ABSTRACT
Objective To compare the effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab with no treatment in preventing hospital admission or death in higher-risk patients infected with SARS-CoV-2 in the community. Design Retrospective cohort study of non-hospitalised adult patients with COVID-19 using the Secure Anonymised Information Linkage (SAIL) Databank. Setting A real-world cohort study was conducted within the SAIL Databank (a secure trusted research environment containing anonymised, individual, population-scale electronic health record (EHR) data) for the population of Wales, UK. Participants Adult patients with COVID-19 in the community, at higher risk of hospitalisation and death, testing positive for SARS-CoV-2 between 16th December 2021 and 22nd April 2022. Interventions Molnupiravir, nirmatrelvir-ritonavir, and sotrovimab given in the community by local health boards and the National Antiviral Service in Wales. Main outcome measures All-cause admission to hospital or death within 28 days of a positive test for SARS-CoV-2. Statistical analysis Cox proportional hazard model with treatment status (treated/untreated) as a time-dependent covariate and adjusted for age, sex, number of comorbidities, Welsh Index of Multiple Deprivation, and vaccination status. Secondary subgroup analyses were by treatment type, number of comorbidities, and before and on or after 20th February 2022, when omicron BA.1 and omicron BA.2 were the dominant subvariants in Wales. Results Between 16th December 2021 and 22nd April 2022, 7,103 higher-risk patients were eligible for inclusion in the study. Of these, 2,040 received treatment with molnupiravir (359, 17.6%), nirmatrelvir-ritonavir (602, 29.5%), or sotrovimab (1,079, 52.9%). Patients in the treatment group were younger (mean age 53 vs 57 years), had fewer comorbidities, and a higher proportion had received four or more doses of the COVID-19 vaccine (36.3% vs 17.6%). Within 28 days of a positive test, 628 (9.0%) patients were admitted to hospital or died (84 treated and 544 untreated). The primary analysis indicated a lower risk of hospitalisation or death at any point within 28 days in treated participants compared to those not receiving treatment. The adjusted hazard rate was 35% (95% CI: 18-49%) lower in treated than untreated participants. There was no indication of the superiority of one treatment over another and no evidence of a reduction in risk of hospitalisation or death within 28 days for patients with no or only one comorbidity. In patients treated with sotrovimab, the event rates before and on or after 20th February 2022 were similar (5.0% vs 4.9%) with no significant difference in the hazard ratios for sotrovimab between the time periods. Conclusions In higher-risk adult patients in the community with COVID-19, those who received treatment with molnupiravir, nirmatrelvir-ritonavir, or sotrovimab were at lower risk of hospitalisation or death than those not receiving treatment.
Subject(s)
Death , COVID-19ABSTRACT
Introduction: Ethnicity information is recorded routinely in electronic health records (EHRs); however, to date, there is no national standard or framework for harmonisation of the existing records. Methods and analysis The national ethnicity-spine uses anonymised individual-level population-scale ethnicity data from 26 EHR available through the Secure Anonymised Information Linkage (SAIL) Databank. A total of 46 million ethnicity records for 4,297,694 individuals in Wales-UK over 22 years (between 2000 and 2021) have been compiled in a harmonised, deduplicated longitudinal research ready data asset. We serialised this data and compared distribution of records over time for four selection approaches (Latest, Mode, Weighted-Mode and Composite) across age bands, sex, deprivation quintiles, health board, and residential location, against the ONS census 2011. The distribution of the dominant group (White) is minimally affected based on the four different selection approaches. Across all other ethnicity categorisations, the Mixed group was most susceptible to variation in distribution depending on the selection approach used and varied from a 0.6% prevalence across the Latest and Mode approach to a 1.1% prevalence for the Weighted-Mode, compared to the 3.1% prevalence for the Composite approach. Substantial alignment was observed with ONS census with the Latest group method (kappa= 0.68, 95% CI [0.67,0.71]) across all sub-groups. Conclusion We provides a reproducible EHR based resource enabling the investigation and evaluation of health inequalities related to ethnic groups in Wales. This generalisable method informs opportunities for the transferability of this methodology across the UK to platforms with comparable routine data sources. Ethics and dissemination This work was supported by the Con-COV team funded by Medical Research Council, Health Data Research UK, ADR Wales funded by ADR UK through the Economic and Social Research Council, and the Wales COVID-19 Evidence Centre, funded by Health and Care Research Wales.
