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1.
Lancet Digit Health ; 2022 Jun 08.
Article in English | MEDLINE | ID: covidwho-1882680

ABSTRACT

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK.

2.
Br J Health Psychol ; 2022 Jun 01.
Article in English | MEDLINE | ID: covidwho-1868582

ABSTRACT

OBJECTIVES: Using the Health Belief Model as a conceptual framework, we investigated the association between attitudes towards COVID-19, COVID-19 vaccinations, and vaccine hesitancy and change in these variables over a 9-month period in a UK cohort. METHODS: The COPE study cohort (n = 11,113) was recruited via an online survey at enrolment in March/April 2020. The study was advertised via the HealthWise Wales research registry and social media. Follow-up data were available for 6942 people at 3 months (June/July 2020) and 5037 at 12 months (March/April 2021) post-enrolment. Measures included demographics, perceived threat of COVID-19, perceived control, intention to accept or decline a COVID-19 vaccination, and attitudes towards vaccination. Logistic regression models were fitted cross-sectionally at 3 and 12 months to assess the association between motivational factors and vaccine hesitancy. Longitudinal changes in motivational variables for vaccine-hesitant and non-hesitant groups were examined using mixed-effect analysis of variance models. RESULTS: Fear of COVID-19, perceived susceptibility to COVID-19, and perceived personal control over COVID-19 infection transmission decreased between the 3- and 12-month surveys. Vaccine hesitancy at 12 months was independently associated with low fear of the disease and more negative attitudes towards COVID-19 vaccination. Specific barriers to COVID-19 vaccine uptake included concerns about safety and efficacy in light of its rapid development, mistrust of government and pharmaceutical companies, dislike of coercive policies, and perceived lack of relaxation in COVID-19-related restrictions as the vaccination programme progressed. CONCLUSIONS: Decreasing fear of COVID-19, perceived susceptibility to the disease, and perceptions of personal control over reducing infection-transmission may impact future COVID-19 vaccination uptake.

3.
PLoS One ; 17(5): e0267176, 2022.
Article in English | MEDLINE | ID: covidwho-1862263

ABSTRACT

BACKGROUND: Pregnancy can be a stressful time and the COVID-19 pandemic has affected all aspects of life. This study aims to investigate the pandemic impact on pregnancy experience, rates of primary childhood immunisations and the differences in birth outcomes in during 2020 to those of previous years. METHODS: Self-reported pregnancy experience: 215 expectant mothers (aged 16+) in Wales completed an online survey about their experiences of pregnancy during the pandemic. The qualitative survey data was analysed using codebook thematic analysis. Population-level birth outcomes in Wales: Stillbirths, prematurity, birth weight and Caesarean section births before (2016-2019) and during (2020) the pandemic were compared using anonymised individual-level, population-scale routine data held in the Secure Anonymised Information Linkage (SAIL) Databank. Uptake of the first three scheduled primary childhood immunisations were compared between 2019 and 2020. FINDINGS: The pandemic had a negative impact on the mental health of 71% of survey respondents, who reported anxiety, stress and loneliness; this was associated with attending scans without their partner, giving birth alone, and minimal contact with midwives. There was no significant difference in annual outcomes including gestation and birth weight, stillbirths, and Caesarean sections for infants born in 2020 compared to 2016-2019. There was an increase in late term births (≥42 weeks gestation) during the first lockdown (OR: 1.28, p = 0.019) and a decrease in moderate to late preterm births (32-36 weeks gestation) during the second lockdown (OR: 0.74, p = 0.001). Fewer babies were born in 2020 (N = 29,031) compared to 2016-2019 (average N = 32,582). All babies received their immunisations in 2020, but there were minor delays in the timings of immunisations. Those due at 8-weeks were 8% less likely to be on time (within 28-days) and at 16-weeks, they were 19% less likely to be on time. INTERPRETATION: Whilst the pandemic had a negative impact on mothers' experiences of pregnancy. Population-level data suggests that this did not translate to adverse birth outcomes for babies born during the pandemic.


Subject(s)
COVID-19 , Premature Birth , Birth Weight , COVID-19/epidemiology , Cesarean Section , Child , Communicable Disease Control , Female , Humans , Infant , Infant, Newborn , Mothers , Pandemics , Pregnancy , Premature Birth/epidemiology , Stillbirth/epidemiology , Wales/epidemiology
4.
Age Ageing ; 51(5)2022 05 01.
Article in English | MEDLINE | ID: covidwho-1821683

ABSTRACT

BACKGROUND: COVID-19 vaccinations have been prioritised for high risk individuals. AIM: Determine individual-level risk factors for care home residents testing positive for SARS-CoV-2. STUDY DESIGN: Longitudinal observational cohort study using individual-level linked data from the Secure Anonymised Information Linkage (SAIL) databank. SETTING: Fourteen thousand seven hundred and eighty-six older care home residents (aged 65+) living in Wales between 1 September 2020 and 1 May 2021. Our dataset consisted of 2,613,341 individual-level daily observations within 697 care homes. METHODS: We estimated odds ratios (ORs [95% confidence interval]) using multilevel logistic regression models. Our outcome of interest was a positive SARS-CoV-2 PCR test. We included time-dependent covariates for the estimated community positive test rate of COVID-19, hospital inpatient status, vaccination status and frailty. Additional covariates were included for age, sex and specialist care home services. RESULTS: The multivariable regression model indicated an increase in age (OR 1.01 [1.00,1.01] per year), community positive test rate (OR 1.13 [1.12,1.13] per percent increase), hospital inpatients (OR 7.40 [6.54,8.36]), and residents in care homes with non-specialist dementia care (OR 1.42 [1.01,1.99]) had an increased odds of a positive test. Having a positive test prior to the observation period (OR 0.58 [0.49,0.68]) and either one or two doses of a vaccine (0.21 [0.17,0.25] and 0.05 [0.02,0.09], respectively) were associated with a decreased odds. CONCLUSIONS: Care providers need to remain vigilant despite the vaccination rollout, and extra precautions should be taken when caring for the most vulnerable. Minimising potential COVID-19 infection for care home residents when admitted to hospital should be prioritised.


