Department of Obstetrics and Gynecology, Division of Molecular Medicine, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Diseases, University of Science and Technology of China, Hefei, Anhui, China.
School of Basic Medical Sciences, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, University of Science & Technology of China, Hefei, Anhui, China.
Rev Med Virol. 2021 May;31(3):e2181. doi: 10.1002/rmv.2181. Epub 2020 Nov 5.
This study aimed to assess the diagnostic test accuracy (DTA) of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) serological test methods and the kinetics of antibody positivity. Systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We included articles evaluating the diagnostic accuracy of serological tests and the kinetics of antibody positivity. MEDLINE through PubMed, Scopus, medRxiv and bioRxiv were sources of articles. Methodological qualities of included articles were appraised using QUADAS-2 while Metandi performs bivariate meta-analysis of DTA using a generalized linear mixed-model approach. Stata 14 and Review Manager 5.3 were used for data analysis. The summary sensitivity/specificity of chemiluminescence immunoassay (CLIA), enzyme-linked immunosorbent assay (ELISA) and lateral flow immunoassay (LFIA) were 92% (95% CI: 86%-95%)/99% (CI: 97%-99%), 86% (CI: 82%-89%)/99% (CI: 98%-100%) and 78% (CI: 71%-83%)/98% (95% CI: 96%-99%), respectively. Moreover, CLIA-based assays produced nearly 100% sensitivity within 11-15 days post-symptom onset (DPSO). Based on antibody type, the sensitivity of ELISA-total antibody, CLIA-IgM/G and CLIA-IgG gauged at 94%, 92% and 92%, respectively. The sensitivity of CLIA-RBD assay reached 96%, while LFIA-S demonstrated the lowest sensitivity, 71% (95% CI: 58%-80%). CLIA assays targeting antibodies against RBD considered the best DTA. The antibody positivity rate increased corresponding with DPSO, but there was some decrement when moving from acute phase to convalescent phase of infection. As immunoglobulin isotope-related DTA was heterogeneous, our data have insufficient evidence to recommend CLIA/ELISA for clinical decision-making, but likely to have comparative advantage over RT-qPCR in certain circumstances and geographic regions.
本研究旨在评估严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）血清学检测方法的诊断测试准确性（DTA）和抗体阳性的动力学。本研究遵循系统评价和荟萃分析的首选报告项目进行了系统评价和荟萃分析。我们纳入了评估血清学检测诊断准确性和抗体阳性动力学的文章。MEDLINE 通过 PubMed、Scopus、medRxiv 和 bioRxiv 是文章的来源。使用 QUADAS-2 评估纳入文章的方法学质量，而 Metandi 使用广义线性混合模型方法对 DTA 进行双变量荟萃分析。Stata 14 和 Review Manager 5.3 用于数据分析。化学发光免疫分析（CLIA）、酶联免疫吸附测定（ELISA）和侧向流动免疫分析（LFIA）的汇总敏感性/特异性分别为 92%（95%CI：86%-95%）/99%（CI：97%-99%）、86%（CI：82%-89%）/99%（CI：98%-100%）和 78%（CI：71%-83%）/98%（95%CI：96%-99%）。此外，CLIA 基于的检测在症状出现后 11-15 天内产生了近 100%的敏感性（DPSO）。基于抗体类型，ELISA-总抗体、CLIA-IgM/G 和 CLIA-IgG 的敏感性分别为 94%、92%和 92%。CLIA-RBD 检测的敏感性达到 96%，而 LFIA-S 的敏感性最低，为 71%（95%CI：58%-80%）。针对 RBD 抗体的 CLIA 检测被认为具有最佳的 DTA。抗体阳性率随着 DPSO 的增加而增加，但从感染的急性期到恢复期，阳性率有所下降。由于免疫球蛋白同功型 DTA 存在异质性，我们的数据没有足够的证据推荐 CLIA/ELISA 用于临床决策，但在某些情况下和地理区域可能比 RT-qPCR 具有比较优势。
