Objectives Emerging severe acute respiratory syndrome coronavirus 2 (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 used a tiered high-throughput SARS-CoV-2 screening program to characterize variants in a supraregional health system over 76 days. Combining targeted reverse transcription–polymerase chain reaction (RT-PCR) and selective sequencing, we screened SARS-CoV-2 reactive samples from all hospitals within our health care system for genotyping dominant and emerging variants. Results The median turnaround for genotyping was 2 days using the high-throughput RT-PCR–based screen, allowing us to rapidly characterize the emerging Delta variant. In our population, the Delta variant is associated with a lower cycle threshold 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. Combining RT-PCR–based screening with selective sequencing allows for rapid genotyping of variants and dynamic system improvement.

Aims: Emerging SARS-CoV-2 variant strains are associated with increased transmissibility, more severe disease, and reduced effectiveness of treatments. Genomic surveillance for identifying variants would better inform resource allocation and hotspot control. Yet, the implementation of variant surveillance has been regionally variable and prohibitively slow. To improve the availability of 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 turn-around for genotyping was two days using the high-throughput qPCR-based screen, allowing us to rapidly characterize the emerging Delta variant. Consistent with prior work, in our population, the Delta variant is associated with a lower CT value (a surrogate for viral load), 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.