Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland.
J Clin Virol. 2021 May;138:104796. doi: 10.1016/j.jcv.2021.104796. Epub 2021 Mar 16.
Antigen-detecting rapid diagnostic tests (Ag-RDTs) can complement molecular diagnostics for COVID-19. The recommended temperature for storage of SARS-CoV-2 Ag-RDTs ranges between 2-30 °C. In the global South, mean temperatures can exceed 30 °C. In the global North, Ag-RDTs are often used in external testing facilities at low ambient temperatures. We assessed analytical sensitivity and specificity of eleven commercially-available SARS-CoV-2 Ag-RDTs using different storage and operational temperatures, including short- or long-term storage and operation at recommended temperatures or at either 2-4 °C or at 37 °C. The limits of detection of SARS-CoV-2 Ag-RDTs under recommended conditions ranged from 1.0×10- 5.5×10 genome copies/mL of infectious SARS-CoV-2 cell culture supernatant. Despite long-term storage at recommended conditions, 10 min pre-incubation of Ag-RDTs and testing at 37 °C resulted in about ten-fold reduced sensitivity for five out of 11 SARS-CoV-2 Ag-RDTs, including both Ag-RDTs currently listed for emergency use by the World Health Organization. After 3 weeks of storage at 37 °C, eight of the 11 SARS-CoV-2 Ag-RDTs exhibited about ten-fold reduced sensitivity. Specificity of SARS-CoV-2 Ag-RDTs using cell culture supernatant from common respiratory viruses was not affected by storage and testing at 37 °C, whereas false-positive results occurred at outside temperatures of 2-4 °C for two out of six tested Ag-RDTs, again including an Ag-RDT recommended by the WHO. In summary, elevated temperatures impair sensitivity, whereas low temperatures impair specificity of SARS-CoV-2 Ag-RDTs. Consequences may include false-negative test results at clinically relevant virus concentrations compatible with transmission and false-positive results entailing unwarranted quarantine assignments. Storage and operation of SARS-CoV-2 Ag-RDTs at recommended conditions is essential for successful usage during the pandemic.
抗原检测快速诊断试剂盒（Ag-RDT）可与 COVID-19 的分子诊断互补。推荐的 SARS-CoV-2 Ag-RDT 储存温度范围在 2-30°C 之间。在全球南方，平均温度可能会超过 30°C。在全球北方，Ag-RDT 通常在外部测试设施中于环境低温下使用。我们评估了 11 种市售 SARS-CoV-2 Ag-RDT 在不同储存和操作温度下的分析灵敏度和特异性，包括短期或长期储存以及在推荐温度或 2-4°C 或 37°C 下操作。在推荐条件下，SARS-CoV-2 Ag-RDT 的检测下限范围为 1.0×10-5.5×10 拷贝/ml 传染性 SARS-CoV-2 细胞培养上清液。尽管在推荐条件下长期储存，但在 10 分钟预孵育后，Ag-RDT 测试温度为 37°C，导致 11 种 SARS-CoV-2 Ag-RDT 中有 5 种的灵敏度降低了约十倍，包括目前被世界卫生组织列为紧急使用的两种 Ag-RDT。在 37°C 下储存 3 周后，11 种 SARS-CoV-2 Ag-RDT 中有 8 种的灵敏度降低了约十倍。在 37°C 下储存和测试时，SARS-CoV-2 Ag-RDT 对常见呼吸道病毒的细胞培养上清液的特异性不受影响，而在 2-4°C 的外部温度下，两种测试的 Ag-RDT 中有两种会出现假阳性结果，其中再次包括世界卫生组织推荐的一种 Ag-RDT。总之，高温会降低灵敏度，而低温会降低 SARS-CoV-2 Ag-RDT 的特异性。后果可能包括在与传播相容的临床相关病毒浓度下出现假阴性检测结果和在不必要的隔离分配下出现假阳性结果。在大流行期间，SARS-CoV-2 Ag-RDT 的储存和操作符合推荐条件是成功使用的关键。
