Fact-check: Have Hungarian researchers proven that Covid “escaped” from a lab? Not quite.

The news that Hungarian researchers may have found a version of the SARS-CoV-2 virus which may be the “ancestor” of the virus which caused the pandemic – i.e. the missing link in the evolution of the virus – had a nice run in both the British press and on social media platforms.

At the same time, the articles suggest that the Hungarian discovery may actually be a confirmation of the theory which has been popular for a long time, but never proven scientifically: namely, that the virus escaped from a laboratory in Wuhan – given that the analysis shows that the recently identified variant may have gotten into the sample from animals which are often used in the lab. The Telegraph’s article even announced that “Early ‘lab-grown’ Covid virus found in sample lends weight to” the lab-escapee theories, and the Express wrote about a breakthrough in discovering the origin of the virus, not to mention the long title of the article in the Daily Mail, to name just a few.

It seems, however, that the explanation is much more prosaic: the samples analyzed by Hungarian researchers are of such poor quality, that according to other experts, it is not possible to draw overly confident conclusions from them – even so, such mutations in the virus that got into the sample as a contaminant can still be identified that rule out the possibility of the virus being an ancestor of SARS-CoV-2. The timing of the sampling would indeed allow for the possibility that this virus variant appeared in a Chinese lab before the official start of the outbreak – but it also it also allows the possibility that the virus developed after the outbreak started, with nothing else pointing to the former possibility.

What did the Hungarian scientists find?

The so far unknown version of the virus was found by István Csabai, university professor at the Department of Physics of Complex Systems at ELTE’s Faculty of Natural Sciences, and Norbert Solymosi, adjunct professor at the University of Veterinary Medicine. They published two preprint papers on Research Square, which publishes such works. The first one was published on 23 December, in cooperation with three other ELTE researchers, but no one paid any attention to it. The second one was published on 7 February, and this is the one that was picked up by the media.

“Both the press and various social media platforms like Twitter have contributed claims to the studies which we never made. Since I am first and foremost a physicist and data scientist – or at most a bioinformatician, I do not wish to provide any far-reaching virological or epidemiological interpretations, especially since the question has become even more politicized in recent weeks,”

István Csabai, lead author of the two studies said in response to Telex’s inquiry.

The virus was discovered in an unexpected place: in soil samples collected on Antarctica at the end of 2018 and at the beginning of 2019. However, there is no evidence – and the studies do not claim there is – that SARS-CoV-2 was present in Antarctica almost a year before the pandemic’s breakout in China. At the end of 2019, the samples were sent for sequencing (genetic analysis) to the laboratory of a Shanghai-based company, Sangon Biotech, where they were contaminated with the coronavirus from other samples.

The interesting thing about the newly discovered variant is that it has mutations that researchers believe could bridge the gap between SARS-CoV-2, which is spread among humans, and its closest relatives known so far, which were found in bats. If this were true, this could mean that they may have found a trace of the so far unknown ancestor of the virus which caused the pandemic.

This virus truly may have come from a lab

In their second study, however, the Hungarian researchers identified DNA belonging to humans, monkeys and hamsters, which may suggest that they stumbled upon traces of a virus which had been examined in a lab. If, however, a virus which can potentially be the ancestor of the now well-known coronavirus had indeed been present in China at the dawn of the pandemic, at the time when it had barely been reported that a few people were diagnosed with a strange, pneumonia-like illness, and it had been found in a sample originating from a lab, this could actually suggest that the pandemic was indeed caused by a virus which escaped from a lab in the first place – but this is the conclusion the mentioned news articles get to, the researchers have made no such statements.

The theory that the virus escaped from a laboratory goes in two directions at this point, as some believe that a virus of natural origin, collected from nature and tested in a laboratory, could have gotten out, while others believe that the virus itself could have been purposely modified in the laboratory.

In any case, cell lines from hamsters and monkeys are often used for virology experiments in laboratories. However, even at the very beginning of the outbreak, it was quite common practice for laboratories to test the new virus on animal cell lines, so the sample found by the Hungarian researchers is not necessarily a culprit in itself.

