Vaccine xxx (xxxx) xxx

Contents lists available at ScienceDirect

Vaccine
journal homepage: www.elsevier.com/locate/vaccine

COVID-19 booster vaccination uptake and infection breakthrough

amongst health care workers in Wales: A national prospective cohort
study
Stuart Bedston a,⇑, Emily Lowthian b, Christopher I. Jarvis c, Ashley Akbari d, Jillian Beggs e, Declan Bradley f,
Simon de Lusignan g, Rowena Griffiths h, Laura Herbert h, Richard Hobbs g, Steven Kerr i, Jane Lyons h,
William Midgley h, Rhiannon K. Owen h, Jennifer K. Quint j, Ruby Tsang g, Fatemeh Torabi h, Aziz Sheikh k,
Ronan A. Lyons h
a
Population Data Science, Swansea University Medical School, Faculty of Medicine, Health & Life Science, Swansea University, UK
b
Department of Education and Childhood Studies, School of Social Sciences, Swansea University, UK
c
London School of Hygiene and Tropical Medicine, UK
d
Population Data Science, Swansea University Medical School, Faculty of Medicine, Health & Life Science, Swansea University, UK
e
Usher Institute, University of Edinburgh, UK
f
Centre for Public Health, Queen’s University Belfast, Belfast, UK. And Public Health Agency, Belfast, UK
g
Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
h
Population Data Science, Swansea University Medical School, Faculty of Medicine, Health & Life Science, Swansea University, UK
i
Usher Institute, The University of Edinburgh, Edinburgh, UK
j
National Heart & Lung Institute, Faculty of Medicine, Imperial College London, UK
k
Usher Institute and HDR UK BREATHE Hub, University of Edinburgh, UK

a r t i c l e i n f o a b s t r a c t

Article history: Background: From September 2021, Health Care Workers (HCWs) in Wales began receiving a COVID-19
Received 30 November 2022 booster vaccination. This is the first dose beyond the primary vaccination schedule. Given the emergence
Received in revised form 10 January 2023 of new variants, vaccine waning vaccine, and increasing vaccination hesitancy, there is a need to under-
Accepted 11 January 2023
stand booster vaccine uptake and subsequent breakthrough in this high-risk population.
Available online xxxx
Methods: We conducted a prospective, national-scale, observational cohort study of HCWs in Wales
using anonymised, linked data from the SAIL Databank. We analysed uptake of COVID-19 booster vacci-
Keywords:
nations from September 2021 to February 2022, with comparisons against uptake of the initial primary
COVID-19
Health care workers
vaccination schedule. We also analysed booster breakthrough, in the form of PCR-confirmed SARS-Cov-2
Booster infection, comparing to the second primary dose. Cox proportional hazard models were used to estimate
Vaccination associations for vaccination uptake and breakthrough regarding staff roles, socio-demographics, house-
Uptake hold composition, and other factors.
Breakthrough Results: We derived a cohort of 73,030 HCWs living in Wales (78% female, 60% 18–49 years old). Uptake
was quickest amongst HCWs aged 60 + years old (aHR 2.54, 95%CI 2.45–2.63), compared with those aged
18–29. Asian HCWs had quicker uptake (aHR 1.18, 95%CI 1.14–1.22), whilst Black HCWs had slower
uptake (aHR 0.67, 95%CI 0.61–0.74), compared to white HCWs. HCWs residing in the least deprived areas
were slightly quicker to have received a booster dose (aHR 1.12, 95%CI 1.09–1.16), compared with those
in the most deprived areas. Strongest associations with breakthrough infections were found for those liv-
ing with children (aHR 1.52, 95%CI 1.41–1.63), compared to two-adult only households. HCWs aged

⇑ Corresponding author.
E-mail addresses: [email protected] (S. Bedston), [email protected] (E. Lowthian), [email protected] (C.I. Jarvis), A.Akbari@Swansea.
ac.uk (A. Akbari), [email protected] (J. Beggs), [email protected] (D. Bradley), [email protected] (S. de Lusignan), Rowena.Griffiths@Swansea.
ac.uk (R. Griffiths), [email protected] (L. Herbert), [email protected] (R. Hobbs), [email protected] (S. Kerr), [email protected] (J. Lyons), w.h.
[email protected] (W. Midgley), [email protected] (R.K. Owen), [email protected] (J.K. Quint), [email protected] (R. Tsang), Fatemeh.Torabi@Swan-
sea.ac.uk (F. Torabi), [email protected] (A. Sheikh), [email protected] (R.A. Lyons).

