High-Throughput Adaptable SARS-CoV-2 Screening for Rapid Identification of Dominant and Emerging Regional Variants

Objectives

Emerging SARS-CoV-2 variant strains can be associated with increased transmissibility, more severe disease, and reduced effectiveness of treatments. To improve the availability of regional variant surveillance, we describe a variant genotyping system that is rapid, accurate, adaptable, and able to detect new low-level variants built with existing hospital infrastructure.

Methods

We use a tiered high-throughput SARS-CoV-2 screening program to characterizes variants in a supra-regional health system over 76 days. Combining targeted qPCR and selective sequencing, we screen positive SARS-CoV-2 samples from all hospitals within our health care system for genotyping dominant and emerging variants.

Results

The median turnaround for genotyping was two days using the high-throughput qPCR-based screen, allowing us to rapidly characterize the emerging Delta variant. In our population, the Delta variant is associated with a lower CT value, lower age at infection, and increased vaccine breakthrough cases. Detection of low-level and potentially emerging variants highlights the utility of a tiered approach.

Conclusions

These findings underscore the need for fast, low-cost, high-throughput monitoring of regional viral sequences as the pandemic unfolds and the emergence of SARS-CoV-2 variants increases. Combing qPCR-based screening with selective sequencing allows for rapid genotyping of variants and dynamic system improvement.

Key messages

• A tiered approach that uses qPCR-based screening to identify dominant variants and sequencing for unique variants maximizes throughput, turnaround time, and information gleaned from each sample.

• In our population, the Delta variant became dominant in less than a month and is associated with lower CT, lower age at infection, and increased breakthrough cases.

• We identified low-level variants, including the variant of interest B.1.621 and a Delta variant with an E484K mutation in our population using existing hospital infrastructure.