The Lancet Regional Health. Europe (Jan 2024)
Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohortResearch in context
- Peter D. Kirwan,
- Victoria J. Hall,
- Sarah Foulkes,
- Ashley D. Otter,
- Katie Munro,
- Dominic Sparkes,
- Anna Howells,
- Naomi Platt,
- Jonathan Broad,
- David Crossman,
- Chris Norman,
- Diane Corrigan,
- Christopher H. Jackson,
- Michelle Cole,
- Colin S. Brown,
- Ana Atti,
- Jasmin Islam,
- Anne M. Presanis,
- Andre Charlett,
- Daniela De Angelis,
- Susan Hopkins,
- Tracy Lewis,
- Steve Bain,
- Rebeccah Thomas,
- John Geen,
- Carla Pothecary,
- Sean Cutler,
- John Northfield,
- Cathy Price,
- Johanne Tomlinson,
- Sarah Knight,
- Emily Macnaughton,
- Ekaterina Watson,
- Rajeka Lazarus,
- Aaran Sinclair,
- Joanne Galliford,
- Bridgett Masunda,
- Tabitha Mahungu,
- Alison Rodger,
- Esther Hanison,
- Simon Warren,
- Swati Jain,
- Mariyam Mirfenderesky,
- Natasha Mahabir,
- Rowan Pritchard-Jones,
- Diane Wycherley,
- Claire Gabriel,
- Elijah Matovu,
- Philippa Bakker,
- Simantee Guha,
- S. Gormley,
- James Pethick,
- Georgina Butt,
- Stacey Pepper,
- Luke Bedford,
- Paul Ridley,
- Jane Democratis,
- Manjula Meda,
- Anu Chawla,
- Fran Westwell,
- Nagesh Kalakonda,
- Sheena Khanduri,
- Allison Doel,
- Sumita Pai,
- Christian Hacon,
- Davis Nwaka,
- Veronica Mendez Moro,
- A. Moody,
- Cressida Auckland,
- Stephanie Prince,
- Thushan de Silva,
- Helen Shulver,
- A. Shah,
- C. Jones,
- Banerjee Subhro-Osuji,
- Angela Houston,
- Tim Planche,
- Martin Booth,
- Christopher Duff,
- Jonnie Aeron-Thomas,
- Ray Chaudhuri,
- David Hilton,
- Hannah Jory,
- Zehra'a Al-Khafaji,
- Philippa Kemsley,
- Ruth Longfellow,
- David Boss,
- Simon Brake,
- Louise Coke,
- Ngozi Elumogo,
- Scott Latham,
- Chinari Subudhi,
- Ina Hoad,
- Claire Thomas,
- Nihil Chitalia,
- Tracy Edmunds,
- Helen Ashby,
- John Elliott,
- Beverley Wilkinson,
- Abby Rand,
- Catherine Thompson,
- K. Agwuh,
- Anna Grice,
- Kelly Moran,
- Vijayendra Waykar,
- Yvonne Lester,
- Lauren Sach,
- Kathryn Court,
- Nikki White,
- Clair Favager,
- Kyra Holliday,
- Jayne Harwood,
- Brendan Payne,
- Karen Burns,
- Lynda Fothergill,
- Alejandro Arenas-Pinto,
- Abigail Severn,
- Kerryanne Brown,
- Katherine Gray,
- Jane Dare,
- Qi Zheng,
- Kathryn Hollinshead,
- Robert Shorten,
- Alun Roebuck,
- Christopher Holmes,
- Martin Wiselka,
- Barzo Faris,
- Liane Marsh,
- Cressida Auckland,
- Clare McAdam,
- Lisa Ditchfield,
