抽象的
当使用WHO列出的SARS-COV-2抗原检测快速测试时,专业的鼻腔采样是鼻咽采样的可靠替代方法。这种侵入性较小的方法可以通过较少的训练来执行,并可以促进抗原测试策略的快速缩放。
To the Editor:
抗原检测快速诊断测试(AG-RDT)可能在SARS-COV-2的创新测试策略中起着重要作用[1,2]。Currently, most Ag-RDTs require nasopharyngeal (NP) sampling performed by qualified healthcare professionals. Nasal sampling would enable scaling of antigen testing strategies. The term nasal sampling is often not used uniformly but can be differentiated in anterior nasal sampling (entire absorbent tip of the swab, usually 1 to 1.5 cm, inserted into nostril), and nasal mid-turbinate (as described below) [3]。
我们进行了一项前瞻性诊断准确性研究,目的是直接比较专业收集的鼻涡轮酯(NMT)的性能versusNP SWAB,使用WHO名单的SARS-COV-2 AG-RDT。参考标准是从组合的NP/口咽(OP)拭子收集的RT-PCR。该研究一直持续到根据AG-RDT获得30个正NP拭子样品,这是WHO紧急使用列表程序推荐的最低限度,以证明样本类型等效性[4]。This manufacturer-independent study was conducted in partnership with the Foundation of Innovative New Diagnostics (FIND), the WHO collaborating centre for COVID-19 diagnostics.
Adults at high risk for SARS-CoV-2 infection according to clinical suspicion who attended the ambulatory SARS-CoV-2 testing facility of Charité University Hospital Berlin, Germany, were enrolled from 11 to 18 November 2020. Participants were excluded if either of the swabs for the Ag-RDT or the RT-PCR reference standard could not be collected.
参与者必须用组织吹到鼻子后。之后,根据使用说明,使用制造商的测试套件中提供的特定鼻拭子在鼻子的两侧收集了一个NMT样本,这也对应于美国CDC说明[3]。简而言之,在将患者的头部向后倾斜70度时,将拭子插入每个鼻孔约2厘米,平行于口感,直到在涡轮上达到电阻,然后在鼻壁上旋转3-4次。随后,根据RT-PCR的机构建议,AG-RDT的单独的NP-SWAB(在制造商测试套件中提供)和合并的OP/NP-SWAB(将Copan放置在1 mL AMIES培养基中的ESWAB)鼻子的不同侧面。
评估的AG-RDT是标准的Q covid-19 Ag测试(sd生物传感器有限公司京畿道,柯rea; henceforth called STANDARD Q) [5]。Study procedures followed the same process as described in the prior study by Lindneret al.[6]。While the test is commercially available as NP-sampling kit, the nasal-sampling kit is currently available for “research use only” by the manufacturer. The instructions for use of the two test kits showed differences, with a more elaborate extraction process (stirring the swab at least 10versus5次)和更高量的提取样品(4versus3滴)用于测试鼻样品。
Of 181 patients invited, 180 (99.4%) consented to participate. One patient was excluded as both swabs for the Ag-RDT could not be obtained. The average age of participants was 36.2 years (Standard Deviation [sd] 12.2)有48.0%的女性和14.5%的合并症。在测试当天,有96.1%的参与者患有一种或多种与Covid-19的症状。在表现时症状的持续时间平均为4.2天(sd2.6). Among the 179 participants, 41 (22.9%) tested positive for SARS-CoV-2 by RT-PCR (表格1).
