Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
Graduate School of Health Sciences, University of Bern, Bern, Switzerland.
PLoS Med. 2020 Sep 22;17(9):e1003346. doi: 10.1371/journal.pmed.1003346. eCollection 2020 Sep.
BACKGROUND: 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? METHODS AND FINDINGS: 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. CONCLUSIONS: 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.
背景:无症状严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染的程度存在争议。我们进行了一项实时系统评价和荟萃分析,以解决三个问题:(1)在感染 SARS-CoV-2 的人群中,完全无症状的比例是多少?(2)在诊断时无症状的 SARS-CoV-2 感染者中,有多少比例会随后出现症状?(3)无症状或症状前感染者在 SARS-CoV-2 传播中占多大比例?
方法和发现:我们使用每日更新的 SARS-CoV-2 文献数据库,在 2020 年 3 月 25 日、4 月 20 日和 6 月 10 日检索了 PubMed、Embase、bioRxiv 和 medRxiv。纳入了通过逆转录酶聚合酶链反应(RT-PCR)诊断为 SARS-CoV-2 的人群的研究,这些研究记录了随访期间和随访开始和结束时的症状状态,或建模研究。一位审阅者提取数据,第二位审阅者验证提取结果,如果存在分歧,则通过讨论或第三位审阅者解决。对经验研究的偏倚风险采用了病例系列的改编检查表进行评估,对建模研究的相关性和可信度采用了已发表的检查表进行评估。我们共纳入了 94 项研究。在 79 项研究中,感染 SARS-CoV-2 且整个感染期间无症状的总体估计比例为 20%(95%置信区间 [CI] 17%-25%),79 项研究中预测区间为 3%-67%。有证据表明,参与者选择偏倚影响了这一估计。在对 SARS-CoV-2 进行筛查然后进行随访的七个研究中,31%(95%CI 26%-37%,预测区间 24%-38%)的患者无症状。由于存在异质性,无法总结无症状感染者的比例。与有症状感染者的接触者相比,无症状感染者的二次攻击率较低(相对风险 0.35,95%CI 0.10-1.27)。拟合数据的建模研究发现,无症状个体比有症状个体的所有 SARS-CoV-2 感染中,由无症状个体传播的比例更高。本研究的局限性包括: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,且存在选择偏倚的风险;我们未考虑 RT-PCR 结果可能出现假阴性的情况,这会低估无症状感染的比例;且数据库不包含所有的来源。
结论:本实时系统评价的结果表明,大多数感染 SARS-CoV-2 的人在感染过程中不会一直无症状。无症状和症状前感染对 SARS-CoV-2 总体传播的贡献意味着,需要继续采取综合预防措施,包括增强手部卫生、佩戴口罩、检测追踪、隔离策略和保持社交距离。
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