Point-of-care serological assays for delayed SARS-CoV-2 case identification among health-care workers in the UK: a prospective multicentre cohort study
Point-of-care serological assays for delayed SARS-CoV-2 case identification among health-care workers in the UK: a prospective multicentre cohort study
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DOI：
10.1016/s2213-2600(20)30315-5
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发表时间：
2020-09-01
影响因子：
76.2
通讯作者：
Davies, Gary W.
中科院分区：
文献类型：
--
作者：
Pallett, Scott J. C.;Rayment, Michael;Davies, Gary W.
背景医护人员是严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染的高危人群。在COVID-19大流行的早期阶段，通过PCR检测对轻度至中度SARS-CoV-2感染的个人进行急性诊断的能力有限，而且很大一部分疑似感染的医护人员没有接受检测。我们的目的是调查床旁和实验室血清学检测的性能及其在晚期病例识别中的实用性，并估计SARS-CoV-2血清阳性率。方法我们在2020年4月8日至6月12日期间进行了一项前瞻性多中心队列研究，分两个阶段。根据英国公共卫生部（PHE）的病例定义，具有轻度至中度症状的症状性卫生保健工作者有资格在COVID-19症状出现后14天参加。自2019年12月1日以来，如果卫生保健工作者没有出现PHE定义的COVID-19症状，则将其招募到无症状队列中。在第1阶段，两种即时侧流血清学检测试剂盒，Onsite CTK Biotech COVID-19裂解IgG/IgM快速检测试剂盒（CTK Bitotech，波威，CA，USA）和Encode SARS-CoV-2分离IgM/IgG一步快速检测装置（Zhuhai Encode Medical Engineering，Zhuhai，China）进行了针对实验室免疫测定的性能评价。（EDI Novel Coronavirus COVID-19 IgG ELISA试剂盒[Epitope Diagnostics，San Diego，CA，USA]）在300份来自医护人员的样本和100份COVID-19前阴性对照样本中进行检测。在第2阶段（n=6440），对1299名受试者进行了血清监测。（93.4%）的1391名卫生保健工作者报告症状，在一个子集的无症状卫生保健工作者（405 [8.0%]的5049）。结果有变化的测试性能之间的侧流血清学检测;然而，Encode检测显示出合理的IgG灵敏度（127/136; 93.4% [95% CI 87.8-96.9]）和特异性（99/100; 99.0% [94.6-100.0]），与实验室免疫测定结果一致（282/300; 94.0% [91.3-96.7]）。相比之下，Onsite检测试剂盒的灵敏度（120/136; 88.2% [95% CI 81.6-93.1]）、特异性（94/100; 94.0% [87.4-97.8]）和一致性（254/300; 84.7% [80.6-88.7]）降低。在所有检测中，70例PCR阳性病例中有5例（7%）为阴性。在74/800个检测卡（9.3%）（35/400个Encode检测试剂盒[8.8%]; 39/400个Onsite检测试剂盒[9.8%]）中记录了侧向流血清学检测试剂盒条带的晚期变化，但这些变化中仅7个（均为Onsite检测试剂盒）与实验室免疫测定一致。在第2阶段，无症状卫生保健工作者的血清阳性率估计为10.6%（95%CI 7.6-13.6），有症状卫生保健工作者的血清阳性率估计为44.7%（42.0-47.4）。整个劳动力的血清阳性率估计为18.0%（95%CI 17.0-18.9）。解释虽然用侧向流血清学测定和ELISA都观察到良好的阳性预测值，但只有在通过严格的临床病例定义修改预测试概率时才发生这种一致性。侧流血清学检测条带的后期开发将排除邮寄策略和潜在的家庭检测。在所有检测中，卫生保健工作者对假阴性结果的识别表明，在现阶段对IgG结果的解释要谨慎;就目前而言，在政府关于物理距离的建议的支持下，检测可能最好在临床环境中进行。版权所有（c）2020 Elsevier Ltd.保留所有权利。
Background Health-care workers constitute a high-risk population for acquisition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Capacity for acute diagnosis via PCR testing was limited for individuals with mild to moderate SARS-CoV-2 infection in the early phase of the COVID-19 pandemic and a substantial proportion of health-care workers with suspected infection were not tested. We aimed to investigate the performance of point-of-care and laboratory serology assays and their utility in late case identification, and to estimate SARS-CoV-2 seroprevalence.Methods We did a prospective multicentre cohort study between April 8 and June 12, 2020, in two phases. Symptomatic health-care workers with mild to moderate symptoms were eligible to participate 14 days after onset of COVID-19 symptoms, as per the Public Health England (PHE) case definition. Health-care workers were recruited to the asymptomatic cohort if they had not developed PHE-defined COVID-19 symptoms since Dec 1, 2019. In phase 1, two point-of-care lateral flow serological assays, the Onsite CTK Biotech COVID-19 split IgG/IgM Rapid Test (CTK Bitotech, Poway, CA, USA) and the Encode SARS-CoV-2 split IgM/IgG One Step Rapid Test Device (Zhuhai Encode Medical Engineering, Zhuhai, China), were evaluated for performance against a laboratory immunoassay (EDI Novel Coronavirus COVID-19 IgG ELISA kit [Epitope Diagnostics, San Diego, CA, USA]) in 300 samples from health-care workers and 100 pre-COVID-19 negative control samples. In phase 2 (n=6440), serosurveillance was done among 1299 (93.4%) of 1391 health-care workers reporting symptoms, and in a subset of asymptomatic health-care workers (405 [8.0%] of 5049).Findings There was variation in test performance between the lateral flow serological assays; however, the Encode assay displayed reasonable IgG sensitivity (127 of 136; 93.4% [95% CI 87.8-96.9]) and specificity (99 of 100; 99.0% [94.6-100.0]) among PCR-proven cases and good agreement (282 of 300; 94.0% [91.3-96.7]) with the laboratory immunoassay. By contrast, the Onsite assay had reduced sensitivity (120 of 136; 88.2% [95% CI 81.6-93.1]) and specificity (94 of 100; 94.0% [87.4-97.8]) and agreement (254 of 300; 84.7% [80.6-88.7]). Five (7%) of 70 PCR-positive cases were negative across all assays. Late changes in lateral flow serological assay bands were recorded in 74 (9.3%) of 800 cassettes (35 [8.8%] of 400 Encode assays; 39 [9.8%] of 400 Onsite assays), but only seven (all Onsite assays) of these changes were concordant with the laboratory immunoassay. In phase 2, seroprevalence among the workforce was estimated to be 10.6% (95% CI 7.6-13.6) in asymptomatic health-care workers and 44.7% (42.0-47.4) in symptomatic health-care workers. Seroprevalence across the entire workforce was estimated at 18.0% (95% CI 17.0-18.9).Interpretation Although a good positive predictive value was observed with both lateral flow serological assays and ELISA, this agreement only occurred if the pre-test probability was modified by a strict clinical case definition. Late development of lateral flow serological assay bands would preclude postal strategies and potentially home testing. Identification of false-negative results among health-care workers across all assays suggest caution in interpretation of IgG results at this stage; for now, testing is perhaps best delivered in a clinical setting, supported by government advice about physical distancing. Copyright (c) 2020 Elsevier Ltd. All rights reserved.