Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales

BackgroundUndervaccination (receiving fewer than the recommended number of SARS-CoV-2 vaccine doses) could be associated with increased risk of severe COVID-19 outcomes—ie, COVID-19 hospitalisation or death—compared with full vaccination (receiving the recommended number of SARS-CoV-2 vaccine doses). We sought to determine the factors associated with undervaccination, and to investigate the risk of severe COVID-19 outcomes in people who were undervaccinated in each UK nation and across the UK.MethodsWe used anonymised, harmonised electronic health record data with whole population coverage to carry out cohort studies in England, Northern Ireland, Scotland, and Wales. Participants were required to be at least 5 years of age to be included in the cohorts. We estimated adjusted odds ratios for undervaccination as of June 1, 2022. We also estimated adjusted hazard ratios (aHRs) for severe COVID-19 outcomes during the period June 1 to Sept 30, 2022, with undervaccination as a time-dependent exposure. We combined results from nation-specific analyses in a UK-wide fixed-effect meta-analysis. We estimated the reduction in severe COVID-19 outcomes associated with a counterfactual scenario in which everyone in the UK was fully vaccinated on June 1, 2022.FindingsThe numbers of people undervaccinated on June 1, 2022 were 26 985 570 (45·8%) of 58 967 360 in England, 938 420 (49·8%) of 1 885 670 in Northern Ireland, 1 709 786 (34·2%) of 4 992 498 in Scotland, and 773 850 (32·8%) of 2 358 740 in Wales. People who were younger, from more deprived backgrounds, of non-White ethnicity, or had a lower number of comorbidities were less likely to be fully vaccinated. There was a total of 40 393 severe COVID-19 outcomes in the cohorts, with 14 156 of these in undervaccinated participants. We estimated the reduction in severe COVID-19 outcomes in the UK over 4 months of follow-up associated with a counterfactual scenario in which everyone was fully vaccinated on June 1, 2022 as 210 (95% CI 94–326) in the 5–15 years age group, 1544 (1399–1689) in those aged 16–74 years, and 5426 (5340–5512) in those aged 75 years or older. aHRs for severe COVID-19 outcomes in the meta-analysis for the age group of 75 years or older were 2·70 (2·61–2·78) for one dose fewer than recommended, 3·13 (2·93–3·34) for two fewer, 3·61 (3·13–4·17) for three fewer, and 3·08 (2·89–3·29) for four fewer.InterpretationRates of undervaccination against COVID-19 ranged from 32·8% to 49·8% across the four UK nations in summer, 2022. Undervaccination was associated with an elevated risk of severe COVID-19 outcomes

Waning of first- and second-dose ChAdOx1 and BNT162b2 COVID-19 vaccinations: a pooled target trial study of 12.9 million individuals in England, Northern Ireland, Scotland and Wales

BackgroundSeveral SARS-CoV-2 vaccines have been shown to provide protection against COVID-19 hospitalization and death. However, some evidence suggests that notable waning in effectiveness against these outcomes occurs within months of vaccination. We undertook a pooled analysis across the four nations of the UK to investigate waning in vaccine effectiveness (VE) and relative vaccine effectiveness (rVE) against severe COVID-19 outcomes.MethodsWe carried out a target trial design for first/second doses of ChAdOx1(Oxford–AstraZeneca) and BNT162b2 (Pfizer–BioNTech) with a composite outcome of COVID-19 hospitalization or death over the period 8 December 2020 to 30 June 2021. Exposure groups were matched by age, local authority area and propensity for vaccination. We pooled event counts across the four UK nations.ResultsFor Doses 1 and 2 of ChAdOx1 and Dose 1 of BNT162b2, VE/rVE reached zero by approximately Days 60–80 and then went negative. By Day 70, VE/rVE was –25% (95% CI: –80 to 14) and 10% (95% CI: –32 to 39) for Doses 1 and 2 of ChAdOx1, respectively, and 42% (95% CI: 9 to 64) and 53% (95% CI: 26 to 70) for Doses 1 and 2 of BNT162b2, respectively. rVE for Dose 2 of BNT162b2 remained above zero throughout and reached 46% (95% CI: 13 to 67) after 98 days of follow-up.ConclusionsWe found strong evidence of waning in VE/rVE for Doses 1 and 2 of ChAdOx1, as well as Dose 1 of BNT162b2. This evidence may be used to inform policies on timings of additional doses of vaccine

Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals in England, Northern Ireland, Scotland, and Wales

