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SARS-CoV-2 感染的普遍筛查:快速综述。

Universal screening for SARS-CoV-2 infection: a rapid review.

机构信息

RTI International, Research Triangle Park, North Carolina, USA.

Department of Public Health, Health Services Research and Health Technology Assessment, UMIT - University for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria.

出版信息

Cochrane Database Syst Rev. 2020 Sep 15;9(9):CD013718. doi: 10.1002/14651858.CD013718.


DOI:10.1002/14651858.CD013718
PMID:33502003
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8453488/
Abstract

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by the novel betacoronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Most people infected with SARS-CoV-2 have mild disease with unspecific symptoms, but about 5% become critically ill with respiratory failure, septic shock and multiple organ failure. An unknown proportion of infected individuals never experience COVID-19 symptoms although they are infectious, that is, they remain asymptomatic. Those who develop the disease, go through a presymptomatic period during which they are infectious. Universal screening for SARS-CoV-2 infections to detect individuals who are infected before they present clinically, could therefore be an important measure to contain the spread of the disease. OBJECTIVES: We conducted a rapid review to assess (1) the effectiveness of universal screening for SARS-CoV-2 infection compared with no screening and (2) the accuracy of universal screening in people who have not presented to clinical care for symptoms of COVID-19. SEARCH METHODS: An information specialist searched Ovid MEDLINE and the Centers for Disease Control (CDC) COVID-19 Research Articles Downloadable Database up to 26 May 2020. We searched Embase.com, the CENTRAL, and the Cochrane Covid-19 Study Register on 14 April 2020. We searched LitCovid to 4 April 2020. The World Health Organization (WHO) provided records from daily searches in Chinese databases and in PubMed up to 15 April 2020. We also searched three model repositories (Covid-Analytics, Models of Infectious Disease Agent Study [MIDAS], and Society for Medical Decision Making) on 8 April 2020. SELECTION CRITERIA: Trials, observational studies, or mathematical modelling studies assessing screening effectiveness or screening accuracy among general populations in which the prevalence of SARS-CoV2 is unknown. DATA COLLECTION AND ANALYSIS: After pilot testing review forms, one review author screened titles and abstracts. Two review authors independently screened the full text of studies and resolved any disagreements by discussion with a third review author. Abstracts excluded by a first review author were dually reviewed by a second review author prior to exclusion. One review author independently extracted data, which was checked by a second review author for completeness and accuracy. Two review authors independently rated the quality of included studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool for diagnostic accuracy studies and a modified form designed originally for economic evaluations for modelling studies. We resolved differences by consensus. We synthesized the evidence in narrative and tabular formats. We rated the certainty of evidence for days to outbreak, transmission, cases missed and detected, diagnostic accuracy (i.e. true positives, false positives, true negatives, false negatives) using the GRADE approach. MAIN RESULTS: We included 22 publications. Two modelling studies reported on effectiveness of universal screening. Twenty studies (17 cohort studies and 3 modelling studies) reported on screening test accuracy. Effectiveness of screening We included two modelling studies. One study suggests that symptom screening at travel hubs, such as airports, may slightly slow but not stop the importation of infected cases (assuming 10 or 100 infected travellers per week reduced the delay in a local outbreak to 8 days or 1 day, respectively). We assessed risk of bias as minor or no concerns, and certainty of evidence was low, downgraded for very serious indirectness. The second modelling study provides very low-certainty evidence that screening of healthcare workers in emergency departments using laboratory tests may reduce transmission to patients and other healthcare workers (assuming a transmission constant of 1.2 new infections per 10,000 people, weekly screening reduced infections by 5.1% within 30 days). The certainty of evidence was very low, downgraded for high risk of bias (major concerns) and indirectness. No modelling studies reported on harms of screening. Screening test accuracy All 17 cohort studies compared an index screening strategy to a reference reverse transcriptase polymerase chain reaction (RT-PCR) test. All but one study reported on the accuracy of single point-in-time screening and varied widely in prevalence of SARS-CoV-2, settings, and methods of measurement. We assessed the overall risk of bias as unclear in 16 out of 17 studies, mainly due to limited information on the index test and reference standard. We rated one study as being at high risk of bias due to the inclusion of two separate populations with likely different prevalences. For several screening strategies, the estimates of sensitivity came from small samples. For single point-in-time strategies, for symptom assessment, the sensitivity from 12 cohorts (524 people) ranged from 0.00 to 0.60 (very low-certainty evidence) and the specificity from 12 cohorts (16,165 people) ranged from 0.66 to 1.00 (low-certainty evidence). For screening using direct temperature measurement (3 cohorts, 822 people), international travel history (2 cohorts, 13,080 people), or exposure to known infected people (3 cohorts, 13,205 people) or suspected infected people (2 cohorts, 954 people), sensitivity ranged from 0.00 to 0.23 (very low- to low-certainty evidence) and specificity ranged from 0.90 to 1.00 (low- to moderate-certainty evidence). For symptom assessment plus direct temperature measurement (2 cohorts, 779 people), sensitivity ranged from 0.12 to 0.69 (very low-certainty evidence) and specificity from 0.90 to 1.00 (low-certainty evidence). For rapid PCR test (1 cohort, 21 people), sensitivity was 0.80 (95% confidence interval (CI) 0.44 to 0.96; very low-certainty evidence) and specificity was 0.73 (95% CI 0.39 to 0.94; very low-certainty evidence). One cohort (76 people) reported on repeated screening with symptom assessment and demonstrates a sensitivity of 0.44 (95% CI 0.29 to 0.59; very low-certainty evidence) and specificity of 0.62 (95% CI 0.42 to 0.79; low-certainty evidence). Three modelling studies evaluated the accuracy of screening at airports. The main outcomes measured were cases missed or detected by entry or exit screening, or both, at airports. One study suggests very low sensitivity at 0.30 (95% CI 0.1 to 0.53), missing 70% of infected travellers. Another study described an unrealistic scenario to achieve a 90% detection rate, requiring 0% asymptomatic infections. The final study provides very uncertain evidence due to low methodological quality. AUTHORS' CONCLUSIONS: The evidence base for the effectiveness of screening comes from two mathematical modelling studies and is limited by their assumptions. Low-certainty evidence suggests that screening at travel hubs may slightly slow the importation of infected cases. This review highlights the uncertainty and variation in accuracy of screening strategies. A high proportion of infected individuals may be missed and go on to infect others, and some healthy individuals may be falsely identified as positive, requiring confirmatory testing and potentially leading to the unnecessary isolation of these individuals. Further studies need to evaluate the utility of rapid laboratory tests, combined screening, and repeated screening. More research is also needed on reference standards with greater accuracy than RT-PCR. Given the poor sensitivity of existing approaches, our findings point to the need for greater emphasis on other ways that may prevent transmission such as face coverings, physical distancing, quarantine, and adequate personal protective equipment for frontline workers.

