The question of the origin of SARS-CoV-2 continues to occupy scientists, the media, and the public intensely even 5 years after the onset of the COVID-19 pandemic. Where the virus came from, when and where humans were first infected, and whether the spread could have been prevented — these questions are more than just of epidemiological interest. After all, pandemic-related measures such as lockdowns, mask mandates, and school closures have faced significant resistance from parts of the population, and the repercussions still persist today.
While it is crucial to investigate the causes and to identify errors in the communication and implementation of these measures, the spread of unfounded assumptions about the origin of the pandemic-triggering virus is not helpful. However, this is precisely what happens with remarkable regularity: Recently, reports about previously withheld assessments from the German Federal Intelligence Service suggested that SARS-CoV-2 might be a genetically modified virus from a Chinese laboratory, garnering media attention. Ultimately, no new insights emerged from this, as the expert group involved could not provide source data for scientific evaluation.
Reports like these influence public opinion on the origin of SARS-CoV-2 even without solid new data and reinforce long-standing proponents of the lab leak hypothesis. This hypothesis can be politically leveraged to deepen the existing divide between a science-oriented audience and a science-skeptical or hostile public. A corresponding positioning has been evident since mid-April on several official US government websites that previously informed about COVID-19, testing options, and vaccinations. Objective and reliable information about the disease and the virus is no longer available. This does not contribute to a factual discussion of the different approaches to the debate about the origin of SARS-CoV-2.
Different Scenarios, Few Evidence
The discourse on the origin of SARS-CoV-2 is primarily shaped by two assumptions: The first is that the virus jumped to humans through natural means — most likely from a bat via another animal acting as an intermediate host. This assumption is still shared by the majority of the scientific community. The second hypothesis posits an origin in a laboratory. Here, two lines of argument have developed: SARS-CoV-2 could be a newly isolated virus modified for research purposes that was accidentally released, or an unknown virus could have infected individuals during sampling from bats or during laboratory investigations, who then unknowingly carried the pathogen outside. In the latter case, one cannot strictly speak of a laboratory accident, as no modifications to the virus occurred in this scenario.
What evidence supports the current assumptions about the origin of the virus? To prove a zoonotic origin, an animal intermediate host must be identified through which SARS-CoV-2 jumped to humans, or a direct predecessor of the virus must be found in a bat population. The laboratory accident theory could be confirmed by demonstrably infected employees or by protocols documenting the presence of the virus in a laboratory before the pandemic began. Neither assumption is currently sufficiently substantiated — however, the available evidence for each hypothesis can be weighed.
From Nature or the Laboratory?
Early investigations of environmental samples pointed to the Huanan Seafood Wholesale Market — one of four markets in Wuhan where live wild animals are sold — as the starting point of the pandemic. Since the first SARS-CoV pandemic in 2003, it has been known that wild animals traded in such markets can carry potentially human-pathogenic pathogens. However, according to Chinese health authorities, samples from living animals present at the market were not taken at the time of the outbreak. Very quickly, citing infection control, the entire animal stock was culled, cages and market stalls were disinfected, and the market was closed.
Whether swabs from living animals were taken and stored contrary to official statements remains unknown to this day. What is certain, however, is that viral sequences of SARS-CoV-2 have been detected in all four wild animal markets in Wuhan. Particularly striking are sequence data that demonstrate both genetic material from SARS-CoV-2 and from the raccoon dogs traded there. Raccoon dogs are susceptible to the virus and were already considered potential intermediate hosts for SARS-CoV-2 before the discovery of the genetic mixtures at the Huanan Seafood Wholesale Market.
The sequences come from cage swabs taken at the beginning of the pandemic by employees of the Chinese Center for Disease Control and Prevention. The animals were kept in cages in the southwestern part of the market. There, and in the immediate vicinity, around 150 of the first infection cases from the early phase of the pandemic were identified.
Spillover Events
The raw data from these swabs were only made accessible on the genomic data platform Global Initiative on Sharing All Influenza Data in 2023 and could be analyzed by a team led by Canadian virologist Angela Rasmussen. This analysis represents the most compelling evidence to date for a zoonotic origin of SARS-CoV-2. Many other findings from recent years also support the assumption that the virus — similar to the first SARS pandemic in 2003 — jumped from bats to humans via an animal intermediate host.
One of the most significant findings is the early presence of two lineages (A and B) of the virus at the Huanan Seafood Wholesale Market. Therefore, there must have been at least two spillover events before SARS-CoV-2 spread pandemic-wise through lineage B.
Not only raccoon dogs but also other illegally traded wild animals could have been intermediate hosts of the virus. A 2021 study listed 38 species, 31 of which are protected, that were known to have been offered at the markets in Wuhan between May 2017 and November 2019. Among them are neither bats nor pangolins, which were temporarily suspected of being transmitters, but many other animals known to be susceptible to SARS-CoV-2. Furthermore, the breeding of raccoon dogs for fur production is legal in China, according to the authors of the study. However, prices for such products have fallen in recent years, leading to bred animals often being sold alongside wild animals at markets.
