Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1

Area of Science:

• Virology
• Molecular Diagnostics
• Epidemiology

Background:

• Viral mutations in SARS-CoV-2 can affect molecular diagnostic assay performance.
• Specific mutations, like S gene target failure, can indicate particular SARS-CoV-2 variants for rapid detection.
• Emerging variants may possess mutations impacting transmission, infectivity, and immune evasion.

Approach:

• Described partial ORF1ab gene target failure (pOGTF) using cobas SARS-CoV-2 assays.
• Defined pOGTF as a ≥2 thermocycle delay in ORF1ab gene detection versus the E gene.
• Assessed pOGTF sensitivity and specificity for SARS-CoV-2 lineage BA.2.12.1.

Key Points:

• pOGTF demonstrated 97% sensitivity and 99% specificity for SARS-CoV-2 BA.2.12.1.
• Observed increasing pOGTF rates closely correlated with BA.2.12.1 sequencing data and local test positivity.
• BA.2.12.1 possesses spike L452Q and S704L mutations.

Conclusions:

• pOGTF serves as an effective proxy for tracking SARS-CoV-2 BA.2.12.1.
• This method provides faster variant surveillance compared to whole-genome sequencing.
• pOGTF benefits laboratories lacking advanced sequencing capabilities.