Rapid CRISPR-based surveillance of SARS-CoV-2 in asymptomatic college students captures the leading edge of a community-wide outbreak

Abstract Importance The re-opening of colleges and universities through the US during the COVID-19 pandemic is a significant public health challenge. The development of accessible and practical approaches for SARS-CoV-2 detection in the college population is paramount for deploying recurrent surveillance testing as an essential strategy for virus detection, containment, and mitigation. Objectives In this study, we set out to determine the prevalence of SARS-CoV-2 in asymptomatic subjects in a university community, using, for the first time, CREST, a CRISPR-Cas13-based test that we developed for accessible and large scale viral surveillance1. Study Design, Setting, and Participants We enrolled 1,808 asymptomatic persons to undergo SARS-CoV-2 testing. We compared viral prevalence in self-collected oropharyngeal swab samples obtained in two time periods: May 28th-June 11th and June 23rd-July 2nd, 2020. We detected viral genomes in these samples using CREST, and we corroborated our results with a point-of-reference RT-qPCR test. Positive samples were confirmed by a clinical laboratory and reported to the local Public Health Department. Results All the 732 tests performed between late May to early June were negative. In contrast, tests performed on 1,076 samples collected between late June to early July revealed eight positive cases by CREST, confirmed by RT-qPCR and CLIA-diagnostic testing. The average age of the positive cases was 21.7 years; all individuals self-identified as students. These metrics showed that CREST was effective at capturing positive SARS-CoV-2 cases in our student population. Notably, the viral loads detected in these asymptomatic cases resemble those seen in clinical samples, highlighting the potential of covert viral transmission. Conclusions and Relevance Our study revealed a substantial shift in SARS-CoV-2 prevalence in a young and asymptomatic population, and uncovered the leading wave of a local outbreak that coincided with rising case counts in the surrounding county and the state of California. Moreover, and most notably, the almost perfect concordance between CRISPR- and PCR-based testing indicated that CREST using self-collected OP swabs is reliable and it allows expanding options for large-scale surveillance testing and detection of SARS-CoV-2 outbreaks, as is required to resume operations in higher education institutions in the US and abroad. Key Points Question Are CRISPR-based methods a reliable and accessible option to capture SARS-CoV-2 outbreaks in a college population? Findings We tested 1,808 asymptomatic individuals from a university population for SARS-CoV-2, using, for the first time, a CRISPR-based assay for virus surveillance. We detected eight positive cases, corroborated by RT-qPCR and confirmed by a clinical laboratory. Our CRISPR-based method captured a change in viral prevalence coinciding with the relaxation of lockdown measures and the rise of COVID-19 cases in the community. Significance We demonstrate that CRISPR-based methods offer scalable and reliable SARS-CoV-2 testing for virus surveillance and allow capturing the leading edge of an outbreak.