The main question is the timing: more specifically, exactly when the samples from Antarctica were sequenced: if that had happened in December 2019, then simply based on the timing it couldn’t be excluded that a version of SARS-CoV-2 unknown to us until now did indeed exist in a lab sample before it was officially discovered. But, if this happened in early 2020, then what most likely happened was that a sample of the virus which had been routinely examined simply got mixed into the sample from Antarctica. Neither the Hungarian researchers, nor other scientists are in possession of data which would make it possible to decide this, so in order to decide whether the first potential scenario could have happened, we must rely on other factors.

There is nothing unusual about sequenced lab samples getting mixed up in such a lab – if they are not handled carefully enough.

“These are very sensitive technologies, and it is a usual occurrence that such a mixing happens. An uglier term for it is ‘contamination’ but the term ‘transfer’ is also used – they both describe the same thing,”

Gábor Kemenesi, virologist at the University of Pécs, who researches coronaviruses found in bats told Telex.

This doesn’t prove an escape from a lab

Following the publication of the two studies, a number of respected scientists have voiced their opinions on social media about the Hungarian researchers’ results.

Jesse Bloom, a researcher studying the evolution of viruses at Bloom Lab within the Fred Hutchinson Cancer Research Center in the US analyzed the data himself, and confirmed the main conclusions of the first study written by the Hungarian researchers. On the other hand, he pointed out that the three key mutations identified by István Csabai and his colleagues are interesting because previous research which had aimed to identify the potential ancestor of the SARS-CoV-2 virus had come up with two theoretical versions of this ancestral virus, and one of them has these exact three mutations. However he also stated the following:

• This is not the first time these mutations have surfaced. They have been previously identified in several viral strains. In other words, even if this were an early strain of the virus, it still wouldn't be a strain which is older than the ones we were already familiar with.
• Just because a version of the virus is genetically more similar to its ancestor than another version, it does not necessarily mean that it appeared earlier, since the evolution of viruses is not that linear.
• Moreover, it is likely that the samples were not contaminated by just one, but by several different versions, and these got mixed together.

Kristian Andersen, immunologist at the Scripps Research Institute in the US, who at the beginning of the pandemic headed one of the first genetic examinations researching the origins of the virus, also analysed the Hungarian researchers’ data. He, however, clearly stated that

the Hungarian researchers’ work did not prove that the ancestor of the virus had gotten out of a lab. In fact, the data suggest quite the opposite.

He added that the Hungarian studies are all right, but the conclusions others had drawn from them are unfounded.

The Hungarian scientists identified three contaminated samples in which they found pieces of the SARS-CoV-2 virus, and then they used these pieces to assemble the genome of the virus. “Here's the problem though – the samples are *super* messy,” Andersen writes, and even shows a specific example, pointing out that there are so many mismatches that it is impossible to confidently determine the genome of the virus(es) which had contaminated these samples.

Andersen also pointed out that other than the three mutations mentioned above, there are other mutations present in the samples which actually contradict the assumption that this might be the earliest viral strain discovered so far. One of the mutations (H655Y), for example, can be found in both the Omicron and the Gamma variant, and it seems to be a derived mutation, meaning that it was not present in the “ancestral virus”. There is, in fact, another mutation (S:68-75) which is most definitely a derivative as it appeared at a later stage of the virus’s evolution. Due to this Andrersen states that it can be most definitely established that this is not an ancestor of the virus.

One cannot deduce much anyways

Gábor Kemenesi agreed with all of the above and emphasized that one need not go into such concrete refutations to question whether the ancestor of SARS-CoV-2 has been found. He pointed out the difficulty of the task with the following example:

“This is a huge set of mixed samples. Imagine three kinds of spaghetti that are broken up into pieces, and then mixed up nicely, after which you try to figure out where each piece belongs. While at the same time, a bunch of different things got mixed in there which aren’t even spaghetti.

In order to be able to say with sufficient certainty, using the technology, that a mutation is present at a certain position, so-called coverage is also needed. If you don't have enough coverage to confirm that the mutation is there, you can't be certain. So there really is no point in talking about mutations based on the sequencing of a sample which is as contaminated and mixed as this one, given that the technology doesn’t support the message. To be honest, this is a technically interesting case which was picked up by the media.”

Overall, therefore, the interpretations which claim that the Hungarian researchers may have found the ancestor of the SARS-CoV-2 virus seem exaggerated, and those that see their studies as a confirmation of the laboratory escape theory are explicitly misleading.