https://doi.org/10.1016/j.vaccine.2023.01.023
0264-410X/Ó 2023 The Authors. Published by Elsevier Ltd.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Please cite this article as: S. Bedston, E. Lowthian, C.I. Jarvis et al., COVID-19 booster vaccination uptake and infection breakthrough amongst health care
workers in Wales: A national prospective cohort study, Vaccine, https://doi.org/10.1016/j.vaccine.2023.01.023
S. Bedston, E. Lowthian, C.I. Jarvis et al. Vaccine xxx (xxxx) xxx

60 + years old were less likely to get breakthrough infections, compared to those aged 18–29 (aHR 0.42,
95%CI 0.38–0.47).
Conclusion: Vaccination uptake was consistently lower among black HCWs, as well as those from
deprived areas. Whilst breakthrough infections were highest in households with children.
Ó 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://
creativecommons.org/licenses/by/4.0/).

1. Introduction General Practitioner (GP) attendances, prescribed and dispensed

medications, hospital admissions, and death (Table SM2). We con-
Several COVID-19 vaccines have been shown to be safe and ducted separate analyses of uptake of the two primary doses as
highly effective against hospitalisation, to a lesser extent at pre- well as the 2021 booster dose for this cohort up to 31st January
venting infection, albeit with effectiveness waning over time [1– 2022, followed by analyses of breakthrough of the second primary
8]. As we move beyond the primary vaccination schedule and tran- and booster doses over the same time period.
sition to subsequent booster doses, effectiveness of policy becomes
determined by the willingness of individuals to receive booster
2.2. Definitions of outcomes
doses and the ability of health systems to deliver them in a timely
manner at scale. Engagement with a vaccination programme is
For uptake, our outcomes were dates of administration of avail-
complicated by the inequality, both at a structural and individual
able COVID-19 vaccinations as part of the primary-two-dose vacci-
level. In the global landscape, high-income countries have high
nation schedule and the subsequent 2021 booster vaccination.
availability of vaccines, unlike lower-income countries [1,2]. Addi-
Vaccinations available were Pfizer-BioNTech (BNT162b2), Mod-
tionally, there are also disparities in vaccine uptake across sociode-
erna (mRNA-1273) and Oxford-AstraZeneca (ChAdOx1 nCoV-19).
mographic characteristics [3–6]. Health care workers (HCWs) have
For vaccine breakthrough infections, our outcomes were dates
typically been prioritised to receive a vaccine due to their
of COVID-19 infections as determined by a positive COVID-19
increased risk of exposure to SARS-CoV-2 and their potential to
RT-PCR test. A new infection was defined at the date of a positive
transmit infection to patients [7]. It has been suggested that eth-
test with at least 90 since the previous positive test.
nicity, sentiment towards the organisation they work for, disability
status, flu vaccine uptake, social pressure, and information from
trusted sources were associated with first and second dose uptake 2.3. Cohort and sample selection
for HCWs [8,9].
In the UK, HCWs received an early primary course of a COVID- Those initially selected were recorded as being employed as a
19 vaccination. Following advice from the Joint Committee on Vac- HCW and living in Wales from 1st January 2020 to 8th December
cination and Immunisation (JCVI), administration of booster doses 2020 (Fig. 1). General exclusion criteria were applied to ensure reli-
began on 16th September 2021 [10]. To be eligible for a booster able records were being used for analysis: HCWs were included
dose, HCWs had to be at least six months post their previous dose. only if they had linked primary care (GP) records, valid vaccination
Given the timing, the majority of HCWs would have met these cri- records, and were not recorded as shielding. Sub-samples were
teria. From December 2021 onwards, the Omicron variant caused a then defined for the analyses of uptake and failure separately.
large wave of SARS-CoV-2 community infection rates in Wales. To
respond to this, in line with guidance, NHS Wales increased the
2.4. Characteristics and confounders
availability of booster dose vaccination, reduced the timing from
6 to 3 months, making it possible for all eligible groups to receive
Across both sets of uptake and breakthrough analyses, the main
a booster dose before the end of 2021, approximately 70% of the
characteristics of interest were: HCW staff group, whether working
adult population [11].
in a patient-facing role, age, sex, ethnic group, body mass index
Given the importance of the booster dose, research must attend
(BMI), number of QCovid co-morbidities [14,15], household com-
to questions around vaccine inequality and disparities among
position, and socioeconomic status (SES) at baseline. We consid-
HCWs, as well as questions around breakthrough infections (those
ered the following variables as potential confounders: urban/
who were administered a booster dose, who went on to become
rural classification of the HCW home address, number of previous
infected). Therefore, in this study, we aimed to investigate the role
PCR tests, and health board of residence (geographical NHS admin-
of socio-demographics, household composition, prior SARS-CoV-2
istrative area). Staff roles were identified as to whether they were
infection, and staff role characteristics in relation to uptake of
patient-facing, and categorised into nine groups: nursing and mid-
the booster vaccination as well as breakthrough infections for
wifery, clinical services, administrative, estates and ancillary (e.g.,
HCWs, with comparisons being to the initial two-dose primary
porter, security, housekeeping, catering), medical and dental, allied
schedule.
health professionals, technical staff, healthcare scientists, and stu-
dents. To overcome the incompleteness of the recording of ethnic-
2. Material and methods ity in any single given data source, ethnicity was identified using
multiple data sources and recorded in line with groups defined
2.1. Study design and data sources by the Office for National Statistics: White, Asian, Black, Mixed
and Other [16]. Household composition was determined using
We constructed a prospective, national-scale, observational the number of adults and children living at the same residence at
cohort study of HCWs in Wales. We used anonymised individual- baseline [17]. Socioeconomic status was defined as the Welsh
level, linked electronic health records (EHR) and administrative Index of Multiple Deprivation 2019 quintile for the HCWs area of
data sources available within the Secure Anonymised Information residence [18]. BMI was the only measure with severe missing data
Linkage (SAIL) Databank [12,13]. These data sources included NHS (47% missing based on GP records over the previous five years). For
Wales workforce records, population demographics, residential computational efficiency, we performed a single imputation of log
history, COVID-19 RT-PCR testing results, COVID-19 vaccinations, BMI, using the outcomes and the other covariates. For the uptake
2
S. Bedston, E. Lowthian, C.I. Jarvis et al. Vaccine xxx (xxxx) xxx

