COVID-19 vaccine waning and effectiveness and side effects of boosters: a prospective community study from the ZOE COVID Study

TY - JOUR

T1 - COVID-19 vaccine waning and effectiveness and side effects of boosters

T2 - a prospective community study from the ZOE COVID Study

AU - Menni, Cristina

AU - May, Anna

AU - Polidori, Lorenzo

AU - Louca, Panayiotis

AU - Wolf, Jonathan

AU - Capdevila, Joan

AU - Hu, Christina

AU - Ourselin, Sebastien

AU - Steves, Claire

AU - Valdes, Ana M.

AU - Spector, Tim

N1 - Funding Information: This work was supported by ZOE through a grant from the UK Department of Health and Social Care. This research was funded in whole, or in part, by the Wellcome Trust (WT212904/Z/18/Z; WT203148/Z/16/Z). For the purpose of open access, the authors have applied a CC BY public copyright to any Author Accepted Manuscript version arising from this submission. TwinsUK is funded by the Wellcome Trust (212904/Z/18/Z), Medical Research Council (MRC), Versus Arthritis, EU Horizon 2020, Chronic Disease Research Foundation (CDRF), ZOE Global, and the National Institute for Health Research (NIHR) Clinical Research Network and Biomedical Research Centre based at Guy's and St Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London (London, UK). CM is funded by CDRF. AMV is funded by the UK Research and Innovation–MRC Covid-Rapid Response grant MR/V027883/1. This work was supported by core funding from the Wellcome–Engineering and Physical Sciences Research Council Centre for Medical Engineering (WT203148/Z/16/Z). This research was funded or supported by the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London and supported by the NIHR Clinical Research Facility at Guy's and St Thomas'. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the UK Department of Health. We express our sincere thanks to all the participant users of the app, including study volunteers enrolled in cohorts within the Coronavirus Pandemic Epidemiology consortium. We thank the staff of ZOE, the Department of Twin Research at King's College London, the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital (Boston, MA, USA), and researchers and staff at Lund University (Lund, Sweden) for their tireless work in contributing to the running of the study and data collection. Funding Information: This work was supported by ZOE through a grant from the UK Department of Health and Social Care. This research was funded in whole, or in part, by the Wellcome Trust (WT212904/Z/18/Z; WT203148/Z/16/Z). For the purpose of open access, the authors have applied a CC BY public copyright to any Author Accepted Manuscript version arising from this submission. TwinsUK is funded by the Wellcome Trust (212904/Z/18/Z), Medical Research Council (MRC), Versus Arthritis, EU Horizon 2020, Chronic Disease Research Foundation (CDRF), ZOE Global, and the National Institute for Health Research (NIHR) Clinical Research Network and Biomedical Research Centre based at Guy's and St Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London (London, UK). CM is funded by CDRF. AMV is funded by the UK Research and Innovation–MRC Covid-Rapid Response grant MR/V027883/1. This work was supported by core funding from the Wellcome–Engineering and Physical Sciences Research Council Centre for Medical Engineering (WT203148/Z/16/Z). This research was funded or supported by the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London and supported by the NIHR Clinical Research Facility at Guy's and St Thomas'. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the UK Department of Health. We express our sincere thanks to all the participant users of the app, including study volunteers enrolled in cohorts within the Coronavirus Pandemic Epidemiology consortium. We thank the staff of ZOE, the Department of Twin Research at King's College London, the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital (Boston, MA, USA), and researchers and staff at Lund University (Lund, Sweden) for their tireless work in contributing to the running of the study and data collection. Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

