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严重急性呼吸综合征冠状病毒2的长而细的传播链在低至中等繁殖数情况下可能数周未被发现:对控制和消除策略的影响。

Long, thin transmission chains of Severe Acute Respiratory Syndrome Coronavirus 2 may go undetected for several weeks at low to moderate reproduction numbers: Implications for containment and elimination strategy.

作者信息

Killeen Gerry F, Kearney Patricia M, Perry Ivan J, Conroy Niall

机构信息

School of Biological, Earth & Environmental Sciences, University College Cork, Cork, Ireland.

Environmental Research Institute, University College Cork, Cork, Ireland.

出版信息

Infect Dis Model. 2021;6:474-489. doi: 10.1016/j.idm.2021.02.002. Epub 2021 Feb 23.

DOI:10.1016/j.idm.2021.02.002
PMID:33644500
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7901309/
Abstract

Severe Acute Respiratory Syndrome Coronavirus 1 (SARS-CoV-1) infections almost always caused overt symptoms, so effective case and contact management enabled its effective eradication within months. However, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) usually causes only mild symptoms, so transmission chains may grow to include several individuals before at least one index case becomes ill enough to self-report for diagnosis and care. Here, simple mathematical models were developed to evaluate the implications of delayed index case detection for retrospective contact tracing and management responses. Specifically, these simulations illustrate how: (1) Contact tracing and management may effectively contain most but not all large SARS-CoV-2 clusters arising at foci with high reproduction numbers because rapidly expanding transmission chains ensure at least one overtly symptomatic index case occurs within two viral generations a week or less apart. (2) However, lower reproduction numbers give rise to thinner transmission chains extending through longer sequences of non-reporting asymptomatic and paucisymptomatic individuals, often spanning three or more viral generations (≥2 weeks of transmission) before an overtly symptomatic index case occurs. (3) Consequently, it is not always possible to fully trace and contain such long, thin transmission chains, so the community transmission they give rise to is underrepresented in surveillance data. (4) Wherever surveillance systems are weak and/or transmission proceeds within population groups with lower rates of overt clinical symptoms and/or self-reporting, case and contact management effectiveness may be more severely limited, even at the higher reproduction numbers associated with larger outbreaks. (5) Because passive surveillance platforms may be especially slow to detect the thinner transmission chains that occur at low reproduction numbers, establishing satisfactory confidence of elimination may require that no confirmed cases are detected for two full months, throughout which presumptive preventative measures must be maintained to ensure complete collapse of undetected residual transmission. (6) Greater scope exists for overcoming these limitations by enhancing field surveillance for new suspected cases than by improving diagnostic test sensitivity. (7) While population-wide active surveillance may enable complete traceability and containment, this goal may also be achievable through enhanced passive surveillance for paucisymptomatic infections, combining readily accessible decentralized testing with population hypersensitization to self-reporting with mild symptoms. Containment and elimination of SARS-CoV-2 will rely far more upon presumptive, population-wide prevention measures than was necessary for SARS-CoV-1, necessitating greater ambition, political will, investment, public support, persistence and patience. Nevertheless, case and contact management may be invaluable for at least partially containing SARS-CoV-2 transmission, especially larger outbreaks, but only if enabled by sufficiently sensitive surveillance. Furthermore, consistently complete transmission chain containment may be enabled by focally enhanced surveillance around manageably small numbers of outbreaks in the end stages of successful elimination campaigns, so that their endpoints may be accelerated and sustained.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f95/8660591/80e8bd1d1b7b/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f95/8660591/2f889b678cda/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f95/8660591/309c53f6d3dd/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f95/8660591/b20f51e4a365/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f95/8660591/26d45741769c/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f95/8660591/08f7d9cebb1f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f95/8660591/588c1f1b85a2/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f95/8660591/f6ab146a69ad/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f95/8660591/80e8bd1d1b7b/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f95/8660591/2f889b678cda/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f95/8660591/309c53f6d3dd/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f95/8660591/b20f51e4a365/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f95/8660591/26d45741769c/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f95/8660591/08f7d9cebb1f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f95/8660591/588c1f1b85a2/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f95/8660591/f6ab146a69ad/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f95/8660591/80e8bd1d1b7b/gr8.jpg
摘要

严重急性呼吸综合征冠状病毒1(SARS-CoV-1)感染几乎总会引发明显症状,因此有效的病例及接触者管理使得在数月内就能有效根除该病毒。然而,严重急性呼吸综合征冠状病毒2(SARS-CoV-2)通常仅引发轻微症状,所以传播链可能会不断延伸,纳入数名个体,直至至少有一名指示病例病情严重到足以自行报告以接受诊断和治疗。在此,我们构建了简单的数学模型,以评估指示病例检测延迟对回顾性接触者追踪及管理应对措施的影响。具体而言,这些模拟结果表明:(1)接触者追踪及管理可能有效控制大多数,但并非全部在繁殖数较高的聚集点出现的大型SARS-CoV-2聚集性疫情,因为迅速扩张的传播链确保在一周或更短时间内的两个病毒代次内至少出现一例有明显症状的指示病例。(2)然而,较低的繁殖数会导致传播链更稀疏,延伸经过更长序列的未报告的无症状和症状轻微个体,通常在出现有明显症状的指示病例之前跨越三个或更多病毒代次(≥2周的传播时间)。(3)因此,并非总能完全追踪并控制如此长且稀疏的传播链,所以它们引发的社区传播在监测数据中未得到充分体现。(4)无论何处,只要监测系统薄弱和/或传播在出现明显临床症状和/或自行报告率较低的人群中发生,病例及接触者管理的有效性可能会受到更严重限制,即使在与较大规模疫情相关的较高繁殖数情况下也是如此。(5)由于被动监测平台可能特别难以检测到在低繁殖数情况下出现的更稀疏传播链,要确定消除疫情的可靠信心可能需要在整整两个月内未检测到确诊病例,在此期间必须维持推定的预防措施,以确保未检测到的残余传播完全终止。(6)通过加强对新疑似病例的现场监测来克服这些限制的空间,比通过提高诊断测试敏感性更大。(7)虽然全人群主动监测可能实现完全可追溯性和控制,但通过加强对症状轻微感染的被动监测,将易于获取的分散检测与人群对轻微症状自行报告的高度敏感性相结合,也可能实现这一目标。与SARS-CoV-1相比,控制和消除SARS-CoV-2将更依赖于推定的全人群预防措施,这需要更大的抱负、政治意愿、投资、公众支持、坚持和耐心。尽管如此,病例及接触者管理对于至少部分控制SARS-CoV-2传播,尤其是较大规模疫情,可能具有重要价值,但前提是要有足够灵敏的监测。此外,在成功消除疫情的最后阶段,通过围绕可管理的少量疫情进行重点强化监测,可能实现始终如一地完全控制传播链,从而加速并维持其终结。

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