BackgroundCurrent UK vaccination policy is to offer future COVID-19 booster doses to individuals at high risk of serious illness from COVID-19, but it is still uncertain which groups of the population could benefit most. In response to an urgent request from the UK Joint Committee on Vaccination and Immunisation, we aimed to identify risk factors for severe COVID-19 outcomes (ie, COVID-19-related hospitalisation or death) in individuals who had completed their primary COVID-19 vaccination schedule and had received the first booster vaccine.MethodsWe constructed prospective cohorts across all four UK nations through linkages of primary care, RT-PCR testing, vaccination, hospitalisation, and mortality data on 30 million people. We included individuals who received primary vaccine doses of BNT162b2 (tozinameran; Pfizer–BioNTech) or ChAdOx1 nCoV-19 (Oxford–AstraZeneca) vaccines in our initial analyses. We then restricted analyses to those given a BNT162b2 or mRNA-1273 (elasomeran; Moderna) booster and had a severe COVID-19 outcome between Dec 20, 2021, and Feb 28, 2022 (when the omicron (B.1.1.529) variant was dominant). We fitted time-dependent Poisson regression models and calculated adjusted rate ratios (aRRs) and 95% CIs for the associations between risk factors and COVID-19-related hospitalisation or death. We adjusted for a range of potential covariates, including age, sex, comorbidities, and previous SARS-CoV-2 infection. Stratified analyses were conducted by vaccine type. We then did pooled analyses across UK nations using fixed-effect meta-analyses.FindingsBetween Dec 8, 2020, and Feb 28, 2022, 16 208 600 individuals completed their primary vaccine schedule and 13 836 390 individuals received a booster dose. Between Dec 20, 2021, and Feb 28, 2022, 59 510 (0·4%) of the primary vaccine group and 26 100 (0·2%) of those who received their booster had severe COVID-19 outcomes. The risk of severe COVID-19 outcomes reduced after receiving the booster (rate change: 8·8 events per 1000 person-years to 7·6 events per 1000 person-years). Older adults (≥80 years vs 18–49 years; aRR 3·60 [95% CI 3·45–3·75]), those with comorbidities (≥5 comorbidities vs none; 9·51 [9·07–9·97]), being male (male vs female; 1·23 [1·20–1·26]), and those with certain underlying health conditions—in particular, individuals receiving immunosuppressants (yes vs no; 5·80 [5·53–6·09])—and those with chronic kidney disease (stage 5 vs no; 3·71 [2·90–4·74]) remained at high risk despite the initial booster. Individuals with a history of COVID-19 infection were at reduced risk (infected ≥9 months before booster dose vs no previous infection; aRR 0·41 [95% CI 0·29–0·58]).InterpretationOlder people, those with multimorbidity, and those with specific underlying health conditions remain at increased risk of COVID-19 hospitalisation and death after the initial vaccine booster and should, therefore, be prioritised for additional boosters, including novel optimised versions, and the increasing array of COVID-19 therapeutics

Inequalities in coverage of COVID-19 vaccination: A population register based cross-sectional study in Wales, UK

The COVID-19 pandemic has highlighted existing health inequalities for ethnic minority groups and those living in more socioeconomically deprived areas in the UK. With higher levels of severe outcomes in these groups, equitable vaccination coverage should be prioritised. The aim of this study was to identify inequalities in coverage of COVID-19 vaccination in Wales, UK and to highlight areas which may benefit from routine enhanced surveillance and targeted interventions.Records within the Wales Immunisation System (WIS) population register were linked to the Welsh Demographic Service Dataset (WDSD) and central list of shielding patients, held within the Secure Anonymised Information Linkage (SAIL) Databank. Ethnic group was derived from the 2011 census and over 20 administrative electronic health record (EHR) data sources. Uptake of first dose of any COVID-19 vaccine was analysed over time, with the odds of being vaccinated as at 25th April 2021 by sex, health board of residence, rural/urban classification, deprivation quintile and ethnic group presented. Using logistic regression models, analyses were adjusted for age group, care home resident status, health and social care worker status and shielding status.This study included 1,256,412 individuals aged 50 years and over. Vaccine coverage increased steadily from 8th December 2020 until mid-April 2021. Overall uptake of first dose of COVID-19 vaccine in this group was 92.1%. After adjustment the odds of being vaccinated were lower for individuals who were male, resident in the most deprived areas, resident in an urban area and an ethnic group other than White. The largest inequality was seen between ethnic groups, with the odds of being vaccinated 0.22 (95 %CI 0.21–0.24) if in any Black ethnic group compared to any White ethnic group.Ongoing monitoring of inequity in uptake of vaccinations is required, with better targeted interventions and engagement with deprived and ethnic communities to improve vaccination uptake