Subject(s)
COVID-19 , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/prevention & control , Humans , Length of Stay , Risk Factors , SARS-CoV-2 , Vaccination , Wales/epidemiology
5.
Br J Cancer ; 2022 May 02.
Article in English | MEDLINE | ID: covidwho-1821578

ABSTRACT

BACKGROUND: COVID-19 pandemic responses impacted behaviour and health services. We estimated the impact on incidence, stage and healthcare pathway to diagnosis for female breast, colorectal and non-small cell lung cancers at population level in Wales. METHODS: Cancer e-record and hospital admission data linkage identified adult cases, stage and healthcare pathway to diagnosis (population ~2.5 million). Using multivariate Poisson regressions, we compared 2019 and 2020 counts and estimated incidence rate ratios (IRR). RESULTS: Cases decreased 15.2% (n = -1011) overall. Female breast annual IRR was 0.81 (95% CI: 0.76-0.86, p < 0.001), colorectal 0.80 (95% CI: 0.79-0.81, p < 0.001) and non-small cell lung 0.91 (95% CI: 0.90-0.92, p < 0.001). Decreases were largest in 50-69 year olds for female breast and 80+ year olds for all cancers. Stage I female breast cancer declined 41.6%, but unknown stage increased 55.8%. Colorectal stages I-IV declined (range 26.6-29.9%), while unknown stage increased 803.6%. Colorectal Q2-2020 GP-urgent suspected cancer diagnoses decreased 50.0%, and 53.9% for non-small cell lung cancer. Annual screen-detected female breast and colorectal cancers fell 47.8% and 13.3%, respectively. Non-smal -cell lung cancer emergency presentation diagnoses increased 9.5% (Q2-2020) and 16.3% (Q3-2020). CONCLUSION: Significantly fewer cases of three common cancers were diagnosed in 2020. Detrimental impacts on outcomes varied between cancers. Ongoing surveillance with health service optimisation will be needed to mitigate impacts.

6.
PLoS One ; 16(10): e0258484, 2021.
Article in English | MEDLINE | ID: covidwho-1770697

ABSTRACT

Public perceptions of pandemic viral threats and government policies can influence adherence to containment, delay, and mitigation policies such as physical distancing, hygienic practices, use of physical barriers, uptake of testing, contact tracing, and vaccination programs. The UK COVID-19 Public Experiences (COPE) study aims to identify determinants of health behaviour using the Capability, Opportunity, Motivation (COM-B) model using a longitudinal mixed-methods approach. Here, we provide a detailed description of the demographic and self-reported health characteristics of the COPE cohort at baseline assessment, an overview of data collected, and plans for follow-up of the cohort. The COPE baseline survey was completed by 11,113 UK adult residents (18+ years of age). Baseline data collection started on the 13th of March 2020 (10-days before the introduction of the first national COVID-19 lockdown in the UK) and finished on the 13th of April 2020. Participants were recruited via the HealthWise Wales (HWW) research registry and through social media snowballing and advertising (Facebook®, Twitter®, Instagram®). Participants were predominantly female (69%), over 50 years of age (68%), identified as white (98%), and were living with their partner (68%). A large proportion (67%) had a college/university level education, and half reported a pre-existing health condition (50%). Initial follow-up plans for the cohort included in-depth surveys at 3-months and 12-months after the first UK national lockdown to assess short and medium-term effects of the pandemic on health behaviour and subjective health and well-being. Additional consent will be sought from participants at follow-up for data linkage and surveys at 18 and 24-months after the initial UK national lockdown. A large non-random sample was recruited to the COPE cohort during the early stages of the COVID-19 pandemic, which will enable longitudinal analysis of the determinants of health behaviour and changes in subjective health and well-being over the course of the pandemic.


Subject(s)
COVID-19/epidemiology , Health Behavior , Adult , Aged , COVID-19/virology , Female , Humans , Interviews as Topic , Longitudinal Studies , Male , Mental Health , Middle Aged , Pandemics , Prospective Studies , SARS-CoV-2/isolation & purification , Surveys and Questionnaires , United Kingdom/epidemiology
7.
Int J Popul Data Sci ; 5(4): 1697, 2020.
Article in English | MEDLINE | ID: covidwho-1754159