Fig. 1. Flow diagram of sample selection for the separate vaccine uptake and failure analyses from a cohort of 87,340 HCWs living in Wales. Discrepancies between counts are
due to rounding.

analyses only, time since previous infection was included, derived if specific subgroups had different responses to getting vaccinated
from PCR testing. after testing positive via RT-PCR, we tested for interactions
between the post-infection intervals and the other characteristics
of interest.
2.5. Statistical analysis
We analysed the rate of vaccine breakthrough also using Cox
proportional hazard modelling. Follow-up started from 14 days
We used Cox proportional hazard models to analyse the rate of
post second and booster dose. We report unadjusted and adjusted
uptake for each dose, separately. We report unadjusted and
hazard ratios (HR) with 95% confidence intervals (95%CI) based on
adjusted hazard ratios (HR) with 95% confidence intervals (CIs)
robust standard errors, stratifying the baseline by health board and
based on robust standard errors, stratifying the baseline by health
by vaccine type. Adjusted hazard ratios (aHR) were estimated by
board. Adjusted hazard ratios (aHR) were estimated by including
including main effects for all characteristics and confounders. We
main effects for all characteristics and confounders. The impact
censored participants if they were no longer employed as a HCW,
of testing positive for COVID-19 prior to vaccination was captured
moved out of Wales, died before becoming infected, or end of
using a time-varying measure, with post-infection time divided
follow-up was reached.
into intervals: 0–3, 4–7, 8–11, 12–25, 26 or more weeks. To check
3
S. Bedston, E. Lowthian, C.I. Jarvis et al. Vaccine xxx (xxxx) xxx

Table 1
Descriptive counts and column percentages of the cohort of HCWs in Wales (n = 73,030).

Characteristic n Col. %
Staff group
Nursing and midwifery registered 20,050 27.5
Add prof scientific and technical 2,470 3.4
Additional clinical services 17,470 23.9
Administrative and clerical 15,230 20.9
Allied health professionals 4,600 6.3
Estates and ancillary 6,460 8.8
Healthcare scientists 1,600 2.2
Medical and dental 5,150 7.1
Patient facing status
Patient facing 49,990 68.5
Non-patient facing 15,960 21.9
Undetermined 7,080 9.7
Sex
Female 57,170 78.3
Male 15,860 21.7
Age
18–29 9,260 12.7
30–39 16,610 22.7
40–49 17,950 24.6
50–59 21,180 29.0
60+ 8,030 11.0
Ethnicity
White 67,580 92.5
Asian 3,720 5.1
Mixed 740 1.0
Other 360 0.5
Black 590 0.8
Unknown 50 0.1
Number of co-morbidities
0 47,300 64.8
1 19,950 27.3
2+ 5,770 7.9
BMI
<18.5 1,350 1.8
18.5–24.9 22,010 30.1
25.0–29.9 23,640 32.4
30.0–34.9 15,670 21.5
35.0–39.9 6,860 9.4
40.0+ 3,500 4.8
Household composition
1 adult 6,580 9.0
2 adults 15,130 20.7
3 + adults 19,700 27.0
1 adult, 1 + children 3,970 5.4
2 adults, 1 + children 17,490 23.9
3 + adults, 1 + children 10,160 13.9
Area of deprivation quintile
1 - Most deprived 10,990 15.1
2 14,120 19.3
3 13,980 19.1
4 15,170 20.8
5 - Least deprived 18,760 25.7
Urban/rural classification
Urban city and town 53,950 73.9
Rural town and fringe 11,450 15.7
Rural village and dispersed 7,620 10.4
Weeks since previous infection at 8th Dec 2020
Uninfected 64,530 71.3
0–3 weeks 6,060 6.7
4–7 weeks 7,500 8.3
8–11 weeks 4,700 5.2
12–25 weeks 2,890 3.2
26 + weeks 4,840 5.3
Number of prior PCR tests
0 37,090 50.8
1 20,940 28.7
2 8,990 12.3
3 3,310 4.5
4+ 2,700 3.7
Residing health board
Aneurin Bevan 12,180 16.7
Betsi Cadwaladr 14,040 19.2
Cardiff and Vale 13,520 18.5