Subject(s)
COVID-19ABSTRACT
BackgroundThe imposition of restrictions on social mixing early in the COVID-19 pandemic was followed by a reduction in asthma exacerbations in multiple settings internationally. Temporal trends in social mixing, incident acute respiratory infections (ARI) and asthma exacerbations following relaxation of COVID-19 restrictions have not yet been described. MethodsWe conducted a population-based longitudinal study in 2,312 UK adults with asthma between November 2020 and April 2022. Details of face covering use, social mixing, incident ARI and moderate/severe asthma exacerbations were collected via monthly on-line questionnaires. Temporal changes in these parameters were visualised using Poisson generalised additive models. Multilevel logistic regression was used to test for associations between incident ARI and risk of asthma exacerbations, adjusting for potential confounders. ResultsRelaxation of COVID-19 restrictions from April 2021 coincided with reduced face covering use (p<0.001), increased frequency of indoor visits to public places and other households (p<0.001) and rising incidence of COVID-19 (p<0.001), non-COVID-19 ARI (p<0.001) and moderate/severe asthma exacerbations (p=0.007). Incident non-COVID-19 ARI associated independently with increased risk of asthma exacerbation (adjusted odds ratio 5.75, 95% CI 4.75 to 6.97) as did incident COVID-19, both prior to emergence of the omicron variant of SARS-CoV-2 (5.89, 3.45 to 10.04) and subsequently (5.69, 3.89 to 8.31). ConclusionsRelaxation of COVID-19 restrictions coincided with decreased face covering use, increased social mixing and a rebound in ARI and asthma exacerbations. Associations between incident ARI and risk of moderate/severe asthma exacerbation were similar for non-COVID-19 ARI and COVID-19, both before and after emergence of the SARS-CoV-2 omicron variant. FundingBarts Charity, UKRI
Subject(s)
COVID-19 , Respiratory Tract Infections , AsthmaABSTRACT
Prospective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted such a study in 9003 adults from the United Kingdom (UK) general population receiving SARS-COV-2 vaccines as part of the national vaccination programme. Data relating to incidence and type of reactive symptoms after vaccination were captured using online questionnaires, along with information on 56 potential determinants of symptom risk. Titres of combined IgG/IgA/IgM responses to SARS-CoV-2 spike (S) glycoprotein were determined in eluates of dried blood spots collected from all participants before and after vaccination. 4262 (47.3%) participants experienced systemic reactive symptoms after a first vaccine dose. Factors associating with lower risk of such symptoms included older age (aOR per additional 10 years of age 0.85, 95% CI 0.81–0.90), male vs. female sex (aOR 0.59, 95% CI 0.53–0.65) and receipt of an mRNA vaccine vs. ChAdOx1 nCoV-19 (0.29, 0.26–0.32 for BNT162b2; 0.06, 0.01–0.26 for mRNA-1273). Higher risk of such symptoms was associated with a history of symptomatic SARS-CoV-2 infection prior to vaccination (2.23, 1.78–2.81) and presence vs. absence of self-rated anxiety or depression at cohort enrolment (1.24, 1.12–1.39). Post-vaccination anti-S titres were higher among participants who experienced reactive symptoms after vaccination vs. those who did not (P < 0.001). We conclude that factors influencing risk of systemic symptoms after SARS-CoV-2 vaccination include demographic characteristics, pre-vaccination SARS-CoV-2 serostatus and vaccine type. Participants experiencing reactive symptoms following SARS-CoV-2 vaccination had higher post-vaccination titres of IgG/A/M anti-S antibodies. Improved public understanding of the frequency of reactogenic symptoms and their positive association with vaccine immunogenicity could potentially increase vaccine uptake.
Subject(s)
COVID-19ABSTRACT
Multimorbidity is defined as the coexistence of two or more chronic health conditions in an individual. The objective of this study was to examine how diseases in a cluster of physical-mental health multimorbidity with a high all-cause mortality (psychosis, diabetes, and congestive heart failure) develop and coexist over time, and to assess the associated impact of different temporal sequences on mortality. Population-scale, individual-level, anonymised, linked, demographic, administrative and electronic health record data were modelled using multi-state models for 1,675,585 individuals over a 20-year period (2000–2019). Cox regression models were used to estimate baseline hazards for transitions between states, adjusted for gender, age, and area-level deprivation. Our findings suggest that the order of disease acquisition in physical-mental health multimorbidity had an important impact and complex relationship on patient mortality. Individuals developing diabetes, psychosis, and congestive heart failure, in that order, had an increased all-cause mortality rate compared to the development of the same conditions in a different order, resulting in the highest loss in expectation of life of 13 years at age 50 compared to the general population. Congestive heart failure as a single condition and in combination with psychosis had an equally high loss in expectation of life. Identification and therapeutic targets for psychosis and congestive heart failure may be beneficial within 5 years following an initial diagnosis of diabetes. The use of multi-state models offers a flexible framework to assess temporal sequences of diseases and associated patient outcomes, and allows identification of potential risk factors, screening opportunities, and therapeutic targets in multimorbidity.
