Origins of COVID-19
SciLine reaches out to our network of scientific experts and poses commonly asked questions about newsworthy topics. Reporters can use these responses in news stories, with attribution to the expert.
What are Quotes from Experts?
October 7, 2021
How likely is it that an animal-to-human zoonotic spillover event is responsible for the origin of SARS-CoV-2, given current evidence?
Maciej F. Boni, Ph.D.
“Well, this is where all the evidence points now. We have coronaviruses from a number of bat populations and probably will find coronaviruses in some other mammal populations—maybe some badgers, some mink, or some other animals in the wild that typically are sometimes hosts to coronaviruses. So this is the most likely source of the virus—that it crossed over from one of these animal populations, about two years ago, over into human populations.” (Posted October 7, 2021 | Download Video)
Susan R. Weiss, Ph.D.
“I think that SARS-CoV-2 very, very likely has an origin as a zoonotic spillover, and this is based on several things. Firstly, the last two coronavirus epidemics were clearly caused by spillovers from bats into intermediate species, and then into humans. And in addition, we know there are many, many coronaviruses—including sarbeco or SARS-related viruses—in bat populations now currently.” (Posted October 7, 2021 | Download Video)
“It is extremely likely. There is strong precedence from the first SARS. SARS1 entered humans not once but at least twice directly from the wildlife trade, which is extensive in China’s Hubei province. Civets infected with SARS1 were in fact found close to Wuhan, as the SARS1 outbreaks were in Southern China. The majority of early SARS2 cases in Wuhan were linked to markets now known to have sold animals susceptible to SARS-CoV-2. Extremely close relatives to SARS-CoV-2, particularly at the protein level, have recently been found in bats in Laos. No scientist could have designed SARS-CoV-2 in a lab. SARS-CoV-2 has not been ‘pre-adapted’ to humans but is pantropic as are other spillover viruses—for example rabies virus and Ebola virus—which means it can spread easily from humans to animals and back.” (Posted October 7, 2021)
“As a scientist and a researcher, I am inclined to follow evidence. Although a ‘lab leak’ (defined here as a naturally occurring virus leaked by accident from a lab) is a possibility, there is zero bona fide evidence to support this notion. One can acknowledge how such a scenario might be more appealing to conspiracy theorists—those with dramatic inclinations. And it makes for a better sci fi movie. However, evidence from basic virology principles and past epidemics/pandemics (in addition to an Occam’s razor approach to this issue) favor a zoonotic spillover theory to the origin of SARS-CoV-2. Bottom line at the moment: More evidence is needed to support the lab-leak origin of SARS-CoV-2. I’m sure, with time, if indeed this is the origin of the pandemic, investigations will determine this with the needed accuracy.
“There is enough informatic evidence that suggests SARS-CoV-2 sequences did not exist in research datasets in the Sequence Read Archive prior to pandemic—inferring that the SARS-CoV-2 RNA did not exist in any of the sequencing datasets submitted by researchers. On the other hand, a strong homology to numerous sequence reads was found in metavirome datasets generated from infected animals such as pangolins and bats in datasets submitted before February. 2020.” (Posted October 7, 2021)
How likely is it that a lab release event is responsible for the origin of SARS-CoV-2, given current evidence?
Maciej F. Boni, Ph.D.
“This question has been discussed a lot, both in the media and by scientists over the past two years. And there’s still no evidence that the virus could have originated in a lab or that it could have been made in a lab or that it could have escaped or leaked out of a lab in any way. All the current evidence points to a natural origin, which is a crossing over from the natural context that human and animal populations have with each other routinely in East and Southeast Asia.” (Posted October 7, 2021 | Download Video)
Susan R. Weiss, Ph.D.
“I think there are kind of two points to make here. The first is that there’s really no evidence of this virus ever being available in a lab. The second reason is that, I think it’s really highly unlikely to impossible for anyone to have genetically constructed this virus, because there really is no virus identified that has a backbone like this virus, and you can’t really de novo create a virus using genetic manipulations. And thirdly, related to that, is that it would be really impossible for anyone to know how to design a virus that would have the properties of this virus. What I mean by that is a virus that would spread asymptomatically. There is no way of looking at SARS-CoV-2 and knowing that.” (Posted October 7, 2021 | Download Video)
“It is extremely unlikely—a vanishingly small, unfalsifiable possibility. There is zero credible scientific evidence for a lab leak. The intelligence community has ruled out SARS-CoV-2 being a bioweapon. There is no evidence that the Wuhan Institute of Virology or any other Wuhan lab was working on SARS-CoV-2 or any virus close enough to be a progenitor. There is no epidemiological link at all to the Wuhan Institute of Viorology. The only lab scenario left is a that lab worker was unknowingly infected with SARS-CoV-2 via a bat or bat sample that the lab did not know contained this novel virus and then not one but two SARS-CoV-2 lineages spread via this lab worker to people at multiple wet markets. SARS-CoV-2 is unlikely to have come directly from bats. A progenitor of SARS-CoV-2 similar to BANAL-20-52 likely circulated in another animal before spilling over to humans.” (Posted October 7, 2021)
From a public health perspective, how important is it to understand the origin of the virus?