4
S. Bedston, E. Lowthian, C.I. Jarvis et al. Vaccine xxx (xxxx) xxx

Table 1 (continued)

Characteristic n Col. %
Cwm Taf Morgannwg 13,880 19.0
Hywel Dda 7,990 10.9
Powys 740 1.0
Swansea Bay 10,680 14.6

Fig. 2. Weekly frequencies of (a) vaccine uptake and (b) PCR tests for HCWs in Wales up to 28th February 2022, overlaid when each variant became dominant.

For each Cox model, we checked the assumption that hazard 3. Results
ratios were proportional over time by plotting the Schoenfeld
residuals for each coefficient. The trend lines for which are Across our cohort of 73,030 HCWs (Table 1), nursing and mid-
included in the Supplementary Material. Analysis was carried out wifery was the most common staff group (27.5%), and health care
using R v4.1.2 and the survival package [19]. scientists being the smallest group (2.2%). The majority of HCWs
were patient facing (68.5%). Most HCWs were female (78.3%), aged
2.6. Ethics and permissions between 40 and 59 (53.6%), of White ethnicity (92.5%), and have no
COVID-specific clinical risks (64.8%). Over a quarter (25.7%) were
We conducted this research within the SAIL Databank following residing in the least deprived areas of Wales, with HCWs living
permission and approval of the independent Information Gover- in households of three or more adults being the most common
nance Review Panel (IGRP) project number 0911. arrangement (27.0%), next were households of two adults with
one or more children (23.9%), and a small proportion living alone
2.7. Reporting
with a child (5.4%).
Vaccination of HCWs began in early December (Fig. 2a), with
We used the Strengthening the Reporting of Observational stud-
two peaks for the first dose, and sharper and more rapid uptake
ies in Epidemiology (STROBE) checklist to guide our transparent
for the second and booster dose. Meanwhile mass testing became
reporting of our work [20]. Due to disclosure rules imposed by our
available from September 2020 (Fig. 2b), with both the autumn
secure and trusted research environment, counts between 1 and 9
and winter months in 2020 and 2021 showing greater testing. Sub-
have been suppressed, and counts 10 and above have been rounded
sequently, greater infection followed, with waves of positive tests
to nearest 10.
between September and January 2021.

2.8. Role of funding source

3.1. Vaccination uptake
The funding source had no involvement in data collection, study
design, data analysis, interpretation of findings or the decision to Of the 73,030 HCWs in our sample, 69,800 (95.6%) were admin-
publish. istered with their first primary dose across the 15-month study
5
S. Bedston, E. Lowthian, C.I. Jarvis et al. Vaccine xxx (xxxx) xxx

Fig. 3. Cumulative incidence of uptake for HCWs in Wales up to 28th February 2022. Observations were censored upon no longer being a HCW or they had moved out of
Wales.

