CAS Key Laboratory of Special Pathogens and Biosafety, Centre for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China; University of Chinese Academy of Sciences, Beijing, 100049, China; Sino-Africa Joint Research Centre, Nairobi, 62000 - 00200, Kenya.
CAS Key Laboratory of Special Pathogens and Biosafety, Centre for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
Anal Chim Acta. 2022 Apr 1;1200:339590. doi: 10.1016/j.aca.2022.339590. Epub 2022 Feb 15.
The global public health crisis and economic losses resulting from the current novel coronavirus disease (COVID-19) pandemic have been dire. The most used real-time reverse transcription polymerase chain reaction (RT-PCR) method needs expensive equipment, technical expertise, and a long turnaround time. Therefore, there is a need for a rapid, accurate, and alternative technique of diagnosis that is deployable at resource-poor settings like point-of-care. This study combines heat deactivation and a novel mechanical lysis method by bead beating for quick and simple sample preparation. Then, using an optimized reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay to target genes encoding the open reading frame 8 (ORF8), spike and nucleocapsid proteins of the novel coronavirus, SARS-CoV-2. The test results can be read simultaneously in fluorometric and colorimetric readouts within 40 min from sample collection. We also calibrated a template transfer tool to simplify sample addition into LAMP reactions when pipetting skills are needed. Most importantly, validation of the direct RT-LAMP system based on multiplexing primers S1:ORF8 in a ratio (1:0.8) using 143 patients' nasopharyngeal swab samples showed a diagnostic performance of 99.30% accuracy, with 98.81% sensitivity and 100% selectivity, compared to commercial RT-PCR kits. Since our workflow does not rely on RNA extraction and purification, the time-to-result is two times faster than other workflows with FDA emergency use authorization. Considering all its strengths: speed, simplicity, accuracy and extraction-free, the system can be useful for optimal point-of-care testing of COVID-19.
当前新型冠状病毒病(COVID-19)大流行造成的全球公共卫生危机和经济损失是严重的。最常用的实时逆转录聚合酶链反应(RT-PCR)方法需要昂贵的设备、技术专业知识和较长的周转时间。因此,需要一种快速、准确和替代的诊断技术,可在资源匮乏的环境(如即时护理)中部署。本研究结合热失活和新型机械珠磨裂解方法,用于快速简单的样品制备。然后,使用优化的逆转录环介导等温扩增(RT-LAMP)检测针对新型冠状病毒 SARS-CoV-2 的开放阅读框 8(ORF8)、刺突和核衣壳蛋白编码基因的检测。测试结果可以在从样本采集开始的 40 分钟内,通过荧光和比色读数同时读取。我们还校准了模板转移工具,以简化在需要移液技能时将样品加入 LAMP 反应中。最重要的是,使用基于多重引物 S1:ORF8 的直接 RT-LAMP 系统(比例为 1:0.8)对 143 例鼻咽拭子样本进行验证,与商业 RT-PCR 试剂盒相比,该系统的诊断性能达到了 99.30%的准确率,灵敏度为 98.81%,特异性为 100%。由于我们的工作流程不依赖于 RNA 提取和纯化,因此与获得 FDA 紧急使用授权的其他工作流程相比,结果时间快了两倍。考虑到所有优势:速度、简单性、准确性和无需提取,该系统可用于优化即时护理 COVID-19 检测。