Subject(s)
Heart Failure , Diabetes Mellitus , Psychotic DisordersABSTRACT
BACKGROUND: Vitamin D metabolites support innate immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory pathogens. Randomized controlled trials of vitamin D to prevent coronavirus disease 2019 (Covid-19) have not yet reported. METHODS: We randomly assigned 6200 U.K. adults to receive an offer of a postal finger-prick 25-hydroxyvitamin D (25[OH]D) test with provision of a 6-month supply of higher-dose vitamin D (3200 IU/d, n=1550) or lower-dose vitamin D (800 IU/d, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, vs. no offer of testing or supplementation (n=3100). The primary outcome was the proportion of participants experiencing at least one swab test- or doctor-confirmed acute respiratory infection (ARI) of any cause at six months. Secondary outcomes included incidence of swab test-confirmed Covid-19. RESULTS: Of 3100 participants offered testing, 2958 (95.4%) accepted, and 2690 (86.8%) had 25(OH)D <75 nmol/L and were sent vitamin D supplements (1356 higher-dose, 1334 lower-dose). 76 (5.0%) vs. 87 (5.7%) vs. 136 (4.6%) participants in higher-dose vs. lower-dose vs. no-offer groups experienced at least one ARI of any cause (odds ratio [OR] for higher-dose vs. no-offer 1.09, 95% CI 0.82-1.46; lower-dose vs. no-offer 1.26, 0.96-1.66). 45 (3.0%) vs. 55 (3.6%) vs. 78 (2.6%) participants in higher-dose vs. lower-dose vs. no-offer groups developed Covid-19 (OR for higher-dose vs. no-offer 1.13, 0.78-1.63; lower-dose vs. no-offer 1.39, 0.98-1.97). CONCLUSIONS: Among adults with a high baseline prevalence of vitamin D insufficiency, implementation of a test-and-treat approach to vitamin D replacement did not reduce risk of all-cause ARI or Covid-19.
Subject(s)
Coronavirus Infections , Severe Acute Respiratory Syndrome , Addison Disease , Respiratory Tract Infections , COVID-19ABSTRACT
Summary Background Antibody responses to SARS-CoV-2 vaccination vary for reasons that remain poorly understood. Methods We tested for presence of combined IgG, IgA and IgM (IgGAM) anti-spike antibodies before and after administration of two doses of ChAdOx1 nCoV-19 (ChAdOx1, Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) in UK adults participating in a population-based longitudinal study who received their first dose of vaccine from December 15, 2020 to July 10, 2021. Information on sixty-six potential sociodemographic, behavioural, clinical, pharmacological and nutritional determinants of serological response to vaccination was captured using serial online questionnaires. We used logistic regression to estimate multivariable-adjusted odds ratios (aORs) for associations between independent variables and risk of seronegativity following two vaccine doses. Participants who were seronegative after receiving two vaccine doses were offered an additional antibody test following subsequent administration of a ‘booster’ dose of BNT162b2 or mRNA-1273 (Moderna) from September 23 to December 12, 2021. Findings Serology results following two vaccine doses were available for 9,101 participants, of whom 5,770 (63.4%) received ChAdOx1 and 3,331 (36.6%) received BNT162b2. Anti-spike IgGAM was undetectable in 378 (4.2%) participants at a median of 8.6 weeks (IQR 6.4-10.7 weeks) after their second dose of vaccine. Seronegativity following two doses of SARS-CoV-2 vaccination was associated with administration of ChAdOx1 vs BNT162b2 (aOR 7.03, 95% CI 4.39-11.24), shorter interval between first and second vaccine doses (aOR 2.37, 1.06-5.26, for <6 weeks vs >10 weeks; aOR 1.59, 1.18-2.13, for 6-10 weeks vs >10 weeks), poorer self-assessed general health (aOR 3.33, 1.49-7.46, for poor vs excellent), immunodeficiencies (aOR 6.75, 2.63-17.35) and prescription of systemic immunosuppressants (aOR 3.76, 2.44-5.78). By contrast, pre-vaccination SARS-CoV-2 seropositivity (aOR 0.16, 0.04-0.70, for symptomatic seropositives vs seronegatives) and supplemental vitamin D intake (aOR 0.73, 0.53-0.99) were associated with reduced risk of post-vaccination seronegativity. 247/378 (65.3%) of participants who were seronegative after two doses of ChAdOx1 vs BNT162b2 provided a third sample at a median of 7.8 weeks (IQR 5.8-10.4) after receiving a booster dose of BNT162b2 or mRNA-1273: eight (3.2%) of them remained seronegative after three vaccine doses, all of whom either had a primary immunodeficiency or were taking systemic immunosuppressant drugs. Interpretation We identify multiple determinants of antibody responses to two doses of ChAdOx1 or BNT162b2, many of which are potentially modifiable. Booster doses of BNT162b2 or mRNA-1273 were highly effective in achieving seroconversion in those who failed to mount antibody responses following two doses of ChAdOx1 or BNT162b2. Study registration https://clinicaltrials.gov/ct2/show/NCT04330599 Funding Barts Charity, Fischer Family Trust, The Exilarch’s Foundation, DSM Nutritional Products, Health Data Research UK Research in