Department of Public Health Information, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Lancet Microbe. 2021 Feb;2(2):e79-e87. doi: 10.1016/S2666-5247(20)30200-7. Epub 2021 Jan 19.
Virological detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through RT-PCR has limitations for surveillance. Serological tests can be an important complementary approach. We aimed to assess the practical performance of RT-PCR-based surveillance protocols and determine the extent of undetected SARS-CoV-2 infection in Shenzhen, China.
We did a cohort study in Shenzhen, China and attempted to recruit by telephone all RT-PCR-negative close contacts (defined as those who lived in the same residence as, or shared a meal, travelled, or socially interacted with, an index case within 2 days before symptom onset) of all RT-PCR-confirmed cases of SARS-CoV-2 detected since January, 2020, via contact tracing. We measured anti-SARS-CoV-2 antibodies in serum samples from RT-PCR-negative close contacts 2-15 weeks after initial virological testing by RT-PCR, using total antibody, IgG, and IgM ELISAs. In addition, we did a serosurvey of volunteers from neighbourhoods with no reported cases, and from neighbourhoods with reported cases. We assessed rates of infection undetected by RT-PCR, performance of RT-PCR over the course of infection, and characteristics of individuals who were seropositive on total antibody ELISA but RT-PCR negative.
Between April 12 and May 4, 2020, we enrolled and collected serological samples from 2345 (53·0%) of 4422 RT-PCR-negative close contacts of cases of RT-PCR-confirmed SARS-CoV-2. 1175 (50·1%) of 2345 were close contacts of cases diagnosed in Shenzhen with contact tracing details, and of these, 880 (74·9%) had serum samples collected more than 2 weeks after exposure to an index case and were included in our analysis. 40 (4·5%) of 880 RT-PCR-negative close contacts were positive on total antibody ELISA. The seropositivity rate with total antibody ELISA among RT-PCR-negative close contacts, adjusted for assay performance, was 4·1% (95% CI 2·9-5·7), which was significantly higher than among individuals residing in neighbourhoods with no reported cases (0·0% [95% CI 0·0-1·1]). RT-PCR-positive individuals were 8·0 times (95% CI 5·3-12·7) more likely to report symptoms than those who were RT-PCR-negative but seropositive, but both groups had a similar distribution of sex, age, contact frequency, and mode of contact. RT-PCR did not detect 48 (36% [95% CI 28-44]) of 134 infected close contacts, and false-negative rates appeared to be associated with stage of infection.
Even rigorous RT-PCR testing protocols might miss a substantial proportion of SARS-CoV-2 infections, perhaps in part due to difficulties in determining the timing of testing in asymptomatic individuals for optimal sensitivity. RT-PCR-based surveillance and control protocols that include rapid contact tracing, universal RT-PCR testing, and mandatory 2-week quarantine were, nevertheless, able to contain community spread in Shenzhen, China.
The Bill & Melinda Gates Foundation, Special Foundation of Science and Technology Innovation Strategy of Guangdong Province, and Key Project of Shenzhen Science and Technology Innovation Commission.
通过 RT-PCR 对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）进行病毒学检测对监测有局限性。血清学检测可能是一种重要的补充方法。我们旨在评估基于 RT-PCR 的监测方案的实际性能，并确定在中国深圳未检测到 SARS-CoV-2 感染的程度。
我们在中国深圳进行了一项队列研究，并试图通过电话招募所有 RT-PCR 阴性的密切接触者（定义为与确诊的 SARS-CoV-2 病例同住一住所、共同用餐、共同旅行或在症状出现前 2 天内共同社交的密切接触者），这些病例是通过接触追踪自 2020 年 1 月以来检测到的。我们使用总抗体、IgG 和 IgM ELISA 在 RT-PCR 初次病毒学检测后 2-15 周，从 RT-PCR 阴性的密切接触者的血清样本中测量抗 SARS-CoV-2 抗体。此外，我们对无报告病例的社区和有报告病例的社区的志愿者进行了血清学调查。我们评估了 RT-PCR 漏检的感染率、RT-PCR 检测过程中的性能以及总抗体 ELISA 呈阳性但 RT-PCR 阴性的个体特征。
2020 年 4 月 12 日至 5 月 4 日期间，我们招募并收集了 4422 名 RT-PCR 确诊 SARS-CoV-2 病例的 2345 名（53.0%）RT-PCR 阴性密切接触者的血清样本。在这 2345 名患者中，有 1175 名（50.1%）是通过接触追踪在深圳确诊的病例的密切接触者，其中 880 名（74.9%）有暴露于指数病例后 2 周以上的血清样本，并纳入我们的分析。880 名 RT-PCR 阴性密切接触者中有 40 名（4.5%）在总抗体 ELISA 上呈阳性。在考虑了检测性能的情况下，RT-PCR 阴性密切接触者的总抗体 ELISA 阳性率为 4.1%（95%CI 2.9-5.7），显著高于无报告病例社区的个体（0.0%[95%CI 0.0-1.1]）。RT-PCR 阳性个体报告症状的可能性是 RT-PCR 阴性但血清学阳性个体的 8.0 倍（95%CI 5.3-12.7），但两组的性别、年龄、接触频率和接触模式分布相似。RT-PCR 未能检测到 134 名感染密切接触者中的 48 名（36%[95%CI 28-44]），且假阴性率似乎与感染阶段有关。
即使是严格的 RT-PCR 检测方案也可能会错过相当一部分 SARS-CoV-2 感染，部分原因可能是难以确定无症状个体的检测时间以获得最佳敏感性。然而，包括快速接触追踪、普遍的 RT-PCR 检测和强制性 2 周隔离在内的基于 RT-PCR 的监测和控制方案仍能控制中国深圳的社区传播。
比尔及梅琳达·盖茨基金会、广东省科技计划项目、深圳市科技计划项目。
