Public Health England, London, UK
Department of Health and Social Care, London, UK.
BMJ Open. 2021 Nov 24;11(11):e056636. doi: 10.1136/bmjopen-2021-056636.
Importations of novel variants of concern (VOC), particularly B.1.617.2, have become the impetus behind recent outbreaks of SARS-CoV-2. Concerns around the impact on vaccine effectiveness, transmissibility and severity are now driving the public health response to these variants. This paper analyses the patterns of growth in hospitalisations and confirmed cases for novel VOCs by age groups, geography and ethnicity in the context of changing behaviour, non-pharmaceutical interventions (NPIs) and the UK vaccination programme. We seek to highlight where strategies have been effective and periods that have facilitated the establishment of new variants.
We have algorithmically linked the most complete testing and hospitalisation data in England to create a data set of confirmed infections and hospitalisations by SARS-CoV-2 genomic variant. We have used these linked data sets to analyse temporal, geographic and demographic distinctions.
The setting is England from October 2020 to July 2021. Participants included all COVID-19 tests that included RT-PCR CT gene target data or underwent sequencing and hospitalisations that could be linked to these tests.
To calculate the instantaneous growth rate for VOCs we have developed a generalised additive model fit to multiple splines and varying day of the week effects. We have further modelled the instantaneous reproduction number R for the B.1.1.7 and B.1.617.2 variants and included a doubly interval censored model to temporally adjust the confirmed variant cases.
We observed a clear replacement of the predominant B.1.1.7 by the B.1.617.2 variant without observing sustained exponential growth in other novel variants. Modelled exponential growth of RT PCR gene target triple-positive cases was initially detected in the youngest age groups, although we now observe across all ages a very small doubling time of 10.7 (95% CI 9.1 to 13.2) days and 8 (95% CI 6.9 to 9.1) days for cases and hospitalisations, respectively. We observe that growth in RT PCR gene target triple-positive cases was first detected in the Indian ethnicity group in late February, with a peak of 0.06 (95% CI 0.07 to 0.05) in the instantaneous growth rate, but is now maintained by the white ethnicity groups, observing a doubling time of 6.8 (95% CI 4.9 to 11) days. R analysis indicates a reproduction number advantage of 0.45 for B.1.617.2 relative to B.1.1.7, with the R value peaking at 1.85 for B.1.617.2.
Our results illustrate a clear transmission advantage for the B.1.617.2 variant and the growth in hospitalisations illustrates that this variant is able to maintain exponential growth within age groups that are largely doubly vaccinated. There are concerning signs of intermittent growth in the B.1.351 variant, reaching a 28-day doubling time peak in March 2021, although this variant is presently not showing any evidence of a transmission advantage over B.1.617.2. Step 1b of the UK national lockdown easing was sufficient to precipitate exponential growth in B.1.617.2 cases for most regions and younger adult age groups. The final stages of NPI easing appeared to have a negligible impact on the growth of B.1.617.2 with every region experiencing sustained exponential growth from step 2. Nonetheless, early targeted local NPIs appeared to markedly reduced growth of B.1.617.2. Later localised interventions, at a time of higher prevalence and greater geographic dispersion of this variant, appeared to have a negligible impact on growth.
新型变异株(VOC),尤其是 B.1.617.2 的输入已成为近期 SARS-CoV-2 爆发的动力。人们对疫苗效力、传染性和严重程度的担忧,正推动着对这些变异株的公共卫生应对。本文分析了在行为变化、非药物干预(NPIs)和英国疫苗接种计划背景下,新型 VOC 按年龄组、地理位置和族裔划分的住院和确诊病例的增长模式。我们旨在强调策略有效的地方和有利于新变异株建立的时期。
我们通过算法将英格兰最完整的检测和住院数据链接起来,创建了一个包含 SARS-CoV-2 基因组变异的确诊感染和住院的数据集。我们使用这些链接数据集来分析时间、地理和人口统计学上的区别。
地点是 2020 年 10 月至 2021 年 7 月的英格兰。参与者包括所有包含 RT-PCR CT 基因靶标数据的 COVID-19 检测或接受过测序和可与这些检测相关联的住院治疗。
为了计算 VOC 的瞬时增长率,我们开发了一个广义加性模型,拟合多个样条和变化的每周日效应。我们进一步对 B.1.1.7 和 B.1.617.2 变体的瞬时繁殖数 R 进行建模,并包括一个双重区间 censored 模型,以时间调整确诊的变体病例。
我们观察到 B.1.1.7 被 B.1.617.2 变体明显取代,而其他新型变体没有观察到持续的指数增长。虽然我们现在在所有年龄组中观察到非常小的倍增时间为 10.7(95%CI 9.1 至 13.2)天和 8(95%CI 6.9 至 9.1)天,但我们现在观察到 RT-PCR 基因目标三重阳性病例的增长率最初在最年轻的年龄组中检测到。我们观察到,在 2 月底,印度族裔群体首次检测到 RT-PCR 基因目标三重阳性病例,瞬时增长率为 0.06(95%CI 0.07 至 0.05),但现在由白人族群维持,观察到倍增时间为 6.8(95%CI 4.9 至 11)天。R 分析表明,B.1.617.2 相对于 B.1.1.7 的繁殖数优势为 0.45,B.1.617.2 的 R 值峰值为 1.85。
我们的结果表明,B.1.617.2 变体具有明显的传播优势,住院增长率表明,该变体能够在大部分双重接种的年龄组中保持指数增长。B.1.351 变体出现了令人担忧的间歇性增长迹象,在 2021 年 3 月达到了 28 天倍增时间的峰值,尽管该变体目前在传播优势方面没有超过 B.1.617.2 的迹象。英国国家封锁放松的第 1b 步足以引发大多数地区和年轻成年年龄组的 B.1.617.2 病例指数增长。最后阶段的 NPI 放松对 B.1.617.2 的增长几乎没有影响,每个地区都在持续的指数增长。尽管如此,早期有针对性的地方非药物干预措施明显减少了 B.1.617.2 的增长。后来在该变体的流行率更高和地理分布更广的时期,局部干预措施的影响微乎其微。