Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort

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; SIREN Study Group; Anne M Presanis; Andre Charlett; Daniela De Angelis; Susan Hopkins

doi:10.1016/j.lanepe.2023.100809

Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort

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, SIREN Study Group, Anne M Presanis, Andre CharlettDaniela De Angelis, Susan Hopkins

^*Corresponding author for this work

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

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Abstract

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.

Original language	English
Article number	100809
Number of pages	12
Journal	The Lancet Regional Health - Europe
Volume	36
Early online date	14 Dec 2023
DOIs	https://doi.org/10.1016/j.lanepe.2023.100809
Publication status	Published - Jan 2024

Keywords

SARS-CoV-2
Vaccine effectiveness
Asymptomatic
Symptomatic
Healthcare worker
Cohort study

UN SDGs

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

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Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort (code)
Crossman, D. C. (Creator), GitHub, 2023
https://github.com/SIREN-study/SARS-CoV-2-booster-vaccination
Dataset: Software

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Kirwan, P. D., Hall, V. J., Foulkes, S., Otter, A. D., Munro, K., Sparkes, D., Howells, A., Platt, N., Broad, J., Crossman, D., Norman, C., Corrigan, D., Jackson, C. H., Cole, M., Brown, C. S., Atti, A., Islam, J., SIREN Study Group, Presanis, A. M., ... Hopkins, S. (2024). Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort. The Lancet Regional Health - Europe, 36, Article 100809. https://doi.org/10.1016/j.lanepe.2023.100809

@article{f6a0c109df94470e842138252b072271,

title = "Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort",

abstract = "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.",

keywords = "SARS-CoV-2, Vaccine effectiveness, Asymptomatic, Symptomatic, Healthcare worker, Cohort study",

author = "Kirwan, {Peter D} and Hall, {Victoria J} and Sarah Foulkes and Otter, {Ashley D} and Katie Munro and Dominic Sparkes and Anna Howells and Naomi Platt and Jonathan Broad and David Crossman and Chris Norman and Diane Corrigan and Jackson, {Christopher H} and Michelle Cole and Brown, {Colin S} and Ana Atti and Jasmin Islam and {SIREN Study Group} and Presanis, {Anne M} and Andre Charlett and {De Angelis}, Daniela and Susan Hopkins",

note = "Funding: UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, Bristol, and others.",

year = "2024",

month = jan,

doi = "10.1016/j.lanepe.2023.100809",

language = "English",

volume = "36",

journal = "The Lancet Regional Health - Europe",

issn = "2666-7762",

publisher = "Elsevier",

}

Kirwan, PD, Hall, VJ, Foulkes, S, Otter, AD, Munro, K, Sparkes, D, Howells, A, Platt, N, Broad, J, Crossman, D, Norman, C, Corrigan, D, Jackson, CH, Cole, M, Brown, CS, Atti, A, Islam, J, SIREN Study Group, Presanis, AM, Charlett, A, De Angelis, D & Hopkins, S 2024, 'Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort', The Lancet Regional Health - Europe, vol. 36, 100809. https://doi.org/10.1016/j.lanepe.2023.100809

TY - JOUR

T1 - Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort

AU - Kirwan, Peter D

AU - Hall, Victoria J

AU - Foulkes, Sarah

AU - Otter, Ashley D

AU - Munro, Katie

AU - Sparkes, Dominic

AU - Howells, Anna

AU - Platt, Naomi

AU - Broad, Jonathan

AU - Crossman, David

AU - Norman, Chris

AU - Corrigan, Diane

AU - Jackson, Christopher H

AU - Cole, Michelle

AU - Brown, Colin S

AU - Atti, Ana

AU - Islam, Jasmin

AU - SIREN Study Group

AU - Presanis, Anne M

AU - Charlett, Andre

AU - De Angelis, Daniela

AU - Hopkins, Susan

N1 - Funding: UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, Bristol, and others.

PY - 2024/1

Y1 - 2024/1

N2 - 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.

AB - 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.

KW - SARS-CoV-2

KW - Vaccine effectiveness

KW - Asymptomatic

KW - Symptomatic

KW - Healthcare worker

KW - Cohort study

U2 - 10.1016/j.lanepe.2023.100809

DO - 10.1016/j.lanepe.2023.100809

M3 - Article

C2 - 38111727

SN - 2666-7762

VL - 36

JO - The Lancet Regional Health - Europe

JF - The Lancet Regional Health - Europe

M1 - 100809

ER -

Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort

Abstract

Keywords

UN SDGs

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Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort (code)

Cite this