context Evidence before this study We searched PubMed, medRxiv, and Google Scholar for papers published from January 1, 2020, to February 1, 2022, using the search terms (antibody OR humoral OR serologic* OR immunogenic*) AND (SARS-CoV-2 vaccine OR ChAdOx1 or BNT162b2 coronavirus), with no language restrictions. Population-based studies investigating multiple potential determinants of vaccine immunogenicity in people with known pre-vaccination SARS-CoV-2 serostatus are lacking. Added value of this study This large population-based study, conducted in a population with known pre-vaccination SARS-CoV-2 serostatus, examines a comprehensive range of potential sociodemographic, behavioural, clinical, pharmacological and nutritional determinants of antibody responses to administration of two major SARS-CoV-2 vaccines (i.e., ChAdOx1 or BNT162b2), many of which have not previously been investigated. It is also the first population-based study to characterise antibody responses to booster doses of SARS-CoV-2 vaccines in adults who were seronegative after their primary course of vaccination. Implications of all the available evidence Increased risk of seronegativity following two doses of SARS-CoV-2 vaccines was associated with administration of ChAdOx1 vs BNT162b2, shorter interval between first and second vaccine doses, poorer self-assessed general health, immunocompromise and SARS-CoV-2 seronegativity pre-vaccination. Regular intake of vitamin D supplements was associated with reduced risk of post-vaccination seronegativity. Randomised controlled trials are now needed to test for causality. Booster doses of BNT162b2 or mRNA-1273 were highly effective in achieving seroconversion in the majority of people who failed to mount antibody responses following a primary course of vaccination, the few exceptions being a subset of those with primary immunodeficiency or systemic immunosuppressant drugs.
Subject(s)
Immunologic Deficiency SyndromesABSTRACT
ABSTRACT Objectives Examine if pre-COVID-19 pandemic (prior March 2020) health-related behaviours during primary school are associated with i) being tested for SARS-CoV-2 and ii) testing positive between 1 March 2020 to 31 August 2021. Design Retrospective cohort study using an online cohort survey (January 2018 to February 2020) linked to routine PCR SARS-CoV-2 test results. Setting Children attending primary schools in Wales (2018-2020), UK who were part of the HAPPEN school network. Participants Complete linked records of eligible participants were obtained for n=7,062 individuals. 39.1% (n=2,764) were tested (age 10.6±0.9, 48.9% girls) and 8.1% (n=569) tested positive for SARS-CoV-2 (age 10.6±1.0, 54.5% girls). Main outcome measures Logistic regression of health-related behaviours and demographics were used to determine Odds Ratios (OR) of factors associated with i) being tested for SARS-CoV-2 and ii) testing positive for SARS-CoV-2. Results Consuming sugary snacks (1-2 days/week OR=1.24, 95% CI 1.04 – 1.49; 5-6 days/week 1.31, 1.07 – 1.61; reference 0 days) can swim 25m (1.21, 1.06 – 1.39) and age (1.25, 1.16 – 1.35) were associated with an increased likelihood of being tested for SARS-CoV-2. Eating breakfast (1.52, 1.01 – 2.27), weekly physical activity ≥ 60 mins (1-2 days 1.69, 1.04 – 2.74; 3-4 days 1.76, 1.10 – 2.82, reference 0 days), out of school club participation (1.06, 1.02 – 1.10), can ride a bike (1.39, 1.00 – 1.93), age (1.16, 1.05 – 1.28) and girls (1.21, 1.00 – 1.46) were associated with an increased likelihood of testing positive for SARS-CoV-2. Living in least deprived quintiles 4 (0.64, 0.46 – 0.90) and 5 (0.64, 0.46 – 0.89) compared to the most deprived quintile was associated with a decreased likelihood. Conclusions Associations may be related to parental health literacy and monitoring behaviours. Physically active behaviours may include co-participation with others, and exposure to SARS-CoV-2. A risk versus benefit approach must be considered given the importance of health-related behaviours for development. STRENGTHS AND LIMITATIONS Investigation of the association of pre-pandemic child health-related behaviour measures with subsequent SARS-CoV-2 testing and infection. Reporting of multiple child health behaviours linked at an individual-level to routine records of SARS-CoV-2 testing data through the SAIL Databank. Child-reported health behaviours were measured before the COVID-19 pandemic (1 January 2018 to 28 February 2020) which may not reflect behaviours during COVID-19. Health behaviours captured through the national-scale HAPPEN survey represent children attending schools that engaged with the HAPPEN Wales primary school network and may not be representative of the whole population of Wales. The period of study for PCR-testing for and testing positive for SARS-CoV-2 includes a time frame with varying prevalence rates, approaches to testing children (targeted and mass testing) and restrictions which were not measured in this study.