COVID-19 vaccine uptake and effectiveness in adults aged 50 years and older in Wales UK: a 1.2m population data-linkage cohort approach

Vaccination programs against COVID-19 vary globally with estimates of vaccine effectiveness (VE) affected by vaccine type, schedule, strain, outcome, and recipient characteristics. This study assessed VE of BNT162b2 and ChAdOx1 vaccines against PCR positive SARS-CoV-2 infection, hospital admission, and death among adults aged 50 years and older in Wales, UK during the period 7 December 2020 to 18 July 2021, when Alpha, followed by Delta, were the predominant variants. We used individual-level linked routinely collected data within the Secure Anonymized Information Linkage (SAIL) Databank. Data were available for 1,262,689 adults aged 50 years and over; coverage of one dose of any COVID-19 vaccine in this population was 92.6%, with coverage of two doses 90.4%. VE against PCR positive infection at 28-days or more post first dose of any COVID-19 vaccine was 16.0% (95%CI 9.6–22.0), and 42.0% (95%CI 36.5–47.1) seven or more days after a second dose. VE against hospital admission was higher at 72.9% (95%CI 63.6–79.8) 28 days or more post vaccination with one dose of any vaccine type, and 84.9% (95%CI 78.2–89.5) at 7 or more days post two doses. VE for one dose against death was estimated to be 80.9% (95%CI 72.1–86.9). VE against PCR positive infection and hospital admission was higher for BNT162b2 compared to ChAdOx1. In conclusion, vaccine uptake has been high among adults in Wales and VE estimates are encouraging, with two doses providing considerable protection against severe outcomes. Continued roll-out of the vaccination programme within Wales, and globally, is crucial in our fight against COVID-19

Uptake of COVID-19 vaccinations amongst 3,433,483 children and young people: meta-analysis of UK prospective cohorts

SARS-CoV-2 infection in children and young people (CYP) can lead to life-threatening COVID-19, transmission within households and schools, and the development of long COVID. Using linked health and administrative data, we investigated vaccine uptake among 3,433,483 CYP aged 5–17 years across all UK nations between 4th August 2021 and 31st May 2022. We constructed national cohorts and undertook multi-state modelling and meta-analysis to identify associations between demographic variables and vaccine uptake. We found that uptake of the first COVID-19 vaccine among CYP was low across all four nations compared to other age groups and diminished with subsequent doses. Age and vaccination status of adults living in the same household were identified as important risk factors associated with vaccine uptake in CYP. For example, 5–11 year-olds were less likely to receive their first vaccine compared to 16–17 year-olds (adjusted Hazard Ratio [aHR]: 0.10 (95%CI: 0.06–0.19)), and CYP in unvaccinated households were less likely to receive their first vaccine compared to CYP in partially vaccinated households (aHR: 0.19, 95%CI 0.13–0.29)

Clinical coding of long Covid in Wales: A cohort study of 3.5 million people using linked health and demographic data

Objectives ‘Long COVID’ (LC) is broadly defined as signs and symptoms that continue or develop after the acute phase of COVID-19, and can affect cardiovascular, respiratory and other organ systems. Using electronic health records, we investigated clinical coding of LC in primary and secondary care for the population of Wales. Methods We conducted a cohort study for the population of Wales, using anonymised individual-level linked data in the Secure Anonymised Information Linkage (SAIL) Databank. We used the Welsh COVID-19 e-cohort (doi:10.1136/bmjopen-2020-043010), which consists of all people (adults and children) alive and resident in Wales from 1st January 2020. To this e-cohort we linked primary and secondary care, COVID-19 testing, and ethnic group data. We then calculated the proportion of people with a LC diagnosis code (in primary and secondary care data) overall and stratified by demographic variables. Results Of 3.5m residents, 7,696 (0.2%) had a LC clinical diagnosis. Compared with the general population, a higher proportion of people with LC were female, middle age, white, and hospitalised within 28 days of a confirmed COVID-19 infection. LC affected all socioeconomic groups, as assessed using the Welsh Index of Multiple Deprivation. When looking at LC diagnosis codes in primary care, 30.9% of practices in SAIL have not used these codes at all. And the number of recorded events was low until the end of January 2021, after which there was an increase in coding. These findings are likely a substantial underestimate of LC prevalence in Wales. Earlier estimates from self-reported surveys, such as the Office for National Statistics, are much higher, ranging anywhere between 3-5%. Conclusion Low recording rates of LC and variation between practices could be due to a delay in introducing clinical coding and lack of presentation/recording. Understanding prevalence of LC is vital for addressing the scale of the problem. Therefore developing additional data-driven approaches is necessary to obtain an accurate prevalence estimate