Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales

Steven Kerr; Stuart Bedston; Genevieve Cezard; Alexia Sampri; Siobhan Murphy; Declan T Bradley; Kirsty Morrison; Ashley Akbari; William Whiteley; Christopher Sullivan; Lynsey Patterson; Kamlesh Khunti; Spiros Denaxas; Thomas Bolton; Samaira Khan; Alan Keys; David Weatherill; Karen Mooney; Jan Davies; Lewis Ritchie; Jim McMenamin; Frank Kee; Angela Wood; Ronan A Lyons; Cathie Sudlow; Chris Robertson; Aziz Sheikh; The HDR UK COALESCE Consortium

doi:10.1016/S0140-6736(23)02467-4

Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales

Steven Kerr, Stuart Bedston, Genevieve Cezard, Alexia Sampri, Siobhan Murphy, Declan T Bradley, Kirsty Morrison, Ashley Akbari, William Whiteley, Christopher Sullivan, Lynsey Patterson, Kamlesh Khunti, Spiros Denaxas, Thomas Bolton, Samaira Khan, Alan Keys, David Weatherill, Karen Mooney, Jan Davies, Lewis RitchieJim McMenamin, Frank Kee, Angela Wood, Ronan A Lyons, Cathie Sudlow, Chris Robertson, Aziz Sheikh, The HDR UK COALESCE Consortium

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

Background: Undervaccination (receiving fewer than the recommended number of SARS-CoV-2 vaccine doses) could be associated with increased risk of severe COVID-19 outcomes?ie, COVID-19 hospitalisation or death?compared with full vaccination (receiving the recommended number of SARS-CoV-2 vaccine doses). We sought to determine the factors associated with undervaccination, and to investigate the risk of severe COVID-19 outcomes in people who were undervaccinated in each UK nation and across the UK.
Methods
We used anonymised, harmonised electronic health record data with whole population coverage to carry out cohort studies in England, Northern Ireland, Scotland, and Wales. Participants were required to be at least 5 years of age to be included in the cohorts. We estimated adjusted odds ratios for undervaccination as of June 1, 2022. We also estimated adjusted hazard ratios (aHRs) for severe COVID-19 outcomes during the period June 1 to Sept 30, 2022, with undervaccination as a time-dependent exposure. We combined results from nation-specific analyses in a UK-wide fixed-effect meta-analysis. We estimated the reduction in severe COVID-19 outcomes associated with a counterfactual scenario in which everyone in the UK was fully vaccinated on June 1, 2022.

Findings
The numbers of people undervaccinated on June 1, 2022 were 26 985 570 (45·8%) of 58 967 360 in England, 938 420 (49·8%) of 1 885 670 in Northern Ireland, 1 709 786 (34·2%) of 4 992 498 in Scotland, and 773 850 (32·8%) of 2 358 740 in Wales. People who were younger, from more deprived backgrounds, of non-White ethnicity, or had a lower number of comorbidities were less likely to be fully vaccinated. There was a total of 40 393 severe COVID-19 outcomes in the cohorts, with 14 156 of these in undervaccinated participants. We estimated the reduction in severe COVID-19 outcomes in the UK over 4 months of follow-up associated with a counterfactual scenario in which everyone was fully vaccinated on June 1, 2022 as 210 (95% CI 94–326) in the 5–15 years age group, 1544 (1399–1689) in those aged 16–74 years, and 5426 (5340–5512) in those aged 75 years or older. aHRs for severe COVID-19 outcomes in the meta-analysis for the age group of 75 years or older were 2·70 (2·61–2·78) for one dose fewer than recommended, 3·13 (2·93–3·34) for two fewer, 3·61 (3·13–4·17) for three fewer, and 3·08 (2·89–3·29) for four fewer.

Interpretation
Rates of undervaccination against COVID-19 ranged from 32·8% to 49·8% across the four UK nations in summer, 2022. Undervaccination was associated with an elevated risk of severe COVID-19 outcomes.