ABSTRACT

Introduction: COVID-19 risk prediction algorithms can be used to identify at-risk individuals from short-term serious adverse COVID-19 outcomes such as hospitalisation and death. It is important to validate these algorithms in different and diverse populations to help guide risk management decisions and target vaccination and treatment programs to the most vulnerable individuals in society. Objectives: To validate externally the QCOVID risk prediction algorithm that predicts mortality outcomes from COVID-19 in the adult population of Wales, UK. Methods: We conducted a retrospective cohort study using routinely collected individual-level data held in the Secure Anonymised Information Linkage (SAIL) Databank. The cohort included individuals aged between 19 and 100 years, living in Wales on 24th January 2020, registered with a SAIL-providing general practice, and followed-up to death or study end (28th July 2020). Demographic, primary and secondary healthcare, and dispensing data were used to derive all the predictor variables used to develop the published QCOVID algorithm. Mortality data were used to define time to confirmed or suspected COVID-19 death. Performance metrics, including R2 values (explained variation), Brier scores, and measures of discrimination and calibration were calculated for two periods (24th January-30th April 2020 and 1st May-28th July 2020) to assess algorithm performance. Results: 1,956,760 individuals were included. 1,192 (0.06%) and 610 (0.03%) COVID-19 deaths occurred in the first and second time periods, respectively. The algorithms fitted the Welsh data and population well, explaining 68.8% (95% CI: 66.9-70.4) of the variation in time to death, Harrell's C statistic: 0.929 (95% CI: 0.921-0.937) and D statistic: 3.036 (95% CI: 2.913-3.159) for males in the first period. Similar results were found for females and in the second time period for both sexes. Conclusions: The QCOVID algorithm developed in England can be used for public health risk management for the adult Welsh population.


Subject(s)
COVID-19 , Adult , Aged , Aged, 80 and over , Algorithms , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Wales/epidemiology , Young Adult
8.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-330024

ABSTRACT

Background: Throughout the pandemic, research, public health, and policy emphasised prediction and surveillance of excess deaths, which have mostly occurred in older individuals with underlying conditions, highlighting importance of baseline mortality risk, infection rate (IR) and pandemic-related relative risk (RR). We now use national, pre- and post-pandemic electronic health records (EHR) to develop and validate a model incorporating these factors for prediction of excess deaths. Methods: In development (Clinical Practice Research Datalink) and validation (NHS Digital Trusted Research Environment) cohorts in primary and secondary care EHR in England, we included 3·8 million and 35·1 million individuals aged ≥30 years, respectively. For model development, we predicted excess deaths using baseline one-year all-cause mortality risk and assumed RR=3 and IR=10%. For model validation, we observed number of excess deaths from March 2020 to March 2021. We used baseline mortality risk, IR and RR (assumed and observed) to predict excess deaths related to COVID-19. Findings: Among individuals with at least one high-risk condition, baseline (pre-pandemic) 1-year mortality risk at one year was 4·46% (95% CI 4·41–4·51) and 3.55% (3.54-3.57) in development and validation cohorts, respectively. In our original published model, we predicted 73,498 COVID-19 deaths over 1 year for the population of England. From 1st March 2020 to 1st March 2021, there were 127,020 observed excess deaths. Observed RR was 4·34 (4·31-4·38, 95% CI) and IR was 6·27% (6·26-6·28, 95%CI). In the validation cohort, predicted excess deaths over one year were 100,338 compared with the observed 127,020 deaths with a ratio of predicted to observed excess deaths of 0.79. We found that vaccination had a negligible effect on overall RR or IR between 1st December 2020 and 1st March 2021, compared to the likely effect of under-reported COVID-19 cases from the pre-vaccination period. Interpretation: We show that a simple, parsimonious model incorporating baseline mortality risk, one-year infection rate and relative risk of the pandemic can be used to predict excess deaths. Our analyses show that EHR could inform pandemic planning and surveillance, despite limited use in emergency preparedness to-date. Although infection dynamics are important in prediction of morbidity and mortality, future models should take greater account of underlying conditions and their associated risks. Funding Information: The British Heart Foundation Data Science Centre (grant No SP/19/3/34678, awarded to Health Data Research (HDR) UK) funded co-development (with NHS Digital) of the trusted research environment, provision of linked datasets, data access, user software licences, computational usage, and data management and wrangling support, with additional contributions from the HDR UK data and connectivity component of the UK Government Chief Scientific Adviser’s National Core Studies programme to coordinate national Covid-19 priority research. Consortium partner organisations funded the time of contributing data analysts, biostatisticians, epidemiologists, and clinicians. AB, MAM, MHD and LP were supported by research funding from AstraZeneca. AB has received funding from the National Institute for Health Research (NIHR), British Medical Association, and UK Research and Innovation. AB, SD and HH are part of the BigData@Heart Consortium, funded by the Innovative Medicines Initiative-2 Joint Undertaking under grant agreement No 116074. K.K. is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands (ARC EM) and NIHR Lifestyle BRC. Declaration of Interests: JBM and TM are employees of AstraZeneca. KK is chair of the ethnicity subgroup of the Independent Scientific Advisory Group for Emergencies (SAGE) and director of the University of Leicester Centre for Black Minority Ethnic Health. KK and AB are trustees of the South Asian Health Foundation (SAHF). CS is Director of the BHF Data Science Centre. All other authors report no competing interests. Ethics Approval Statement: Approval for the study in CPRD was granted by the Independent Scientific Advisory Committee (20_074R) of the Medicines and Healthcare products Regulatory Agency in the UK in accordance with the Declaration of Helsinki. The North East-Newcastle and North Tyneside 2 research ethics committee provided ethical approval for the CVD- COVID-UK research programme (REC No 20/NE/0161).

