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Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1

Title: Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1
Authors: Rodino, KG; Peaper, DR; Kelly, BJ; Bushman, F; Marques, A; Adhikari, H; Tu, ZJ; Rolon, RM; Westblade, LF; Green, DA; Berry, GJ; Wu, F; Annavajhala, MK; Uhlemann, AC; Parikh, BA; McMillen, T; Jani, K; Esther Babady, N; Hahn, AM; Koch, RT; Grubaugh, ND; Rhoads, DD; Billig, K; Breban, M; Vogels, C; Pham, K; Chen, N; Chaguza, C; Tikhonova, I; Castaldi, C; Mane, S; De Kumar, B; Ferguson, D; Kerantzas, N; Landry, M; Schulz, W
Source: Journal of Clinical Microbiology , 60 (6) , Article e0060022. (2022)
Publisher Information: American Society for Microbiology
Publication Year: 2022
Collection: University College London: UCL Discovery
Subject Terms: cycle threshold (CT) value; ORF1ab gene; partial ORF1ab gene target failure (pORF1ab); RT-PCR; SARS-CoV-2; whole-genome sequencing (WGS)
Description: 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.
Document Type: article in journal/newspaper
File Description: text
Language: English
Relation: https://discovery.ucl.ac.uk/id/eprint/10161182/1/Partial%20ORF1ab%20Gene%20Target%20Failure%20with%20Omicron%20BA.2.12.1.pdf; https://discovery.ucl.ac.uk/id/eprint/10161182/
Availability: https://discovery.ucl.ac.uk/id/eprint/10161182/1/Partial%20ORF1ab%20Gene%20Target%20Failure%20with%20Omicron%20BA.2.12.1.pdf; https://discovery.ucl.ac.uk/id/eprint/10161182/
Rights: open
Accession Number: edsbas.856877D8
Database: BASE