Original language	English
Journal	The Lancet
Early online date	15 Jan 2024
DOIs	https://doi.org/10.1016/S0140-6736(23)02467-4
Publication status	E-pub ahead of print - 15 Jan 2024

Bibliographical note

We thank Dave Kelly from Albasoft for his support with making primary care data available, and Lynn Morrice, Wendy Inglis Humphrey, and Laura Gonzalez Rienda for their support with project management and administration. This work uses data provided by patients and collected by the NHS as part of their care and support. We would also like to acknowledge all data providers who make anonymised data available for research. We wish to acknowledge the collaborative partnership that enabled acquisition and access to the de-identified data in Wales, which led to this output. The collaboration was led by the Swansea University Health Data Research UK team under the direction of the Welsh Government Technical Advisory Cell and includes the following groups and organisations: the Secure Anonymised Information Linkage Databank, Administrative Data Research Wales, NHS Wales Informatics Service, Public Health Wales, NHS Shared Services Partnership, and the Welsh Ambulance Service Trust. All research conducted has been completed under the permission and approval of the Secure Anonymised Information Linkage Independent Information Governance Review Panel (project number: 0911). We acknowledge the help provided by the staff of the Honest Broker Service (HBS) within the Business Services Organisation Northern Ireland (BSO). The HBS is funded by the BSO and the Department of Health. The authors alone are responsible for the interpretation of the data and any views or opinions presented are solely those of the author and do not necessarily represent those of the BSO. Research in Northern Ireland was conducted under approval by the HBS Governance Board approval number 064. KK is supported by the National Institute for Health Research Applied Research Collaboration East Midlands and Leicester Biomedical Research Centre. This work was supported by the UK Research and Innovation National Core Studies: Data and Connectivity (MC_PC_20029 or MC_PC_20058), with further support from Health Data Research UK (HDR UK), an initiative funded by UK Research and Innovation, Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities. This work was also carried out with the support of the BHF Data Science Centre at HDR UK (SP/19/3/34678). This study makes use of de-identified data held in NHS England's Secure Data Environment service for England and made available via the BHF Data Science Centre's CVD-COVID-UK/COVID-IMPACT consortium. The BHF Data Science Centre (grant No SP/19/3/34678, awarded to HDR UK) funded co-development (with NHS England) of the trusted research environment, provision of linked datasets, data access, user software licences, computational usage, and data management and wrangling support, with additional contributions from the HDR UK Data and Connectivity component of the UK Government Chief Scientific Adviser's National Core Studies programme to coordinate national COVID-19 priority research. Consortium partner organisations funded the time of contributing data analysts, biostatisticians, epidemiologists, and clinicians.

Data Availability Statement

The analysis code can be found at https://github.com/HDRUK/COALESCE. The phenotyping and analysis code in England can be found at https://github.com/BHFDSC/CCU051_01. The data that were used in this study are highly sensitive and are not available publicly.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S0140-6736(23)02467-4Licence: CC BY

Cite this

Kerr, S., Bedston, S., Cezard, G., Sampri, A., Murphy, S., Bradley, D. T., Morrison, K., Akbari, A., Whiteley, W., Sullivan, C., Patterson, L., Khunti, K., Denaxas, S., Bolton, T., Khan, S., Keys, A., Weatherill, D., Mooney, K., Davies, J., ... The HDR UK COALESCE Consortium (2024). Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales. The Lancet. Advance online publication. https://doi.org/10.1016/S0140-6736(23)02467-4

Kerr, S, Bedston, S, Cezard, G, Sampri, A, Murphy, S, Bradley, DT, Morrison, K, Akbari, A, Whiteley, W, Sullivan, C, Patterson, L, Khunti, K, Denaxas, S, Bolton, T, Khan, S, Keys, A, Weatherill, D, Mooney, K, Davies, J, Ritchie, L, McMenamin, J, Kee, F, Wood, A, Lyons, RA, Sudlow, C, Robertson, C, Sheikh, A & The HDR UK COALESCE Consortium 2024, 'Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales', The Lancet. https://doi.org/10.1016/S0140-6736(23)02467-4

