Objective To assess the performance of rapid antigen tests with unsupervised nasal and combined oropharyngeal and nasal self-sampling during the omicron period. Design Prospective cross sectional diagnostic test accuracy study. Setting Three public health service covid-19 test sites in the Netherlands, 21 December 2021 to 10 February 2022. Participants 6497 people with covid-19 symptoms aged ≥16 years presenting for testing. Interventions Participants had a swab sample taken for reverse transcription polymerase chain reaction (RT-PCR, reference test) and received one rapid antigen test to perform unsupervised using either nasal self-sampling (during the emergence of omicron, and when omicron accounted for >90% of infections, phase 1) or with combined oropharyngeal and nasal self-sampling in a subsequent (phase 2; when omicron accounted for >99% of infections). The evaluated tests were Flowflex (Acon Laboratories; phase 1 only), MPBio (MP Biomedicals), and Clinitest (Siemens-Healthineers). Main outcome measures The main outcomes were sensitivity, specificity, and positive and negative predictive values of each self-test, with RT-PCR testing as the reference standard. Results During phase 1, 45.0% (n=279) of participants in the Flowflex group, 29.1% (n=239) in the MPBio group, and 35.4% ((n=257) in the Clinitest group were confirmatory testers (previously tested positive by a self-test at own initiative). Overall sensitivities with nasal self-sampling were 79.0% (95% confidence interval 74.7% to 82.8%) for Flowflex, 69.9% (65.1% to 74.4%) for MPBio, and 70.2% (65.6% to 74.5%) for Clinitest. Sensitivities were substantially higher in confirmatory testers (93.6%, 83.6%, and 85.7%, respectively) than in those who tested for other reasons (52.4%, 51.5%, and 49.5%, respectively). Sensitivities decreased from 87.0% to 80.9% (P=0.16 by χ2 test), 80.0% to 73.0% (P=0.60), and 83.1% to 70.3% (P=0.03), respectively, when transitioning from omicron accounting for 29% of infections to >95% of infections. During phase 2, 53.0% (n=288) of participants in the MPBio group and 44.4% (n=290) in the Clinitest group were confirmatory testers. Overall sensitivities with combined oropharyngeal and nasal self-sampling were 83.0% (78.8% to 86.7%) for MPBio and 77.3% (72.9% to 81.2%) for Clinitest. When combined oropharyngeal and nasal self-sampling was compared with nasal self-sampling, sensitivities were found to be slightly higher in confirmatory testers (87.4% and 86.1%, respectively) and substantially higher in those testing for other reasons (69.3% and 59.9%, respectively). Conclusions Sensitivities of three rapid antigen tests with nasal self-sampling decreased during the emergence of omicron but was only statistically significant for Clinitest. Sensitivities appeared to be substantially influenced by the proportion of confirmatory testers. Sensitivities of MPBio and Clinitest improved after the addition of oropharyngeal to nasal self-sampling. A positive self-test result justifies prompt self-isolation without the need for confirmatory testing. Individuals with a negative self-test result should adhere to general preventive measures because a false negative result cannot be ruled out. Manufacturers of MPBio and Clinitest may consider extending their instructions for use to include combined oropharyngeal and nasal self-sampling, and other manufacturers of rapid antigen tests should consider evaluating this as well. Individual participant data collected during the study will be available, after deidentification of all participants. Data will be available to researchers who provide a methodologically sound proposal to achieve the aims in the approved proposal. Proposals should be directed to the corresponding author to gain access to the data. Data requestors will need to sign a data sharing agreement. The study protocol is available upon request by contacting Karel Moons at k.g.m.moons@umcutrecht.nl

中文翻译：

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对 omicron 时期有症状的人进行无监督自我采样的 covid-19 快速抗原检测的诊断准确性：横断面研究

