Abstract：
Diagnostic tests were heralded as crucial during the Coronavirus disease (COVID-19) pandemic with most of the key methods using bioanalytical approaches that detected larger molecules (RNA, protein antigens or antibodies) rather than conventional clinical biochemical techniques. Nucleic Acid Amplification Tests (NAATs), like the Polymerase Chain Reaction (PCR), and other molecular methods, like sequencing (that often work in combination with NAATs), were essential to the diagnosis and management during COVID-19. This was exemplified both early in the pandemic but also later on, following the emergence of new genetic SARS-CoV-2 variants. The 100 day mission to respond to future pandemic threats highlights the need for effective diagnostics, therapeutics and vaccines. Of the three, diagnostics represents the first opportunity to manage infectious diseases while also being the most poorly supported in terms of the infrastructure needed to demonstrate effectiveness. Where performance targets exist, they are not well served by consensus on how to demonstrate they are being met; this includes analytical factors such as limit of detection (LOD) false positive results as well as how to approach clinical evaluation. The selection of gold standards or use of epidemiological factors such as predictive value, reference ranges or clinical thresholds are seldom correctly considered. The attention placed on molecular diagnostic tests during COVID-19 illustrates important considerations and assumptions on the use of these methods for infectious disease diagnosis and beyond. In this manuscript, we discuss state-of-the-art approaches to diagnostic evaluation and explore how they may be better tailored to diagnostic techniques like NAATs to maximise the impact of these highly versatile bioanalytical tools, both generally and during future outbreaks.
摘要：
在冠状病毒病(COVID-19)大流行期间，诊断测试被认为是至关重要的，大多数关键方法都使用生物分析方法检测到较大的分子(RNA，蛋白质抗原或抗体），而不是常规的临床生化技术。核酸扩增试验(NAAT),如聚合酶链反应（PCR），和其他分子方法，如测序（通常与NAAT结合使用），对COVID-19期间的诊断和管理至关重要。这在大流行的早期和后来都得到了体现，随着新的SARS-CoV-2遗传变异的出现。应对未来大流行威胁的100天任务强调了有效诊断的必要性，疗法和疫苗。在这三个人中,诊断是管理传染病的第一个机会，同时在证明有效性所需的基础设施方面也是最缺乏支持的。如果存在绩效目标，在如何证明它们符合的问题上,没有达成共识;这包括分析因素,如检测限(LOD)假阳性结果,以及如何进行临床评估.金标准的选择或使用流行病学因素，如预测价值，参考范围或临床阈值很少被正确考虑。COVID-19期间对分子诊断测试的关注说明了使用这些方法进行传染病诊断及以后的重要考虑因素和假设。在这份手稿中,我们讨论了最先进的诊断评估方法，并探讨了如何更好地针对NAAT等诊断技术，以最大限度地发挥这些高度通用的生物分析工具的影响。无论是在一般情况下还是在未来的疫情爆发期间。
