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Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1

Rodino, KG; Peaper, DR; Kelly, BJ; Bushman, F; Marques, A; Adhikari, H; Tu, ZJ; ... Schulz, W; + view all (2022) Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1. Journal of Clinical Microbiology , 60 (6) , Article e0060022. 10.1128/jcm.00600-22. Green open access

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Abstract

Mutations in the genome of SARS-CoV-2 can affect the performance of molecular diagnostic assays. In some cases, such as S-gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here, we describe partial ORF1ab gene target failure (pOGTF) on the cobas SARS-CoV-2 assays, defined by a $2-thermocycle delay in detection of the ORF1ab gene compared to that of the E-gene. We demonstrate that pOGTF is 98.6% sensitive and 99.9% specific for SARS-CoV-2 lineage BA.2.12.1, an emerging variant in the United States with spike L452Q and S704L mutations that may affect transmission, infectivity, and/ or immune evasion. Increasing rates of pOGTF closely mirrored rates of BA.2.12.1 sequences uploaded to public databases, and, importantly, increasing local rates of pOGTF also mirrored increasing overall test positivity. Use of pOGTF as a proxy for BA.2.12.1 provides faster tracking of the variant than whole-genome sequencing and can benefit laboratories without sequencing capabilities.

Type: Article
Title: Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1128/jcm.00600-22
Publisher version: https://doi.org/10.1128/jcm.00600-22
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: cycle threshold (CT) value, ORF1ab gene, partial ORF1ab gene target failure (pORF1ab), RT-PCR, SARS-CoV-2, whole-genome sequencing (WGS)
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10161182
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