9.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329777

ABSTRACT

We describe our analyses of data from over 49.7 million people in England, representing near-complete coverage of the relevant population, to assess the risk of myocarditis and pericarditis following BNT162b2 and ChAdOx1 COVID-19 vaccination. A self-controlled case series (SCCS) design has previously reported increased risk of myocarditis after first ChAdOx1, BNT162b2, and mRNA-1273 dose and after second doses of mRNA COVID-19 vaccines in England. Here, we use a cohort design to estimate hazard ratios for hospitalised or fatal myocarditis/pericarditis after first and second doses of BNT162b2 and ChAdOx1 vaccinations. SCCS and cohort designs are subject to different assumptions and biases and therefore provide the opportunity for triangulation of evidence. In contrast to the findings from the SCCS approach previously reported for England, we found evidence for lower incidence of hospitalised or fatal myocarditis/pericarditis after first ChAdOx1 and BNT162b2 vaccination, as well as little evidence to suggest higher incidence of these events after second dose of either vaccination.

10.
Age Ageing ; 51(5)2022 05 01.
Article in English | MEDLINE | ID: covidwho-1740783

ABSTRACT

BACKGROUND: defining features of the COVID-19 pandemic in many countries were the tragic extent to which care home residents were affected and the difficulty in preventing the introduction and subsequent spread of infection. Management of risk in care homes requires good evidence on the most important transmission pathways. One hypothesised route at the start of the pandemic, prior to widespread testing, was the transfer of patients from hospitals that were experiencing high levels of nosocomial events. METHODS: we tested the hypothesis that hospital discharge events increased the intensity of care home cases using a national individually linked health record cohort in Wales, UK. We monitored 186,772 hospital discharge events over the period from March to July 2020, tracking individuals to 923 care homes and recording the daily case rate in the homes populated by 15,772 residents. We estimated the risk of an increase in case rates following exposure to a hospital discharge using multi-level hierarchical logistic regression and a novel stochastic Hawkes process outbreak model. FINDINGS: in regression analysis, after adjusting for care home size, we found no significant association between hospital discharge and subsequent increases in care home case numbers (odds ratio: 0.99, 95% CI: 0.82, 1.90). Risk factors for increased cases included care home size, care home resident density and provision of nursing care. Using our outbreak model, we found a significant effect of hospital discharge on the subsequent intensity of cases. However, the effect was small and considerably less than the effect of care home size, suggesting the highest risk of introduction came from interaction with the community. We estimated that approximately 1.8% of hospital discharged patients may have been infected. INTERPRETATION: there is growing evidence in the UK that the risk of transfer of COVID-19 from the high-risk hospital setting to the high-risk care home setting during the early stages of the pandemic was relatively small. Although access to testing was limited to initial symptomatic cases in each care home at this time, our results suggest that reduced numbers of discharges, selection of patients and action taken within care homes following transfer all may have contributed to the mitigation. The precise key transmission routes from the community remain to be quantified.


Subject(s)
COVID-19 , COVID-19/epidemiology , Hospitals , Humans , Nursing Homes , Pandemics/prevention & control , Patient Discharge , United Kingdom/epidemiology
11.
Br J Psychiatry ; 221(1): 417-424, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1731562

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has disproportionately affected people with mental health conditions. AIMS: We investigated the association between receiving psychotropic drugs, as an indicator of mental health conditions, and COVID-19 vaccine uptake. METHOD: We conducted a cross-sectional analysis of a prospective cohort of the Northern Ireland adult population using national linked primary care registration, vaccination, secondary care and pharmacy dispensing data. Univariable and multivariable logistic regression analyses investigated the association between anxiolytic, antidepressant, antipsychotic, and hypnotic use and COVID-19 vaccination status, accounting for age, gender, deprivation and comorbidities. Receiving any COVID-19 vaccine was the primary outcome. RESULTS: There were 1 433 814 individuals, of whom 1 166 917 received a COVID-19 vaccination. Psychotropic medications were dispensed to 267 049 people. In univariable analysis, people who received any psychotropic medication had greater odds of receiving COVID-19 vaccination: odds ratio (OR) = 1.42 (95% CI 1.41-1.44). However, after adjustment, psychotropic medication use was associated with reduced odds of vaccination (ORadj = 0.90, 95% CI 0.89-0.91). People who received anxiolytics (ORadj = 0.63, 95% CI 0.61-0.65), antipsychotics (ORadj = 0.75, 95% CI 0.73-0.78) and hypnotics (ORadj = 0.90, 95% CI 0.87-0.93) had reduced odds of being vaccinated. Antidepressant use was not associated with vaccination (ORadj = 1.02, 95% CI 1.00-1.03). CONCLUSIONS: We found significantly lower odds of vaccination in people who were receiving treatment with anxiolytic and antipsychotic medications. There is an urgent need for evidence-based, tailored vaccine support for people with mental health conditions.


Subject(s)
Anti-Anxiety Agents , Antipsychotic Agents , COVID-19 , Adult , Anti-Anxiety Agents/therapeutic use , Antidepressive Agents/therapeutic use , Antipsychotic Agents/therapeutic use , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Cross-Sectional Studies , Humans , Hypnotics and Sedatives/therapeutic use , Prospective Studies , Psychotropic Drugs/therapeutic use , Vaccination
12.
Hum Vaccin Immunother ; 18(1): 2031774, 2022 12 31.
Article in English | MEDLINE | ID: covidwho-1722106

ABSTRACT

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.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Aged , COVID-19/epidemiology , COVID-19/prevention & control , Humans , Middle Aged , SARS-CoV-2 , Wales/epidemiology
13.
PLoS One ; 17(2): e0264023, 2022.
Article in English | MEDLINE | ID: covidwho-1714774

