Promoting inclusion in clinical trials-a rapid review of the literature and recommendations for action.

BACKGROUND: Without inclusion of diverse research participants, it is challenging to understand how study findings will translate into the real world. Despite this, a lack of inclusion of those from under-served groups in research is a prevailing problem due to multi-faceted barriers acting at multiple levels. Therefore, we rapidly reviewed international published literature, in relation to clinical trials, on barriers relating to inclusion, and evidence of approaches that are effective in overcoming these. METHODS: A rapid literature review was conducted searching PubMed for peer-reviewed articles that discussed barriers to inclusion or strategies to improve inclusion in clinical trial research published between 2010 and 2021. Grey literature articles were excluded. RESULTS: Seventy-two eligible articles were included. The main barriers identified were language and communication, lack of trust, access to trials, eligibility criteria, attitudes and beliefs, lack of knowledge around clinical trials, and logistical and practical issues. In relation to evidence-based strategies and enablers, two key themes arose: [1] a multi-faceted approach is essential [2]; no single strategy was universally effective either within or between trials. The key evidence-based strategies identified were cultural competency training, community partnerships, personalised approach, multilingual materials and staff, communication-specific strategies, increasing understanding and trust, and tackling logistical barriers. CONCLUSIONS: Many of the barriers relating to inclusion are the same as those that impact trial design and healthcare delivery generally. However, the presentation of these barriers among different under-served groups may be unique to each population's particular circumstances, background, and needs. Based on the literature, we make 15 recommendations that, if implemented, may help improve inclusion within clinical trials and clinical research more generally. The three main recommendations include improving cultural competency and sensitivity of all clinical trial staff through training and ongoing personal development, the need to establish a diverse community advisory panel for ongoing input into the research process, and increasing recruitment of staff from under-served groups. Implementation of these recommendations may help improve representation of under-served groups in clinical trials which would improve the external validity of associated findings.

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study.

BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4-6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5-8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (-19%; 95% CI -20 to -16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18-39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27-41% of this effect. INTERPRETATION: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. FUNDING: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.

COVID-19 vaccination uptake amongst ethnic minority communities in England: a linked study exploring the drivers of differential vaccination rates.

BACKGROUND: Despite generally high coronavirus disease 2019 (COVID-19) vaccination rates in the UK, vaccination hesitancy and lower take-up rates have been reported in certain ethnic minority communities. METHODS: We used vaccination data from the National Immunisation Management System (NIMS) linked to the 2011 Census and individual health records for subjects aged ≥40 years (n = 24 094 186). We estimated age-standardized vaccination rates, stratified by ethnic group and key sociodemographic characteristics, such as religious affiliation, deprivation, educational attainment, geography, living conditions, country of birth, language skills and health status. To understand the association of ethnicity with lower vaccination rates, we conducted a logistic regression model adjusting for differences in geographic, sociodemographic and health characteristics. ResultsAll ethnic groups had lower age-standardized rates of vaccination compared with the white British population, whose vaccination rate of at least one dose was 94% (95% CI: 94%-94%). Black communities had the lowest rates, with 75% (74-75%) of black African and 66% (66-67%) of black Caribbean individuals having received at least one dose. The drivers of these lower rates were partly explained by accounting for sociodemographic differences. However, modelled estimates showed significant differences remained for all minority ethnic groups, compared with white British individuals. CONCLUSIONS: Lower COVID-19 vaccination rates are consistently observed amongst all ethnic minorities.

The effect of COVID rehabilitation for ongoing symptoms Post HOSPitalisation with COVID-19 (PHOSP-R): protocol for a randomised parallel group controlled trial on behalf of the PHOSP consortium.