@article{984a846d89a2451aa4e7d9a9f87682b8,

title = "Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales",

abstract = "Background: Undervaccination (receiving fewer than the recommended number of SARS-CoV-2 vaccine doses) could be associated with increased risk of severe COVID-19 outcomes?ie, COVID-19 hospitalisation or death?compared with full vaccination (receiving the recommended number of SARS-CoV-2 vaccine doses). We sought to determine the factors associated with undervaccination, and to investigate the risk of severe COVID-19 outcomes in people who were undervaccinated in each UK nation and across the UK.MethodsWe used anonymised, harmonised electronic health record data with whole population coverage to carry out cohort studies in England, Northern Ireland, Scotland, and Wales. Participants were required to be at least 5 years of age to be included in the cohorts. We estimated adjusted odds ratios for undervaccination as of June 1, 2022. We also estimated adjusted hazard ratios (aHRs) for severe COVID-19 outcomes during the period June 1 to Sept 30, 2022, with undervaccination as a time-dependent exposure. We combined results from nation-specific analyses in a UK-wide fixed-effect meta-analysis. We estimated the reduction in severe COVID-19 outcomes associated with a counterfactual scenario in which everyone in the UK was fully vaccinated on June 1, 2022.FindingsThe numbers of people undervaccinated on June 1, 2022 were 26 985 570 (45·8%) of 58 967 360 in England, 938 420 (49·8%) of 1 885 670 in Northern Ireland, 1 709 786 (34·2%) of 4 992 498 in Scotland, and 773 850 (32·8%) of 2 358 740 in Wales. People who were younger, from more deprived backgrounds, of non-White ethnicity, or had a lower number of comorbidities were less likely to be fully vaccinated. There was a total of 40 393 severe COVID-19 outcomes in the cohorts, with 14 156 of these in undervaccinated participants. We estimated the reduction in severe COVID-19 outcomes in the UK over 4 months of follow-up associated with a counterfactual scenario in which everyone was fully vaccinated on June 1, 2022 as 210 (95% CI 94–326) in the 5–15 years age group, 1544 (1399–1689) in those aged 16–74 years, and 5426 (5340–5512) in those aged 75 years or older. aHRs for severe COVID-19 outcomes in the meta-analysis for the age group of 75 years or older were 2·70 (2·61–2·78) for one dose fewer than recommended, 3·13 (2·93–3·34) for two fewer, 3·61 (3·13–4·17) for three fewer, and 3·08 (2·89–3·29) for four fewer.InterpretationRates of undervaccination against COVID-19 ranged from 32·8% to 49·8% across the four UK nations in summer, 2022. Undervaccination was associated with an elevated risk of severe COVID-19 outcomes.",

author = "Steven Kerr and Stuart Bedston and Genevieve Cezard and Alexia Sampri and Siobhan Murphy and Bradley, {Declan T} and Kirsty Morrison and Ashley Akbari and William Whiteley and Christopher Sullivan and Lynsey Patterson and Kamlesh Khunti and Spiros Denaxas and Thomas Bolton and Samaira Khan and Alan Keys and David Weatherill and Karen Mooney and Jan Davies and Lewis Ritchie and Jim McMenamin and Frank Kee and Angela Wood and Lyons, {Ronan A} and Cathie Sudlow and Chris Robertson and Aziz Sheikh and {The HDR UK COALESCE Consortium}",

note = "We thank Dave Kelly from Albasoft for his support with making primary care data available, and Lynn Morrice, Wendy Inglis Humphrey, and Laura Gonzalez Rienda for their support with project management and administration. This work uses data provided by patients and collected by the NHS as part of their care and support. We would also like to acknowledge all data providers who make anonymised data available for research. We wish to acknowledge the collaborative partnership that enabled acquisition and access to the de-identified data in Wales, which led to this output. The collaboration was led by the Swansea University Health Data Research UK team under the direction of the Welsh Government Technical Advisory Cell and includes the following groups and organisations: the Secure Anonymised Information Linkage Databank, Administrative Data Research Wales, NHS Wales Informatics Service, Public Health Wales, NHS Shared Services Partnership, and the Welsh Ambulance Service Trust. All research conducted has been completed under the permission and approval of the Secure Anonymised Information Linkage Independent Information Governance Review Panel (project number: 0911). We acknowledge the help provided by the staff of the Honest Broker Service (HBS) within the Business Services Organisation Northern Ireland (BSO). The HBS is funded by the BSO and the Department of Health. The authors alone are responsible for the interpretation of the data and any views or opinions presented are solely those of the author and do not necessarily represent those of the BSO. Research in Northern Ireland was conducted under approval by the HBS Governance Board approval number 064. KK is supported by the National Institute for Health Research Applied Research Collaboration East Midlands and Leicester Biomedical Research Centre. This work was supported by the UK Research and Innovation National Core Studies: Data and Connectivity (MC_PC_20029 or MC_PC_20058), with further support from Health Data Research UK (HDR UK), an initiative funded by UK Research and Innovation, Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities. This work was also carried out with the support of the BHF Data Science Centre at HDR UK (SP/19/3/34678). This study makes use of de-identified data held in NHS England's Secure Data Environment service for England and made available via the BHF Data Science Centre's CVD-COVID-UK/COVID-IMPACT consortium. The BHF Data Science Centre (grant No SP/19/3/34678, awarded to HDR UK) funded co-development (with NHS England) of the trusted research environment, provision of linked datasets, data access, user software licences, computational usage, and data management and wrangling support, with additional contributions from the HDR UK Data and Connectivity component of the UK Government Chief Scientific Adviser's National Core Studies programme to coordinate national COVID-19 priority research. Consortium partner organisations funded the time of contributing data analysts, biostatisticians, epidemiologists, and clinicians.",

