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

Version 4.0: This update primarily cleaned up the prior versions. The preprint is now ready for journal submission. A graphical abstract has been added.

ABSTRACT

An active debate exists over the safety of synthetic biology and other advanced research tools used on dangerous pathogens. Here we develop methods and criteria to identify occult lab acquired infections (LAIs) and distinguish them from community-acquired infections. We then apply these tools to a test case. Using these methods, we identify nine potential LAI SARS-CoV-2 infections from May 2020 to January 2021, sequenced at the Clinical Molecular Microbiology Laboratory, University of North Carolina (UNC) Hospital, Chapel Hill, NC. While the laboratory from which they may have acquired cannot be known with certainty, using the criteria herein, including the response to our inquiry and genome sequence comparison, all of the potential LAIs have a probability of being SARS-CoV-2 variants being actively studied at premier coronavirus laboratories on the UNC Campus, ostensibly under BSL-3 conditions. In particular, three of the sequences possess the R685G substitution in the spike protein, which mutates the furin cleavage site. The corresponding SNV C23615G  is vanishingly rare in wild-type sequences, but it has been utilized in several artificially modified spike sequences, mostly in connection with vaccine research. Consequently, this observation supports the hypothesis of LAIs. We could however find no public records of reported LAIs from the UNC during this period and conclude it is likely these potential LAIs were unknown to the laboratory itself as knowingly failing to report infections under these circumstances would be a violation of a number of statutes and regulations.