INTRODUCTION: Many adults hospitalised with COVID-19 have persistent symptoms such as fatigue, breathlessness and brain fog that limit day-to-day activities. These symptoms can last over 2 years. Whilst there is limited controlled studies on interventions that can support those with ongoing symptoms, there has been some promise in rehabilitation interventions in improving function and symptoms either using face-to-face or digital methods, but evidence remains limited and these studies often lack a control group. METHODS AND ANALYSIS: This is a nested single-blind, parallel group, randomised control trial with embedded qualitative evaluation comparing rehabilitation (face-to-face or digital) to usual care and conducted within the PHOSP-COVID study. The aim of this study is to determine the effectiveness of rehabilitation interventions on exercise capacity, quality of life and symptoms such as breathlessness and fatigue. The primary outcome is the Incremental Shuttle Walking Test following the eight week intervention phase. Secondary outcomes include measures of function, strength and subjective assessment of symptoms. Blood inflammatory markers and muscle biopsies are an exploratory outcome. The interventions last eight weeks and combine symptom-titrated exercise therapy, symptom management and education delivered either in a face-to-face setting or through a digital platform ( www.yourcovidrecovery.nhs.uk ). The proposed sample size is 159 participants, and data will be intention-to-treat analyses comparing rehabilitation (face-to-face or digital) to usual care. ETHICS AND DISSEMINATION: Ethical approval was gained as part of the PHOSP-COVID study by Yorkshire and the Humber Leeds West Research NHS Ethics Committee, and the study was prospectively registered on the ISRCTN trial registry (ISRCTN13293865). Results will be disseminated to stakeholders, including patients and members of the public, and published in appropriate journals. Strengths and limitations of this study • This protocol utilises two interventions to support those with ongoing symptoms of COVID-19 • This is a two-centre parallel-group randomised controlled trial • The protocol has been supported by patient and public involvement groups who identified treatments of symptoms and activity limitation as a top priority.

'Self-Management Intervention through Lifestyle Education for Kidney health' (the SMILE-K study): protocol for a single-blind longitudinal randomised controlled trial with nested pilot study.

INTRODUCTION: Many people living with chronic kidney disease (CKD) are expected to self-manage their condition. Patient activation is the term given to describe the knowledge, skills and confidence a person has in managing their own health and is closely related to the engagement in preventive health behaviours. Self-management interventions have the potential to improve remote disease management and health outcomes. We are testing an evidence-based and theory-based digital self-management structured 10-week programme developed for peoples with CKD called 'My Kidneys & Me'. The primary aim of the study (Self-Management Intervention through Lifestyle Education for Kidney health (SMILE-K)) is to assess the effect on patient activation levels. METHODS AND ANALYSIS: A single-blind randomised controlled trial (RCT) with a nested pilot study will assess the feasibility of the intervention and study design before continuation to a full RCT. Individuals aged 18 years or older, with established CKD stage 3-4 (eGFR of 15-59 mL/min/1.73 m2) will be recruited through both primary and secondary care pathways. Participants will be randomised into two groups: intervention group (receive My Kidneys & Me in addition to usual care) and control group (usual care). The primary outcome of the nested pilot study is feasibility and the primary outcome of the full RCT is the Patient Activation Measu (PAM-13). The full RCT will assess the effect of the programme on online self-reported outcomes which will be assessed at baseline, after 10 weeks, and then after 20 weeks in both groups. A total sample size of N=432 participants are required based on a 2:1 randomisation. A substudy will measure physiological changes (eg, muscle mass, physical function) and patient experience (qualitative semi-structured interviews). ETHICS AND DISSEMINATION: This study was fully approved by the Research Ethics Committee-Leicester South on the 19 November 2020 (reference: 17/EM/0357). All participants are required to provide informed consent obtained online. The results are expected to be published in scientific journals and presented at clinical research conferences. This is protocol version 1.0 dated 27 January 2021. TRIAL REGISTRATION NUMBER: ISRCTN18314195.

Effectiveness of an intervention for reducing sitting time and improving health in office workers: three arm cluster randomised controlled trial.