在NMT-或NP-SPAPLE上均未观察到无效的Ag-RDT结果。四名患者通过NMT检测阳性,但不能通过NP采样。一名患者仅通过NP抽样呈阳性。阳性百分比协议为93.5%(95%CI 79.3-98.2);包括NMT的一个假阳性结果,一个带有NP的结果。负数百分比为95.9%(95%CI 91.4–98.1)。评估者间的可靠性很高(NMT的Kappa为0.95; NP为0.98)。在双正对的测试带强度的半定量读数中,没有显着的差异(NMT高8个,NP高9个)。对于三个测试结果的结果,必须进行第三个读者,该结果非常弱。
The STANDARD Q Ag-RDT with NMT-sampling showed a sensitivity of 80.5% (33/41 PCR positives detected; CI 66.0–89.8) and specificity of 98.6% (95% CI 94.9–99.6) compared to RT-PCR. The sensitivity with NP-sampling was 73.2% (30/41 PCR positives detected; 95% CI 58.1–84.3) and specificity was 99.3% (95% CI 96.0–100). In patients with high viral load (>7.0 log10SARS-CoV2 RNA copies/swab), the sensitivity of the Ag-RDT with NMT-sampling was 100% (19/19 PCR positives detected; 95% CI 83.9–100) and 94.7% (18/19 PCR positives detected; 95% CI 76.4–99.7) with NP-sampling. In contrast, the Ag-RDT more frequently did not detect patients with lower viral load or with symptoms >7 days (表格1), as commonly observed in studies on Ag-RDTs [7,8]。
The strengths of the study are the standardised sampling methods, two independent blinded readers and an additional semi-quantitative assessment of Ag-RDT results. The cohort was representative, judging from the comparable sensitivity observed in the recent independent validation study of STANDARD Q (sensitivity 76.6%; 95% CI 62.8–86.4) [9]。该研究受到限制,因为它是在单个中心进行的。从理论上讲,先前的NMT样品收集可能对低病毒负荷患者的NP样品的测试结果负面影响。
In conclusion, this study demonstrates that sensitivity of a WHO-listed SARS-CoV-2 Ag-RDT using professional nasal-sampling kit is at least equal to that of NP-sampling kit, although confidence intervals overlap. Of note, differences in the instructions for use of the test procedures could have contributed to different sensitivities. NMT-sampling can be performed with less training, reduces patient discomfort, and enables scaling of antigen testing strategies. Additional studies of patient self-sampling should be considered to further facilitate scale-up of Ag-RDT testing [6]。
Acknowledgements
Heike Rössig, Mia Wintel, Franka Kausch, Elisabeth Linzbach, Katja von dem Busche, Stephanie Padberg, Melanie Bothmann, Zümrüt Tuncer, Stefanie Lunow, Beate Zimmer, Astrid Barrera Pesek, Sabrina Pein, Nicole Buchholz, Verena Haack, Oliver Deckwart.
脚注
DRKS00021220 - German Clinical Trial Registry
Data availability:可用数据;- 根据本文的结果 - 研究协议 - 分析代码的取消识别数据,直到出版后5年,提供了一个合理的建议,所有研究网站都同意分享数据建议,应针对相应的作者
Author contributions:AKL,LJK,FL和CMD设计了研究并制定了标准操作程序。AKL并实施了研究设计,招募了患者,进行了实验室工作,并领导了手稿的写作。FPM和JS协调并监督研究地点。CR,SB,CH,AB招募的患者。MGE协调了测试设施。MGA和FT领导了数据分析。TCJ和JH负责PCR测试,并为数据解释做出了贡献。JAS支持研究设计设置和数据的解释。所有作者都审查了手稿。
支持声明:The study was supported by FIND, Heidelberg University Hospital and Charité University Hospital internal funds, as well as a grant of the Ministry of Science, Research and the Arts of Baden-Württemberg, Germany. FIND provided input on the study design, and data analysis in collaboration with the rest of the study team. Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg; DOI: http://dx.doi.org/10.13039/501100003542; Foundation for Innovative New Diagnostics (FIND).
Conflict of interest: Dr. Lindner has nothing to disclose.
Conflict of interest: Dr. Nikolai has nothing to disclose.
利益冲突:罗哈特博士没有什么可披露的。
Conflict of interest: Dr. Burock has nothing to disclose.
利益冲突:Hülso博士没有什么可披露的。
Conflict of interest: Dr. Bölke has nothing to disclose.
Conflict of interest: Dr. Gertler has nothing to disclose.
利益冲突:丽莎·约翰娜·克鲁格(Lisa JohannaKrüger)无话可说。
利益冲突:Gaeddert博士没有什么可披露的。
利益冲突:Tobian先生无话可说。
Conflict of interest: Dr. Lainati has nothing to disclose.
利益冲突:Seybold博士没有什么可披露的。
利益冲突:琼斯博士没有什么可披露的。
Conflict of interest: Dr. Hofmann has nothing to disclose.
Conflict of interest: Dr. Sacks reports grants from UK Department of International Development (DFID, recently replaced by FCMO), grants from World Health Organization (WHO), grants from Unitaid, during the conduct of the study.
Conflict of interest: Dr. Mockenhaupt has nothing to disclose.
Conflict of interest: Dr. Denkinger reports grants from Foundation of Innovative Diagnostics, grants from Ministry of Science, Research and Culture, State of Baden Wuerttemberg, Germany, during the conduct of the study.
- 已收到2020年12月6日。
- Accepted2021年1月24日。
- ©作者2021。
This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact权限{at} ersnet.org