ABSTRACT

INTRODUCTION: School-based COVID-19 mitigation strategies have greatly impacted the primary school day (children aged 3-11) including: wearing face coverings, two metre distancing, no mixing of children, and no breakfast clubs or extra-curricular activities. This study examines these mitigation measures and association with COVID-19 infection, respiratory infection, and school staff wellbeing between October to December 2020 in Wales, UK. METHODS: A school staff survey captured self-reported COVID-19 mitigation measures in the school, participant anxiety and depression, and open-text responses regarding experiences of teaching and implementing measures. These survey responses were linked to national-scale COVID-19 test results data to examine association of measures in the school and the likelihood of a positive (staff or pupil) COVID-19 case in the school (clustered by school, adjusted for school size and free school meals using logistic regression). Linkage was conducted through the SAIL (Secure Anonymised Information Linkage) Databank. RESULTS: Responses were obtained from 353 participants from 59 primary schools within 15 of 22 local authorities. Having more direct non-household contacts was associated with a higher likelihood of COVID-19 positive case in the school (1-5 contacts compared to none, OR 2.89 (1.01, 8.31)) and a trend to more self-reported cold symptoms. Staff face covering was not associated with a lower odds of school COVID-19 cases (mask vs. no covering OR 2.82 (1.11, 7.14)) and was associated with higher self-reported cold symptoms. School staff reported the impacts of wearing face coverings on teaching, including having to stand closer to pupils and raise their voices to be heard. 67.1% were not able to implement two metre social distancing from pupils. We did not find evidence that maintaining a two metre distance was associated with lower rates of COVID-19 in the school. CONCLUSIONS: Implementing, adhering to and evaluating COVID-19 mitigation guidelines is challenging in primary school settings. Our findings suggest that reducing non-household direct contacts lowers infection rates. There was no evidence that face coverings, two metre social distancing or stopping children mixing was associated with lower odds of COVID-19 or cold infection rates in the school. Primary school staff found teaching challenging during COVID-19 restrictions, especially for younger learners and those with additional learning needs.


Subject(s)
COVID-19 , Physical Distancing , SARS-CoV-2 , Schools , Students , Adolescent , Adult , COVID-19/epidemiology , COVID-19/prevention & control , Child , Humans , Male , Middle Aged , Wales/epidemiology
14.
PLoS Med ; 19(2): e1003927, 2022 02.
Article in English | MEDLINE | ID: covidwho-1705011

ABSTRACT

BACKGROUND: Several countries restricted the administration of ChAdOx1 to older age groups in 2021 over safety concerns following case reports and observed versus expected analyses suggesting a possible association with cerebral venous sinus thrombosis (CVST). Large datasets are required to precisely estimate the association between Coronavirus Disease 2019 (COVID-19) vaccination and CVST due to the extreme rarity of this event. We aimed to accomplish this by combining national data from England, Scotland, and Wales. METHODS AND FINDINGS: We created data platforms consisting of linked primary care, secondary care, mortality, and virological testing data in each of England, Scotland, and Wales, with a combined cohort of 11,637,157 people and 6,808,293 person years of follow-up. The cohort start date was December 8, 2020, and the end date was June 30, 2021. The outcome measure we examined was incident CVST events recorded in either primary or secondary care records. We carried out a self-controlled case series (SCCS) analysis of this outcome following first dose vaccination with ChAdOx1 and BNT162b2. The observation period consisted of an initial 90-day reference period, followed by a 2-week prerisk period directly prior to vaccination, and a 4-week risk period following vaccination. Counts of CVST cases from each country were tallied, then expanded into a full dataset with 1 row for each individual and observation time period. There was a combined total of 201 incident CVST events in the cohorts (29.5 per million person years). There were 81 CVST events in the observation period among those who a received first dose of ChAdOx1 (approximately 16.34 per million doses) and 40 for those who received a first dose of BNT162b2 (approximately 12.60 per million doses). We fitted conditional Poisson models to estimate incidence rate ratios (IRRs). Vaccination with ChAdOx1 was associated with an elevated risk of incident CVST events in the 28 days following vaccination, IRR = 1.93 (95% confidence interval (CI) 1.20 to 3.11). We did not find an association between BNT162b2 and CVST in the 28 days following vaccination, IRR = 0.78 (95% CI 0.34 to 1.77). Our study had some limitations. The SCCS study design implicitly controls for variables that are constant over the observation period, but also assumes that outcome events are independent of exposure. This assumption may not be satisfied in the case of CVST, firstly because it is a serious adverse event, and secondly because the vaccination programme in the United Kingdom prioritised the clinically extremely vulnerable and those with underlying health conditions, which may have caused a selection effect for individuals more prone to CVST. Although we pooled data from several large datasets, there was still a low number of events, which may have caused imprecision in our estimates. CONCLUSIONS: In this study, we observed a small elevated risk of CVST events following vaccination with ChAdOx1, but not BNT162b2. Our analysis pooled information from large datasets from England, Scotland, and Wales. This evidence may be useful in risk-benefit analyses of vaccine policies and in providing quantification of risks associated with vaccination to the general public.


