Waning effectiveness of BNT162b2 and ChAdOx1 covid-19 vaccines over six months since second dose: OpenSAFELY cohort study using linked electronic health records

Abstract Objective To estimate waning of covid-19 vaccine effectiveness over six months after second dose. Design Cohort study, approved by NHS England. Setting Linked primary care, hospital, and covid-19 records within the OpenSAFELY-TPP database. Participants Adults without previous SARS-CoV-2 infection were eligible, excluding care home residents and healthcare professionals. Exposures People who had received two doses of BNT162b2 or ChAdOx1 (administered during the national vaccine rollout) were compared with unvaccinated people during six consecutive comparison periods, each of four weeks. Main outcome measures Adjusted hazard ratios for covid-19 related hospital admission, covid-19 related death, positive SARS-CoV-2 test, and non-covid-19 related death comparing vaccinated with unvaccinated people. Waning vaccine effectiveness was quantified as ratios of adjusted hazard ratios per four week period, separately for subgroups aged ≥65 years, 18-64 years and clinically vulnerable, 40-64 years, and 18-39 years. Results 1 951 866 and 3 219 349 eligible adults received two doses of BNT162b2 and ChAdOx1, respectively, and 2 422 980 remained unvaccinated. Waning of vaccine effectiveness was estimated to be similar across outcomes and vaccine brands. In the ≥65 years subgroup, ratios of adjusted hazard ratios for covid-19 related hospital admission, covid-19 related death, and positive SARS-CoV-2 test ranged from 1.19 (95% confidence interval 1.14 to 1.24)to 1.34 (1.09 to 1.64) per four weeks. Despite waning vaccine effectiveness, rates of covid-19 related hospital admission and death were substantially lower among vaccinated than unvaccinated adults up to 26 weeks after the second dose, with estimated vaccine effectiveness ≥80% for BNT162b2, and ≥75% for ChAdOx1. By weeks 23-26, rates of positive SARS-CoV-2 test in vaccinated people were similar to or higher than in unvaccinated people (adjusted hazard ratios up to 1.72 (1.11 to 2.68) for BNT162b2 and 1.86 (1.79 to 1.93) for ChAdOx1). Conclusions The rate at which estimated vaccine effectiveness waned was consistent for covid-19 related hospital admission, covid-19 related death, and positive SARS-CoV-2 test and was similar across subgroups defined by age and clinical vulnerability. If sustained to outcomes of infection with the omicron variant and to booster vaccination, these findings will facilitate scheduling of booster vaccination.


Risk group
Residents in a care home for older adults 1 Staff in a care home for older adults All those 80 years of age and over 2 Frontline health and social care workers 3 All those 75 years of age and over 4a All those 70 years of age and over 4b Individuals aged 16 to 69 in a high risk group a 5 All those 65 years of age and over 6 Individuals aged 16 to 65 years in an at-risk group a 7 All those 60 years of age and over 8 All those 55 years of age and over 1 9 All those 50 years of age and over 10 All those 40 years of age and over 11 All those 30 years of age and over 2 12 All those 18 years of age and over a See COVID-19: the green book, chapter 14a for definitions of the high-risk and at-risk groups.  At-risk A code corresponding to one or more of the following: severe obesity (BMI 40+ kg/m 2 ); learning disability including Down's syndrome; serious mental illness; chronic heart disease; chronic respiratory disease; chronic liver disease; chronic kidney disease; chronic neurological disease; diabetes; immunosuppressed (diagnosis of permenant immunosuppression or asplenia, or currently taking immunosuppresant medication). 0; 1. 15 February 2021 (eligibility date for at-rosk individuals).

JCVI group
Priority groups 2-9 are as defined by the JCVI expert advisory group, and we further define groups 10, 11 and 12 are defined as those aged 40-49, 30-39 and 18-29 years, respectively, who were not assigned to JCVI groups 4 (high risk) or 6 (at-risk).  SARS-CoV-2 tests were identified using SGSS records and based on swab date. Both polymerase chain reaction (PCR) and lateral flow tests will be included, without differentiation between symptomatic and asymptomatic infection.

Integer
Between 18 May 2020 (when widespread testing became available in England) and the earliest date of eligibility for first dose in the subgroup.

Waning vaccine effectiveness in risk-based subgroups
This subsection provides additional results for the waning of vaccine effectiveness across the four risk-based subgroups. Supplementary Table 5 gives the event counts / person-years for each subgroup, outcome and comparison period; Supplementary Tables 6  and 7 give the unadjusted and adjusted hazard ratios (respectively) for each subgroup, outcome and comparison period; Supplementary Table 8 gives the per-comparison-period ratio of adjusted hazard ratios. The unadjusted and adjusted hazard ratios are also plotted in Supplementary Figures 24, 25 and 26 for BNT162b2 vs unvaccinated, ChAdOx1 vs unvaccinated and BNT162b2 vs ChAdOx1 respectively. The unadjusted and adjusted hazard ratios with any SARS-CoV-2 test as the outcome are plotted in Supplementary         * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories.  * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories.   * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories.   * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories.  * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories. * Estimates correspond to a 1-year increase in age (or age-squared as indicated) within the given age categories.

Waning vaccine effectiveness in risk-and sex-based subgroups
This subsection provides additional results for the waning of vaccine effectiveness across eight subgroups: the four risk-based subgroups, each split into females and males. Supplementary Tables 51 and 52 give the event counts / person-years for each subgroup, outcome and comparison period for females and males respectively. Supplementary Tables 53 and 54 give the unadjusted hazard ratios for females and males respectively. Supplementary Tables 55 and 56 give the adjusted hazard ratios for females and males respectively. Supplementary Tables 57 and 58 give the per-comparison-period ratio of adjusted hazard ratios for females and males respectively. The adjusted hazard ratios are plotted in Supplementary Figures 32 and 33 for BNT162b2 vs unvaccinated and ChAdOx1 vs unvaccinated respectively. The adjusted hazard ratios with any SARS-CoV-2 test as the outcome are plotted in Supplementary Figures 34 and 35 for BNT162b2 vs unvaccinated and ChAdOx1 vs unvaccinated respectively.

Waning vaccine effectiveness in older adults
This subsection provides additional results for the waning of vaccine effectiveness across two additional subgroups: 65-74 years and 75+ years. Supplementary Table 59 gives the event counts / person-years for each subgroup, outcome and comparison period. Supplementary Tables 60 and 61 give the unadjusted and adjusted hazard ratios respectively. Supplementary Table 57 gives the per-comparison-period ratio of adjusted hazard ratios. The adjusted hazard ratios are plotted in Supplementary Figures 36 and 37 for BNT162b2 vs unvaccinated and ChAdOx1 vs unvaccinated respectively. The adjusted hazard ratios with any SARS-CoV-2 test as the outcome are plotted in Supplementary Figures 38 and 39 for BNT162b2 vs unvaccinated and ChAdOx1 vs unvaccinated respectively.