摘要

背景:新型冠状病毒病(COVID-19)是由新型贝塔冠状病毒,即严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)引起的。大多数感染 SARS-CoV-2 的人患有轻度疾病,症状不特异,但约 5%的患者会出现呼吸衰竭、感染性休克和多器官衰竭等严重疾病。尽管有传染性,但相当一部分感染 SARS-CoV-2 的个体从未出现 COVID-19 症状,即处于无症状感染状态。那些患有这种疾病的人,在出现症状之前会经历一个无症状期,在此期间他们具有传染性。因此,对 SARS-CoV-2 感染进行普遍筛查,以发现尚未出现临床症状的感染者,可能是控制疾病传播的重要措施。

目的:我们进行了一项快速综述,以评估(1)与无筛查相比,对 SARS-CoV-2 感染进行普遍筛查的效果,以及(2)对尚未因 COVID-19 症状而到临床就诊的人群进行普遍筛查的准确性。

检索方法:信息专家检索了 Ovid MEDLINE 和美国疾病控制与预防中心(CDC)COVID-19 研究文章可下载数据库,检索截止日期为 2020 年 5 月 26 日。我们还检索了 Embase.com、CENTRAL 和 Cochrane Covid-19 研究注册中心(2020 年 4 月 14 日)、LitCovid(2020 年 4 月 4 日)、世界卫生组织(WHO)每日检索的中文数据库和 PubMed(2020 年 4 月 15 日)。我们还于 2020 年 4 月 8 日检索了三个模型存储库(Covid-Analytics、Models of Infectious Disease Agent Study [MIDAS] 和 Society for Medical Decision Making)。