window. Of the 69,560 eligible for their second dose within the (aHR 0.77, 95%CI 0.74–0.80) as well as a booster dose (aHR 0.83,
study, 68,610 (98.6%) were administered with their second dose. 95%CI 0.80–0.87), compared to those living in two-adult house-
Finally, of the 65,720 eligible, 59,960 (91.2%) were administered holds. Of those who had been infected, uptake was rare during
with a booster dose,. Cumulative incidences for each dose are the subsequent four weeks following infection (aHR 0.07, 95%CI
shown in Fig. 3.From our analysis of time to vaccination (Fig. 4), 0.06–0.08), in line with policy. However, we found a small reduc-
we found that staff groups had small variations in their uptake of tion in uptake for those who it had been at least six months since
the first and second primary doses as well as their booster dose, their previous infection (aHR 0.87, 95%CI 0.85–0.89). Finally, sev-
with the first dose showing the largest variations. The staff group eral characteristics were minimally associated with booster
with the highest likelihood of booster vaccine uptake was the Med- uptake, these included; number of co-morbidities, BMI, urban
ical and Dental group (aHR 1.15, 95%CI 1.11–1.19), with the refer- and rural classification, and number of prior PCR tests.
ence category being Nursing and Midwifery Registered staff. In
reverse, Additional Clinical Services were the least likely to be vac-
cinated with the booster vaccine (aHR 0.84, 95%CI 0.82–0.86). A 3.2. Vaccine breakthrough
clear gradient was observed across age, with the steepest gradient
being observed for the booster vaccine. Those aged 60 + were 2.54 We found that the unadjusted overall crude rate of infection
(95%CI 2.45–2.63) times more likely to be vaccinated for the boos- was greater for the booster dose compared to the second dose
ter dose compared to those aged 18–29 years. Males and had the (Table 2). However, the dominant variant transitioned from Delta
same uptake (aHR 1.00, 95%CI 0.98–1.02). HCWs of a Black ethnic to, the more transmissible [21], Omicron during the booster uptake
background were the least likely to receive a first primary dose as period (Fig. 2b), our survival analysis takes this into account
well as a booster dose, compared to White HCWs (Booster aHR (Fig. 5). Of the 63,580 HCWs who had received a second dose
0.67, 95%CI 0.61–0.74). HCWs of a Mixed ethnic background were and were considered susceptible 14 days after administration,
also less likely to receive their first primary dose and booster dose 5,820 (9.1%) became infected, at a rate of 160 per 1,000 person-
(Booster aHR 0.89 95%CI 0.82–0.97). Asian HCWs were more likely years. For the 55,560 HCWs who received a booster dose and were
to be administered with both a primary dose and booster dose susceptible, 8,500 (15.3%) became infected, a rate of 510 per 1,000
(Booster aHR 1.18, 95%CI 1.14–1.22). In addition, we observed a person-years. From our analysis (Fig. 5), characteristics associated
small socioeconomic gradient for the booster dose, whereby those with booster vaccine breakthrough were similar to those found for
in least deprived areas were more likely to have a first primary the second primary dose, with a few exceptions. Across both doses,
dose (aHR 1.25 95%CI 1.22–1.28) as well as a booster dose (aHR Nursing and Midwifery staff, along with Allied Health Professionals
1.12, 95%CI 1.09–1.16). Meanwhile, we found that single parent and Additional Clinical Service staff were found to have a slightly
households were the least likely to receive both a primary dose higher risk of breakthrough, compared to the other staff groups.
Non-patient facing HCWs had a marginally higher risk of break-
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S. Bedston, E. Lowthian, C.I. Jarvis et al. Vaccine xxx (xxxx) xxx

Fig. 4. Hazard ratios (95% confidence interval) of uptake for (a) first and (b) second dose primary dose and (c) booster dose of COVID-19 vaccinations by HCW characteristics.

through at second dose, compared to those in patient facing role lower risk of breakthrough infection at second dose (aHR 0.72,
(aHR 1.09, 95%CI 1.02–1.17), but the opposite was observed for 95%CI 0.62–0.83), compared to White HCWs.Household composi-
the booster dose (aHR 0.92, 95%CI 0.87–0.97). Regarding demo- tion showed considerable associations with vaccine breakthrough.
graphics, we found that males were associated with less break- Compared to two-adult only households, we found that house-
through than females (aHR 0.90 (0.83–0.96) and 0.84 (0.79–0.89), holds with two adults and at least one child were at increased risk
for second dose and booster, respectively). Each older age group of breakthrough infection post second primary dose (aHR 1.80, 95%
was at substantially less risk than those aged 18–29, with those CI 1.64–1.97), as well as post booster dose (aHR 1.52, 05%CI 1.41–
aged 60 + having the least risk across their second primary dose 1.63). Similar associations were found for HCWs living with chil-
(aHR 0.36, 95%CI 0.32–0.41) and their booster dose (aHR 0.43, dren by themselves or with three or more adults. Meanwhile, we
95%CI 0.37–0.49). We found few differences among ethnicity found that HCWs living alone had the same risk as those living
groups, except that HCWs with of an Asian ethnicity were at a with one other adult, and those living in a three-adult household

7
S. Bedston, E. Lowthian, C.I. Jarvis et al. Vaccine xxx (xxxx) xxx

Table 2
Descriptive counts of HCWs who had received a second dose and booster dose, alongside counts and rates of infection per 1,000 person-years.