- Zaman Qazzafi,
- G. Boyd,
- N. Wong,
- Sarah Brand,
- Jack Squires,
- John Ashcroft,
- Ismaelette Del Rosario,
- Joanne Howard,
- Emma Ward,
- Gemma Harrison,
- Joely Morgan,
- Claire Corless,
- Robert Shorten,
- Ruth Penn,
- Nick Wong,
- Manny Bagary,
- Nadezda Starkova,
- Mandy Beekes,
- Mandy Carnahan,
- Shivani Khan,
- Shekoo Mackay,
- Keneisha Lewis,
- Graham Pickard,
- Joy Dawson,
- Lauren Finlayson,
- Euan Cameron,
- Anne Todd,
- Sebastien Fagegaltier,
- Sally Mavin,
- Alexandra Cochrane,
- Andrew Gibson,
- Sam Donaldson,
- Kate Templeton,
- Martin Malcolm,
- Beth Smith,
- Devesh Dhasmana,
- Susan Fowler,
- Antonia Ho,
- Michael Murphy,
- Claire Beith,
- Manish Patel,
- Elizabeth Boyd,
- Val Irvine,
- Alison Grant,
- Rebecca Temple-Purcell,
- Clodagh Loughrey,
- Elinor Hanna,
- Frances Johnston,
- Angel Boulos,
- Fiona Thompson,
- Yuri Protaschik,
- Susan Regan,
- Tracy Donaghy,
- Maurice O'Kane,
- Omolola Akinbami,
- Paola Barbero,
- Tim Brooks,
- Meera Chand,
- Ferdinando Insalata,
- Palak Joshi,
- Anne-Marie O'Connell,
- Mary Ramsay,
- Ayoub Saei,
- Maria Zambon,
- Ezra Linley,
- Simon Tonge,
- Enemona Adaji,
- Omoyeni Adebiyi,
- Nick Andrews,
- Joanna Conneely,
- Paul Conneely,
- Angela Dunne,
- Simone Dyer,
- Hannah Emmett,
- Nipunadi Hettiarachchi,
- Nishanthan Kapirial,
- Jameel Khawam,
- Edward Monk,
- Sophie Russell,
- Andrew Taylor-Kerr,
- Jean Timeyin,
- Silvia D'Arcangelo,
- Cathy Rowe,
- Amanda Semper,
- Eileen Gallagher,
- Robert Kyffin,
- Lisa Cromey,
- Desmond Areghan,
- Jennifer Bishop,
- Melanie Dembinsky,
- Laura Dobbie,
- Josie Evans,
- David Goldberg,
- Lynne Haahr,
- Annelysse Jorgenson,
- Ayodeji Matuluko,
- Laura Naismith,
- Desy Nuryunarsih,
- Alexander Olaoye,
- Caitlin Plank,
- Lesley Price,
- Nicole Sergenson,
- Sally Stewart,
- Andrew Telfer,
- Jennifer Weir,
- Ellen De Lacy,
- Yvette Ellis,
- Susannah Froude,
- Guy Stevens,
- Linda Tyson,
- Susanna Dunachie,
- Paul Klenerman,
- Chris Duncan,
- Rebecca Payne,
- Lance Turtle,
- Alex Richter,
- Thushan De Silva,
- Eleanor Barnes,
- Daniel Wootton,
- Oliver Galgut,
- Jonathan Heeney,
- Helen Baxendale,
- Javier Castillo-Olivares,
- Rupert Beale,
- Edward Carr,
- Wendy Barclay,
- Maya Moshe,
- Massimo Palmarini,
- Brian Willett,
- John Kenneth Baillie,
- Jennie Evans,
- Erika Aquino
Affiliations
- Peter D. Kirwan
- MRC Biostatistics Unit, University of Cambridge, United Kingdom; Corresponding author.