Subject(s)
COVID-19ABSTRACT
Objectives: To estimate the impact of the COVID-19 pandemic on cardiovascular disease (CVD) and CVD management using routinely collected medication data as a proxy. Design: Descriptive and interrupted time series analysis using anonymised individual-level population-scale data for 1.32 billion records of dispensed CVD medications across 15.8 million individuals in England, Scotland and Wales. Setting: Community dispensed CVD medications with 100% coverage from England, Scotland and Wales, plus primary care prescribed CVD medications from England (including 98% English general practices). Participants: 15.8 million individuals aged 18+ years alive on 1st April 2018 dispensed at least one CVD medicine in a year from England, Scotland and Wales. Main outcome measures: Monthly counts, percent annual change (1st April 2018 to 31st July 2021) and annual rates (1st March 2018 to 28th February 2021) of medicines dispensed by CVD/ CVD risk factor; prevalent and incident use. Results: Year-on-year change in dispensed CVD medicines by month were observed, with notable uplifts ahead of the first (11.8% higher in March 2020) but not subsequent national lockdowns. Using hypertension as one example of the indirect impact of the pandemic, we observed 491,203 fewer individuals initiated antihypertensive treatment across England, Scotland and Wales during the period March 2020 to end May 2021 than would have been expected compared to 2019. We estimated that this missed antihypertension treatment could result in 13,659 additional CVD events should individuals remain untreated, including 2,281 additional myocardial infarctions (MIs) and 3,474 additional strokes. Incident use of lipid-lowering medicines decreased by an average 14,793 per month in early 2021 compared with the equivalent months prior to the pandemic in 2019. In contrast, the use of incident medicines to treat type-2 diabetes (T2DM) increased by approximately 1,642 patients per month. Conclusions: Management of key CVD risk factors as proxied by incident use of CVD medicines has not returned to pre-pandemic levels in the UK. Novel methods to identify and treat individuals who have missed treatment are urgently required to avoid large numbers of additional future CVD events, further adding indirect cost of the COVID-19 pandemic.
Subject(s)
Myocardial Infarction , Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Hypertension , COVID-19 , StrokeABSTRACT
Background: Prospective population-based studies investigating multiple determinants of pre-vaccination antibody responses to SARS-CoV-2 are lacking.Methods: We did a prospective population-based study in SARS-CoV-2 vaccine-naive UK adults between May 1 and Nov 2, 2020. Information on 88 potential risk factors was obtained through online questionnaires, and combined IgG/IgA/IgM responses to SARS-CoV-2 spike glycoprotein were determined in dried blood spots. We used logistic and linear regression to estimate adjusted odds ratios (aORs) and adjusted geometric mean ratios (aGMRs) for potential determinants of SARS-CoV-2 seropositivity (all participants) and antibody titres (seropositive participants only), respectively.Findings: 1696 (15.2%) of 11,130 participants were seropositive. Factors independently associated with increased risk included frontline health/care occupation (aOR 1.86, 95% CI 1.49–2.33), international travel (1.22, 1.08–1.37), BMI >30 vs <25 kg/m² (1.22, 1.05–1.42), Asian/Asian British vs White ethnicity (1.65, 1.10–2.47), and alcohol consumption ≥15 vs 0 units/week (1.26, 1.06–1.49). Light physical exercise associated with decreased risk (0.80, 0.69–0.93, for ≥10 vs 0–4 h/week). Higher titres associated with frontline health/care occupation (aGMR 1.26, 95% CI 1.13–1.41), international travel (1.10, 1.04–1.16), BMI >30 vs <25 kg/m² (1.09, 1.01–1.17), and Asian/Asian British vs White ethnicity (1.23, 1.03–1.46); these associations were not substantially attenuated by adjustment for disease severity.Interpretation: Higher alcohol consumption and reduced physical exercise represent new modifiable risk factors for SARS-CoV-2 infection. Recognised associations between Asian/Asian British ethnic origin and obesity and increased risk of SARS-CoV-2 seropositivity were independent of other sociodemographic, clinical, or behavioural factors investigated.Funding: Barts Charity, Health Data Research UK.Declaration of Interest: JS declares receipt of payments from Reach plc for news stories written about recruitment to, and findings of, the COVIDENCE UK study. AS is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group and its Standing Committee on Pandemics. He is also a member of the UK Government’s NERVTAG’s Risk Stratification Subgroup. ARM declares receipt of funding in the last 36 months to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd, DSM Nutritional Products Ltd, Thornton & Ross Ltd, Cytoplan Ltd and Hyphens Pharma Ltd. ARM also declares support for attending meetings from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd and Abiogen Pharma Ltd. ARM also declares participation on the Data and Safety Monitoring Board for the Chair, DSMB, VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology). ARM also declares unpaid work as a Programme Committee member for the Vitamin D Workshop. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord Ltd, Synergy Biologics Ltd and Cytoplan Ltd.Ethical Approval: COVIDENCE UK was sponsored by Queen Mary University of London and approved by Leicester South Research Ethics Committee (ref 20/EM/0117). It is registered withClinicalTrials.gov (NCT04330599).