Second dose Booster dose

Characteristic n (%) Infected (rate) n (%) Infected (rate)
Total 63,580 (100.0%) 5,820 (160) 55,560 (100.0%) 8,500 (510)
Vaccine name
PB 55,760 (87.7%) 4,620 (140) 48,910 (88.0%) 8,060 (510)
AZ 7,590 (11.9%) 1,160 (300) 40 (0.1%) –
MD 240 (0.4%) 40 (430) 6,620 (11.9%) 440 (410)
Staff group
Nursing and midwifery registered 17,400 (27.4%) 1,650 (160) 15,380 (27.7%) 2,680 (570)
Add prof scientific and technical 2,200 (3.5%) 190 (150) 1,990 (3.6%) 310 (490)
Additional clinical services 14,590 (22.9%) 1,550 (180) 12,300 (22.1%) 2,070 (560)
Administrative and clerical 13,640 (21.5%) 1,290 (170) 11,710 (21.1%) 1,390 (430)
Allied health professionals 4,090 (6.4%) 330 (140) 3,690 (6.6%) 650 (570)
Estates and ancillary 5,560 (8.8%) 400 (120) 4,910 (8.8%) 610 (390)
Healthcare scientists 1,460 (2.3%) 100 (120) 1,310 (2.4%) 190 (460)
Medical and dental 4,650 (7.3%) 290 (100) 4,270 (7.7%) 610 (440)
Patient facing status
Patient facing 43,070 (67.7%) 3,960 (160) 37,790 (68.0%) 6,220 (530)
Non-patient facing 14,200 (22.3%) 1,270 (160) 12,320 (22.2%) 1,600 (440)
Undetermined 6,320 (9.9%) 590 (170) 5,460 (9.8%) 680 (440)
Sex
Female 49,700 (78.2%) 4,780 (170) 43,130 (77.6%) 6,920 (530)
Male 13,880 (21.8%) 1,040 (130) 12,440 (22.4%) 1,580 (410)
Age
18–29 7,560 (11.9%) 1,000 (230) 5,590 (10.1%) 1,160 (780)
30–39 14,130 (22.2%) 1,780 (220) 11,500 (20.7%) 2,110 (650)
40–49 15,750 (24.8%) 1,630 (170) 14,260 (25.7%) 2,430 (560)
50–59 19,000 (29.9%) 1,130 (100) 17,860 (32.2%) 2,250 (390)
60+ 7,140 (11.2%) 280 (70) 6,360 (11.4%) 570 (270)
Ethnicity
White 58,910 (92.6%) 5,500 (160) 51,310 (92.3%) 7,850 (510)
Asian 3,270 (5.1%) 200 (100) 3,090 (5.6%) 490 (500)
Mixed 610 (1.0%) 50 (150) 510 (0.9%) 70 (440)
Other 300 (0.5%) 20 (120) 270 (0.50%) 40 (510)
Black 470 (0.7%) 50 (180) 360 (0.7%) 50 (460)
Unknown 30 (0.0%) – 20 (0.0%) –
Number of co-morbidities
0 41,240 (64.9%) 3,800 (160) 36,050 (64.9%) 5,620 (520)
1 17,290 (27.2%) 1,600 (160) 15,100 (27.2%) 2,280 (500)
2+ 5,060 (8.0%) 420 (140) 4,410 (7.9%) 600 (450)
BMI
<18.5 1,140 (1.8%) 110 (160) 950 (1.7%) 130 (470)
18.5–24.9 19,040 (29.9%) 1,800 (160) 16,120 (29.0%) 2,640 (550)
25.0–29.9 20,610 (32.4%) 1,820 (150) 18,140 (32.7%) 2,740 (500)
30.0–34.9 13,750 (21.6%) 1,240 (150) 12,200 (21.9%) 1,800 (480)
35.0–39.9 5,990 (9.%) 550 (160) 5,430 (9.8%) 770 (460)
40.0+ 3,060 (4.8%) 310 (170) 2,730 (4.9%) 420 (510)
Household composition
1 adult 5,700 (9.0%) 350 (110) 5,030 (9.1%) 540 (350)
2 adults 13,330 (21.0%) 760 (100) 11,960 (21.5%) 1,310 (350)
3 + adults 17,150 (27.0%) 1,240 (120) 15,420 (27.7%) 2,290 (480)
1 adult, 1 + children 3,330 (5.2%) 490 (250) 2,590 (4.7%) 510 (710)
2 adults, 1 + children 15,340 (24.1%) 1,970 (220) 13,130 (23.6%) 2,490 (640)
3 + adults, 1 + children 8,740 (13.7%) 1,010 (200) 7,440 (13.4%) 1,360 (610)
Area of deprivation quintile
1 - Most deprived 9,290 (14.6%) 1,000 (180) 7,900 (14.2%) 1,210 (510)
2 12,120 (19.1%) 1,230 (170) 10,450 (18.8%) 1,670 (530)
3 12,150 (19.1%) 1,110 (160) 10,500 (18.9%) 1,590 (500)
4 13,310 (20.9%) 1,100 (140) 11,740 (21.1%) 1,760 (490)
5 - Least deprived 16,710 (26.3%) 1,380 (140) 14,970 (26.9%) 2,270 (500)
Urban/rural classification
Urban city and town 46,800 (73.6%) 4,350 (160) 40,990 (73.8%) 6,450 (520)
Rural town and fringe 10,000 (15.7%) 950 (160) 8,680 (15.6%) 1,300 (490)
Rural village and dispersed 6,780 (10.7%) 520 (130) 5,900 (10.6%) 750 (410)
Number of prior PCR tests
0 32,960 (51.8%) 2,860 (150) 16,110 (29.0%) 2,030 (410)
1 18,140 (28.5%) 1,710 (160) 14,600 (26.3%) 2,120 (480)
2 7,600 (11.9%) 720 (160) 10,070 (18.1%) 1,620 (530)
3 2,710 (4.3%) 290 (180) 5,920 (10.7%) 1,030 (580)
4+ 2,180 (3.4%) 250 (190) 8,860 (15.9%) 1,710 (640)
Residing health board
Aneurin Bevan 10,550 (16.6%) 1,020 (170) 9,280 (16.7%) 1,460 (530)
Betsi Cadwaladr 12,470 (19.6%) 1,100 (150) 10,570 (19.0%) 1,460 (450)
Cardiff and Vale 12,010 (18.9%) 870 (130) 10,670 (19.2%) 1,680 (500)
Cwm Taf Morgannwg 11,890 (18.7%) 1,170 (170) 10,690 (19.2%) 1,720 (530)

