Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvaniagrid.25879.31, Philadelphia, Pennsylvania, USA.
Department of Laboratory Medicine, Yale Universitygrid.47100.32, New Haven, Connecticut, USA.
J Clin Microbiol. 2022 Jun 15;60(6):e0060022. doi: 10.1128/jcm.00600-22. Epub 2022 May 18.
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.
SARS-CoV-2 基因组中的突变会影响分子诊断检测的性能。在某些情况下，如 S 基因靶标失败，其影响可以作为特定 SARS-CoV-2 变体的独特指标，并提供快速检测的方法。在这里，我们描述了 cobas SARS-CoV-2 检测中的部分 ORF1ab 基因靶标失败（pOGTF），其定义为与 E 基因相比，ORF1ab 基因的检测延迟≥2 个热循环。我们证明，pOGTF 对在美国出现的具有刺突 L452Q 和 S704L 突变的新兴变体 SARS-CoV-2 谱系 BA.2.12.1 的敏感性为 98.6%，特异性为 99.9%，这些突变可能会影响传播、感染力和/或免疫逃避。pOGTF 发生率的增加与上传至公共数据库的 BA.2.12.1 序列的发生率密切相关，重要的是，当地 pOGTF 发生率的增加也与总检测阳性率的增加相吻合。使用 pOGTF 作为 BA.2.12.1 的替代物比全基因组测序更快地追踪变体，并且可以使没有测序能力的实验室受益。
