The temporal association of introducing and lifting non-pharmaceutical interventions with the time-varying reproduction number (R) of SARS-CoV-2: a modelling study across 131 countries.
The temporal association of introducing and lifting non-pharmaceutical interventions with the time-varying reproduction number (R) of SARS-CoV-2: a modelling study across 131 countries.
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DOI：
10.1016/s1473-3099(20)30785-4
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发表时间：
2021-03
期刊：
影响因子：
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通讯作者：
Usher Network for COVID-19 Evidence Reviews (UNCOVER) group
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作者：
Li Y;Campbell H;Kulkarni D;Harpur A;Nundy M;Wang X;Nair H;Usher Network for COVID-19 Evidence Reviews (UNCOVER) group
许多国家实施了非药物干预措施（NPI），以减少严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2）的传播，SARS-CoV-2是COVID-19的病原体。在一些取消了部分NPI的国家，COVID-19病例有所回升。我们的目的是从131个国家的广泛角度了解引入和取消NPI与SARS-CoV-2传播水平的关联，该传播水平由随时间变化的生殖数量（R）衡量。在这项建模研究中，我们将来自伦敦卫生与热带医学学院（英国伦敦）的国家级每日R估计数据与来自牛津COVID-19政府响应跟踪器的国家特定非营利组织政策数据（2020年1月1日至7月20日）相关联。我们将阶段定义为所有NPI保持不变的时间段，并根据NPI的状态将每个国家的时间轴划分为各个阶段。我们计算了R比率，即每个阶段的每日R与前一阶段最后一天（即NPI状态改变之前）的R之间的比率，作为NPI状态与SARS-CoV-2传播之间关联的度量。然后，我们使用对数线性回归对R比率进行建模，在相应的NPI变化后的前28天的每一天，将每个NPI的引入和放松作为自变量。在一项特别分析中，我们估计了重新引入具有最大效果的多个NPI的效果，并在观察到的序列中，以应对SARS-CoV-2可能的复苏。来自131个国家的790个阶段被纳入分析。在学校关闭、工作场所关闭、公共活动禁令、呆在家里的要求和内部行动限制的实施之后，R比率随着时间的推移呈下降趋势;与引入前最后一天相比，引入后第28天的R降低了3%至24%，尽管仅在公共活动禁令中降低显著（R比0.76，95% CI 0.58 - 1.00）;对于所有其他NPI，95% CI的上限均高于1。随着时间的推移，在学校关闭，禁止公共活动，禁止超过10人的公共集会，要求呆在家里，和内部行动限制的放松后，R比率呈上升趋势;与放松前的最后一天相比，放松后第28天的R增加范围为11%至25%，虽然只有在学校重新开放的情况下才有显著增加，（R比1·24，95% CI 1·00-1·52）和解除十人以上公众集会禁令（1.25，1.03 - 1.51）;对于所有其他NPI，95% CI的下限低于1。在引入NPI后中位8天（IQR 6-9）观察到R最大降低60%，在放松后甚至更长时间（17天[14-20]）观察到R最大增加60%。为应对COVID-19可能的死灰复燃，禁止十人以上公共活动和公共集会的控制策略估计会降低R，R比为0·71（95% CI 0.55 - 0.93），第28天降至0.62（0.47 - 0.82）如果增加关闭工作场所的措施，第28天为0.58（0.41 - 0.81），如果增加了关闭工作场所和内部行动限制的措施，以及0.48（0.32 - 0.71），如果增加了关闭工作场所、内部行动限制和呆在家里的要求的措施。个别NPI，包括学校关闭、工作场所关闭、公共活动禁令、禁止十人以上聚会、呆在家里的要求和内部行动限制，与减少SARS-CoV-2传播有关，但引入和取消这些NPI的效果会延迟1-3周，取消NPI时延迟时间会更长。这些研究结果提供了额外的证据，可以告知决策者关于引入和取消不同NPI的时机的决定，尽管R应该在其已知的局限性的背景下进行解释。威康信托机构战略支持基金和数据驱动创新倡议。
Non-pharmaceutical interventions (NPIs) were implemented by many countries to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19. A resurgence in COVID-19 cases has been reported in some countries that lifted some of these NPIs. We aimed to understand the association of introducing and lifting NPIs with the level of transmission of SARS-CoV-2, as measured by the time-varying reproduction number (R), from a broad perspective across 131 countries. In this modelling study, we linked data on daily country-level estimates of R from the London School of Hygiene & Tropical Medicine (London, UK) with data on country-specific policies on NPIs from the Oxford COVID-19 Government Response Tracker, available between Jan 1 and July 20, 2020. We defined a phase as a time period when all NPIs remained the same, and we divided the timeline of each country into individual phases based on the status of NPIs. We calculated the R ratio as the ratio between the daily R of each phase and the R from the last day of the previous phase (ie, before the NPI status changed) as a measure of the association between NPI status and transmission of SARS-CoV-2. We then modelled the R ratio using a log-linear regression with introduction and relaxation of each NPI as independent variables for each day of the first 28 days after the change in the corresponding NPI. In an ad-hoc analysis, we estimated the effect of reintroducing multiple NPIs with the greatest effects, and in the observed sequence, to tackle the possible resurgence of SARS-CoV-2. 790 phases from 131 countries were included in the analysis. A decreasing trend over time in the R ratio was found following the introduction of school closure, workplace closure, public events ban, requirements to stay at home, and internal movement limits; the reduction in R ranged from 3% to 24% on day 28 following the introduction compared with the last day before introduction, although the reduction was significant only for public events ban (R ratio 0·76, 95% CI 0·58–1·00); for all other NPIs, the upper bound of the 95% CI was above 1. An increasing trend over time in the R ratio was found following the relaxation of school closure, bans on public events, bans on public gatherings of more than ten people, requirements to stay at home, and internal movement limits; the increase in R ranged from 11% to 25% on day 28 following the relaxation compared with the last day before relaxation, although the increase was significant only for school reopening (R ratio 1·24, 95% CI 1·00–1·52) and lifting bans on public gatherings of more than ten people (1·25, 1·03–1·51); for all other NPIs, the lower bound of the 95% CI was below 1. It took a median of 8 days (IQR 6–9) following the introduction of an NPI to observe 60% of the maximum reduction in R and even longer (17 days [14–20]) following relaxation to observe 60% of the maximum increase in R. In response to a possible resurgence of COVID-19, a control strategy of banning public events and public gatherings of more than ten people was estimated to reduce R, with an R ratio of 0·71 (95% CI 0·55–0·93) on day 28, decreasing to 0·62 (0·47–0·82) on day 28 if measures to close workplaces were added, 0·58 (0·41–0·81) if measures to close workplaces and internal movement restrictions were added, and 0·48 (0·32–0·71) if measures to close workplaces, internal movement restrictions, and requirements to stay at home were added. Individual NPIs, including school closure, workplace closure, public events ban, ban on gatherings of more than ten people, requirements to stay at home, and internal movement limits, are associated with reduced transmission of SARS-CoV-2, but the effect of introducing and lifting these NPIs is delayed by 1–3 weeks, with this delay being longer when lifting NPIs. These findings provide additional evidence that can inform policy-maker decisions on the timing of introducing and lifting different NPIs, although R should be interpreted in the context of its known limitations. Wellcome Trust Institutional Strategic Support Fund and Data-Driven Innovation initiative.