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S. Bedston, E. Lowthian, C.I. Jarvis et al. Vaccine xxx (xxxx) xxx

Table 2 (continued)

Second dose Booster dose

Characteristic n (%) Infected (rate) n (%) Infected (rate)
Hywel Dda 6,910 (10.9%) 610 (150) 5,970 (10.7%) 830 (460)
Powys 660 (1.0%) 60 (140) 560 (1.0%) 80 (480)
Swansea Bay 9,090 (14.3%) 1,000 (190) 7,830 (14.1%) 1,280 (570)

Fig. 5. Hazard ratios (95% confidence interval) of infection for second primary dose and booster dose, separately.

had increased risk (aHR 1.15 (1.05–1.26) and 1.27 (1.18–1.36), for Amongst HCWs, we found no evidence of associations for
second dose and booster, respectively). breakthrough of either the second primary dose or booster dose
regarding number of co-morbidities, BMI, socio-economic status,

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S. Bedston, E. Lowthian, C.I. Jarvis et al. Vaccine xxx (xxxx) xxx

and urban/rural classification. The estimates in full are available in risk of a breakthrough infection, whereas those living alone did
Table SM4. not; however, this was only for the primary course and not booster
dose [41]. We also found that older age was associated with a
lower likelihood of a breakthrough infection for both the second
4. Discussion and booster dose. This aligns with Oster et al. (2022) who found
a much lower risk of breakthrough infections for those aged 45
We show that socio-demographics are strongly associated with and over. Studies have pointed to the benefit of the booster dose,
both uptake of COVID-19 vaccines as well as breakthrough infec- although breakthrough infections occurred, vaccinations still pro-
tions in HCWs. HCWs of a younger age and either a Black or Mixed vide important protection against infection [42,43].
ethnicity were less likely to have a COVID-19 vaccination, as were Our study benefitted from having a large cohort of HCWs over-
those residing in a more deprived area or living with children. Rel- time, and due to the SAIL Databank, were able to link to multiple
atively fewer associations were found for the second primary dose, demographic and health data sources. Nevertheless, there were also
as compared to the first primary and booster doses, we attribute several limitations: first, we did not have access to information on
this to the primary vaccination schedule being anticipated as two HCWs not directly employed by NHS Wales, for example, agency
doses and the booster programme being devised later on, as well staff, for whom exposure could be greater and potentially coming
as requiring people to book their own appointment, at a time when from more disadvantaged parts of society. Second, SES was based
compliance with social restrictions was in decline [22]. Indeed, on residing area of the HCW as we did not have access to individual
those who were residing in a household with one or more children measures of SES, such as educational qualifications or household
were more likely to be infected by SARS-CoV-2 despite being vac- income, these would have enabled a deeper understanding of
cinated with a primary, or booster course. We explore our findings socioeconomic disadvantage, with potential of identifying different
in relation to policy, practice and wider research. mechanisms within inequality structures. Thirdly, due to the data
In terms of socio-demographics, younger HCWs had a slower linkage methods and availability of primary health care in the SAIL
rate of uptake. This is a concern as unvaccinated HCWs may pose Databank, we only had access to data on approximately 84% of
a risk to vulnerable patients [23–26]. Building on this, HCWs of a HCWs in Wales. Lastly, with the exception of one coefficient, esti-
Black or Mixed ethnic group were less likely to receive a booster mated uptake amongst administrative staff, the proportional haz-
vaccination, compared with White HCWs. Historical marginalisa- ards assumption appeared to be reasonably met across all the Cox
tion of ethnic minorities, alongside previous unethical research models (Figures SM1,2,3 4,5,6). We expect the departure from pro-
and under-representation in clinical trials, may have led to low portionality is due to the way in which this group was initially
trust in government bodies, which has further reduced since the deprioritised in favour of the more patient-facing roles.
pandemic [27]. However, HCWs of an Asian background were more
