COVID-19 Vaccine Waning and Effectiveness and Side Effects of Boosters: A Prospective Community Study From the ZOE COVID Study

Background: COVID-19 vaccines have greatly reduced hospitalisations and deaths. We report on waning of vaccine effectiveness and data on booster doses in a UK community setting.Methods: We measured infection rates from PCR/lateral flow tests in 614,477 individuals from the Zoe COVID Study in the 8 months after two doses of BNT162b2 (n=198,415), ChAdOx1 nCoV-19 (n=405,239) or mRNA-1273 (n=10,823). Of these, n=61,872 tested positive to SARS-Cov2. 212,216 individuals who received a booster dose by 23/11/2021 were investigated for risk of infection and systemic side effects.Findings: Vaccine effectiveness against infection decreased for all three vaccines at 5-8 months compared to one month after primary vaccination but remained above 75% and protection against hospitalisation remained high. Drops in effectiveness were larger in individuals aged 55 or older and in those with comorbidities. For BNT162b2: 83.0%[95%CI:82.0%,83.8%] in under 55s compared to 76.3% [95%CI: 74.0%,78.5%] in the older group. For ChAdOx1 nCoV-19: 76.7%[95%CI:75.9%,77.6%] in <55, compared to 67.8% [95%CI: 65.1%,70.2%] in the older group. Effectiveness for both homologous and heterologous boosters after BNT162b2 primary vaccination was above 92.5%[95%CI:86.0%,96.0%]. Heterologous boosters after ChAdOx1 nCov19 primary vaccination resulted in over 88.8%[95%CI: 84.5%,92.0%] effectiveness. Systemic side-effects after boosters (15.9% overall) were higher for heterologous than for homologous boosters (OR=1.5 [1.5, 1.6]; p < 0.0001).Interpretation: After 5 months, vaccine effectiveness remains above 76.7% for the BNT162b2, ChAdOx1 nCoV-19 and mRNA-1273 vaccines among individuals aged <55 years. Booster doses restore effectiveness. Homologous booster schedules have fewer systemic side effectsFunding Information: This work was supported by Zoe Limited via a grant from the Department of Health and Social Care. The Dept of Twin Research receives grant support from the Wellcome Trust (212904/Z/18/Z) and the Medical Research Council (MRC)/British Heart Foundation Ancestry and Biological Informative Markers for Stratification of Hypertension (AIMHY; MR/M016560/1), European Union, Chronic Disease Research Foundation (CDRF), Zoe Global Ltd, NIH and the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. CM is funded by the Chronic Disease Research Foundation. SO is funded by the Wellcome/EPSRC Centre for Medical Engineering (WT203148/Z/16/Z), Wellcome Flagship Programme (WT213038/Z/18/Z). The BMEIS is supported by the Wellcome EPSRC Centre for Medical Engineering at King’s College London (WT 203148/Z/16/Z) and the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. AMV is funded by UKRI/MRC Covid-Rapid Response grant MR/V027883/1.Declaration of Interests: TDS, AMV, CS and SO are consultants to Zoe Ltd (“Zoe”). JW, AM, LP and JC are employees of Zoe Ltd. Other authors have no conflict of interest to declare.Ethics Approval Statement: Ethical approval for use of the app for research purposes in the UK was obtained from King’s College London Ethics Committee (review reference LRS-19/20-18210), and all users provided consent for non-commercial use.