Subject(s)
COVID-19/prevention & control , SARS-CoV-2/pathogenicity , Sinus Thrombosis, Intracranial/etiology , Adult , Aged , COVID-19 Vaccines/adverse effects , Case-Control Studies , Cohort Studies , Humans , Male , Middle Aged , United Kingdom , Vaccination/statistics & numerical data , Wales
15.
PLoS Med ; 19(2): e1003926, 2022 02.
Article in English | MEDLINE | ID: covidwho-1699720

ABSTRACT

BACKGROUND: Thromboses in unusual locations after the Coronavirus Disease 2019 (COVID-19) vaccine ChAdOx1-S have been reported, although their frequency with vaccines of different types is uncertain at a population level. The aim of this study was to estimate the population-level risks of hospitalised thrombocytopenia and major arterial and venous thromboses after COVID-19 vaccination. METHODS AND FINDINGS: In this whole-population cohort study, we analysed linked electronic health records from adults living in England, from 8 December 2020 to 18 March 2021. We estimated incidence rates and hazard ratios (HRs) for major arterial, venous, and thrombocytopenic outcomes 1 to 28 and >28 days after first vaccination dose for ChAdOx1-S and BNT162b2 vaccines. Analyses were performed separately for ages <70 and ≥70 years and adjusted for age, age2, sex, ethnicity, and deprivation. We also prespecified adjustment for anticoagulant medication, combined oral contraceptive medication, hormone replacement therapy medication, history of pulmonary embolism or deep vein thrombosis, and history of coronavirus infection in analyses of venous thrombosis; and diabetes, hypertension, smoking, antiplatelet medication, blood pressure lowering medication, lipid lowering medication, anticoagulant medication, history of stroke, and history of myocardial infarction in analyses of arterial thromboses. We selected further covariates with backward selection. Of 46 million adults, 23 million (51%) were women; 39 million (84%) were <70; and 3.7 million (8.1%) Asian or Asian British, 1.6 million (3.5%) Black or Black British, 36 million (79%) White, 0.7 million (1.5%) mixed ethnicity, and 1.5 million (3.2%) were of another ethnicity. Approximately 21 million (46%) adults had their first vaccination between 8 December 2020 and 18 March 2021. The crude incidence rates (per 100,000 person-years) of all venous events were as follows: prevaccination, 140 [95% confidence interval (CI): 138 to 142]; ≤28 days post-ChAdOx1-S, 294 (281 to 307); >28 days post-ChAdOx1-S, 359 (338 to 382), ≤28 days post-BNT162b2-S, 241 (229 to 253); >28 days post-BNT162b2-S 277 (263 to 291). The crude incidence rates (per 100,000 person-years) of all arterial events were as follows: prevaccination, 546 (95% CI: 541 to 555); ≤28 days post-ChAdOx1-S, 1,211 (1,185 to 1,237); >28 days post-ChAdOx1-S, 1678 (1,630 to 1,726), ≤28 days post-BNT162b2-S, 1,242 (1,214 to 1,269); >28 days post-BNT162b2-S, 1,539 (1,507 to 1,572). Adjusted HRs (aHRs) 1 to 28 days after ChAdOx1-S, compared with unvaccinated rates, at ages <70 and ≥70 years, respectively, were 0.97 (95% CI: 0.90 to 1.05) and 0.58 (0.53 to 0.63) for venous thromboses, and 0.90 (0.86 to 0.95) and 0.76 (0.73 to 0.79) for arterial thromboses. Corresponding aHRs for BNT162b2 were 0.81 (0.74 to 0.88) and 0.57 (0.53 to 0.62) for venous thromboses, and 0.94 (0.90 to 0.99) and 0.72 (0.70 to 0.75) for arterial thromboses. aHRs for thrombotic events were higher at younger ages for venous thromboses after ChAdOx1-S, and for arterial thromboses after both vaccines. Rates of intracranial venous thrombosis (ICVT) and of thrombocytopenia in adults aged <70 years were higher 1 to 28 days after ChAdOx1-S (aHRs 2.27, 95% CI: 1.33 to 3.88 and 1.71, 1.35 to 2.16, respectively), but not after BNT162b2 (0.59, 0.24 to 1.45 and 1.00, 0.75 to 1.34) compared with unvaccinated. The corresponding absolute excess risks of ICVT 1 to 28 days after ChAdOx1-S were 0.9 to 3 per million, varying by age and sex. The main limitations of the study are as follows: (i) it relies on the accuracy of coded healthcare data to identify exposures, covariates, and outcomes; (ii) the use of primary reason for hospital admission to measure outcome, which improves the positive predictive value but may lead to an underestimation of incidence; and (iii) potential unmeasured confounding. CONCLUSIONS: In this study, we observed increases in rates of ICVT and thrombocytopenia after ChAdOx1-S vaccination in adults aged <70 years that were small compared with its effect in reducing COVID-19 morbidity and mortality, although more precise estimates for adults aged <40 years are needed. For people aged ≥70 years, rates of arterial or venous thrombotic events were generally lower after either vaccine compared with unvaccinated, suggesting that either vaccine is suitable in this age group.


Subject(s)
COVID-19 Vaccines , Thrombocytopenia/etiology , Vaccination , Adult , Aged , Cohort Studies , England/epidemiology , Female , Humans , Incidence , Male , Middle Aged , SARS-CoV-2/pathogenicity , Thrombocytopenia/epidemiology , Vaccination/adverse effects
16.
BMJ Open ; 12(2): e050062, 2022 02 14.
Article in English | MEDLINE | ID: covidwho-1691320