year = "2024",

month = jan,

day = "15",

doi = "10.1016/S0140-6736(23)02467-4",

language = "English",

journal = "The Lancet",

issn = "0140-6736",

publisher = "ACADEMIC PRESS INC ELSEVIER SCIENCE",

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TY - JOUR

T1 - Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales

AU - Kerr, Steven

AU - Bedston, Stuart

AU - Cezard, Genevieve

AU - Sampri, Alexia

AU - Murphy, Siobhan

AU - Bradley, Declan T

AU - Morrison, Kirsty

AU - Akbari, Ashley

AU - Whiteley, William

AU - Sullivan, Christopher

AU - Patterson, Lynsey

AU - Khunti, Kamlesh

AU - Denaxas, Spiros

AU - Bolton, Thomas

AU - Khan, Samaira

AU - Keys, Alan

AU - Weatherill, David

AU - Mooney, Karen

AU - Davies, Jan

AU - Ritchie, Lewis

AU - McMenamin, Jim

AU - Kee, Frank

AU - Wood, Angela

AU - Lyons, Ronan A

AU - Sudlow, Cathie

AU - Robertson, Chris

AU - Sheikh, Aziz

AU - The HDR UK COALESCE Consortium

N1 - We thank Dave Kelly from Albasoft for his support with making primary care data available, and Lynn Morrice, Wendy Inglis Humphrey, and Laura Gonzalez Rienda for their support with project management and administration. This work uses data provided by patients and collected by the NHS as part of their care and support. We would also like to acknowledge all data providers who make anonymised data available for research. We wish to acknowledge the collaborative partnership that enabled acquisition and access to the de-identified data in Wales, which led to this output. The collaboration was led by the Swansea University Health Data Research UK team under the direction of the Welsh Government Technical Advisory Cell and includes the following groups and organisations: the Secure Anonymised Information Linkage Databank, Administrative Data Research Wales, NHS Wales Informatics Service, Public Health Wales, NHS Shared Services Partnership, and the Welsh Ambulance Service Trust. All research conducted has been completed under the permission and approval of the Secure Anonymised Information Linkage Independent Information Governance Review Panel (project number: 0911). We acknowledge the help provided by the staff of the Honest Broker Service (HBS) within the Business Services Organisation Northern Ireland (BSO). The HBS is funded by the BSO and the Department of Health. The authors alone are responsible for the interpretation of the data and any views or opinions presented are solely those of the author and do not necessarily represent those of the BSO. Research in Northern Ireland was conducted under approval by the HBS Governance Board approval number 064. KK is supported by the National Institute for Health Research Applied Research Collaboration East Midlands and Leicester Biomedical Research Centre. This work was supported by the UK Research and Innovation National Core Studies: Data and Connectivity (MC_PC_20029 or MC_PC_20058), with further support from Health Data Research UK (HDR UK), an initiative funded by UK Research and Innovation, Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities. This work was also carried out with the support of the BHF Data Science Centre at HDR UK (SP/19/3/34678). This study makes use of de-identified data held in NHS England's Secure Data Environment service for England and made available via the BHF Data Science Centre's CVD-COVID-UK/COVID-IMPACT consortium. The BHF Data Science Centre (grant No SP/19/3/34678, awarded to HDR UK) funded co-development (with NHS England) of the trusted research environment, provision of linked datasets, data access, user software licences, computational usage, and data management and wrangling support, with additional contributions from the HDR UK Data and Connectivity component of the UK Government Chief Scientific Adviser's National Core Studies programme to coordinate national COVID-19 priority research. Consortium partner organisations funded the time of contributing data analysts, biostatisticians, epidemiologists, and clinicians.