OBJECTIVES: To evaluate the effectiveness of an intervention, with and without a height adjustable desk, on daily sitting time, and to investigate the relative effectiveness of the two interventions, and the effectiveness of both interventions on physical behaviours and physical, biochemical, psychological, and work related health and performance outcomes. DESIGN: Cluster three arm randomised controlled trial with follow-up at three and 12 months. SETTING: Local government councils in Leicester, Liverpool, and Greater Manchester, UK. PARTICIPANTS: 78 clusters including 756 desk based employees in defined offices, departments, or teams from two councils in Leicester, three in Greater Manchester, and one in Liverpool. INTERVENTIONS: Clusters were randomised to one of three conditions: the SMART Work and Life (SWAL) intervention, the SWAL intervention with a height adjustable desk (SWAL plus desk), or control (usual practice). MAIN OUTCOMES MEASURES: The primary outcome measure was daily sitting time, assessed by accelerometry, at 12 month follow-up. Secondary outcomes were accelerometer assessed sitting, prolonged sitting, standing and stepping time, and physical activity calculated over any valid day, work hours, workdays, and non-workdays, self-reported lifestyle behaviours, musculoskeletal problems, cardiometabolic health markers, work related health and performance, fatigue, and psychological measures. RESULTS: Mean age of participants was 44.7 years, 72.4% (n=547) were women, and 74.9% (n=566) were white. Daily sitting time at 12 months was significantly lower in the intervention groups (SWAL -22.2 min/day, 95% confidence interval -38.8 to -5.7 min/day, P=0.003; SWAL plus desk -63.7 min/day, -80.1 to -47.4 min/day, P<0.001) compared with the control group. The SWAL plus desk intervention was found to be more effective than SWAL at changing sitting time (-41.7 min/day, -56.3 to -27.0 min/day, P<0.001). Favourable differences in sitting and prolonged sitting time at three and 12 month follow-ups for both intervention groups and for standing time for the SWAL plus desk group were observed during work hours and on workdays. Both intervention groups were associated with small improvements in stress, wellbeing, and vigour, and the SWAL plus desk group was associated with improvements in pain in the lower extremity, social norms for sitting and standing at work, and support. CONCLUSIONS: Both SWAL and SWAL plus desk were associated with a reduction in sitting time, although the addition of a height adjustable desk was found to be threefold more effective. TRIAL REGISTRATION: ISRCTN Registry ISRCTN11618007.

Risk of covid-19 related deaths for SARS-CoV-2 omicron (B.1.1.529) compared with delta (B.1.617.2): retrospective cohort study.

OBJECTIVE: To assess the risk of covid-19 death after infection with omicron BA.1 compared with delta (B.1.617.2). DESIGN: Retrospective cohort study. SETTING: England, United Kingdom, from 1 December 2021 to 30 December 2021. PARTICIPANTS: 1 035 149 people aged 18-100 years who tested positive for SARS-CoV-2 under the national surveillance programme and had an infection identified as omicron BA.1 or delta compatible. MAIN OUTCOME MEASURES: The main outcome measure was covid-19 death as identified from death certification records. The exposure of interest was the SARS-CoV-2 variant identified from NHS Test and Trace PCR positive tests taken in the community (pillar 2) and analysed by Lighthouse laboratories. Cause specific Cox proportional hazard regression models (censoring non-covid-19 deaths) were adjusted for sex, age, vaccination status, previous infection, calendar time, ethnicity, index of multiple deprivation rank, household deprivation, university degree, keyworker status, country of birth, main language, region, disability, and comorbidities. Interactions between variant and sex, age, vaccination status, and comorbidities were also investigated. RESULTS: The risk of covid-19 death was 66% lower (95% confidence interval 54% to 75%) for omicron BA.1 compared with delta after adjusting for a wide range of potential confounders. The reduction in the risk of covid-19 death for omicron compared with delta was more pronounced in people aged 18-59 years (number of deaths: delta=46, omicron=11; hazard ratio 0.14, 95% confidence interval 0.07 to 0.27) than in those aged ≥70 years (number of deaths: delta=113, omicron=135; hazard ratio 0.44, 95% confidence interval 0.32 to 0.61, P<0.0001). No evidence of a difference in risk was found between variant and number of comorbidities. CONCLUSIONS: The results support earlier studies showing a reduction in severity of infection with omicron BA.1 compared with delta in terms of hospital admission. This study extends the research to also show a reduction in the risk of covid-19 death for the omicron variant compared with the delta variant.

The impact of obesity on severe disease and mortality in people with SARS-CoV-2: A systematic review and meta-analysis.

