Harritshøj Lene H, Gybel-Brask Mikkel, Afzal Shoaib, Kamstrup Pia R, Jørgensen Charlotte S, Thomsen Marianne Kragh, Hilsted Linda, Friis-Hansen Lennart, Szecsi Pal B, Pedersen Lise, Nielsen Lene, Hansen Cecilie B, Garred Peter, Korsholm Trine-Line, Mikkelsen Susan, Nielsen Kirstine O, Møller Bjarne K, Hansen Anne T, Iversen Kasper K, Nielsen Pernille B, Hasselbalch Rasmus B, Fogh Kamille, Norsk Jakob B, Kristensen Jonas Henrik, Schønning Kristian, Kirkby Nikolai S, Nielsen Alex C Y, Landsy Lone H, Loftager Mette, Holm Dorte K, Nilsson Anna C, Sækmose Susanne G, Grum-Schwensen Birgitte, Aagaard Bitten, Jensen Thøger G, Nielsen Dorte M, Ullum Henrik, Dessau Ram B
Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
J Clin Microbiol. 2021 Apr 20;59(5). doi: 10.1128/JCM.02596-20.
Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to support clinical diagnosis and epidemiological investigations. Recently, assays for large-scale detection of total antibodies (Ab), immunoglobulin G (IgG), and IgM against SARS-CoV-2 antigens have been developed, but there are limited data on the diagnostic accuracy of these assays. This study was a Danish national collaboration and evaluated 15 commercial and one in-house anti-SARS-CoV-2 assays in 16 laboratories. Sensitivity was evaluated using 150 samples from individuals with asymptomatic, mild, or moderate COVID-19, nonhospitalized or hospitalized, confirmed by nucleic acid amplification tests (NAAT); samples were collected 13 to 73 days either from symptom onset or from positive NAAT (patients without symptoms). Specificity and cross-reactivity were evaluated in samples collected prior to the SARS-CoV-2 epidemic from >586 blood donors and patients with autoimmune diseases, cytomegalovirus or Epstein-Barr virus infections, and acute viral infections. A specificity of ≥99% was achieved by all total-Ab and IgG assays except one, DiaSorin Liaison XL IgG (97.2%). Sensitivities in descending order were Wantai ELISA total Ab (96.7%), CUH-NOVO in-house ELISA total Ab (96.0%), Ortho Vitros total Ab (95.3%), YHLO iFlash IgG (94.0%), Ortho Vitros IgG (93.3%), Siemens Atellica total Ab (93.2%), Roche Elecsys total Ab (92.7%), Abbott Architect IgG (90.0%), Abbott Alinity IgG (median 88.0%), DiaSorin Liaison XL IgG (median 84.6%), Siemens Vista total Ab (81.0%), Euroimmun/ELISA IgG (78.0%), and Snibe Maglumi IgG (median 78.0%). However, confidence intervals overlapped for several assays. The IgM results were variable, with the Wantai IgM ELISA showing the highest sensitivity (82.7%) and specificity (99%). The rate of seropositivity increased with time from symptom onset and symptom severity.
需要用于严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的血清学检测来支持临床诊断和流行病学调查。最近，已经开发出用于大规模检测针对SARS-CoV-2抗原的总抗体（Ab）、免疫球蛋白G（IgG）和IgM的检测方法，但关于这些检测方法诊断准确性的数据有限。本研究是一项丹麦全国性合作项目，在16个实验室中对15种商业检测方法和1种内部抗SARS-CoV-2检测方法进行了评估。使用来自无症状、轻度或中度COVID-19患者（非住院或住院）的150份样本评估敏感性，这些样本经核酸扩增检测（NAAT）确诊；样本在症状出现后13至73天或NAAT检测呈阳性后（无症状患者）采集。在SARS-CoV-2疫情之前从超过586名献血者以及患有自身免疫性疾病、巨细胞病毒或EB病毒感染和急性病毒感染的患者中采集的样本中评估特异性和交叉反应性。除一种检测方法DiaSorin Liaison XL IgG（97.2%）外，所有总抗体和IgG检测方法的特异性均达到≥99%。敏感性从高到低依次为：万泰ELISA总抗体（96.7%）、CUH-NOVO内部ELISA总抗体（96.0%）、奥森维特罗斯总抗体（95.3%）、YHLO iFlash IgG（94.0%）、奥森维特罗斯IgG（93.3%）、西门子Atellica总抗体（93.2%）、罗氏Elecsys总抗体（�2.7%）、雅培Architect IgG（90.0%）、雅培Alinity IgG（中位数88.0%）、DiaSorin Liaison XL IgG（中位数84.6%）、西门子Vista总抗体（81.0%）、欧蒙/ELISA IgG（78.0%）和深圳新产业Maglumi IgG（中位数78.0%）。然而，几种检测方法的置信区间存在重叠。IgM检测结果各不相同，万泰IgM ELISA的敏感性（82.7%）和特异性（99%）最高。血清阳性率随症状出现时间和症状严重程度增加而升高。