PY - 2024/1/15

Y1 - 2024/1/15

N2 - Background: Undervaccination (receiving fewer than the recommended number of SARS-CoV-2 vaccine doses) could be associated with increased risk of severe COVID-19 outcomes?ie, COVID-19 hospitalisation or death?compared with full vaccination (receiving the recommended number of SARS-CoV-2 vaccine doses). We sought to determine the factors associated with undervaccination, and to investigate the risk of severe COVID-19 outcomes in people who were undervaccinated in each UK nation and across the UK.MethodsWe used anonymised, harmonised electronic health record data with whole population coverage to carry out cohort studies in England, Northern Ireland, Scotland, and Wales. Participants were required to be at least 5 years of age to be included in the cohorts. We estimated adjusted odds ratios for undervaccination as of June 1, 2022. We also estimated adjusted hazard ratios (aHRs) for severe COVID-19 outcomes during the period June 1 to Sept 30, 2022, with undervaccination as a time-dependent exposure. We combined results from nation-specific analyses in a UK-wide fixed-effect meta-analysis. We estimated the reduction in severe COVID-19 outcomes associated with a counterfactual scenario in which everyone in the UK was fully vaccinated on June 1, 2022.FindingsThe numbers of people undervaccinated on June 1, 2022 were 26 985 570 (45·8%) of 58 967 360 in England, 938 420 (49·8%) of 1 885 670 in Northern Ireland, 1 709 786 (34·2%) of 4 992 498 in Scotland, and 773 850 (32·8%) of 2 358 740 in Wales. People who were younger, from more deprived backgrounds, of non-White ethnicity, or had a lower number of comorbidities were less likely to be fully vaccinated. There was a total of 40 393 severe COVID-19 outcomes in the cohorts, with 14 156 of these in undervaccinated participants. We estimated the reduction in severe COVID-19 outcomes in the UK over 4 months of follow-up associated with a counterfactual scenario in which everyone was fully vaccinated on June 1, 2022 as 210 (95% CI 94–326) in the 5–15 years age group, 1544 (1399–1689) in those aged 16–74 years, and 5426 (5340–5512) in those aged 75 years or older. aHRs for severe COVID-19 outcomes in the meta-analysis for the age group of 75 years or older were 2·70 (2·61–2·78) for one dose fewer than recommended, 3·13 (2·93–3·34) for two fewer, 3·61 (3·13–4·17) for three fewer, and 3·08 (2·89–3·29) for four fewer.InterpretationRates of undervaccination against COVID-19 ranged from 32·8% to 49·8% across the four UK nations in summer, 2022. Undervaccination was associated with an elevated risk of severe COVID-19 outcomes.

AB - Background: Undervaccination (receiving fewer than the recommended number of SARS-CoV-2 vaccine doses) could be associated with increased risk of severe COVID-19 outcomes?ie, COVID-19 hospitalisation or death?compared with full vaccination (receiving the recommended number of SARS-CoV-2 vaccine doses). We sought to determine the factors associated with undervaccination, and to investigate the risk of severe COVID-19 outcomes in people who were undervaccinated in each UK nation and across the UK.MethodsWe used anonymised, harmonised electronic health record data with whole population coverage to carry out cohort studies in England, Northern Ireland, Scotland, and Wales. Participants were required to be at least 5 years of age to be included in the cohorts. We estimated adjusted odds ratios for undervaccination as of June 1, 2022. We also estimated adjusted hazard ratios (aHRs) for severe COVID-19 outcomes during the period June 1 to Sept 30, 2022, with undervaccination as a time-dependent exposure. We combined results from nation-specific analyses in a UK-wide fixed-effect meta-analysis. We estimated the reduction in severe COVID-19 outcomes associated with a counterfactual scenario in which everyone in the UK was fully vaccinated on June 1, 2022.FindingsThe numbers of people undervaccinated on June 1, 2022 were 26 985 570 (45·8%) of 58 967 360 in England, 938 420 (49·8%) of 1 885 670 in Northern Ireland, 1 709 786 (34·2%) of 4 992 498 in Scotland, and 773 850 (32·8%) of 2 358 740 in Wales. People who were younger, from more deprived backgrounds, of non-White ethnicity, or had a lower number of comorbidities were less likely to be fully vaccinated. There was a total of 40 393 severe COVID-19 outcomes in the cohorts, with 14 156 of these in undervaccinated participants. We estimated the reduction in severe COVID-19 outcomes in the UK over 4 months of follow-up associated with a counterfactual scenario in which everyone was fully vaccinated on June 1, 2022 as 210 (95% CI 94–326) in the 5–15 years age group, 1544 (1399–1689) in those aged 16–74 years, and 5426 (5340–5512) in those aged 75 years or older. aHRs for severe COVID-19 outcomes in the meta-analysis for the age group of 75 years or older were 2·70 (2·61–2·78) for one dose fewer than recommended, 3·13 (2·93–3·34) for two fewer, 3·61 (3·13–4·17) for three fewer, and 3·08 (2·89–3·29) for four fewer.InterpretationRates of undervaccination against COVID-19 ranged from 32·8% to 49·8% across the four UK nations in summer, 2022. Undervaccination was associated with an elevated risk of severe COVID-19 outcomes.

U2 - 10.1016/S0140-6736(23)02467-4

DO - 10.1016/S0140-6736(23)02467-4

M3 - Article

SN - 0140-6736

JO - The Lancet

JF - The Lancet

ER -

Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales

Abstract

Bibliographical note

Data Availability Statement

UN SDGs

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