Background: Obesity accompanied by excess ectopic fat storage has been postulated as a risk factor for severe disease in people with SARS-CoV-2 through the stimulation of inflammation, functional immunologic deficit and a pro-thrombotic disseminated intravascular coagulation with associated high rates of venous thromboembolism. Methods: Observational studies in COVID-19 patients reporting data on raised body mass index at admission and associated clinical outcomes were identified from MEDLINE, Embase, Web of Science and the Cochrane Library up to 16 May 2020. Mean differences and relative risks (RR) with 95% confidence intervals (CIs) were aggregated using random effects models. Results: Eight retrospective cohort studies and one cohort prospective cohort study with data on of 4,920 patients with COVID-19 were eligible. Comparing BMI ≥ 25 vs <25 kg/m2, the RRs (95% CIs) of severe illness and mortality were 2.35 (1.43-3.86) and 3.52 (1.32-9.42), respectively. In a pooled analysis of three studies, the RR (95% CI) of severe illness comparing BMI > 35 vs <25 kg/m2 was 7.04 (2.72-18.20). High levels of statistical heterogeneity were partly explained by age; BMI ≥ 25 kg/m2 was associated with an increased risk of severe illness in older age groups (≥60 years), whereas the association was weaker in younger age groups (<60 years). Conclusions: Excess adiposity is a risk factor for severe disease and mortality in people with SARS-CoV-2 infection. This was particularly pronounced in people 60 and older. The increased risk of worse outcomes from SARS-CoV-2 infection in people with excess adiposity should be taken into account when considering individual and population risks and when deciding on which groups to target for public health messaging on prevention and detection measures. Systematic review registration: PROSPERO 2020: CRD42020179783.

Physical activity and sedentary behaviour interventions for people living with both frailty and multiple long-term conditions: a scoping review protocol

IntroductionThe number of people living with multiple long-term conditions (MLTCs) is predicted to rise. Within this population, those also living with frailty are particularly vulnerable to poor outcomes, including decreased function. Increased physical activity, including exercise, has the potential to improve function in those living with both MLTCs and frailty but, to date, the focus has remained on older people and may not reflect outcomes for the growing number of younger people living with MLTCs and frailty. For those with higher burdens of frailty and MLTCs, physical activity may be challenging. Tailoring physical activity in response to symptoms and periods of ill-health, involving family and reducing sedentary behaviour may be important in this population. How the tailoring of interventions has been approached within existing studies is currently unclear. This scoping review aims to map the available evidence regarding these interventions in people living with both frailty and MLTCs.Methods and analysisWe will use a six-stage process: (1) identifying the research questions;(2) identifying relevant studies (via database searches);(3) selecting studies;(4) charting the data;(5) collating and summarising and (6) stakeholder consultation. Studies will be critically appraised using the Mixed Methods Appraisal Tool.Ethics and disseminationAll data in this project will be gathered through database searches. Stakeholder consultation will be undertaken with an established patient and public involvement group. We will disseminate our findings via social media, publication and engagement meetings.

Sociodemographic inequality in COVID-19 vaccination coverage among elderly adults in England: a national linked data study

ObjectiveTo examine inequalities in COVID-19 vaccination rates among elderly adults in England.DesignCohort study.SettingPeople living in private households and communal establishments in England.Participants6 655 672 adults aged ≥70 years (mean 78.8 years, 55.2% women) who were alive on 15 March 2021.Main outcome measuresHaving received the first dose of a vaccine against COVID-19 by 15 March 2021. We calculated vaccination rates and estimated unadjusted and adjusted ORs using logistic regression models.ResultsBy 15 March 2021, 93.2% of people living in England aged 70 years and over had received at least one dose of a COVID-19 vaccine. While vaccination rates differed across all factors considered apart from sex, the greatest disparities were seen between ethnic and religious groups. The lowest rates were in people of black African and black Caribbean ethnic backgrounds, where only 67.2% and 73.8% had received a vaccine, with adjusted odds of not being vaccinated at 5.01 (95% CI 4.86 to 5.16) and 4.85 (4.75 to 4.96) times greater than the white British group. The proportion of individuals self-identifying as Muslim and Buddhist who had received a vaccine was 79.1% and 84.1%, respectively. Older age, greater area deprivation, less advantaged socioeconomic position (proxied by living in a rented home), being disabled and living either alone or in a multigenerational household were also associated with higher odds of not having received the vaccine.ConclusionResearch is now urgently needed to understand why disparities exist in these groups and how they can best be addressed through public health policy and community engagement.

