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Growth, reproduction numbers and factors affecting the spread of SARS-CoV-2 novel variants of concern in the UK from October 2020 to July 2021: a modelling analysis

OBJECTIVES: 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 pa...

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Autores principales: Ward, Thomas, Glaser, Alex, Johnsen, Alexander, Xu, Feng, Hall, Ian, Pellis, Lorenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8613669/
https://www.ncbi.nlm.nih.gov/pubmed/34819293
http://dx.doi.org/10.1136/bmjopen-2021-056636
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author Ward, Thomas
Glaser, Alex
Johnsen, Alexander
Xu, Feng
Hall, Ian
Pellis, Lorenzo
author_facet Ward, Thomas
Glaser, Alex
Johnsen, Alexander
Xu, Feng
Hall, Ian
Pellis, Lorenzo
author_sort Ward, Thomas
collection PubMed
description OBJECTIVES: 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. DESIGN: 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. SETTING AND PARTICIPANTS: 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. METHODS: 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(t) 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. RESULTS: 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(t) analysis indicates a reproduction number advantage of 0.45 for B.1.617.2 relative to B.1.1.7, with the R(t) value peaking at 1.85 for B.1.617.2. CONCLUSIONS: 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.
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spelling pubmed-86136692021-12-01 Growth, reproduction numbers and factors affecting the spread of SARS-CoV-2 novel variants of concern in the UK from October 2020 to July 2021: a modelling analysis Ward, Thomas Glaser, Alex Johnsen, Alexander Xu, Feng Hall, Ian Pellis, Lorenzo BMJ Open Epidemiology OBJECTIVES: 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. DESIGN: 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. SETTING AND PARTICIPANTS: 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. METHODS: 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(t) 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. RESULTS: 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(t) analysis indicates a reproduction number advantage of 0.45 for B.1.617.2 relative to B.1.1.7, with the R(t) value peaking at 1.85 for B.1.617.2. CONCLUSIONS: 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. BMJ Publishing Group 2021-11-24 /pmc/articles/PMC8613669/ /pubmed/34819293 http://dx.doi.org/10.1136/bmjopen-2021-056636 Text en © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Epidemiology
Ward, Thomas
Glaser, Alex
Johnsen, Alexander
Xu, Feng
Hall, Ian
Pellis, Lorenzo
Growth, reproduction numbers and factors affecting the spread of SARS-CoV-2 novel variants of concern in the UK from October 2020 to July 2021: a modelling analysis
title Growth, reproduction numbers and factors affecting the spread of SARS-CoV-2 novel variants of concern in the UK from October 2020 to July 2021: a modelling analysis
title_full Growth, reproduction numbers and factors affecting the spread of SARS-CoV-2 novel variants of concern in the UK from October 2020 to July 2021: a modelling analysis
title_fullStr Growth, reproduction numbers and factors affecting the spread of SARS-CoV-2 novel variants of concern in the UK from October 2020 to July 2021: a modelling analysis
title_full_unstemmed Growth, reproduction numbers and factors affecting the spread of SARS-CoV-2 novel variants of concern in the UK from October 2020 to July 2021: a modelling analysis
title_short Growth, reproduction numbers and factors affecting the spread of SARS-CoV-2 novel variants of concern in the UK from October 2020 to July 2021: a modelling analysis
title_sort growth, reproduction numbers and factors affecting the spread of sars-cov-2 novel variants of concern in the uk from october 2020 to july 2021: a modelling analysis
topic Epidemiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8613669/
https://www.ncbi.nlm.nih.gov/pubmed/34819293
http://dx.doi.org/10.1136/bmjopen-2021-056636
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