likely to be vaccinated compared to White HCWs, which is in line 5. Conclusions
with other studies in terms of Chinese ethnicity [28,29], however
our study is likely to capture other Asian ethnic groups, such as Our study provides national findings that sociodemographic
Indian, Pakistani, and Bangladeshi which have been associated characteristics are associated with lower vaccination uptake in
with lower vaccine uptake [8,29]. The differences across the ethnic HCWs, along with higher risk of breakthrough infections. HCWs
groups highlight the importance of tailored vaccine hesitancy sup- who were younger, residing in a more deprived area, living with
port. Following this, we also found evidence of a small disparity for children, or of a Black or Mixed ethnicity were less likely to receive
those residing in more deprived areas, and those living with a booster vaccination. Likewise, similar characteristics were at a
children. higher risk of a breakthrough infection, particularly after the sec-
The inequality in vaccination uptake prompts the question of ond dose. We encourage governments and their respective health
how public health bodies communicate the benefits of vaccination services to improve communication with the at-risk groups identi-
to the groups with lower uptake identified in this study. Emerging fied in this study, who perhaps have low trust in government, or
research suggests that the ‘‘intention of the majority” along with are vulnerable to misinformation.
strong scientific evidence encourages young people to get vacci-
nated [30]. Moreover, qualitative research has suggested that tack-
ling misinformation may be particularly important for younger Data availability
HCWs and HCWs from ethnic minority groups [31].
Previous attempts to tackle the disparity in vaccinations have The authors do not have permission to share data.
focused on whether to make COVID-19 vaccination mandatory
for HCWs [32–35], whilst this has yet to occur in the UK [36], such Declaration of Competing Interest
mandatory vaccination does exist for other diseases. There are
challenges with either side of mandatory vaccination, as pressure The authors declare that they have no known competing finan-
to receive the vaccine can actually reduce the likelihood of uptake cial interests or personal relationships that could have appeared
[9], as well as increasing an already pressured National Health Ser- to influence the work reported in this paper.
vice [37], and would not alleviate concerns around vaccine safety
amongst the unvaccinated [38]. Hence, it is likely that building Acknowledgements
trust, and sharing factual vaccination information on clinical trials
which represent a diverse range of patients may encourage at-risk This study makes use of anonymised data held in the Secure Anon-
groups to become vaccinated against COVID-19 [39]. ymised Information Linkage (SAIL) Databank. This work uses data
In terms of vaccination breakthrough, we found that living in a provided by patients and collected by the NHS as part of their care
household with children had the largest association for an infec- and support. We would also like to acknowledge all data providers
tion. Given that most children attend school, even in periods of who make anonymised data available for research. We wish to
lockdown for key workers such as HCWs, there is a greater risk acknowledge the collaborative partnership that enabled acquisition
of transmission due to the number of close contacts in school set- and access to the de-identified data, which led to this output. The
tings [40]. Alishaq et al. (2021) also found that those living in fam- collaboration was led by the Swansea University Health Data
ily housing or sharing with non-family members had an increased Research UK team under the direction of the Welsh Government
10
S. Bedston, E. Lowthian, C.I. Jarvis et al. Vaccine xxx (xxxx) xxx

Technical Advisory Cell (TAC) and includes the following groups and Appendix A. Supplementary material
organisations: the SAIL Databank, Administrative Data Research
(ADR) Wales, Digital Health and Care Wales (DHCW), Public Health Supplementary data to this article can be found online at
Wales, NHS Shared Services Partnership (NWSSP) and the Welsh https://doi.org/10.1016/j.vaccine.2023.01.023.
Ambulance Service Trust (WAST). All research conducted has been
completed under the permission and approval of the SAIL indepen-
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