- Victoria J. Hall
- UK Health Security Agency, United Kingdom
- Sarah Foulkes
- UK Health Security Agency, United Kingdom
- Ashley D. Otter
- UK Health Security Agency, United Kingdom
- Katie Munro
- UK Health Security Agency, United Kingdom
- Dominic Sparkes
- UK Health Security Agency, United Kingdom
- Anna Howells
- UK Health Security Agency, United Kingdom
- Naomi Platt
- UK Health Security Agency, United Kingdom
- Jonathan Broad
- UK Health Security Agency, United Kingdom
- David Crossman
- School of Medicine, University of St Andrews, United Kingdom
- Chris Norman
- Health and Care Research Wales, United Kingdom
- Diane Corrigan
- Northern Ireland Public Health Agency, United Kingdom
- Christopher H. Jackson
- MRC Biostatistics Unit, University of Cambridge, United Kingdom
- Michelle Cole
- UK Health Security Agency, United Kingdom
- Colin S. Brown
- UK Health Security Agency, United Kingdom
- Ana Atti
- UK Health Security Agency, United Kingdom
- Jasmin Islam
- UK Health Security Agency, United Kingdom
- Anne M. Presanis
- MRC Biostatistics Unit, University of Cambridge, United Kingdom
- Andre Charlett
- UK Health Security Agency, United Kingdom
- Daniela De Angelis
- MRC Biostatistics Unit, University of Cambridge, United Kingdom; UK Health Security Agency, United Kingdom
- Susan Hopkins
- UK Health Security Agency, United Kingdom
- Tracy Lewis
- Steve Bain
- Rebeccah Thomas
- John Geen
- Carla Pothecary
- Sean Cutler
- John Northfield
- Cathy Price
- Johanne Tomlinson
- Sarah Knight
- Emily Macnaughton
- Ekaterina Watson
- Rajeka Lazarus
- Aaran Sinclair
- Joanne Galliford
- Bridgett Masunda
- Tabitha Mahungu
- Alison Rodger
- Esther Hanison
- Simon Warren
- Swati Jain
- Mariyam Mirfenderesky
- Natasha Mahabir
- Rowan Pritchard-Jones
- Diane Wycherley
- Claire Gabriel
- Elijah Matovu
- Philippa Bakker
- Simantee Guha
- S. Gormley
- James Pethick
- Georgina Butt
- Stacey Pepper
- Luke Bedford
- Paul Ridley
- Jane Democratis
- Manjula Meda
- Anu Chawla
- Fran Westwell
- Nagesh Kalakonda
- Sheena Khanduri
- Allison Doel
- Sumita Pai
- Christian Hacon
- Davis Nwaka
- Veronica Mendez Moro
- A. Moody
- Cressida Auckland
- Stephanie Prince
- Thushan de Silva
- Helen Shulver
- A. Shah
- C. Jones
- Banerjee Subhro-Osuji
- Angela Houston
- Tim Planche
- Martin Booth
- Christopher Duff
- Jonnie Aeron-Thomas
- Ray Chaudhuri
- David Hilton
- Hannah Jory
- Zehra'a Al-Khafaji
- Philippa Kemsley
- Ruth Longfellow
- David Boss
- Simon Brake
- Louise Coke
- Ngozi Elumogo
- Scott Latham
- Chinari Subudhi
- Ina Hoad
- Claire Thomas
- Nihil Chitalia
- Tracy Edmunds
- Helen Ashby
- John Elliott
- Beverley Wilkinson
- Abby Rand
- Catherine Thompson
- K. Agwuh
- Anna Grice
- Kelly Moran
- Vijayendra Waykar
- Yvonne Lester
- Lauren Sach
- Kathryn Court
- Nikki White
- Clair Favager
- Kyra Holliday
- Jayne Harwood
- Brendan Payne
- Karen Burns
- Lynda Fothergill
- Alejandro Arenas-Pinto
- Abigail Severn
- Kerryanne Brown
- Katherine Gray
- Jane Dare
- Qi Zheng
- Kathryn Hollinshead
- Robert Shorten
- Alun Roebuck
- Christopher Holmes
- Martin Wiselka
- Barzo Faris
- Liane Marsh
- Cressida Auckland
- Clare McAdam
- Lisa Ditchfield
- Zaman Qazzafi
- G. Boyd
- N. Wong
- Sarah Brand
- Jack Squires
- John Ashcroft
- Ismaelette Del Rosario
- Joanne Howard
- Emma Ward
- Gemma Harrison
- Joely Morgan
- Claire Corless
- Robert Shorten
- Ruth Penn
- Nick Wong
- Manny Bagary
- Nadezda Starkova
- Mandy Beekes
- Mandy Carnahan
- Shivani Khan
- Shekoo Mackay
- Keneisha Lewis
- Graham Pickard
- Joy Dawson
- Lauren Finlayson
- Euan Cameron
- Anne Todd
- Sebastien Fagegaltier
- Sally Mavin
- Alexandra Cochrane
- Andrew Gibson
- Sam Donaldson
- Kate Templeton
- Martin Malcolm
- Beth Smith
- Devesh Dhasmana
- Susan Fowler
- Antonia Ho
- Michael Murphy
