Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort
Peter Kirwan, Victoria Hall, Sarah Foulkes, Ashley Otter, Katie Munro, Dominic Sparkes, Anna Howells, Naomi Platt, Jonathan Broad, David C. Crossman, Chris Norman, Diane Corrigan, Christopher Jackson, Michelle Cole, Colin Brown, Ana Atti, Jasmin Islam, Tracy R. Lewis, Steve Bain, Rebeccah Thomas, John Geen, Carla Pothecary, Sean Cutler, John Northfield, Cathy J. Price, Johanne Tomlinson, Sarah Knight, Emily MacNaughton, Ekaterina Watson, Rajeka Lazarus, Aaran Sinclair, Joanne Galliford, Bridgett Masunda, Tabitha Mahungu, Alison Rodger, E Hanison, Simon Warren, Swati Jain, Mariyam Mirfenderesky, Natasha Mahabir, Rowan Pritchard‐Jones, Diane Wycherley, Claire Gabriel, Elijah Matovu, Philippa Bakker, Simantee Guha, Sinead Gormley, James Pethick, Georgina Butt, Stacey Pepper, Luke Bedford, Paul Ridley, Jane Democratis, Manjula Meda, Anu Chawla, Fran Westwell, Nagesh Kalakonda, S. Khanduri, Allison Doel, Sumita Pai, Christian Hacon, Davis Nwaka, Veronica Mendez Moro, Anne Marie Moody, Cressida Auckland, Stéphanie A. Prince, Thushan I. de Silva, Helen Shulver, Abhijit Shah, Jones Ch, Banerjee Subhro-Osuji, Angela Houston, Tim Planche, Martin J. Booth, Christopher J. Duff, J Aeron‐Thomas, Ray Chaudhuri, D. R. Hilton, H Jory, Zehra'a Al-Khafaji, Philippa Kemsley, R Longfellow, David S. 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, Ken Agwuh, A. C. Grice, Kelly R. Moran
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. Funding: UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, Bristol, and others.