Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure
Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure
复制标题
DOI：
10.7326/m20-1495
复制
发表时间：
2020-08-18
影响因子：
39.2
通讯作者：
Lessler, Justin
中科院分区：
文献类型：
--
作者：
Kucirka, Lauren M.;Lauer, Stephen A.;Lessler, Justin
背景：基于逆转录酶聚合酶链反应（RT-PCR）的严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）检测正在被用于排除高危人群（如暴露的住院患者和卫生保健工作者）中的感染。至关重要的是要了解该测试的预测值如何随接触和症状出现的时间变化，以避免被阴性测试结果错误地放心。目的：估计感染后每天的假阴性率。设计：文献回顾和汇总分析。背景：先前发表的7项研究使用来自上呼吸道的样本（n = 1330），提供了自症状出现或SARS-CoV-2暴露以来按时间划分的RTPCR性能数据。患者：SARS-CoV-2感染的住院和门诊患者。测量方法：拟合贝叶斯层次模型来估计自暴露和症状发作以来每天的假阴性率。结果：在典型症状出现时间（第5天）之前的感染4天内，感染者假阴性结果的概率从第1天的100% （95% CI， 100%至100%）下降到第4天的67% （CI， 27%至94%）。在症状出现当天，中位假阴性率为38% （CI， 18%至65%）。在第8天（症状出现后3天），这一比例降至20% (CI， 12%至30%)，然后再次开始上升，从第9天的21% （CI， 13%至31%）上升至第21天的66% （CI， 54%至77%）。局限性：由于结果所依据的研究设计的异质性，估计不精确。结论：在解释SARS-CoV-2感染的RT-PCR检测结果时，特别是在感染过程的早期，当使用这些结果作为取消旨在防止进一步传播的预防措施的基础时，必须谨慎。如果临床怀疑程度高，不应仅根据RT-PCR排除感染，应仔细考虑临床和流行病学情况。
Background: Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse transcriptase polymerase chain reaction (RT-PCR) are being used to rule out infection among high-risk persons, such as exposed inpatients and health care workers. It is critical to understand how the predictive value of the test varies with time from exposure and symptom onset to avoid being falsely reassured by negative test results.Objective: To estimate the false-negative rate by day since infection.Design: Literature review and pooled analysis.Setting: 7 previously published studies providing data on RTPCR performance by time since symptom onset or SARS-CoV-2 exposure using samples from the upper respiratory tract (n = 1330).Patients: A mix of inpatients and outpatients with SARS-CoV-2 infection.Measurements: A Bayesian hierarchical model was fitted to estimate the false-negative rate by day since exposure and symptom onset.Results: Over the 4 days of infection before the typical time of symptom onset (day 5), the probability of a false-negative result in an infected person decreases from 100% (95% CI, 100% to 100%) on day 1 to 67% (CI, 27% to 94%) on day 4. On the day of symptom onset, the median false-negative rate was 38% (CI, 18% to 65%). This decreased to 20% (CI, 12% to 30%) on day 8 (3 days after symptom onset) then began to increase again, from 21% (CI, 13% to 31%) on day 9 to 66% (CI, 54% to 77%) on day 21.Limitation: Imprecise estimates due to heterogeneity in the design of studies on which results were based.Conclusion: Care must be taken in interpreting RT-PCR tests for SARS-CoV-2 infection-particularly early in the course of infection-when using these results as a basis for removing precautions intended to prevent onward transmission. If clinical suspicion is high, infection should not be ruled out on the basis of RT-PCR alone, and the clinical and epidemiologic situation should be carefully considered.