
The results of all three studies were reported in late February 2022.
All three studies were agreed on the following details:
- The virus first infected humans in the Huanan Seafood Market.
- Some of the environmental samples – swabs collected from cages holding animals, and warehouses and the drainage system – from the market contained the virus.
- The virus infected humans after infecting animals first – which, according to the papers, rules out the possibility of a lab-leak.
- None of the studies could identify the exact animal in the market that was the intermediate host for the transmission. (But a species of bats has been known to be the primary host.)
- All three studies have nothing to say about reports of COVID-19 transmission before December 2019.
This said, the Chinese study departs from the other two in one important detail: that the market “amplified” the infections. On the other hand, the first of the other two studies, led by Michael Worobey, said the market was “the site of origin of the COVID-19 pandemic”.
The Chinese study also claimed that none of the animals being traded in the wet market had developed an infection of the virus. Its paper only reads that “more work involving international coordination is needed to investigate the real origins of SARS-CoV-2.”
However, one of the authors of Worobey et al. study, Joel Wertheim, who studies evolutionary biology at the University of California, said that the Chinese team had collected its samples after the country’s authorities had shut the market. “The data isn’t completely accurate, therefore,” Wertheim told The Wire Science.
From the pandemic’s early months, the Chinese government has not acknowledged any criticism from the international community of medical and environmental researchers for practices that may have engendered the viral outbreak. China also refused to allow a team from the WHO that had visited Wuhan access to hospitals in the city that treated the virus’s first human cases.
The WHO itself has received flak for being too ‘soft’ on China in exchange for its cooperation during the pandemic.
For these reasons, many scientists worldwide have treated claims by the Chinese government as well as researchers with scepticism. Sunit Singh, a professor of virology and molecular immunology at the Banaras Hindu University, did as well. Has Gao et al. “released genome sequences” of samples collected from the animals “in the public domain? Merely saying that there was no SARS-CoV-2 positivity doesn’t suffice in science,” he told The Wire Science.
Nonetheless, the Chinese team’s finding is in line with that of the WHO. The WHO origins-probe team said in its report that it had tested 457 samples from 188 animals of 18 mammalian species, and that none tested positive for the virus.
The Worobey et al. study’s paper disagreed, however (emphasis added):
“None of the live (known to be susceptible) mammals from species we identify here as present at the Huanan market in November and/or December 2019 have been reported to have been tested for evidence of SARS-CoV-2 infection. The only live mammals from the market among the 188 appear to have been animals such as stray cats, dogs, snakes, rabbits and mice.”
These “known to be susceptible mammals” were raccoon dogs (Nyctereutes procyonoides), hog badgers (genus Arctonyx) and red foxes (Vulpes vulpes). According to Worobey et al., individuals of all three species were present in the market in November and December 2019, and none were tested.
Next, Gao et al. reported that they had found the virus to be present in a “high” 7% of the 923 environmental samples the CCDC had collected. The WHO team had collected a far-fewer 28 such samples, in which it found the virus to be present in two.
Worobey et al. went a step ahead and mapped these samples to their points of origin within the market. According to their paper, the samples “distinctly associated with animals” were “clustered within a small area of the Huanan market, where live mammal sales were most concentrated.”
“The researchers have used this environmental data and used a modelling technique to understand the spatial link between environment samples and location of animals in the market,” molecular virologist Chitra Pattabiraman told The Wire Science. “This was the right approach.”
Pattabiraman was not involved in the study.
Worobey et al. also tracked down the specific locations of 156 of the 174 people who had developed COVID-19 in December 2019 in Hubei province (where Wuhan is located).
“This analysis revealed that although cases in December 2019 occurred across a wide area, a majority clustered in central Wuhan near the west bank of the Yangtze River, with a high density near to, and surrounding, the Huanan market,” the study’s preprint paper reads.
Amesh Adalja, a senior scholar at the department of health and engineering, Johns Hopkins Centre for Health Security, Baltimore, said the clustering of cases around the market is a significant conclusion.
He added that the fact that none of the studies reported any animal testing positive was equally significant – as was the absence of details about reported before December 2019.
“I don’t think we have enough evidence to definitively identify the origin of COVID,” Adalja told The Wire Science. “I think what is necessary is more information about early cases that occurred in 2019, to really understand the early days of COVID-19.”
