Is SNP Genotyping a Better Approach for Monitoring for Known Variants of Concern

At UC Davis we have implemented rapid, inexpensive, high throughput testing for SARS-Cov-2 using technology repurposed from the agricultural biotechnology sector.  As part of Healthy Davis Together, this is providing at least weekly testing for the campus and the City of Davis.   The workflow involves testing saliva samples from asymptomatic individuals without RNA extraction.  To date, we have processed over 400,000 tests and identified more than 1,700 positive individuals.  The IntelliQube qPCR machine is not the rate limiting step, which provides the opportunity for high throughput genotyping of all positive samples for variants of SARS-CoV-2.  Evolution of the virus is inevitable and it is critical to monitor for variants of concern that have higher transmissibility and/or reduce the effectiveness of vaccines.  Genotyping using SNPs that discriminate between known variants of concern is more efficient, less expensive, technically less demanding, and importantly much more rapid than sequencing.  It will not, however, discover new variants and is therefore complementary to sequencing.  In collaboration with LGC, we have developed and deployed 14 SNP assays that can distinguish all the current variants of concern and interest in a redundant fashion.  All positive samples are assayed and genotypes assigned within a few days of sample collection.  Non-wildtype genotypes are validated by sequencing.  This provides rapid resulting to the county health authorities.  In summary, robust genotyping technology is available for monitoring large numbers of positive samples on a global scale; this will be particularly important in geographical areas where sequencing is not feasible.  The regulatory framework for this is more challenging than the technical aspects.

Learning Objectives:

1. Why is it important to monitor for variants of SARS-CoV-2?

2. What are the relative advantages of SNP genotyping and sequencing for surveillance?