Monitoring sociodemographic inequality in COVID-19 vaccination uptake in England: a national linked data study.

BACKGROUND: The UK began an ambitious COVID-19 vaccination programme on 8 December 2020. This study describes variation in vaccination uptake by sociodemographic characteristics between December 2020 and August 2021. METHODS: Using population-level administrative records linked to the 2011 Census, we estimated monthly first dose vaccination rates by age group and sociodemographic characteristics among adults aged 18 years or over in England. We also present a tool to display the results interactively. RESULTS: Our sample included 35 223 466 adults. A lower percentage of males than females were vaccinated in the young and middle age groups (18-59 years) but not in the older age groups. Vaccination rates were highest among individuals of White British and Indian ethnic backgrounds and lowest among Black Africans (aged ≥80 years) and Black Caribbeans (18-79 years). Differences by ethnic group emerged as soon as vaccination roll-out commenced and widened over time. Vaccination rates were also lower among individuals who identified as Muslim, lived in more deprived areas, reported having a disability, did not speak English as their main language, lived in rented housing, belonged to a lower socioeconomic group, and had fewer qualifications. CONCLUSION: We found inequalities in COVID-19 vaccination uptake rates by sex, ethnicity, religion, area deprivation, disability status, English language proficiency, socioeconomic position and educational attainment, but some of these differences varied by age group. Research is urgently needed to understand why these inequalities exist and how they can be addressed.

Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19.

OBJECTIVE: To investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications. RESEARCH DESIGN AND METHODS: In this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors. RESULTS: Cardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8-8.7) (120.6 mg/dL [104.4-156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age <69 years. Preexisting diabetes status had a similar modifying effect on odds of complications, but evidence was strongest for renal injury, cardiac ischemia, and any cardiovascular/renal complication. CONCLUSIONS: Increased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes.

A population-based cohort study of obesity, ethnicity and COVID-19 mortality in 12.6 million adults in England.

Obesity and ethnicity are known risk factors for COVID-19 outcomes, but their combination has not been extensively examined. We investigate the association between body mass index (BMI) and COVID-19 mortality across different ethnic groups using linked national Census, electronic health records and mortality data for adults in England from the start of pandemic (January 2020) to December 2020. There were 30,067 (0.27%), 1,208 (0.29%), 1,831 (0.29%), 845 (0.18%) COVID-19 deaths in white, Black, South Asian and other ethnic minority groups, respectively. Here we show that BMI was more strongly associated with COVID-19 mortality in ethnic minority groups, resulting in an ethnic risk of COVID-19 mortality that was dependant on BMI. The estimated risk of COVID-19 mortality at a BMI of 40 kg/m2 in white ethnicities was equivalent to the risk observed at a BMI of 30.1 kg/m2, 27.0 kg/m2, and 32.2 kg/m2 in Black, South Asian and other ethnic minority groups, respectively.

Ethnic minorities and COVID-19: examining whether excess risk is mediated through deprivation.

BACKGROUND: People from South Asian and black minority ethnic groups are disproportionately affected by the COVID-19 pandemic. It is unknown whether deprivation mediates this excess ethnic risk. METHODS: We used UK Biobank with linked COVID-19 outcomes occurring between 16th March 2020 and 24th August 2020. A four-way decomposition mediation analysis was used to model the extent to which the excess risk of testing positive, severe disease and mortality for COVID-19 in South Asian and black individuals, relative to white individuals, would be eliminated if levels of high material deprivation were reduced within the population. RESULTS: We included 15 044 (53.0% women) South Asian and black and 392 786 (55.2% women) white individuals. There were 151 (1.0%) positive tests, 91 (0.6%) severe cases and 31 (0.2%) deaths due to COVID-19 in South Asian and black individuals compared with 1471 (0.4%), 895 (0.2%) and 313 (0.1%), respectively, in white individuals. Compared with white individuals, the relative risk of testing positive for COVID-19, developing severe disease and COVID-19 mortality in South Asian and black individuals were 2.73 (95% CI: 2.26, 3.19), 2.96 (2.31, 3.61) and 4.04 (2.54, 5.55), respectively. A hypothetical intervention moving the 25% most deprived in the population out of deprivation was modelled to eliminate between 40 and 50% of the excess risk of all COVID-19 outcomes in South Asian and black populations, whereas moving the 50% most deprived out of deprivation would eliminate over 80% of the excess risk of COVID-19 outcomes. CONCLUSIONS: The excess risk of COVID-19 outcomes in South Asian and black communities could be substantially reduced with population level policies targeting material deprivation.