Worobey himself, however, said he had considered some of the Italian research, including one study that suggested that the virus could have been circulating in the European country before December 2019.
“Those cases are false positives: no actual solid information is there that this virus was circulating there,” he told The Wire Science. The outbreak “clearly started in Wuhan in November. The genomes of the virus tell us that.”
Third, the two international studies agreed that the virus had spilled over to humans on two separate occasions, in the market. The Pekar et al. study reported that the first event happened in late November or early December 2019, and introduced lineage B of the virus to humans.
Early on in the pandemic, scientists assigned two major lineages to the virus, according to its genetic characteristics. Lineage ‘A’ shared two nucleotides with the closest known bat viruses; in effect, it was the least different. Lineage ‘B’ was more different.
“As with the SARS-CoV-1 [outbreak] in 2002 and 2003, SARS-CoV-2 emergence likely resulted from multiple zoonotic events,” the team’s paper reads.
Worobey is one of the authors of Pekar et al. paper as well, and said this finding solved a mystery. He told The Wire Science that in the first weeks of the outbreak, lineage A “was being found in a fewer number of samples” than those that had lineage B. “That was hard to square.” Worobey said. This is because a closer relative of the bat coronavirus family should have had a transmission advantage over a more distant relative.
“This, we realised, was likely due to two individual” – and thus independent – “jump-over events” of two separate lineages from animals to humans, according to Worobey. The Chinese study also found that two lineages of the virus had been circulating from the start.
Despite the variety of their conclusions and their only-partial overlaps, all three papers are notable additions to the quest for the novel coronavirus’s origins, especially in furtherance to the WHO team’s limited report.
This said, not all their findings agree with what the WHO team had found. One point of departure was about whether the right animals had been tested. Another seems to be their conclusion that the first human cases of the virus’s outbreak in China occurred in the wet market.
The WHO report had “suggested” instead that the market was not the original source. It had also failed to reach any formal conclusion on the role of the market itself, especially over its hygiene and safety practices.
An incremental affair
There are many tools and techniques that scientists can use to track down the history of a pathogen. Genome-sequencing and spatial mapping are two of them. But the real world proposition of ascertaining a virus’s origins is vastly different from the scientific one. The former has to contend with politics, public perception and, most of all, potentially imperfect and/or unreliable information.
This is why finding the novel coronavirus’s ultimate origin has been an incremental affair. In fact, it may be more rewarding to understand this the other way around: that incremental details are more valuable than they may seem.
“Spillovers, remember, are really hard to catch, which these studies have tried to do by integrating multiple different approaches,” Pattabiraman said. Worobey, Wertheim and Singh also said these studies are on the path to discovering the exact animal that bridged the virus’s jump to humans.
“Viruses don’t jump from a primary host animal to human beings directly. They do use an intermediary host because that is a closely related species,” Singh said. “So they stay there, acclimatise there, evolve there and then jump to human beings.”
According to Wertheim, the “viral genomic data strongly suggests that multiple jumps of virus into humans happened at the market”.
He also said that “the spread in the market happened at a gradual rate” – meaning the virus wasn’t part of a super-spreader event.
“The virus may have come from an animal, say, from any farm in Hubei or from any other place where these susceptible animals were kept,” according to Worobey. So “maybe the infected animals landed in the market from somewhere else. But the first human-to-human transmission started here only, we believe.”
Both Worobey and Wertheim were also confident that the virus couldn’t have leaked from a lab – whereas Adalja said the findings weren’t conclusive, and wouldn’t be until they had more data, especially about cases reported before December 2019. One possibility that remains open concerns how the virus got to the market itself, and where indeed it was ultimately born.
“Several accidents have been reported in the past when unintentional leaks of bacteria or a virus had happened,” Singh added. “This is just to state a matter of fact.”
The most important takeaway for Pattabiraman is that these studies could help scientists understand the bigger family of coronaviruses better. “A pan-coronavirus vaccine” – which is a COVID-19 vaccine that works against all coronaviruses – “is constantly being talked about,” she noted. “The more we know the family of the virus, the better pan-coronavirus vaccine candidate scientists will be able to come up with.”
Worobey and Wertheim also expressed hope that the Chinese authorities would release more data on animal samples they collected in the outbreak’s early days, and that the country will do more to determine how the infected animals reached the market. And, finally, that it will do everything possible to prevent more spillovers in future.