Maciej F. Boni, Ph.D.
“Well for this pandemic, it’s not really a question of public health, it’s a question of understanding where it came from. But for future pandemics, it’s very important to know where it came from because it will help us track and monitor those animal populations so we can identify the next pandemic more quickly.” (Posted October 7, 2021 | Download Video)
Susan R. Weiss, Ph.D.
“I think it’s really important to understand the origin of the virus because we need to know what viruses are out there in bats and other species, and we need to know really their genetic composition so we can know whether they’re very likely to infect humans directly or humans through an intermediate species. So this is really a question of surveillance and knowing what’s possible.” (Posted October 7, 2021 | Download Video)
“It is important for preventing future pandemics.” (Posted October 7, 2021)
What have we already learned about the origins of COVID-19 that can help prevent future outbreaks?
Maciej F. Boni, Ph.D.
“We’ve identified about a dozen viruses that are sort of similar to SARS-CoV-2 that circulate naturally in Southern China and parts of Northern Laos. So at least we know the geographic origin of the viruses that caused SARS-CoV-2. And probably the next steps are to begin more intense monitoring of the bat populations and some other animal populations that live in that part of the world.” (Posted October 7, 2021 | Download Video)
Susan R. Weiss, Ph.D.
“From trying to figure out the origins of COVID-19 we’ve learned that there are a variety of coronaviruses from different lineages and many different bat species and perhaps in other animals, as well. And from this I think we learn that we need to be prepared for a diversity of viruses that could possibly come out of animals. And for that we need to have, to develop really good pan-antiviral therapies as well as vaccines that may be effective against more than one coronavirus.” (Posted October 7, 2021 | Download Video)
“The wildlife trade should be better regulated.” (Posted October 7, 2021)
“Definitive conclusions regarding the origins of SARS-CoV-2 or other coronaviruses are limited by sequencing data and knowledge of the evolutionary trajectories in different viral lineages. We need more complete data for coronavirus sequences in the wild, those already existing in animal reservoirs. Studies of this sort need to be supported and funded by the National Institutes of Health and other agencies. Defunding basic science in general has contributed to our inadequate response to this pandemic and lack of answers regarding the origins of this virus. If such data existed, it would have been more tractable to trace the origins of SARS-CoV-2 in the wild.
“It is unfortunate that the ‘lab leak’ theory is being used to curtail funding to the very studies that we need to support to get a better handle on the evolution of coronaviruses, in general, and to be better prepared for future pandemics. With that being said, transparency and effective regulatory procedures should guide work of this nature.” (Posted October 7, 2021)
March 30, 2021
What new information does the WHO report reveal on the origin of the coronavirus that causes COVID-19?
“A quick read of the report suggests that it does not contain much new solid information that could help us understand the origin of SARS-CoV-2. However, there might be more information forthcoming when the appendices are released. I am looking forward to results from screening of blood donor samples that the report proposes.” (Posted March 30, 2021)
“The report provided much more granular detail on early cases linked to the Huanan Market and importantly other wildlife markets in Wuhan. This is an inconvenient fact for many proponents of the ‘lab leak.’
“Any theory on the origin of SARS-CoV-2 must account for the fact that most of the early cases were linked to at least two and perhaps more wet markets.
“It is not easy to find, and I suspect this was part of the negotiation over wording, but it is clear that many species susceptible to SARS-Cov-2 have been commonly sold at the Huanan Market.
“Intelligence reports that there were sick workers in the Wuhan Institute of Virology, and one person’s wife died, are disputed by the report: ‘The three laboratories in Wuhan working with either CoVs diagnostics and/or CoVs isolation and vaccine development all had high quality biosafety level (BSL3 or 4) facilities that were well-managed, with a staff health monitoring programme with no reporting of COVID-19 compatible respiratory illness during the weeks/months prior to December 2019, and no serological evidence of infection in workers through SARS-CoV-2-specific serology-screening.” Saying there are intelligence reports to the contrary, but not revealing those reports, undermines credibility. And given the information documented in this report, any claim that there were sick workers at the Wuhan Institute of Virology is tantamount to claiming there’s been a conspiracy and cover-up.” (Posted March 30, 2021)
How trustworthy are the data in the WHO report?