Subject(s)
HIV Infections , Alcoholism , COVID-19 , HIV Seropositivity , ObesityABSTRACT
ABSTRACT Objectives 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. Setting Care home residents in Wales (United Kingdom) between 1st September 2020 and 1st May 2021. Participants 14,786 older care home residents (aged 65+). 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 polymerase chain reaction (PCR) test. We included time dependent covariates for the estimated community positive test rate of COVID-19, hospital admissions, and vaccination status. Additional covariates were included for age, positive PCR tests prior to the study, sex, frailty (using the hospital frailty risk score), and specialist care home services. Results The multivariable logistic regression model indicated an increase in age (OR 1.01 [1.00,1.01] per year of age), community positive test rate (OR 1.13 [1.12,1.13] per percent increase in positive test rate), 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 of a positive test. Conclusions Our findings suggest care providers need to stay vigilant despite the vaccination rollout, and extra precautions should be taken when caring for the most vulnerable. Furthermore, minimising potential COVID-19 infection for care home residents admitted to hospital should be prioritised. SUMMARY BOXES Section 1: What is already known on this topic Care home residents are at a high risk of COVID-19 infection, but existing literature has mainly focussed on excess mortality rather than infection risk. In our study we were able to investigate associations between COVID-19 infections and the community positive test rate of COVID-19, the vaccination status of care home residents, hospital admissions, and frailty. Section 2: What this study adds Our study suggests an increased community positive test rate and hospital inpatients had an increased likelihood of a positive SARS-CoV-2 polymerase chain reaction test, whilst one or two doses of vaccination indicated a decreased chance of a positive test. Our findings suggest care providers need to stay vigilant despite the vaccination rollout, and extra precautions should be taken when caring for the most vulnerable, especially in a hospital setting.
Subject(s)
COVID-19ABSTRACT
Background: Risk factors for severe COVID-19 include older age, male sex, obesity, Black or Asian ethnicity and underlying medical conditions. Whether these factors also influence susceptibility to developing COVID-19 is uncertain. Methods: We undertook a prospective, population-based cohort study (COVIDENCE UK) from 1 st May 2020 to 5 th February 2021 . Baseline information on potential risk factors was captured by an online questionnaire. Monthly follow-up questionnaires captured incident COVID-19. We used logistic regression models to estimate multivariable-adjusted odds ratios (aORs) for associations between potential risk factors and risk of COVID-19. Findings: We recorded 446 incident cases of COVID-19 in 15,227 participants (2.9%). Increased risk of developing COVID-19 was independently associated with Asian/Asian British vs . White ethnicity (aOR 2.31, 95% CI 1.35-3.95), household overcrowding (aOR per additional 0.5 people/bedroom 1.26, 1.11-1.43) , any vs . no visits to/from other households in previous week (aOR 1.33, 1.07-1.64), number of visits to indoor public places (aOR per extra visit per week 1.05, 1.01-1.09), frontline occupation excluding health/social care vs. no frontline occupation (aOR 1.49, 1.12-1.98), and raised body mass index (BMI) (aOR 1.51 [1.20-1.90] for BMI 25.0-30.0 kg/m 2 and 1.38 [1.05-1.82] for BMI >30.0 kg/m 2 vs. BMI <25.0 kg/m 2 ). Atopic disease was independently associated with decreased risk (aOR 0.76, 0.59-0.98). No independent associations were seen for age, sex, other medical conditions, diet, or micronutrient supplement use. Interpretation: After rigorous adjustment for factors influencing exposure to SARS-CoV-2, Asian/Asian British ethnicity and raised BMI were associated with increased risk of developing COVID-19, while atopic disease was associated with decreased risk. Trial Registration: It is registered with ClinicalTrials.gov (NCT04330599). Funding: Barts Charity, Health Data Research UK Declaration of Interest: None to declare. Ethical Approval: The study was sponsored by Queen Mary University of London and approved by<br>Leicester South Research Ethics Committee (ref 20/EM/0117).
