Objective To determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (covid-19). Design Systematic review and meta-analysis. Data sources Medline, bioRxiv, and medRxiv from 1 January to 30 April 2020, using subject headings or subheadings combined with text words for the concepts of covid-19 and serological tests for covid-19. Eligibility criteria and data analysis Eligible studies measured sensitivity or specificity, or both of a covid-19 serological test compared with a reference standard of viral culture or reverse transcriptase polymerase chain reaction. Studies were excluded with fewer than five participants or samples. Risk of bias was assessed using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). Pooled sensitivity and specificity were estimated using random effects bivariate meta-analyses. Main outcome measures The primary outcome was overall sensitivity and specificity, stratified by method of serological testing (enzyme linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs), or chemiluminescent immunoassays (CLIAs)) and immunoglobulin class (IgG, IgM, or both). Secondary outcomes were stratum specific sensitivity and specificity within subgroups defined by study or participant characteristics, including time since symptom onset. Results 5016 references were identified and 40 studies included. 49 risk of bias assessments were carried out (one for each population and method evaluated). High risk of patient selection bias was found in 98% (48/49) of assessments and high or unclear risk of bias from performance or interpretation of the serological test in 73% (36/49). Only 10% (4/40) of studies included outpatients. Only two studies evaluated tests at the point of care. For each method of testing, pooled sensitivity and specificity were not associated with the immunoglobulin class measured. The pooled sensitivity of ELISAs measuring IgG or IgM was 84.3% (95% confidence interval 75.6% to 90.9%), of LFIAs was 66.0% (49.3% to 79.3%), and of CLIAs was 97.8% (46.2% to 100%). In all analyses, pooled sensitivity was lower for LFIAs, the potential point-of-care method. Pooled specificities ranged from 96.6% to 99.7%. Of the samples used for estimating specificity, 83% (10 465/12 547) were from populations tested before the epidemic or not suspected of having covid-19. Among LFIAs, pooled sensitivity of commercial kits (65.0%, 49.0% to 78.2%) was lower than that of non-commercial tests (88.2%, 83.6% to 91.3%). Heterogeneity was seen in all analyses. Sensitivity was higher at least three weeks after symptom onset (ranging from 69.9% to 98.9%) compared with within the first week (from 13.4% to 50.3%). Conclusion Higher quality clinical studies assessing the diagnostic accuracy of serological tests for covid-19 are urgently needed. Currently, available evidence does not support the continued use of existing point-of-care serological tests. Study registration PROSPERO CRD42020179452.

中文翻译：

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covid-19 血清学检测的诊断准确性：系统评价和荟萃分析。

目的 确定 2019 年冠状病毒病 (covid-19) 血清学检测的诊断准确性。设计系统回顾和荟萃分析。数据来源 Medline、bioRxiv 和 medRxiv，时间为 2020 年 1 月 1 日至 4 月 30 日，使用主题标题或副标题与 covid-19 概念和 covid-19 血清学测试的文本单词相结合。资格标准和数据分析 合格的研究测量了 covid-19 血清学测试与病毒培养或逆转录酶聚合酶链反应的参考标准相比的敏感性或特异性，或两者。参与者或样本少于五人的研究被排除。使用诊断准确性研究 2 (QUADAS-2) 的质量评估来评估偏倚风险。使用随机效应双变量荟萃分析来估计汇总敏感性和特异性。主要结果指标 主要结果是总体敏感性和特异性，按血清学检测方法（酶联免疫吸附测定 (ELISA)、侧流免疫测定 (LFIA) 或化学发光免疫测定 (CLIA)）和免疫球蛋白类别（IgG、IgM 或两个都）。次要结果是由研究或参与者特征定义的亚组内的层特异性敏感性和特异性，包括症状出现后的时间。结果 确定了 5016 篇参考文献，纳入了 40 项研究。进行了 49 项偏倚风险评估（每个群体和评估方法各一项）。98% (48/49) 的评估存在患者选择偏倚的高风险，73% (36/49) 的评估存在因血清学检测的执行或解释而存在高或不明确偏倚的风险。只有 10% (4/40) 的研究纳入了门诊患者。只有两项研究评估了护理点测试。对于每种测试方法，汇总的敏感性和特异性与测量的免疫球蛋白类别无关。测量 IgG 或 IgM 的 ELISA 的汇总灵敏度为 84.3%（95% 置信区间为 75.6% 至 90.9%），LFIA 的汇总灵敏度为 66.0%（49.3% 至 79.3%），CLIA 的汇总灵敏度为 97.8%（46.2% 至 100%） 。在所有分析中，LFIA（潜在的护理点方法）的汇总敏感性较低。汇总特异性范围为 96.6% 至 99.7%。在用于估计特异性的样本中，83% (10 465/12 547) 来自疫情爆发前接受检测的人群或未被怀疑感染 covid-19 的人群。在 LFIA 中，商业试剂盒的汇总敏感性（65.0%、49.0% 至 78.2%）低于非商业测试的汇总敏感性（88.2%、83.6% 至 91.3%）。所有分析中均存在异质性。与第一周内（从 13.4% 到 50.3%）相比，症状出现后至少三周（从 69.9% 到 98.9%）的敏感性更高。结论 迫切需要更高质量的临床研究来评估 covid-19 血清学检测的诊断准确性。目前，现有证据不支持继续使用现有的护理点血清学检测。研究注册 PROSPERO CRD42020179452。