“I was disappointed that the report engages in speculation on origins based on little to no data. There have been many discussions in the press that the WHO team could not be impartial due to the composition of its membership and control by the Chinese government. Unfortunately, the speculation in the report that ranks various possible origin hypotheses appears to have validated these concerns. The discussion seems aimed at political, rather than scientific, objectives.” (Posted March 30, 2021)
“There is a lot of very detailed data in this report. It’s not the type of data that could be made up. Anyone hoping to find a lack of detail will be disappointed. In the just concluded WHO press conference members of the team expressed their confidence that the data in the report is highly reliable. There was also a rapport established between the scientists – international and Chinese. It’s difficult to describe precisely how this happens but I am confident that the experienced scientists on the team would ‘know’ if scientific facts were being hidden. It’s a skill that successful scientists develop.” (Posted March 30, 2021)
What questions about the origins of SARS-CoV-2 remain unanswered by the report?
“There is still not nearly enough focus on the routine human-animal contacts that occur in East and Southeast Asia. Urban centers have hundreds of live-animal markets, and rural regions of East and Southeast Asia feature a mix of live-animal markets and informal roadside sellers and stalls. Residents do their groceries in these types of stalls or markets every day, and thus every day there are millions of human-animal contacts that pose some unknown level of risk for transmission of viruses between animals and humans. This is the most likely path that SARS-CoV-2 took from the animal population to the human population.” (Posted March 30, 2021)
“Which animal or animals carry the direct progenitor or perhaps SARS-CoV-2 itself remain unanswered. I think that the report did an excellent job of setting up a process to answer this question.
“More science not less is the short answer.
“Investigations on the diversity of sarbecoviruses and other coronaviruses in bats and other species will provide critical data on the evolution and ecology of potential pathogens, guidance for detecting their emergence, and will suggest solutions for design of appropriate countermeasures.
“As you probably know there have been suggestions that scientists should stop investigating the diversity of coronaviruses in bats and other animals. Others have advocated for shutting down fieldwork on bats and other animals as well. Many of the other signers of the Paris Group letter are people who have invested a lot of their career capital pointing to the dangers of either gain of function research or BSL3/4 labs and wish to have this activity shut down or even more tightly regulated than it already is.
“The world must do the opposite if we are going to find the origin of SARS-CoV-2 and be better prepared to prevent the next pandemic of an emergent coronavirus.” (Posted March 30, 2021)*
* Links included in quotes were supplied by the expert.
June 11, 2020
Why is it important to understand the origin of SARS-CoV-2?
“Understanding the origin of SARS-CoV-2 has implications for public health, economic, and political stability as well as basic science. A relatively modest investment in focused surveillance of wildlife would help us contain risk of cross-species transmission of new and known viral threats by identifying reservoirs and vectors for potential pandemic viruses, providing the genetic sequences needed for the development of diagnostics, drugs and vaccines, and yielding information on how viruses evolve and adapt to new host environments. Furthermore, identifying the zoonotic origin of the COVID-19 pandemic will provide the evidence needed to move our political leaders from finger pointing to the international collaboration needed to put this pandemic behind us.” (Posted June 11, 2020)
“Identification of the source for any new zoonotic disease is important. Identification of the natural reservoir for SARS-CoV-2 will allow us to understand how the cross-species transmission of SARS-CoV-2 occurs. The information is critical for developing means to prevent new transmissions into humans. Knowing the hosts that harbor the evolutionary parent of SARS-CoV-2 will help us to develop animal models to test vaccine candidates, study viral pathogenesis, and find new drugs to treat COVID-19. Continuous surveillance of coronaviruses in their natural hosts and in humans will be key to rapid control of new coronavirus outbreaks.” (Posted June 11, 2020)
“Advances in knowledge regarding possible biological niches occupied by SARS-CoV-2 can help scientists and healthcare professionals understand SARS-CoV-2 transmission. This will aid targeted development of therapeutic countermeasures to prevent future animal-to-human transmission or re-introduction of the virus in human populations. For example, consider the repeated outbreaks of another coronavirus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), in the Arabian Peninsula. Although camels appear to be responsible for the continual re-introduction of MERS-CoV into the human population, we now know human-to-human transmission of MERS-CoV is not sustained. This is clearly not the case for SARS-CoV-2, therefore identifying biological niches occupied by the virus and work preventing animal-to-human re-introduction is absolutely necessary to prevent viral reemergence in the human population in the future.” (Posted June 11, 2020)
What do we know about the evolutionary origin of SARS-CoV-2 and how do we know it?