纳入标准:评估一般人群中 SARS-CoV-2 未知流行率的普遍筛查效果或筛查准确性的试验、观察性研究或数学建模研究。

排除标准:排除了重复发表的研究、病例报告、综述和专家意见。

数据收集和分析:在预试验审查表格后,一名审查员筛选了标题和摘要。两名审查员独立筛选了研究的全文,并通过与第三名审查员讨论解决了任何分歧。首先由一名审查员排除的摘要由第二名审查员在排除前进行了双重审查。一名审查员独立提取数据,另一名审查员对其完整性和准确性进行了检查。两名审查员使用针对诊断准确性研究的 QUADAS-2 工具和最初为经济评估设计的修改版,分别独立评估了纳入研究的质量。我们通过共识解决了差异。我们以叙述和表格格式综合证据。我们使用 GRADE 方法,根据发病日、传播、漏诊和检出的病例、诊断准确性(即真阳性、假阳性、真阴性、假阴性)来评估证据的确定性。

主要结果:我们纳入了 22 篇出版物。两项建模研究报告了普遍筛查的效果。20 项研究(17 项队列研究和 3 项建模研究)报告了筛查试验的准确性。筛查效果我们纳入了两项建模研究。一项研究表明,在机场等旅行枢纽进行症状筛查可能会略微减缓,但不会阻止感染病例的输入(假设每周有 10 或 100 名感染旅行者入境,当地疫情的延迟分别为 8 天或 1 天)。我们评估了风险偏倚为轻度或无,证据确定性为低,降级为非常严重的间接性。第二项建模研究提供了非常低确定性的证据,表明在急诊部门使用实验室检测对医护人员进行筛查可能会减少对患者和其他医护人员的传播(假设每 10,000 人传播常数为 1.2 例新感染,每周筛查可在 30 天内将感染减少 5.1%)。证据确定性非常低,降级为高风险偏倚(主要担忧)和间接性。没有建模研究报告筛查的危害。筛查试验准确性所有 17 项队列研究都将指数筛查策略与参考逆转录酶聚合酶链反应(RT-PCR)试验进行了比较。除一项研究外,所有研究均报告了单点筛查的准确性,SARS-CoV-2 的流行率、设置和测量方法差异很大。我们评估了 17 项研究中的 16 项的总体风险偏倚为不确定,主要原因是对指数试验和参考标准的信息有限。我们对一项研究的风险偏倚评为高,原因是纳入了两个可能具有不同流行率的单独人群。对于几种筛查策略,来自小样本的估计敏感性。对于单点筛查策略,对于症状评估,来自 12 项队列(524 人)的敏感性范围为 0.00 至 0.60(低确定性证据),来自 12 项队列(16,165 人)的特异性范围为 0.66 至 1.00(低确定性证据)。对于使用直接体温测量(3 项研究,822 人)、国际旅行史(2 项研究,13080 人)、或接触已知感染者(3 项研究,13205 人)或疑似感染者(2 项研究,954 人)的筛查,敏感性范围为 0.00 至 0.23(低至极低确定性证据),特异性范围为 0.90 至 1.00(低至中等确定性证据)。对于症状评估加直接体温测量(2 项研究,779 人),敏感性范围为 0.12 至 0.69(低确定性证据),特异性范围为 0.90 至 1.00(低确定性证据)。对于快速 PCR 检测(1 项研究,21 人),敏感性为 0.80(95%置信区间[CI]0.44 至 0.96;低确定性证据),特异性为 0.73(95% CI 0.39 至 0.94;低确定性证据)。一项队列研究(76 人)报告了重复进行症状评估和筛查,敏感性为 0.44(95% CI 0.29 至 0.59;低确定性证据),特异性为 0.62(95% CI 0.42 至 0.79;低确定性证据)。三项建模研究评估了在机场进行筛查的准确性。主要结局是在机场入境或出境筛查或两者都筛查时漏诊或检出的病例。一项研究表明,敏感性非常低,为 0.30(95% CI 0.1 至 0.53),错过了 70%的感染旅行者。另一项研究描述了一个不切实际的情景,以达到 90%的检测率,需要 0%的无症状感染。最后一项研究由于方法学质量低而提供了非常不确定的证据。

作者结论:筛查效果的证据来自两项数学建模研究,且受到其假设的限制。低确定性证据表明,在旅行枢纽进行筛查可能会略微减缓感染病例的输入。本综述强调了筛查策略准确性的不确定性和差异。相当一部分感染个体可能被漏诊,进而感染他人,一些健康个体可能被错误地识别为阳性,需要进行确认性检测,可能导致这些个体不必要的隔离。进一步的研究需要评估快速实验室检测、联合筛查和重复筛查的效用。还需要更多的研究来评估参考标准的准确性,以取代 RT-PCR。鉴于现有方法的敏感性较差,我们的研究结果表明,需要更加重视其他方法,如戴口罩、保持身体距离、隔离和为一线工作人员提供充足的个人防护设备,以防止传播。

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