Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1

Area of Science:

• Virology
• Molecular Diagnostics
• Epidemiology

Background:

• Genomic mutations in SARS-CoV-2 can impact molecular diagnostic assay performance.
• S-gene target failure has previously served as an indicator for specific SARS-CoV-2 variants.
• Emerging variants necessitate rapid detection methods to monitor spread and inform public health responses.

Purpose of the Study:

• To describe partial ORF1ab gene target failure (pOGTF) as a potential indicator for SARS-CoV-2 variants.
• To evaluate the sensitivity and specificity of pOGTF for detecting SARS-CoV-2 lineage BA.2.12.1.
• To assess the utility of pOGTF for real-time tracking of variant prevalence.

Main Methods:

• Utilized cobas SARS-CoV-2 assays to identify partial ORF1ab gene target failure (pOGTF), defined by a ≥2-thermocycle delay in ORF1ab gene detection compared to the E-gene.
• Compared pOGTF rates with the prevalence of SARS-CoV-2 lineage BA.2.12.1 sequences in public databases.
• Correlated local pOGTF rates with overall test positivity rates.

Main Results:

• Partial ORF1ab gene target failure (pOGTF) demonstrated 98.6% sensitivity and 99.9% specificity for SARS-CoV-2 lineage BA.2.12.1.
• Observed increasing rates of pOGTF closely mirrored the increasing prevalence of BA.2.12.1 sequences.
• Local pOGTF rates correlated with rising overall SARS-CoV-2 test positivity.

Conclusions:

• Partial ORF1ab gene target failure (pOGTF) is a sensitive and specific marker for SARS-CoV-2 BA.2.12.1.
• pOGTF can serve as a rapid proxy for tracking BA.2.12.1 variant spread, outperforming whole-genome sequencing in speed.
• This method can enhance variant surveillance, particularly for laboratories lacking sequencing capabilities.