Rodino Kyle G, Peaper David R, Kelly Brendan J, Bushman Frederic, Marques Andrew, Adhikari Hriju, Tu Zheng Jin, Rolon Rebecca Marrero, Westblade Lars F, Green Daniel A, Berry Gregory J, Wu Fann, Annavajhala Medini K, Uhlemann Anne-Catrin, Parikh Bijal A, McMillen Tracy, Jani Krupa, Babady N Esther, Hahn Anne M, Koch Robert T, Grubaugh Nathan D, Rhoads Daniel D
medRxiv. 2022 Apr 28:2022.04.25.22274187. doi: 10.1101/2022.04.25.22274187.
Mutations in the viral genome of SARS-CoV-2 can impact 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 thermocycles delay in detection of the ORF1ab gene compared to the E gene. We demonstrate that pOGTF is 97% sensitive and 99% 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 impact 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.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒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基因靶点失效，这种影响可作为特定SARS-CoV-2变体的独特指标，并提供一种快速检测方法。在此，我们描述了cobas SARS-CoV-2检测中部分开放阅读框1ab（ORF1ab）基因靶点失效（pOGTF）的情况，其定义为与E基因相比，ORF1ab基因检测延迟≥2个热循环。我们证明，pOGTF对SARS-CoV-2谱系BA.2.12.1的敏感性为97%，特异性为99%，BA.2.12.1是美国一种新出现的变体，其刺突蛋白存在L452Q和S704L突变，可能影响传播、传染性和/或免疫逃逸。pOGTF发生率的上升与上传到公共数据库的BA.2.12.1序列的发生率密切相关，重要的是，pOGTF本地发生率的上升也与总体检测阳性率的上升相关。将pOGTF用作BA.2.12.1的替代指标，比全基因组测序能更快地追踪该变体，且对没有测序能力的实验室有益。