Subject(s)
COVID-19 , Obesity , Dermatitis, AtopicABSTRACT
Summary Background Risk factors for severe COVID-19 include older age, male sex, obesity, Black or Asian ethnicity and underlying medical conditions. Whether these factors also influence susceptibility to developing COVID-19 is uncertain. Methods We undertook a prospective, population-based cohort study (COVIDENCE UK) from 1 st May 2020 to 5 th February 2021. Baseline information on potential risk factors was captured by an online questionnaire. Monthly follow-up questionnaires captured incident COVID-19. We used logistic regression models to estimate multivariable-adjusted odds ratios (aORs) for associations between potential risk factors and risk of COVID-19. Findings We recorded 446 incident cases of COVID-19 in 15,227 participants (2.9%). Increased risk of developing COVID-19 was independently associated with Asian/Asian British vs . White ethnicity (aOR 2.31, 95% CI 1.35-3.95), household overcrowding (aOR per additional 0.5 people/bedroom 1.26, 1.11-1.43), any vs . no visits to/from other households in previous week (aOR 1.33, 1.07-1.64), number of visits to indoor public places (aOR per extra visit per week 1.05, 1.01-1.09), frontline occupation excluding health/social care vs . no frontline occupation (aOR 1.49, 1.12-1.98), and raised body mass index (BMI) (aOR 1.51 [1.20-1.90] for BMI 25.0-30.0 kg/m 2 and 1.38 [1.05-1.82] for BMI >30.0 kg/m 2 vs . BMI <25.0 kg/m 2 ). Atopic disease was independently associated with decreased risk (aOR 0.76, 0.59-0.98). No independent associations were seen for age, sex, other medical conditions, diet, or micronutrient supplement use. Interpretation After rigorous adjustment for factors influencing exposure to SARS-CoV-2, Asian/Asian British ethnicity and raised BMI were associated with increased risk of developing COVID-19, while atopic disease was associated with decreased risk. Funding Barts Charity, Health Data Research UK
Subject(s)
COVID-19 , Obesity , Dermatitis, AtopicABSTRACT
BackgroundTo externally validate a risk prediction algorithm (QCovid) to estimate mortality outcomes from COVID-19 in adults in England. MethodsPopulation-based cohort study using the ONS Public Health Linked Data Asset, a cohort based on the 2011 Census linked to Hospital Episode Statistics, the General Practice Extraction Service Data for pandemic planning and research, radiotherapy and systemic chemotherapy records. The primary outcome was time to COVID-19 death, defined as confirmed or suspected COVID-19 death as per death certification. Two time periods were used: (a) 24th January to 30th April 2020; and (b) 1st May to 28th July 2020. We evaluated the performance of the QCovid algorithms using measures of discrimination and calibration for each validation time period. FindingsThe study comprises 34,897,648 adults aged 19-100 years resident in England. There were 26,985 COVID-19 deaths during the first time-period and 13,177 during the second. The algorithms had good calibration in the validation cohort in both time periods with close correspondence of observed and predicted risks. They explained 77.1% (95% CI: 76.9% to 77.4%) of the variation in time to death in men in the first time-period (R2); the D statistic was 3.76 (95% CI: 3.73 to 3.79); Harrells C was 0.935 (0.933 to 0.937). Similar results were obtained for women, and in the second time-period. In the top 5% of patients with the highest predicted risks of death, the sensitivity for identifying deaths in the first time period was 65.9% for men and 71.7% for women. People in the top 20% of predicted risks of death accounted for 90.8% of all COVID-19 deaths for men and 93.0% for women. InterpretationThe QCovid population-based risk algorithm performed well, showing very high levels of discrimination for COVID-19 deaths in men and women for both time periods. It has the potential to be dynamically updated as the pandemic evolves and therefore, has potential use in guiding national policy. FundingNational Institute of Health Research RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSPublic policy measures and clinical risk assessment relevant to COVID-19 need to be aided by rigorously developed and validated risk prediction models. A recent living systematic review of published risk prediction models for COVID-19 found most models are subject to a high risk of bias with optimistic reported performance, raising concern that these models may be unreliable when applied in practice. A population-based risk prediction model, QCovid risk prediction algorithm, has recently been developed to identify adults at high risk of serious COVID-19 outcomes, which overcome many of the limitations of previous tools. Added value of this studyCommissioned by the Chief Medical Officer for England, we validated the novel clinical risk prediction model (QCovid) to identify risks of short-term severe outcomes due to COVID-19. We used national linked datasets from general practice, death registry and hospital episode data for a population-representative sample of over 34 million adults. The risk models have excellent discrimination in men and women (Harrells C statistic>0.9) and are well calibrated. QCovid represents a new, evidence-based opportunity for population risk-stratification. Implications of all the available evidenceQCovid has the potential to support public health policy, from enabling shared decision making between clinicians and patients in relation to health and work risks, to targeted recruitment for clinical trials, and prioritisation of vaccination, for example.
