Partial ORF1ab gene target failure with Omicron BA.2.12.1 Journal Article


Authors: Rodino, K. G.; Peaper, D. R.; Kelly, B. J.; Bushman, F.; Marques, A.; Adhikari, H.; Tu, Z. J.; Rolon, R. M.; Westblade, L. F.; Green, D. A.; Berry, G. J.; Wu, F.; Annavajhala, M. K.; Uhlemann, A. C.; Parikh, B. A.; McMillen, T.; Jani, K.; Esther Babady, N.; Hahn, A. M.; Koch, R. T.; Grubaugh, N. D.; Yale SARS-CoV-2 Genomic Surveillance Initiative; Rhoads, D. D.
Article Title: Partial ORF1ab gene target failure with Omicron BA.2.12.1
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. Copyright © 2022 American Society for Microbiology. All Rights Reserved.
Keywords: controlled study; gene mutation; genetics; mutation; nonhuman; united states; sensitivity and specificity; genetic analysis; gene targeting; serine; data base; nucleotide sequence; base sequence; real time polymerase chain reaction; leucine; glutamine; predictive value; virus transmission; receiver operating characteristic; rt-pcr; virus gene; immune evasion; diagnostic test accuracy study; virus infectivity; humans; human; article; whole genome sequencing; coronavirus disease 2019; covid-19; sars-cov-2; sars-cov-2 omicron; cycle threshold (ct) value; orf1ab gene; partial orf1ab gene target failure (porf1ab); whole-genome sequencing (wgs); cycle threshold value; e gene; partial orf1ab gene target failure; sars-cov-2 delta
Journal Title: Journal of Clinical Microbiology
Volume: 60
Issue: 6
ISSN: 0095-1137
Publisher: American Society for Microbiology  
Date Published: 2022-06-01
Start Page: e0060022
Language: English
DOI: 10.1128/jcm.00600-22
PUBMED: 35582905
PROVIDER: scopus
PMCID: PMC9199403
DOI/URL:
Notes: Article -- Export Date: 1 August 2022 -- Source: Scopus
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MSK Authors
  1. Ngolela Esther Babady
    151 Babady
  2. Krupa Vijaykumar Jani
    24 Jani