Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis.
Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis.
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DOI：
10.1371/journal.pmed.1003346
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发表时间：
2020-09
期刊：
影响因子：
15.8
通讯作者：
Low N
中科院分区：
文献类型：
--
作者：
Buitrago-Garcia D;Egli-Gany D;Counotte MJ;Hossmann S;Imeri H;Ipekci AM;Salanti G;Low N
关于无症状严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的水平存在分歧。我们进行了一项活体系统回顾和荟萃分析，以解决三个问题：（1）在感染SARS-CoV-2的人群中，有多大比例的人在感染期间没有任何症状？(2)在确诊时无症状的SARS-CoV-2感染者中，有多少比例会在以后出现症状？(3)在SARS-CoV-2传播中，在整个感染过程中无症状或症状前无症状的人占多大比例？我们使用SARS-CoV-2文献数据库检索了PubMed、Embase、bioRxiv和medRxiv，该数据库于2020年3月25日、2020年4月20日和2020年6月10日每日更新。包括通过逆转录酶PCR（RT-PCR）诊断的SARS-CoV-2患者的研究，这些研究记录了随访或建模研究开始和结束时的随访和症状状态。一位评审员提取数据，第二位评审员验证提取，通过讨论或第三位评审员解决分歧。在实证研究中的偏见的风险进行了评估，与一个适应清单的情况下，系列和相关性和可信度的建模研究进行了评估，使用一个已公布的清单。共纳入94项研究。在79项研究中，感染SARS-CoV-2并在整个感染过程中保持无症状的人群比例的总体估计为20%（95%置信区间[CI] 17-25），预测区间为3%-67%。有一些证据表明，参与者选择中的偏见会影响估计。在7项对特定人群进行SARS-CoV-2筛查并随后随访的研究中，31%（95%CI 26%-37%，预测区间24%-38%）的患者仍无症状。由于异质性，症状前患者的比例无法总结。无症状感染者接触者的二次发病率低于有症状感染者（相对风险0.35，95%CI 0.10-1.27）。与数据拟合的模拟研究发现，所有SARS-CoV-2感染中，症状前个体传播的比例高于无症状个体。该综述的局限性包括，大多数纳入的研究并非旨在估计无症状SARS-CoV-2感染的比例，存在选择偏倚的风险;我们没有考虑假阴性RT-PCR结果的可能影响，这会低估无症状感染的比例;数据库未包括所有来源。这项系统性回顾的发现表明，大多数感染SARS-CoV-2的人在整个感染过程中不会保持无症状。症状前感染者和无症状感染者对SARS-CoV-2总体传播的贡献意味着将继续需要采取综合预防措施，包括加强手部卫生、口罩、检测追踪、隔离策略和社交距离。Diana Buitrago-Garcia及其同事对无症状SARS-CoV-2感染进行了系统回顾和荟萃分析。在感染严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）（2019冠状病毒病（COVID-19）的原因）的整个过程中，将保持无症状的人的比例尚不清楚。仅在一个时间点对人进行评估的研究会高估真正的无症状感染者的比例，因为那些继续出现COVID-19症状的人会被错误地归类为无症状，而不是症状前。无症状SARS-CoV-2感染的数量和传染性将决定什么样的措施将最有效地防止传播。我们使用自动化工作流程进行了一项截至2020年6月10日的实时系统性综述，该工作流程加快了综述过程，并允许在获得相关新证据时更新综述。总体而言，在一系列不同背景下的79项研究中，20%（95%置信区间[CI] 17%-25%，预测区间3%-67%）的SARS-CoV-2感染者在随访期间保持无症状，但研究设计的偏倚限制了这一估计的确定性。在7项对特定人群进行SARS-CoV-2筛查并随后随访的研究中，31%（95%CI 26%-37%，预测区间24%-38%）的患者仍无症状。我们发现一些证据表明，与无症状感染者接触的人感染SARS-CoV-2的可能性低于与有症状感染者接触的人（相对风险0.35，95%CI 0.10-1.27）。这项系统性回顾的发现表明，大多数感染SARS-CoV-2的人在整个感染过程中不会保持无症状。未来的研究应该专门设计来确定无症状SARS-CoV-2感染的真实比例，使用方法来最大限度地减少选择研究参与者和确定随访期间症状状态的偏倚。症状前感染者和无症状感染者对SARS-CoV-2总体传播的贡献意味着将继续需要采取综合预防措施，包括加强手部卫生、口罩、检测追踪、隔离策略和社交距离。
There is disagreement about the level of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a living systematic review and meta-analysis to address three questions: (1) Amongst people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? (2) Amongst people with SARS-CoV-2 infection who are asymptomatic when diagnosed, what proportion will develop symptoms later? (3) What proportion of SARS-CoV-2 transmission is accounted for by people who are either asymptomatic throughout infection or presymptomatic? We searched PubMed, Embase, bioRxiv, and medRxiv using a database of SARS-CoV-2 literature that is updated daily, on 25 March 2020, 20 April 2020, and 10 June 2020. Studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR (RT-PCR) that documented follow-up and symptom status at the beginning and end of follow-up or modelling studies were included. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with an adapted checklist for case series, and the relevance and credibility of modelling studies were assessed using a published checklist. We included a total of 94 studies. The overall estimate of the proportion of people who become infected with SARS-CoV-2 and remain asymptomatic throughout infection was 20% (95% confidence interval [CI] 17–25) with a prediction interval of 3%–67% in 79 studies that addressed this review question. There was some evidence that biases in the selection of participants influence the estimate. In seven studies of defined populations screened for SARS-CoV-2 and then followed, 