ABSTRACT

INTRODUCTION: The novel coronavirus SARS-CoV-2, which emerged in December 2019, has caused millions of deaths and severe illness worldwide. Numerous vaccines are currently under development of which a few have now been authorised for population-level administration by several countries. As of 20 September 2021, over 48 million people have received their first vaccine dose and over 44 million people have received their second vaccine dose across the UK. We aim to assess the uptake rates, effectiveness, and safety of all currently approved COVID-19 vaccines in the UK. METHODS AND ANALYSIS: We will use prospective cohort study designs to assess vaccine uptake, effectiveness and safety against clinical outcomes and deaths. Test-negative case-control study design will be used to assess vaccine effectiveness (VE) against laboratory confirmed SARS-CoV-2 infection. Self-controlled case series and retrospective cohort study designs will be carried out to assess vaccine safety against mild-to-moderate and severe adverse events, respectively. Individual-level pseudonymised data from primary care, secondary care, laboratory test and death records will be linked and analysed in secure research environments in each UK nation. Univariate and multivariate logistic regression models will be carried out to estimate vaccine uptake levels in relation to various population characteristics. VE estimates against laboratory confirmed SARS-CoV-2 infection will be generated using a generalised additive logistic model. Time-dependent Cox models will be used to estimate the VE against clinical outcomes and deaths. The safety of the vaccines will be assessed using logistic regression models with an offset for the length of the risk period. Where possible, data will be meta-analysed across the UK nations. ETHICS AND DISSEMINATION: We obtained approvals from the National Research Ethics Service Committee, Southeast Scotland 02 (12/SS/0201), the Secure Anonymised Information Linkage independent Information Governance Review Panel project number 0911. Concerning English data, University of Oxford is compliant with the General Data Protection Regulation and the National Health Service (NHS) Digital Data Security and Protection Policy. This is an approved study (Integrated Research Application ID 301740, Health Research Authority (HRA) Research Ethics Committee 21/HRA/2786). The Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub meets NHS Digital's Data Security and Protection Toolkit requirements. In Northern Ireland, the project was approved by the Honest Broker Governance Board, project number 0064. Findings will be made available to national policy-makers, presented at conferences and published in peer-reviewed journals.


Subject(s)
COVID-19 Vaccines , COVID-19 , Case-Control Studies , Humans , Observational Studies as Topic , Prospective Studies , Retrospective Studies , SARS-CoV-2 , Scotland/epidemiology , State Medicine
17.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311502

ABSTRACT

Background: Lockdowns and health-system responses to the COVID-19 pandemic impacted citizen behaviour and cancer-related services. Modelling predicted excess cancer mortality, with limited observed cancer incidence data. We determined pandemic impacts on whole-population incidence, stage at diagnosis and referral route-to-diagnosis for: I) female breast (FBC), II) colorectal (CRC), and III) non-small cell lung cancers (NSCLC).Methods: We linked cancer e-record and hospital admission data to identify incident cases, stage and referral route-to-diagnosis outcomes in the Welsh adult population (~2.5 million), imputed missing stage and compared 2019 and 2020 outcomes stratified by age, sex and deprivation, after accounting for seasonal variation.Findings: FBC incidence decreased -19.1% (n=-474);CRC -17.2% (n=-383);NSCLC -7.9% (n=-154);overall decrease -15.2% (n=-1011), greatest in 80+ year-olds and FBC screening-age women. Large incidence decreases started in April 2020. FBC recovered by September, CRC partially recovered, and NSCLC recovered by June, decreasing from October. Stage I FBC declined -33.5% (n=-341), CRC distribution changed little, and for NSCLC, stage II declined -31.4% (n=-71), stage IV by -12.4% (n=-100). CRC and NSCLC Q2 2020 primary care suspected cancer diagnoses decreased by approximately half. The small decline in FBC rebounded above 2019 diagnoses by Q3, followed by CRC in Q4. NSCLC only partially recovered. Annual screen-detected FBC and CRC fell -47.8% (n=-451) and -13.3% (n=-37), respectively. NSCLC emergency presentation diagnoses increased in Q2 and Q3 2020.Interpretation: Impacts differed between cancers, coinciding with dynamic pandemic responses. Large numbers of undiagnosed patients and the on-going pandemic will increase later-stage diagnoses and mortality from 2021 onwards, further impacting citizens and services. Optimising screening and transformation of cancer services and primary care referral will be required, with continued research and surveillance.Funding: This work was supported by Health Data Research UK funding to DATA-CAN, the UK’s Health Data Research Hub for Cancer and Cancer Research UK (C23434/A23706).Declaration of Interest: ML has received an unrestricted educational grant from Pfizer for research unrelated to this work. ML has received honoraria from Pfizer, EMF Serono, Roche and Carnall Farrar unrelated to this work. DWH has received research consultancy fees from Pfizer for research unrelated to this work and his department (Welsh Cancer Intelligence and Surveillance Unit, Public Health Wales) has received analysis partnership funding from Macmillan Cancer Support for unrelated work. All other authors have declared no conflicts of interest.Ethical Approval: This study was approved by the SAIL independent Information Governance Review Panel (IGRP) project number 0911.

