对新型冠状病毒实验室检测技术合理应用的再认识

Re-understanding about the rational application of clinical laboratory determination technologies for COVID-19 diagnosis

新型冠状病毒肺炎(COVID-19)疫情严重危及人类健康和社会经济发展。临床实验室精准的病原学检测是疫情防控的前提。目前,新型冠状病毒实验室检测技术主要包括核酸检测、抗体检测和抗原检测。核酸检测灵敏度高、特异性强,是诊断COVID-19的“金标准”,但对人员、技术、设备、场地等要求高;抗体检测作为核酸检测的补充,可减少漏检,监测疾病进展,但人群普遍接种新型冠状病毒疫苗后会产生“假阳性”;抗原检测方便、快捷,可居家操作,但灵敏度受疾病进程和病毒载量影响大。为了提高大规模核酸检测效率,国家卫生健康委先后推出了5合1、10合1、20合1不同比例的混采检测技术,但因混采管保存液体积成倍增加会导致病毒稀释,有一定的漏检风险,并会使单采复核与流调工作量剧增。随着疫情的持续,病毒株不断变异,实验室检测技术也在不断更新迭代。准确分析、研判现有检测技术的优劣和应用场景,更有利于疫情的科学防控。文章围绕核酸检测“混采”与“混检”、病毒变异对核酸检测性能的影响、核酸检测试剂“内源性”和“外源性”内标的优劣、抗原检测的意义和应用场景、疫苗接种后抗体检测的价值等关键技术问题进行分析,并提出应用建议。

Corona virus disease 2019(COVID-19)epidemic has seriously endangered human health and economic and social development.Accurate etiological determination in clinical laboratories is a prerequisite for epidemic prevention and control.At present,clinical laboratory determination technologies for severe acute respiratory syndrome coronavirus-2 mainly include nucleic acid,antibody and antigen determinations.Nucleic acid determination is a gold standard for the COVID-19 diagnosis with high sensitivity and specificity,but it has high requirements for personnel technical needs and experimental conditions.Antibody determination can be used as a supplement for nucleic acid determination to reduce missed determination and monitor the disease progress,while universal vaccination will affect the interpretation of antibody determination results,like false positivity.Antigen determination is convenient and fast,which can be operated at home,but its sensitivity is greatly affected by the disease process and viral load.In order to improve the efficiency of large-scale population screening,the National Health Commission has successively issued 5-in-1,10-in-1,and 20-in-1 mixed sampling technologies.However,the multiplication of preservation solution in the mixed sampling tube will result in virus dilution and increase the missed determination probability,and mixed sampling also aggravates the workload of epidemiological investigation and subsequent confirmation of the positive specimen in primary screening.With the progress of the COVID-19 epidemic,the SARS-CoV-2 continues to mutate,and the clinical laboratory determination technologies are gradually enriched and improved.Accurate analysis and judgment of the advantages and disadvantages of existing determination technologies and their application scenarios are conducive to the scientific prevention and control of the epidemic.This review will analyzes the following key clinical laboratory determination technical issues and put forward application suggestions,including the“mixed sampling”and“mixed determination”in nucleic acid determination,the impact of virus mutation on the performance of nucleic acid determination,the advantages and disadvantages of“endogenous”and“exogenous”internal standards in nucleic acid determination,the clinical significance and application scenarios of antigen determination and the value of antibody determination after vaccination.