Clinical and laboratory evaluation of SARS-CoV-2 lateral flow assays for use in a national COVID-19 seroprevalence survey
Clinical and laboratory evaluation of SARS-CoV-2 lateral flow assays for use in a national COVID-19 seroprevalence survey
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DOI：
10.1136/thoraxjnl-2020-215732
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发表时间：
2020-12-01
期刊：
影响因子：
10
通讯作者：
Cooke, Graham S.
中科院分区：
文献类型：
--
作者：
Flower, Barnaby;Brown, Jonathan C.;Cooke, Graham S.
背景准确的抗体检测是监测SARS-CoV-2大流行的关键。横向流动免疫分析(LFIA)可以提供大规模的检测。然而，报告的表现各不相同，通常对住院患者的血清进行敏感性分析。为了用于社区检测，需要对非住院个人进行指刺自检评估。方法对276名非住院参与者进行敏感性分析。所有患者经逆转录聚合酶链式反应检测均为SARS-CoV-2阳性，且均为发病后21天。在第一阶段，我们评估了临床上(用手指刺法)和实验室(用血液和血清)的五种LFIA，并与(1)经PCR确认的感染和(2)在两个“内部”ELISA上存在SARS-CoV-2抗体进行了比较。对500份血吸虫病前期血清进行特异性分析。在第二阶段，用血清对另外6个LFIA进行了评估。发现95%(95%可信区间92.2%至97.3%)的感染队列至少有一次ELISA可检测到抗体。LFIA的敏感性是可变的，但在11项评估中有8项明显低于ELISA.在临床和实验室评估的LFIA中，指刺自检对PCR确诊病例的敏感度从21%到92%不等，对复合酶联免疫吸附试验阳性的敏感度从22%到96%不等。指诊和血清检测的一致性最好的是中等(kappa 0.56)，最差的是轻微(kappa 0.13)。所有LFIA都有很高的特异度(97.2%-99.8%)。说明LFIA的敏感性和样本一致性是可变的，强调了评估在预期用途设定中的重要性。这一严格的LFIA评估方法确定了一种高特异度(98.6%(95%可信区间97.1%至99.4%))、中等敏感性(84.4%手指刺伤(95%可信区间70.5%至93.5%))和中等符合率的检测方法，适用于血清阳性率调查。
BackgroundAccurate antibody tests are essential to monitor the SARS-CoV-2 pandemic. Lateral flow immunoassays (LFIAs) can deliver testing at scale. However, reported performance varies, and sensitivity analyses have generally been conducted on serum from hospitalised patients. For use in community testing, evaluation of finger-prick self-tests, in non-hospitalised individuals, is required.MethodsSensitivity analysis was conducted on 276 non-hospitalised participants. All had tested positive for SARS-CoV-2 by reverse transcription PCR and were >= 21 days from symptom onset. In phase I, we evaluated five LFIAs in clinic (with finger prick) and laboratory (with blood and sera) in comparison to (1) PCR-confirmed infection and (2) presence of SARS-CoV-2 antibodies on two 'in-house' ELISAs. Specificity analysis was performed on 500 prepandemic sera. In phase II, six additional LFIAs were assessed with serum.Findings95% (95% CI 92.2% to 97.3%) of the infected cohort had detectable antibodies on at least one ELISA. LFIA sensitivity was variable, but significantly inferior to ELISA in 8 out of 11 assessed. Of LFIAs assessed in both clinic and laboratory, finger-prick self-test sensitivity varied from 21% to 92% versus PCR-confirmed cases and from 22% to 96% versus composite ELISA positives. Concordance between finger-prick and serum testing was at best moderate (kappa 0.56) and, at worst, slight (kappa 0.13). All LFIAs had high specificity (97.2%-99.8%).InterpretationLFIA sensitivity and sample concordance is variable, highlighting the importance of evaluations in setting of intended use. This rigorous approach to LFIA evaluation identified a test with high specificity (98.6% (95%CI 97.1% to 99.4%)), moderate sensitivity (84.4% with finger prick (95% CI 70.5% to 93.5%)) and moderate concordance, suitable for seroprevalence surveys.