ABSTRACT
Fine scale delineation of epitopes recognized by the antibody response to SARS-CoV-2 infection will be critical to understanding disease heterogeneity and informing development of safe and effective vaccines and therapeutics. The Serum Epitope Repertoire Analysis (SERA) platform leverages a high diversity random bacterial display library to identify epitope binding specificities with single amino acid resolution. We applied SERA broadly, across human, viral and viral strain proteomes in multiple cohorts with a wide range of outcomes from SARS-CoV-2 infection. We identify dominant epitope motifs and profiles which effectively classify COVID-19, distinguish mild from severe disease, and relate to neutralization activity. We identify a repertoire of epitopes shared by SARS-CoV-2 and endemic human coronaviruses and determine that a region of amino acid sequence identity shared by the SARS-CoV-2 furin cleavage site and the host protein ENaC-alpha is a potential cross-reactive epitope. Finally, we observe decreased epitope signal for mutant strains which points to reduced antibody response to mutant SARS-CoV-2. Together, these findings indicate that SERA enables high resolution of antibody epitopes that can inform data-driven design and target selection for COVID-19 diagnostics, therapeutics and vaccines.
ABSTRACT
The progress of the COVID-19 pandemic profoundly impacts the health of communities around the world, with unique effects on colleges and universities. Here, we examined the prevalence of SARS-CoV-2 in 1808 asymptomatic individuals on a university campus in California, and compared for the first time the performance of CRISPR- and PCR-based assays for large-scale virus surveillance. Our study revealed that there were no COVID-19 cases in our study population in May/June of 2020. Using the same methods, we demonstrated a substantial shift in prevalence approximately one month later, which coincided with changes in community restrictions and public interactions. This increase in prevalence, in a young and asymptomatic population, indicated the leading wave of a local outbreak, and reflected the rising case counts in the surrounding county. Our results substantiate that large, population-level asymptomatic screening using CRISPR- or PCR-based assays is a feasible and instructive aspect of the public health approach within large campus communities.