Subject(s)
COVID-19ABSTRACT
Background: Reports of ethnic inequalities in COVID-19 outcomes are conflicting and the reasons for any differences in outcomes are unclear. We investigated ethnic inequalities in critical care admission patterns, the need for invasive mechanical ventilation (IMV), and in-hospital mortality, among hospitalised patients with COVID-19. Methods: We undertook a prospective cohort study in which dedicated research staff recruited hospitalised patients with suspected/confirmed COVID-19 from 260 hospitals across England, Scotland and Wales, collecting data directly and from records between 6th February and 8th May 2020 with follow-up until 22nd May 2020. Analysis used hierarchical regression models accounting for confounding, competing risks, and clustering of patients in hospitals. Potential mediators for death were explored with a three-way decomposition mediation analysis. Findings: Of 34,986 patients enrolled, 30,693 (88%) had ethnicity recorded: South Asian (1,388, 5%), East Asian (266, 1%), Black (1,094, 4%), Other Ethnic Minority (2,398, 8%) (collectively Ethnic Minorities), and White groups (25,547, 83%). Ethnic Minorities were younger and more likely to have diabetes (type 1/type 2) but had fewer other comorbidities such as chronic heart disease or dementia than the White group. No difference was seen between ethnic groups in the time from symptom onset to hospital admission, nor in illness severity at admission. Critical care admission was more common in South Asian (odds ratio 1.28, 95% confidence interval 1.09 to 1.52), Black (1.36, 1.14 to 1.62), and Other Ethnic Minority (1.29, 1.13 to 1.47) groups compared to the White group, after adjusting for age, sex and location. This was broadly unchanged after adjustment for deprivation and comorbidities. Patterns were similar for IMV. Higher adjusted mortality was seen in the South Asian (hazard ratio 1.19, 1.05 to 1.36), but not East Asian (1.00, 0.74 to 1.35), Black (1.05, 0.91 to 1.26) or Other Ethnic Minority (0.99, 0.89 to 1.10) groups, compared to the White group. 18% (95% CI, 9% to 56%) of the excess mortality in South Asians was mediated by pre-existing diabetes. Interpretation: Ethnic Minorities in hospital with COVID-19 were more likely to be admitted to critical care and receive IMV than Whites, despite similar disease severity on admission, similar duration of symptoms, and being younger with fewer comorbidities. South Asians are at greater risk of dying, due at least in part to a higher prevalence of pre-existing diabetes. Trial Registration: The study was registered at https://www.isrctn.com/ISRCTN66726260. Funding Statement: This work is supported by grants from: the National Institute for Health Research [award CO-CIN-01], the Medical Research Council [grant MC_PC_19059] and by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford [NIHR award 200907], Wellcome Trust and Department for International Development [215091/Z/18/Z], and the Bill and Melinda Gates Foundation [OPP1209135], and Liverpool Experimental Cancer Medicine Centre for providing infrastructure support for this research (Grant Reference: C18616/A25153). JSN-V-T is seconded to the Department of Health and Social Care, England (DHSC).Declaration of Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: AB Docherty reports grants from Department of Health and Social Care, during the conduct of the study; grants from Wellcome Trust, outside the submitted work; CA Green reports grants from DHSC National Institute of Health Research UK, during the conduct of the study; PW Horby reports grants from Wellcome Trust / Department for International Development / Bill and Melinda Gates Foundation, grants from NIHR , during the conduct of the study; JS Nguyen-Van-Tam reports grants from Department of Health and Social Care, England, during the conduct of the study; and is seconded to the Department of Health and Social Care, England (DHSC); PJM Openshaw reports personal fees from consultancies and from European Respiratory Society; grants from MRC, MRC Global Challenge Research Fund, EU, NIHR Biomedical Research Centre, MRC/GSK, Wellcome Trust, NIHR (HPRU in Respiratory Infection), and NIHR Senior Investigator outside the submitted work. His role as President of the British Society for Immunology was unpaid but travel and accommodation at some meetings was provided by the Society. JK Baillie reports grants from Medical Research Council UK; MG Semple reports grants from DHSC National Institute of Health Research UK, grants from Medical Research Council UK, grants from Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool, during the conduct of the study; other from Integrum Scientific LLC, Greensboro, NC, USA, outside the submitted work. EM Harrison, H Ardwick, J Dunning, R Pius, L Norman, KA Holden, JM Read, G Carson, L Merson, J Lee, D Plotkin, L Sigfrid, S Halpin, C Jackson, and C Gamble, all declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.Ethics Approval Statement: Ethical approval was given by the South Central – Oxford C Research Ethics Committee in England (Ref: 13/SC/0149), and by the Scotland A Research Ethics Committee (Ref: 20/SS/0028).