The Illusion of Biosafety During SARS-CoV-2 Research: Multiple Apparent Occult Lab-Acquired Infections Are Identified Under BSL-3 Conditions at a Premier US-based Coronavirus Laboratory

"Abstract

An active debate exists over the use of synthetic biology and other advanced research tools on dangerous pathogens. Virologists doing gain-of-function and related research on dangerous pathogens, including creating synthetic chimeric infectious clones, believe their work is essential to preventing the next pandemic. Many scientists in related fields do not believe the benefit of the research outweighs the risk of a laboratory-acquired infection, leading to community spread. They also believe that current regulations and guidelines for the funding, conduct, and biosafety reporting of research accidents, that is, infections of laboratory personnel, is inadequate.

The consensus of the virologists’ position is that, if creating synthetic pathogens is conducted under appropriate Biological Safety Laboratory (BSL) standards, the work can be performed safely. However, abundant evidence indicates that laboratory-acquired infections (LAI) still do occur, even under the highest BSL-3 and even BSL-4 standards.

Here we develop methods and criteria to identify occult LAIs and distinguish them from community-acquired infections. We then apply these tools to a test case. 

Using these methods, we identify seven apparent LAI SARS-CoV-2 infections from June 2020 to January 2021, sequenced at the Clinical Molecular Microbiology Laboratory, University of North Carolina (UNC) Hospital, Chapel Hill, NC. ... [U]sing the criteria herein, including the response to our inquiry and genome sequence comparison, all of the LAIs have a high probability of being SARS-CoV-2 variants...

The finding of seven likely occult LAIs in an eight-month period of time from what many consider the premier coronavirus synthetic biology laboratory in the US, or even the world, combined with the apparent failure to identify and report these LAIs by the laboratory or university at large, underscores a failure of current LAI regulations. Although current regulations have mandatory reporting, they do not have a process for finding and reporting occult infections...

Discussion

... From January 2015 to June 2020, UNC-Chapel Hill reported 28 laboratory incidents involving genetically modified organisms to the NIH Office of Science Policy. Of those, at least six incidents involved engineered coronaviruses, specifically SARS- and MERS-associated strains... Notably, each of these incidents involved some level of potential exposure to lab personnel, who were subsequently placed under medical surveillance...

These incidents also highlight systemic failures in risk assessment. Despite conducting experiments with high-consequence respiratory viruses, including synthetic variants designed to enhance infectivity, UNC relied heavily on the personal protective equipment of researchers and assumed containment within the lab. However, as demonstrated herein, viral sequence analysis of eight suspected SARS-CoV-2 LAIs originating from UNC shows that such containment may be illusory. This data suggests that laboratory strains, 'frozen in time' compared to the community phylogeny, found their way into hospital patients without detection or official recognition, paralleling the earlier, documented breaches from 2015–2020."