Impact of cardiometabolic multimorbidity and ethnicity on cardiovascular/renal complications in patients with COVID-19.

OBJECTIVE: Using a large national database of people hospitalised with COVID-19, we investigated the contribution of cardio-metabolic conditions, multi-morbidity and ethnicity on the risk of in-hospital cardiovascular complications and death. METHODS: A multicentre, prospective cohort study in 302 UK healthcare facilities of adults hospitalised with COVID-19 between 6 February 2020 and 16 March 2021. Logistic models were used to explore associations between baseline patient ethnicity, cardiometabolic conditions and multimorbidity (0, 1, 2, >2 conditions), and in-hospital cardiovascular complications (heart failure, arrhythmia, cardiac ischaemia, cardiac arrest, coagulation complications, stroke), renal injury and death. RESULTS: Of 65 624 patients hospitalised with COVID-19, 44 598 (68.0%) reported at least one cardiometabolic condition on admission. Cardiovascular/renal complications or death occurred in 24 609 (38.0%) patients. Baseline cardiometabolic conditions were independently associated with increased odds of in-hospital complications and this risk increased in the presence of cardiometabolic multimorbidity. For example, compared with having no cardiometabolic conditions, 1, 2 or ≥3 conditions was associated with 1.46 (95% CI 1.39 to 1.54), 2.04 (95% CI 1.93 to 2.15) and 3.10 (95% CI 2.92 to 3.29) times higher odds of any cardiovascular/renal complication, respectively. A similar pattern was observed for all-cause death. Compared with the white group, the South Asian (OR 1.19, 95% CI 1.10 to 1.29) and black (OR 1.53 to 95% CI 1.37 to 1.72) ethnic groups had higher risk of any cardiovascular/renal complication. CONCLUSIONS: In hospitalised patients with COVID-19, cardiovascular complications or death impacts just under half of all patients, with the highest risk in those of South Asian or Black ethnicity and in patients with cardiometabolic multimorbidity.

Patterns of multimorbidity and risk of severe SARS-CoV-2 infection: an observational study in the U.K.

BACKGROUND: Pre-existing comorbidities have been linked to SARS-CoV-2 infection but evidence is sparse on the importance and pattern of multimorbidity (2 or more conditions) and severity of infection indicated by hospitalisation or mortality. We aimed to use a multimorbidity index developed specifically for COVID-19 to investigate the association between multimorbidity and risk of severe SARS-CoV-2 infection. METHODS: We used data from the UK Biobank linked to laboratory confirmed test results for SARS-CoV-2 infection and mortality data from Public Health England between March 16 and July 26, 2020. By reviewing the current literature on COVID-19 we derived a multimorbidity index including: (1) angina; (2) asthma; (3) atrial fibrillation; (4) cancer; (5) chronic kidney disease; (6) chronic obstructive pulmonary disease; (7) diabetes mellitus; (8) heart failure; (9) hypertension; (10) myocardial infarction; (11) peripheral vascular disease; (12) stroke. Adjusted logistic regression models were used to assess the association between multimorbidity and risk of severe SARS-CoV-2 infection (hospitalisation/death). Potential effect modifiers of the association were assessed: age, sex, ethnicity, deprivation, smoking status, body mass index, air pollution, 25-hydroxyvitamin D, cardiorespiratory fitness, high sensitivity C-reactive protein. RESULTS: Among 360,283 participants, the median age was 68 [range 48-85] years, most were White (94.5%), and 1706 had severe SARS-CoV-2 infection. The prevalence of multimorbidity was more than double in those with severe SARS-CoV-2 infection (25%) compared to those without (11%), and clusters of several multimorbidities were more common in those with severe SARS-CoV-2 infection. The most common clusters with severe SARS-CoV-2 infection were stroke with hypertension (79% of those with stroke had hypertension); diabetes and hypertension (72%); and chronic kidney disease and hypertension (68%). Multimorbidity was independently associated with a greater risk of severe SARS-CoV-2 infection (adjusted odds ratio 1.91 [95% confidence interval 1.70, 2.15] compared to no multimorbidity). The risk remained consistent across potential effect modifiers, except for greater risk among older age. The highest risk of severe infection was strongly evidenced in those with CKD and diabetes (4.93 [95% CI 3.36, 7.22]). CONCLUSION: The multimorbidity index may help identify individuals at higher risk for severe COVID-19 outcomes and provide guidance for tailoring effective treatment.

