Analysis: Issues surrounding ‘100% lethal’ strain of coronavirus tested in Chinese lab
In early January, a medical research article posted on the preprint server bioRxiv grabbed the attention of the news media worldwide.
The study, which has not yet been peer-reviewed, was reported with headlines implying that Chinese researchers “created” a “100% lethal” new strain of COVID-19 virus which killed all genetically modified, humanized mice in a lab.
Media outlets like WION, Daily Mail and New York Post, as well as numerous social media posts by influencers, mentioned the potential risks of a leak and the possibility of the virus infecting humans.
Some even claimed that this strain was deliberately created in China, suggesting that it could be used as a biological weapon.
Most researchers who conducted the study belong to the Beijing University of Chemical Technology and the Fifth Medical Center of People’s Liberation Army General Hospital. The latter institution’s affiliation with the military also fueled the speculation of their intent.
Some parts of the news reports about this paper have been investigated by fact-checking organizations such as PolitiFact and FactCheck.org, and they concluded that the pangolin coronavirus in question is not a “new strain” of COVID-19 virus.
At Annie Lab, we also investigated the main claims and tried to address some of the unanswered questions while contacting one of the authors and consulting other experts.
Was this ‘new strain’ engineered in the lab?
After the study was widely reported and criticized, Dr. Song Lihua, a researcher at the Beijing University of Chemical Technology and one of the co-authors of the paper, posted a clarification on Jan. 17 on the website ScienceCast, a platform for researchers to discuss their findings.
The virus tested by Song and his colleagues was a mutant of the pangolin coronavirus strain called GX_P2V(short_3UTR). Its origin, GX_P2V, was first reported in a 2020 article in Nature.
A group of researchers from Hong Kong and mainland China discovered six genome sequences of pangolin coronavirus, including GX_P2V, from pangolin tissue samples collected from 2017 to 2018.
According to the study, these pangolin coronaviruses, including GX_P2V, exhibited strong similarity in gene structure to the virus that causes COVID-19, SARS-CoV-2, ranging from 85.5% to 92.4%.
Dr. Siddharth Sridhar, a clinical virologist from the University of Hong Kong’s Medical School, said in an email that virus mutation during growth in cell structure is “completely normal and expected.”
Sridhar also said they are two different viruses, calling GX_P2V “a distant cousin of SARS-CoV-2.”
Song told Annie Lab in an email that after conducting “high-throughput sequencing analysis on the GX_P2V virus that was cultivated in cells,” the researchers noticed a deletion of 104 bases in its 3′ untranslated region (3UTR),” which indicates the GX_P2V virus they were dealing with was “a cell-adapted strain.”
“We have accordingly re-designated this cell-adapted strain as GX_P2V(short_3UTR),” Song said.
In short, the virus mentioned in the controversial paper was mutated, not engineered, from pangolin coronavirus GX_P2V, according to Song. It has a similar structure to SARS-CoV-2, but they are not the same.
Experts say even though different coronaviruses belong to the same family, they vary significantly in terms of their ability to cause illnesses in the host, from asymptomatic infection to lethal harm.
What was the biosafety level?
Another contentious aspect of the research paper was the biosafety level of the laboratory where the study was conducted. Many news outlets and some scientists raised questions and concerns about its safety protocol, mentioning the potential risks of spillover.
Song did not clarify the biosafety level in our email correspondence, but we found another peer-reviewed study published by Song and his research team in the Journal of Medical Virology in August 2023.
In this article titled “Omicron breakthrough infections in wild-type SARS-CoV-2 vaccines elicit high levels of neutralizing antibodies against pangolin coronavirus GX_P2V,” the authors specified that the cultivation of the GX_P2V (short_3UTR) strain was conducted in a biosafety level 2 laboratory.
According to China’s official documentation of biosafety standards, a biosafety level 2 lab is suitable for studying microorganisms that can cause diseases in humans or animals but pose no serious threat in general, such as rubella virus and hepatitis B virus.
However, Sridhar told Annie Lab that studies involving SARS-related coronaviruses in cells or animals should be conducted in biosafety level 3 facilities.
As of this writing, we have yet to receive confirmation from Song about the safety level of the lab test in question.
What actually killed the four ‘human ACE2 transgenic mice’?
The article said there were four mice involved in the study, and all of them died.
After the paper caught worldwide attention, the authors posted a revised version on Jan. 21, adding more possible explanations of death besides the “late-stage brain infection” that was originally suspected in the first version.
In the experiment, they used genetically modified mice designed for biomedical research. Song called them “ACE2 humanized mice” in his email to Annie Lab.
Human ACE2 (hACE2) is an enzyme located within the human body that can act as an entry point — a “receptor” — for coronavirus to infect human cells.
The mice used in the test were developed by Beijing SpePharm Biotechnology Company, according to the research paper.
Song said normal human and mouse brains show low expression of ACE2, whereas the transgenic mice featured high expression of hACE2 in their brain and lung tissues, which was correlated with the high viral loads of GX_P2V(short_3UTR) that were detected in these tissues.
He said the cause of death could be attributed to the high expression of hACE2 found in the brains of these mice obtained from Beijing SpePharm Biotechnology, implying that the genetic modification itself could have contributed to the results as well.
Alina Chan, a molecular biologist and a scientific advisor at the Broad Institute of MIT and Harvard, said in a media interview that SARS-CoV-2 also killed 100% of the humanized mice in a lab environment while asking for more transparency regarding the biosafety level of the research facility.
Can this strain infect humans if the virus gets leaked?
In another media interview, Dr. Mahesh Adalja, a senior scholar at Johns Hopkins Center for Health Security and a spokesperson for the Infectious Diseases Society of America, also questioned the biosafety level but dismissed the “sensational” news coverage surrounding the study.
“This is a specific mouse model that has a lot of receptors all over the body in a way that humans don’t. So I don’t think this necessarily has a major threat to human health… Is China doing this research safely, because that’s the key thing,” he said.
Song told Annie Lab that their findings are limited to genetically modified mice only, noting that “the experimental results obtained with this model cannot be extrapolated to suggest similar infections in humans.”
He said GX_P2V(short_3UTR) only exists in laboratories and not in nature in the first place, and tests found that vaccinated individuals who recovered from Omicron infection or individuals who received four doses of COVID-19 vaccine could elicit cross-protective immunity against the pangolin coronavirus.
In the revised draft, which has not yet been peer-reviewed, the researchers removed the statement about the risk of spillover to human beings that was highlighted by many media outlets and online posts.
Sridhar, however, said it was more accurate to say pangolin coronaviruses were not known to infect humans.
“What may happen in the future is a matter of speculation,” he told Annie Lab.