18.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323239

ABSTRACT

Background: The BNT162b2 mRNA (Pfizer-BioNTech) and ChAdOx1 (Oxford-AstraZeneca) COVID-19 vaccines have demonstrated high efficacy against infection in phase 3 clinical trials and are now being used in national vaccination programmes in the UK and several other countries. There is an urgent need to study the ‘real-world’ effects of these vaccines. The aim of our study was to estimate the effectiveness of the first dose of these COVID-19 vaccines in preventing hospital admissions.Methods: We conducted a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) database comprising of linked vaccination, primary care, Real-Time Polymerase Chain Reaction (RT-PCR) testing, hospitalisation and mortality records for 5.4 million people in Scotland (covering ~99% of population). A time-dependent Cox model and Poisson regression models were fitted to estimate effectiveness against COVID-19 related hospitalisation (defined as 1- Adjusted Hazard Ratio) following the first dose of vaccine.Findings: The first dose of the BNT162b2 vaccine was associated with a vaccine effect of 85% (95% confidence interval [CI] 76 to 91) for COVID-19 related hospitalisation at 28-34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 94% (95% CI 73 to 99). Results of combined vaccine effect for prevention of COVID-19 related hospitalisation were comparable when restricting the analysis to those aged ≥80 years (81%;95% CI 65 to 90 at 28-34 days post-vaccination).Interpretation: A single dose of the BNT162b2 mRNA and ChAdOx1 vaccines resulted in substantial reductions in the risk of COVID-19 related hospitalisation in Scotland.Funding: UK Research and Innovation (Medical Research Council);Research and Innovation Industrial Strategy Challenge Fund;Health Data Research UK.Conflict of Interest: AS is a member of the Scottish Government Chief Medical Officer’s COVID-19Advisory Group and the New and Emerging Respiratory Virus Threats (NERVTAG) Risk Stratification Subgroup. CRS declares funding from the MRC, NIHR, CSO and New Zealand Ministry for Business, Innovation and Employment and Health Research Council during the conduct of this study. SVK is co-chair of the Scottish Government’s Expert Reference Group on COVID-19 and ethnicity, is a member of the Scientific Advisory Group on Emergencies (SAGE) subgroup on ethnicity and acknowledges funding from a NRS Senior Clinical Fellowship, MRC and CSO. All other authors report no conflicts of interest.Ethical Approval: Approvals were obtained from the National Research Ethics Service Committee, Southeast Scotland 02 (reference number: 12/SS/0201) and Public Benefit and Privacy Panel for Health and Social Care (reference number: 1920-0279).

19.
Vaccine ; 40(8): 1180-1189, 2022 02 16.
Article in English | MEDLINE | ID: covidwho-1621088

ABSTRACT

BACKGROUND: While population estimates suggest high vaccine effectiveness against SARS-CoV-2 infection, the protection for health care workers, who are at higher risk of SARS-CoV-2 exposure, is less understood. METHODS: We conducted a national cohort study of health care workers in Wales (UK) from 7 December 2020 to 30 September 2021. We examined uptake of any COVID-19 vaccine, and the effectiveness of BNT162b2 mRNA (Pfizer-BioNTech) against polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection. We used linked and routinely collected national-scale data within the SAIL Databank. Data were available on 82,959 health care workers in Wales, with exposure extending to 26 weeks after second doses. RESULTS: Overall vaccine uptake was high (90%), with most health care workers receiving theBNT162b2 vaccine (79%). Vaccine uptake differed by age, staff role, socioeconomic status; those aged 50-59 and 60+ years old were 1.6 times more likely to get vaccinated than those aged 16-29. Medical and dental staff, and Allied Health Practitioners were 1.5 and 1.1 times more likely to get vaccinated, compared to nursing and midwifery staff. The effectiveness of the BNT162b2 vaccine was found to be strong and consistent across the characteristics considered; 52% three to six weeks after first dose, 86% from two weeks after second dose, though this declined to 53% from 22 weeks after the second dose. CONCLUSIONS: With some variation in rate of uptake, those who were vaccinated had a reduced risk of PCR-confirmed SARS-CoV-2 infection, compared to those unvaccinated. Second dose has provided stronger protection for longer than first dose but our study is consistent with waning from seven weeks onwards.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adolescent , Adult , Cohort Studies , Health Personnel , Humans , Prospective Studies , SARS-CoV-2 , Wales/epidemiology , Young Adult
20.
Age Ageing ; 51(1)2022 01 06.
Article in English | MEDLINE | ID: covidwho-1545894

ABSTRACT

BACKGROUND: vaccinations for COVID-19 have been prioritised for older people living in care homes. However, vaccination trials included limited numbers of older people. AIM: we aimed to study infection rates of SARS-CoV-2 for older care home residents following vaccination and identify factors associated with increased risk of infection. STUDY DESIGN AND SETTING: we conducted an observational data-linkage study including 14,104 vaccinated older care home residents in Wales (UK) using anonymised electronic health records and administrative data. METHODS: we used Cox proportional hazards models to estimate hazard ratios (HRs) for the risk of testing positive for SARS-CoV-2 infection following vaccination, after landmark times of either 7 or 21 days post-vaccination. We adjusted HRs for age, sex, frailty, prior SARS-CoV-2 infections and vaccination type. RESULTS: we observed a small proportion of care home residents with positive polymerase chain reaction (tests following vaccination 1.05% (N = 148), with 90% of infections occurring within 28 days. For the 7-day landmark analysis we found a reduced risk of SARS-CoV-2 infection for vaccinated individuals who had a previous infection; HR (95% confidence interval) 0.54 (0.30, 0.95). For the 21-day landmark analysis, we observed high HRs for individuals with low and intermediate frailty compared with those without; 4.59 (1.23, 17.12) and 4.85 (1.68, 14.04), respectively. CONCLUSIONS: increased risk of infection after 21 days was associated with frailty. We found most infections occurred within 28 days of vaccination, suggesting extra precautions to reduce transmission risk should be taken in this time frame.


Subject(s)
COVID-19 , Aged , Cohort Studies , Humans , Longitudinal Studies , SARS-CoV-2 , Wales/epidemiology
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