目的 评估 omicron 期间无监督鼻腔和口咽鼻联合自采样快速抗原检测的性能。设计前瞻性横断面诊断测试准确性研究。地点 2021 年 12 月 21 日至 2022 年 2 月 10 日，荷兰的三个公共卫生服务 covid-19 测试点。参与者 6497 名年龄≥16 岁、有 covid-19 症状的人前来接受测试。干预措施 参与者采集拭子样本进行逆转录聚合酶链式反应（RT-PCR，参考测试），并接受一项快速抗原测试，以在无人监督的情况下使用鼻腔自我采样进行测试（在 omicron 出现期间，以及当 omicron 占 >90 时）感染百分比，第 1 阶段）或在后续阶段结合口咽部和鼻腔自我采样（第 2 阶段；当 omicron 占感染的 99% 以上时）。评估的测试包括 Flowflex（Acon Laboratories；仅限第一阶段）、MPBio（MP Biomedicals）和 Clintest（Siemens-Healthineers）。主要结果指标 主要结果是每次自检的敏感性、特异性以及阳性和阴性预测值，以 RT-PCR 检测作为参考标准。结果 在第 1 阶段，Flowflex 组中 45.0% (n=279) 的参与者、MPBio 组中 29.1% (n=239) 和 Clintest 组中 35.4% (n=257) 的参与者是验证性测试者（之前测试过）主动自检呈阳性）。鼻腔自我采样的总体灵敏度为 Flowflex 79.0%（95% 置信区间 74.7% 至 82.8%）、MPBio 69.9%（65.1% 至 74.4%）和 70.2% （65。6% 至 74.5%）对于 Clintest。确认性测试人员的敏感性（分别为 93.6%、83.6% 和 85.7%）明显高于因其他原因进行测试的人员（分别为 52.4%、51.5% 和 49.5%）。从 omicron 占 29% 过渡时，灵敏度分别从 87.0% 下降至 80.9%（P=0.16，χ2 检验）、80.0% 至 73.0%（P=0.60）和 83.1% 至 70.3%（P=0.03）。感染率>95%。在第 2 阶段，MPBio 组中 53.0% (n=288) 的参与者和 Clinitest 组中 44.4% (n=290) 的参与者是验证性测试者。MPBio 口咽和鼻腔联合自采样的总体敏感性为 83.0%（78.8% 至 86.7%），Clinite 为 77.3%（72.9% 至 81.2%）。当口咽和鼻联合自采样与鼻自采样进行比较时，确认性测试人员的敏感性略高（分别为 87.4% 和 86.1%），而由于其他原因而进行的测试则显着较高（分别为 69.3% 和 59.9%）。结论 在 omicron 出现期间，三种鼻自采样快速抗原检测的灵敏度有所下降，但仅对 Clinitest 具有统计学意义。敏感性似乎很大程度上受到验证性测试人员比例的影响。添加口咽至鼻腔自采样后，MPBio 和 Clinitest 的灵敏度得到改善。自检结果呈阳性表明立即自我隔离是合理的，无需进行确认性检测。自检结果呈阴性的个人应遵守一般预防措施，因为不能排除假阴性结果。MPBio 和 Clinitest 的制造商可能会考虑扩展其使用说明，以包括口咽和鼻腔联合自我采样，其他快速抗原检测制造商也应考虑对此进行评估。在对所有参与者进行去身份识别后，研究期间收集的个人参与者数据将可供使用。数据将提供给提供方法上合理的提案以实现已批准提案中的目标的研究人员。提案应直接发送给通讯作者以获得数据访问权限。数据请求者需要签署数据共享协议。如需研究方案，请联系 Karel Moons，邮箱为 kgmmoons@umcutrecht.nl 其他快速抗原检测制造商也应考虑对此进行评估。在对所有参与者进行去身份识别后，研究期间收集的个人参与者数据将可供使用。数据将提供给提供方法上合理的提案以实现已批准提案中的目标的研究人员。提案应直接发送给通讯作者以获得数据访问权限。数据请求者需要签署数据共享协议。如需研究方案，请联系 Karel Moons，邮箱为 kgmmoons@umcutrecht.nl 其他快速抗原检测制造商也应考虑对此进行评估。在对所有参与者进行去身份识别后，研究期间收集的个人参与者数据将可供使用。数据将提供给提供方法上合理的提案以实现已批准提案中的目标的研究人员。提案应直接发送给通讯作者以获得数据访问权限。数据请求者需要签署数据共享协议。如需研究方案，请联系 Karel Moons，邮箱为 kgmmoons@umcutrecht.nl 数据将提供给提供方法上合理的提案以实现已批准提案中的目标的研究人员。提案应直接发送给通讯作者以获得数据访问权限。数据请求者需要签署数据共享协议。如需研究方案，请联系 Karel Moons，邮箱为 kgmmoons@umcutrecht.nl 数据将提供给提供方法上合理的提案以实现已批准提案中的目标的研究人员。提案应直接发送给通讯作者以获得数据访问权限。数据请求者需要签署数据共享协议。如需研究方案，请联系 Karel Moons，邮箱为 kgmmoons@umcutrecht.nl