Proponents of the lab leak theory sometimes argue that the strong spread of the virus at the Huanan Seafood Wholesale Market could also have resulted from a superspreader event — meaning an infected person caused a particularly high number of additional infections.
In this scenario, SARS-CoV-2 would not have jumped from animal to human first but rather the other way around: An infected employee of a laboratory could have unknowingly spread the virus at the market or in its immediate vicinity. However, this would have to have occurred twice — otherwise, the early presence of two lineages in the market area would be difficult to explain. It also remains unclear why a similar early concentration of infections was not observed at more obvious locations, such as around the Wuhan Institute of Virology (WIV) or the residences of laboratory personnel.
Recent investigations of genetic data from early environmental samples largely confirm previous findings. In the southwestern area of the market, wild animals that are considered potential intermediate hosts were present in the early phase of the outbreak, and “hotspots” of virus concentrations were identified in the southwestern part of the market where the animals were sold. Genetic traces of these animals were found in several SARS-CoV-2–positive samples. Epidemiological research on SARS-CoV-2 and its spread has provided another important indication of a natural origin of the virus: We now know that spillover events occur much more frequently than previously assumed. Superspreader events, on the other hand, are relatively rare.
Laboratory Safety
In the search for the origin of SARS-CoV-2, another debate has gained momentum: An increasingly unsettled public and many media outlets are now addressing issues such as genetic modification of viruses and inadequate laboratory biosafety levels — often without sufficient differentiation and with alarmist undertones. The term “gain-of-function research” encompasses any type of functional modification of viruses or viral sequences, without placing the term in the correct context: Namely, that this type of modification has been part of scientific methodology in virology for decades and is not inherently associated with an increase in virulence. Without it, there would be no flu vaccines, and the COVID-19 vaccines now available could not have been developed so quickly.
In professional circles, the conditions under which research on potentially dangerous zoonotic viruses takes place, as well as individual techniques used in this research, have long been critically discussed. In the aftermath of the pandemic, this discourse has intensified and, to some extent, become more heated. The possibility that SARS-CoV-2 could have originated in a laboratory continues to provoke sometimes heated and partially media-driven disputes. This type of discourse ultimately harms all involved researchers but does not yield any insights into the origin of SARS-CoV-2. What is certain is that in some laboratories, potentially dangerous work has been conducted under inadequate safety conditions.
Currently, Chinese virologist Zheng-Li Shi, longtime head of the Center for Emerging Infectious Diseases at the WIV and known for her research on bat coronaviruses, is particularly under scrutiny. At the beginning of the pandemic, her research group faced accusations that SARS-CoV-2 had emerged from the WIV from an unknown bat coronavirus that served as a backbone for the development of SARS-CoV-2. Shi and her team have consistently denied these claims. According to Shi, none of the viral sequences present at the WIV were predecessors of SARS-CoV-2.
The trigger for the newly reignited debate was a paper authored by Shi and other scientists largely associated with the WIV, published in March this year in Cell. The article discusses a recently discovered betacoronavirus, HKU5-CoV-2, found in bats in Brazil, which is phylogenetically closely related to the Middle East respiratory syndrome (MERS)–like HKU5-CoV identified in 2021. The virus uses the ACE2 receptor — or orthologous animal receptors — to enter host cells, as Shi and her team determined in laboratory experiments that are now under scrutiny. In a guest article published in March in The New York Times, Ian Lipkin and Ralph Baric, two renowned scientists long involved in coronavirus research, addressed research practices like those employed by Shi’s team for their work with HKU5-CoV-2.
They describe these practices as too risky to be conducted under biological safety level (BSL) 2 because they involve experiments with a new, infectious virus that has the potential to cause severe disease in humans. Such experiments would be more appropriately conducted under the significantly stricter guidelines of BSL 3. At the same time, research on such viruses is necessary to reduce the risk for future epidemics: MERS-like coronaviruses, like the one described in Shi and team’s work, have great potential for jumping to humans and should therefore be monitored epidemiologically.
There are many proposals for how to address this issue, ranging from the international standardization and better monitoring of laboratory safety standards to the refusal of scientific journals to accept publications based on research conducted under dangerous conditions.
Line Between Science and Politics
According to current knowledge, a natural origin of SARS-CoV-2 is still much more likely than a laboratory origin. Even after 5 years, there is not a single solid piece of evidence for a laboratory origin. Presenting the lab leak hypothesis as more or less established is therefore driven more by political interests than by a desire to clarify the origin of the virus. At the same time, the targeted dissemination of one-sidedly weighted information and claims that are not supported by facts causes significant harm: It unsettles, destroys trust in the integrity of scientific institutions and researchers, and weakens decision-makers and communicators in future crisis situations.
Distraction debates are thus strengthened: The search for those responsible takes center stage, while questions about the destruction of natural habitats of wild animals and poor conditions in breeding facilities — both driving factors for spillover — are pushed out of media discourse. Future pandemics are also much more likely to arise from nature than from a laboratory.
The American historian and author John M. Barry pointed out the problem back in 2020: “When you mix science with politics, you get politics.” In this debate, we would do well to keep politically motivated speculations at bay and refocus interest and reporting on what is actually the current state of science.
This story was translated from Univadis Germany.