- Claire Beith
- Manish Patel
- Elizabeth Boyd
- Val Irvine
- Alison Grant
- Rebecca Temple-Purcell
- Clodagh Loughrey
- Elinor Hanna
- Frances Johnston
- Angel Boulos
- Fiona Thompson
- Yuri Protaschik
- Susan Regan
- Tracy Donaghy
- Maurice O'Kane
- Omolola Akinbami
- Paola Barbero
- Tim Brooks
- Meera Chand
- Ferdinando Insalata
- Palak Joshi
- Anne-Marie O'Connell
- Mary Ramsay
- Ayoub Saei
- Maria Zambon
- Ezra Linley
- Simon Tonge
- Enemona Adaji
- Omoyeni Adebiyi
- Nick Andrews
- Joanna Conneely
- Paul Conneely
- Angela Dunne
- Simone Dyer
- Hannah Emmett
- Nipunadi Hettiarachchi
- Nishanthan Kapirial
- Jameel Khawam
- Edward Monk
- Sophie Russell
- Andrew Taylor-Kerr
- Jean Timeyin
- Silvia D'Arcangelo
- Cathy Rowe
- Amanda Semper
- Eileen Gallagher
- Robert Kyffin
- Lisa Cromey
- Desmond Areghan
- Jennifer Bishop
- Melanie Dembinsky
- Laura Dobbie
- Josie Evans
- David Goldberg
- Lynne Haahr
- Annelysse Jorgenson
- Ayodeji Matuluko
- Laura Naismith
- Desy Nuryunarsih
- Alexander Olaoye
- Caitlin Plank
- Lesley Price
- Nicole Sergenson
- Sally Stewart
- Andrew Telfer
- Jennifer Weir
- Ellen De Lacy
- Yvette Ellis
- Susannah Froude
- Guy Stevens
- Linda Tyson
- Susanna Dunachie
- Paul Klenerman
- Chris Duncan
- Rebecca Payne
- Lance Turtle
- Alex Richter
- Thushan De Silva
- Eleanor Barnes
- Daniel Wootton
- Oliver Galgut
- Jonathan Heeney
- Helen Baxendale
- Javier Castillo-Olivares
- Rupert Beale
- Edward Carr
- Wendy Barclay
- Maya Moshe
- Massimo Palmarini
- Brian Willett
- John Kenneth Baillie
- Jennie Evans
- Erika Aquino
- Journal volume & issue
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Vol. 36
p. 100809
Abstract
Summary: Background: The protection of fourth dose mRNA vaccination against SARS-CoV-2 is relevant to current global policy decisions regarding ongoing booster roll-out. We aimed to estimate the effect of fourth dose vaccination, prior infection, and duration of PCR positivity in a highly-vaccinated and largely prior-COVID-19 infected cohort of UK healthcare workers. Methods: Participants underwent fortnightly PCR and regular antibody testing for SARS-CoV-2 and completed symptoms questionnaires. A multi-state model was used to estimate vaccine effectiveness (VE) against infection from a fourth dose compared to a waned third dose, with protection from prior infection and duration of PCR positivity jointly estimated. Findings: 1298 infections were detected among 9560 individuals under active follow-up between September 2022 and March 2023. Compared to a waned third dose, fourth dose VE was 13.1% (95% CI 0.9 to 23.8) overall; 24.0% (95% CI 8.5 to 36.8) in the first 2 months post-vaccination, reducing to 10.3% (95% CI −11.4 to 27.8) and 1.7% (95% CI −17.0 to 17.4) at 2–4 and 4–6 months, respectively. Relative to an infection >2 years ago and controlling for vaccination, 63.6% (95% CI 46.9 to 75.0) and 29.1% (95% CI 3.8 to 43.1) greater protection against infection was estimated for an infection within the past 0–6, and 6–12 months, respectively. A fourth dose was associated with greater protection against asymptomatic infection than symptomatic infection, whilst prior infection independently provided more protection against symptomatic infection, particularly if the infection had occurred within the previous 6 months. Duration of PCR positivity was significantly lower for asymptomatic compared to symptomatic infection. Interpretation: Despite rapid waning of protection, vaccine boosters remain an important tool in responding to the dynamic COVID-19 landscape; boosting population immunity in advance of periods of anticipated pressure, such as surging infection rates or emerging variants of concern. Funding: UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, Bristol, and others.