Obesity, chronic disease, age, and in-hospital mortality in patients with covid-19: analysis of ISARIC clinical characterisation protocol UK cohort.

BACKGROUND: Although age, obesity and pre-existing chronic diseases are established risk factors for COVID-19 outcomes, their interactions have not been well researched. METHODS: We used data from the Clinical Characterisation Protocol UK (CCP-UK) for Severe Emerging Infection developed by the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC). Patients admitted to hospital with COVID-19 from 6th February to 12th October 2020 were included where there was a coded outcome following hospital admission. Obesity was determined by an assessment from a clinician and chronic disease by medical records. Chronic diseases included: chronic cardiac disease, hypertension, chronic kidney disease, chronic pulmonary disease, diabetes and cancer. Mutually exclusive categories of obesity, with or without chronic disease, were created. Associations with in-hospital mortality were examined across sex and age categories. RESULTS: The analysis included 27,624 women with 6407 (23.2%) in-hospital deaths and 35,065 men with 10,001 (28.5%) in-hospital deaths. The prevalence of chronic disease in women and men was 66.3 and 68.5%, respectively, while that of obesity was 12.9 and 11.1%, respectively. Association of obesity and chronic disease status varied by age (p < 0.001). Under 50 years of age, obesity and chronic disease were associated with in-hospital mortality within 28 days of admission in a dose-response manner, such that patients with both obesity and chronic disease had the highest risk with a hazard ratio (HR) of in-hospital mortality of 2.99 (95% CI: 2.12, 4.21) in men and 2.16 (1.42, 3.26) in women compared to patients without obesity or chronic disease. Between the ages of 50-69 years, obesity and chronic disease remained associated with in-hospital COVID-19 mortality, but survival in those with obesity was similar to those with and without prevalent chronic disease. Beyond the age of 70 years in men and 80 years in women there was no meaningful difference between those with and without obesity and/or chronic disease. CONCLUSION: Obesity and chronic disease are important risk factors for in-hospital mortality in younger age groups, with the combination of chronic disease and obesity being particularly important in those under 50 years of age. These findings have implications for targeted public health interventions, vaccination strategies and in-hospital clinical decision making.

Sociodemographic inequality in COVID-19 vaccination coverage among elderly adults in England: a national linked data study.

OBJECTIVE: To examine inequalities in COVID-19 vaccination rates among elderly adults in England. DESIGN: Cohort study. SETTING: People living in private households and communal establishments in England. PARTICIPANTS: 6 655 672 adults aged ≥70 years (mean 78.8 years, 55.2% women) who were alive on 15 March 2021. MAIN OUTCOME MEASURES: Having received the first dose of a vaccine against COVID-19 by 15 March 2021. We calculated vaccination rates and estimated unadjusted and adjusted ORs using logistic regression models. RESULTS: By 15 March 2021, 93.2% of people living in England aged 70 years and over had received at least one dose of a COVID-19 vaccine. While vaccination rates differed across all factors considered apart from sex, the greatest disparities were seen between ethnic and religious groups. The lowest rates were in people of black African and black Caribbean ethnic backgrounds, where only 67.2% and 73.8% had received a vaccine, with adjusted odds of not being vaccinated at 5.01 (95% CI 4.86 to 5.16) and 4.85 (4.75 to 4.96) times greater than the white British group. The proportion of individuals self-identifying as Muslim and Buddhist who had received a vaccine was 79.1% and 84.1%, respectively. Older age, greater area deprivation, less advantaged socioeconomic position (proxied by living in a rented home), being disabled and living either alone or in a multigenerational household were also associated with higher odds of not having received the vaccine. CONCLUSION: Research is now urgently needed to understand why disparities exist in these groups and how they can best be addressed through public health policy and community engagement.