“What we know about the evolutionary origins of SARS-CoV-2 is based on analysis of sequences of this virus and others found in wildlife, domestic animals, and humans. Our database is incomplete. I had planned to join an effort with Chinese scientists to search for viruses even more closely related to SARS-CoV-2 than those reported to date in bats. Unfortunately, deteriorating international relations have put that work on hold.” (Posted June 11, 2020)
“To understand how SARS-CoV-2 has evolved we can compare its nucleotide sequence to sequences from other viruses. The two most closely related viral sequences identified to date have both been obtained from bats and we can show that these bat sequences diverged from SARS-CoV-2 roughly 35 and 50 years ago, respectively. That means that there was a common viral ancestor of a bat virus and SARS-CoV-2 about 35 years ago. However, what we don’t know is what happened in the last 35 years and how the virus eventually was transmitted to humans from some other species. It could have been from a bat species, or it could have been through an intermediary host in another species. To answer this question, we need to search for other more closely related viruses. While much work has been done on identifying viruses in nature, most remain undescribed and there is likely a large reservoir of other coronaviruses in wild mammals. The work on identifying coronaviruses in wild animals is also important because it will help us prepare for the next possible pandemic. Clearly, the world was not prepared well enough this time, but hopefully we will be better prepared next time.” (Posted June 11, 2020)
“Comparing the whole genome sequences between SARS-CoV-2 and coronaviruses that infect other animals has shown that one particular coronavirus that infects horseshoe bats shares 96% genetic similarity with SARS-CoV-2. This suggests that this species of bat is most likely the natural reservoir for SARS-CoV-2. However, one critical part of the viral glycoprotein responsible for binding to the surface of human cells is very different in this bat virus and renders it inefficient to infect human cells. In pangolin coronaviruses, this part of the glycoprotein critical for binding human cells is nearly identical to the SARS-CoV-2 glycoprotein found in infected people, suggesting that gene shuffling between the two viruses may have generated the parent virus of SARS-CoV-2 capable of infecting humans. More importantly, coronaviruses that caused Severe Acute Respiratory Syndrome (SARS) and Middle East respiratory syndrome (MERS) are both the results of glycoprotein gene shuffling between different bat coronaviruses. Thus, obtaining novel biological phenotypes through gene shuffling among coronaviruses may be a common evolutionary mechanism that could lead to new emerging human coronaviruses.
“Another recent striking finding is that coronaviruses infecting three different hosts—humans, bats and pangolins—are under similar strong purifying selection pressure, meaning that they have high levels of mutation rates in their genomes but nearly no changes in their protein sequences. Having similar protein sequences—especially in the glycoprotein that binds to the surface of human cells—may have made the ancestor of SARS-CoV-2 able to readily jump from these animals into humans.” (Posted June 11, 2020)
“Definitive conclusions regarding the origins of SARS-CoV-2 or other coronaviruses are limited by sequencing data and knowledge of the evolutionary trajectories in different viral lineages. We need more complete data for coronavirus sequences in the wild (those already existing in animal reservoirs). Studies of this sort need to be supported and funded by the NIH and other agencies. Defunding basic science in general has contributed to our inadequate response to this pandemic and lack of answers.
“A number of studies have investigated the potential role of bats, pangolins, and other possible precursor, intermediate species in evolution of SARS-CoV-2. These studies provide useful insights into the evolution of SARS-CoV-2 but have thus far lacked strong conclusions regarding the viral origin. Whereas analyses indicate the presence of a similar viral sequence in pangolin lungs, the similarity is not strong enough to either confirm or rule out pangolins as an intermediate host in the recent emergence of SARS-CoV-2. Better understanding of the current pandemic requires additional information on viral sequences and epidemiology that may resolve questions of origin and prevent the reemergence of SARS-CoV-2.” (Posted June 11, 2020)
What do we still need to learn about the origins of SARS-CoV-2?