PY - 2022/7

Y1 - 2022/7

N2 - BackgroundWith the surge of new SARS-CoV-2 variants, countries have begun offering COVID-19 vaccine booster doses to high-risk groups and, more recently, to the adult population in general. However, uncertainty remains over how long primary vaccination series remain effective, the ideal timing for booster doses, and the safety of heterologous booster regimens. We aimed to investigate COVID-19 primary vaccine series effectiveness and its waning, and the safety and effectiveness of booster doses, in a UK community setting.MethodsWe used SARS-CoV-2 positivity rates in individuals from a longitudinal, prospective, community-based study (ZOE COVID Study), in which data were self-reported through an app, to assess the effectiveness of three COVID-19 vaccines (ChAdOx1 nCov19 [Oxford-AstraZeneca], BNT162b2 [Pfizer-BioNtech], and mRNA1273 [Moderna]) against infection in the 8 months after completion of primary vaccination series. In individuals receiving boosters, we investigated vaccine effectiveness and reactogenicity, by assessing 16 self-reported systemic and localised side-effects. We used multivariate Poisson regression models adjusting for confounders to estimate vaccine effectiveness.FindingsWe included 620 793 participants who received two vaccine doses (204 731 [33·0%] received BNT162b2, 405 239 [65·3%] received ChAdOx1 nCoV-19, and 10 823 [1·7%] received mRNA-1273) and subsequently had a SARS-CoV-2 test result between May 23 (chosen to exclude the period of alpha [B.1.1.7] variant dominance) and Nov 23, 2021. 62 172 (10·0%) vaccinated individuals tested positive for SARS-CoV-2 and were compared with 40 345 unvaccinated controls (6726 [16·7%] of whom tested positive). Vaccine effectiveness waned after the second dose: at 5 months, BNT162b2 effectiveness was 82·1% (95% CI 81·3–82·9), ChAdOx1 nCoV-19 effectiveness was 75·7% (74·9–76·4), and mRNA-1273 effectiveness was 84·3% (81·2–86·9). Vaccine effectiveness decreased more among individuals aged 55 years or older and among those with comorbidities. 135 932 individuals aged 55 years or older received a booster (2123 [1·6%] of whom tested positive). Vaccine effectiveness for booster doses in 0–3 months after BNT162b2 primary vaccination was higher than 92·5%, and effectiveness for heterologous boosters after ChAdOx1 nCoV-19 was at least 88·8%. For the booster reactogenicity analysis, in 317 011 participants, the most common systemic symptom was fatigue (in 31 881 [10·1%] participants) and the most common local symptom was tenderness (in 187 767 [59·2%]). Systemic side-effects were more common for heterologous schedules (32 632 [17·9%] of 182 374) than for homologous schedules (17 707 [13·2%] of 134 637; odds ratio 1·5, 95% CI 1·5–1·6, p<0·0001).InterpretationAfter 5 months, vaccine effectiveness remained high among individuals younger than 55 years. Booster doses restore vaccine effectiveness. Adverse reactions after booster doses were similar to those after the second dose. Homologous booster schedules had fewer reported systemic side-effects than heterologous boosters.FundingWellcome Trust, ZOE, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, Medical Research Council

AB - BackgroundWith the surge of new SARS-CoV-2 variants, countries have begun offering COVID-19 vaccine booster doses to high-risk groups and, more recently, to the adult population in general. However, uncertainty remains over how long primary vaccination series remain effective, the ideal timing for booster doses, and the safety of heterologous booster regimens. We aimed to investigate COVID-19 primary vaccine series effectiveness and its waning, and the safety and effectiveness of booster doses, in a UK community setting.MethodsWe used SARS-CoV-2 positivity rates in individuals from a longitudinal, prospective, community-based study (ZOE COVID Study), in which data were self-reported through an app, to assess the effectiveness of three COVID-19 vaccines (ChAdOx1 nCov19 [Oxford-AstraZeneca], BNT162b2 [Pfizer-BioNtech], and mRNA1273 [Moderna]) against infection in the 8 months after completion of primary vaccination series. In individuals receiving boosters, we investigated vaccine effectiveness and reactogenicity, by assessing 16 self-reported systemic and localised side-effects. We used multivariate Poisson regression models adjusting for confounders to estimate vaccine effectiveness.FindingsWe included 620 793 participants who received two vaccine doses (204 731 [33·0%] received BNT162b2, 405 239 [65·3%] received ChAdOx1 nCoV-19, and 10 823 [1·7%] received mRNA-1273) and subsequently had a SARS-CoV-2 test result between May 23 (chosen to exclude the period of alpha [B.1.1.7] variant dominance) and Nov 23, 2021. 62 172 (10·0%) vaccinated individuals tested positive for SARS-CoV-2 and were compared with 40 345 unvaccinated controls (6726 [16·7%] of whom tested positive). Vaccine effectiveness waned after the second dose: at 5 months, BNT162b2 effectiveness was 82·1% (95% CI 81·3–82·9), ChAdOx1 nCoV-19 effectiveness was 75·7% (74·9–76·4), and mRNA-1273 effectiveness was 84·3% (81·2–86·9). Vaccine effectiveness decreased more among individuals aged 55 years or older and among those with comorbidities. 135 932 individuals aged 55 years or older received a booster (2123 [1·6%] of whom tested positive). Vaccine effectiveness for booster doses in 0–3 months after BNT162b2 primary vaccination was higher than 92·5%, and effectiveness for heterologous boosters after ChAdOx1 nCoV-19 was at least 88·8%. For the booster reactogenicity analysis, in 317 011 participants, the most common systemic symptom was fatigue (in 31 881 [10·1%] participants) and the most common local symptom was tenderness (in 187 767 [59·2%]). Systemic side-effects were more common for heterologous schedules (32 632 [17·9%] of 182 374) than for homologous schedules (17 707 [13·2%] of 134 637; odds ratio 1·5, 95% CI 1·5–1·6, p<0·0001).InterpretationAfter 5 months, vaccine effectiveness remained high among individuals younger than 55 years. Booster doses restore vaccine effectiveness. Adverse reactions after booster doses were similar to those after the second dose. Homologous booster schedules had fewer reported systemic side-effects than heterologous boosters.FundingWellcome Trust, ZOE, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, Medical Research Council

UR - http://www.scopus.com/inward/record.url?scp=85132025189&partnerID=8YFLogxK

U2 - 10.1016/S1473-3099(22)00146-3

DO - 10.1016/S1473-3099(22)00146-3

M3 - Article

SN - 1473-3099

VL - 22

SP - 1002

EP - 1010

JO - Lancet Infectious Diseases

JF - Lancet Infectious Diseases

IS - 7

ER -