31% (95% CI 26%–37%, prediction interval 24%–38%) remained asymptomatic. The proportion of people that is presymptomatic could not be summarised, owing to heterogeneity. The secondary attack rate was lower in contacts of people with asymptomatic infection than those with symptomatic infection (relative risk 0.35, 95% CI 0.10–1.27). Modelling studies fit to data found a higher proportion of all SARS-CoV-2 infections resulting from transmission from presymptomatic individuals than from asymptomatic individuals. Limitations of the review include that most included studies were not designed to estimate the proportion of asymptomatic SARS-CoV-2 infections and were at risk of selection biases; we did not consider the possible impact of false negative RT-PCR results, which would underestimate the proportion of asymptomatic infections; and the database does not include all sources. The findings of this living systematic review suggest that most people who become infected with SARS-CoV-2 will not remain asymptomatic throughout the course of the infection. The contribution of presymptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention measures, with enhanced hand hygiene, masks, testing tracing, and isolation strategies and social distancing, will continue to be needed. Diana Buitrago-Garcia and co-workers present a systematic review and meta-analysis on asymptomatic SARS-CoV-2 infections. The proportion of people who will remain asymptomatic throughout the course of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is not known. Studies that assess people at just one time point will overestimate the proportion of true asymptomatic infection because those who go on to develop COVID-19 symptoms will be wrongly classified as asymptomatic rather than presymptomatic. The amount, and infectiousness, of asymptomatic SARS-CoV-2 infection will determine what kind of measures will prevent transmission most effectively. We did a living systematic review through 10 June 2020, using automated workflows that speed up the review processes and allow the review to be updated when relevant new evidence becomes available. Overall, in 79 studies in a range of different settings, 20% (95% confidence interval [CI] 17%–25%, prediction interval 3%–67%) of people with SARS-CoV-2 infection remained asymptomatic during follow-up, but biases in study designs limit the certainty of this estimate. In seven studies of defined populations screened for SARS-CoV-2 and then followed, 31% (95% CI 26%–37%, prediction interval 24%–38%) remained asymptomatic. We found some evidence that SARS-CoV-2 infection in contacts of people with asymptomatic infection is less likely than in contacts of people with symptomatic infection (relative risk 0.35, 95% CI 0.10–1.27). The findings of this living systematic review suggest that most people who become infected with SARS-CoV-2 will not remain asymptomatic throughout the course of infection. Future studies should be designed specifically to determine the true proportion of asymptomatic SARS-CoV-2 infections, using methods to minimise biases in the selection of study participants and ascertainment of symptom status during follow-up. The contribution of presymptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention measures, with enhanced hand hygiene, masks, testing tracing, and isolation strategies and social distancing, will continue to be needed.
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影响因子：
168.9
作者：
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通讯作者：
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DOI：
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发表时间：
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