“The whole length genomic sequences of SARS-CoVs and MERS-CoVs are almost identical (>99% similarity) to coronaviruses from civets and dromedary camels, respectively. This demonstrates that civets and dromedary camels are the intermediate hosts for SARS-CoV and MERS-CoV, respectively. However, coronaviruses that are nearly identical to SARS-CoV-2 have not been identified from any animals. The bat coronavirus that is most closely related to SARS-CoV-2 still has more than one thousand different bases in its genome. Therefore, it is unlikely to serve as direct ancestor of SARS-CoV-2. As of now, only relatively small numbers of bat coronavirus sequences have been characterized. Viral sequences from a large number of wild bats and other animals are urgently needed to identify the immediate hosts of SARS-CoV-2. It is possible that there are other not yet identified hosts infected with coronaviruses that can jump to human populations.” (Posted June 11, 2020)
Is it likely that SARS-CoV-2 existed in a laboratory at some point—either naturally or as an engineered organism?
“I know of no evidence to support the speculation that SARS-CoV-2 was engineered in a laboratory in China, the US or anywhere else.” (Posted June 11, 2020)
“There has been a lot of speculation on whether SARS-CoV-2 was genetically engineered. There is nothing in the nucleotide sequences that would suggest engineering. The patterns that we see in the sequences are completely compatible with the usual process of mutation, selection, and natural exchange of genetic material between different viral strains. Viruses evolve very fast and there is a vast reservoir of viral genetic material in wild animals, so it is not surprising to see a virus such as SARS-CoV-2 suddenly emerge. In fact, virologists have been expecting this and warned about it for years.” (Posted June 11, 2020)
“Based on the current available coronavirus genome sequences, there is no evidence that SARS-CoV-2 is an engineered product or an isolate in a research laboratory.” (Posted June 11, 2020)
“Cumulative evidence to date supports the conclusion that this virus is naturally occurring (there are many coronaviruses in the wild). There is no evidence whatsoever to support that this virus was engineered in a lab or genetically modified.
“We meticulously examined sequences with high similarity to SARS-CoV-2 in all sequencing data sets in the NCBI Sequence Read Archive—the National Institutes of Health’s primary archive of sequencing data. We find no viral sequences with 100% identity to SARS-CoV-2, thus this viral sequence did not exist in the archive before the pandemic. The simplest explanation, and the most probable, is that coronaviruses continue to circulate in the wild and introductions to animals or humans can occur. However, if this virus was isolated from a biological source and maintained in a laboratory before the outbreak, the sequence of the virus and the data from this lab were not published, shared publicly, or known to other scientists. This is very unlikely, but it remains a possibility.” (Posted June 11, 2020)
How will human expansion into previously uninhabited environments change the likelihood of pandemics?
“The history of emerging infectious diseases has taught us that, while the causes are largely anthropogenic, they are not deliberate. We contribute to their emergence through our destruction of wildlife habitats, bushmeat consumption, the exotic pet trade, climate change, and the international travel and trade that facilitate the global spread of infectious diseases.” (Posted June 11, 2020)
“Many genetically different coronaviruses have been identified in bats. It is well documented that bat coronaviruses can infect different animals and humans through cross-species transmission. Seven distinct bat coronaviruses have been found in human infections; three of them have led to epidemic or pandemic (SARS, MERS, and COVID-19). Human expansion into previously uninhabited environments can substantially increase the chance of contracting new coronaviruses or other pathogenic viruses. Thus, to prevent new coronavirus transmissions, direct human contact with live or dead wild animals should be maximally reduced or avoided in the future.” (Posted June 11, 2020)
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Maciej F. Boni, Ph.D., associate professor of biology, Pennsylvania State University
I lived and worked in southern Vietnam for eight years, ran field epidemiology studies, and visited hundreds of markets and farms during my time there. I was based at the Oxford University Clinical Research Unit in Ho Chi Minh City at the time.
Feng Gao, M.D, professor of medicine, Division of Infectious Diseases, Department of Medicine, Duke University Medical Center
I have no conflicts of interests.
Robert F. Garry, Jr., Ph.D., professor of microbiology and immunology, Tulane Medical School
I am the co-founder of Zalgen Labs, a biotechnology company developing countermeasures to emerging viruses.
Massa Shoura, Ph.D., postdoctoral fellow in pathology and genetics, Stanford University
No conflict of interest.
Rasmus Nielsen, Ph.D., professor of integrative biology and statistics, University of California, Berkeley
W. Ian Lipkin, M.D., John Snow Professor of Epidemiology, director, Center for Infection and Immunity, Mailman School of Public Health, Columbia University
Susan R. Weiss, Ph.D., professor of microbiology, Perelman School of Medicine, University of Pennsylvania
I am on two scientific advisory boards at Immunome, Inc., and Ocugen, Inc., for which I get paid, but I do not get any research support for my lab from them.
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