Impact of vaccination on the association of COVID-19 with cardiovascular diseases: An OpenSAFELY cohort study.

Infection with SARS-CoV-2 is associated with an increased risk of arterial and venous thrombotic events, but the implications of vaccination for this increased risk are uncertain. With the approval of NHS England, we quantified associations between COVID-19 diagnosis and cardiovascular diseases in different vaccination and variant eras using linked electronic health records for ~40% of the English population. We defined a 'pre-vaccination' cohort (18,210,937 people) in the wild-type/Alpha variant eras (January 2020-June 2021), and 'vaccinated' and 'unvaccinated' cohorts (13,572,399 and 3,161,485 people respectively) in the Delta variant era (June-December 2021). We showed that the incidence of each arterial thrombotic, venous thrombotic and other cardiovascular outcomes was substantially elevated during weeks 1-4 after COVID-19, compared with before or without COVID-19, but less markedly elevated in time periods beyond week 4. Hazard ratios were higher after hospitalised than non-hospitalised COVID-19 and higher in the pre-vaccination and unvaccinated cohorts than the vaccinated cohort. COVID-19 vaccination reduces the risk of cardiovascular events after COVID-19 infection. People who had COVID-19 before or without being vaccinated are at higher risk of cardiovascular events for at least two years.

Characterising patterns of COVID-19 and long COVID symptoms: evidence from nine UK longitudinal studies.

Multiple studies across global populations have established the primary symptoms characterising Coronavirus Disease 2019 (COVID-19) and long COVID. However, as symptoms may also occur in the absence of COVID-19, a lack of appropriate controls has often meant that specificity of symptoms to acute COVID-19 or long COVID, and the extent and length of time for which they are elevated after COVID-19, could not be examined. We analysed individual symptom prevalences and characterised patterns of COVID-19 and long COVID symptoms across nine UK longitudinal studies, totalling over 42,000 participants. Conducting latent class analyses separately in three groups ('no COVID-19', 'COVID-19 in last 12 weeks', 'COVID-19 > 12 weeks ago'), the data did not support the presence of more than two distinct symptom patterns, representing high and low symptom burden, in each group. Comparing the high symptom burden classes between the 'COVID-19 in last 12 weeks' and 'no COVID-19' groups we identified symptoms characteristic of acute COVID-19, including loss of taste and smell, fatigue, cough, shortness of breath and muscle pains or aches. Comparing the high symptom burden classes between the 'COVID-19 > 12 weeks ago' and 'no COVID-19' groups we identified symptoms characteristic of long COVID, including fatigue, shortness of breath, muscle pain or aches, difficulty concentrating and chest tightness. The identified symptom patterns among individuals with COVID-19 > 12 weeks ago were strongly associated with self-reported length of time unable to function as normal due to COVID-19 symptoms, suggesting that the symptom pattern identified corresponds to long COVID. Building the evidence base regarding typical long COVID symptoms will improve diagnosis of this condition and the ability to elicit underlying biological mechanisms, leading to better patient access to treatment and services.

Leafier Communities, Healthier Hearts: An Australian Cohort Study of 104,725 Adults Tracking Cardiovascular Events and Mortality Across 10 Years of Linked Health Data.

OBJECTIVE: Green space reduces cardiovascular disease (CVD) risk, but few studies examine what types of green space matter, which is an important consideration as cities densify and apartments become more common. METHOD: Participants were 86,727 in houses and 17,998 in apartments from the 45 and Up Study (Sax Institute) baseline survey with 10 years of linked hospitalisation and death data used to define: (i) all-cause; and (ii) CVD-mortality; (iii) fatal and non-fatal CVD events; and (iv) acute myocardial infarction (AMI). Associations with total green space, tree canopy cover and open grass within 1.6 km buffers were assessed using survival analysis adjusted for potential confounders. RESULTS: Mean percentage green space indicators were all higher among participants in houses than in apartments. Among residents of houses, a 10% increase in total green space was associated with reduced risk of CVD mortality (HR 0.97, 95%CI 0.95-1.00). A 10% increase in tree canopy cover was associated with reduced risks of all-cause mortality (HR 0.97, 95%CI 0.95-0.99), CVD mortality (HR 0.96, 95%CI 0.93-0.98), and fatal or non-fatal AMI (HR 0.93, 95%CI 0.89-0.96). In contrast, a 10% increase in open grass was associated with an increased risk of fatal or non-fatal AMI (HR 1.15, 95%CI 1.09-1.20) in residents of houses. Among residents of apartments, a 10% increase in total green space was associated with increased risk of all-cause mortality (HR 1.04, 95%CI 1.00-1.08) and CVD mortality (HR 1.03, 95%CI 1.00-1.08). CONCLUSIONS: Urban reforestation may be a population-level intervention to protect cardiovascular health, especially for people living in houses. The intersection of urban greening and cardiovascular health among residents of apartments warrants further investigation.

Association of COVID-19 With Major Arterial and Venous Thrombotic Diseases: A Population-Wide Cohort Study of 48 Million Adults in England and Wales.

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a prothrombotic state, but long-term effects of COVID-19 on incidence of vascular diseases are unclear. METHODS: We studied vascular diseases after COVID-19 diagnosis in population-wide anonymized linked English and Welsh electronic health records from January 1 to December 7, 2020. We estimated adjusted hazard ratios comparing the incidence of arterial thromboses and venous thromboembolic events (VTEs) after diagnosis of COVID-19 with the incidence in people without a COVID-19 diagnosis. We conducted subgroup analyses by COVID-19 severity, demographic characteristics, and previous history. RESULTS: Among 48 million adults, 125 985 were hospitalized and 1 319 789 were not hospitalized within 28 days of COVID-19 diagnosis. In England, there were 260 279 first arterial thromboses and 59 421 first VTEs during 41.6 million person-years of follow-up. Adjusted hazard ratios for first arterial thrombosis after COVID-19 diagnosis compared with no COVID-19 diagnosis declined from 21.7 (95% CI, 21.0-22.4) in week 1 after COVID-19 diagnosis to 1.34 (95% CI, 1.21-1.48) during weeks 27 to 49. Adjusted hazard ratios for first VTE after COVID-19 diagnosis declined from 33.2 (95% CI, 31.3-35.2) in week 1 to 1.80 (95% CI, 1.50-2.17) during weeks 27 to 49. Adjusted hazard ratios were higher, for longer after diagnosis, after hospitalized versus nonhospitalized COVID-19, among Black or Asian versus White people, and among people without versus with a previous event. The estimated whole-population increases in risk of arterial thromboses and VTEs 49 weeks after COVID-19 diagnosis were 0.5% and 0.25%, respectively, corresponding to 7200 and 3500 additional events, respectively, after 1.4 million COVID-19 diagnoses. CONCLUSIONS: High relative incidence of vascular events soon after COVID-19 diagnosis declines more rapidly for arterial thromboses than VTEs. However, incidence remains elevated up to 49 weeks after COVID-19 diagnosis. These results support policies to prevent severe COVID-19 by means of COVID-19 vaccines, early review after discharge, risk factor control, and use of secondary preventive agents in high-risk patients.

The nexus between urban green space, housing type, and mental health.

INTRODUCTION: Momentum for urban densification is increasing opportunities for apartment-living, but can result in reduced green space availability that negatively influences mental health. However, in contexts where apartment-living is atypical and commonly viewed as secondary to house-ownership, it may be a stressful antecedent condition (or marker of selective processes aligned with psychological distress) wherein occupants could benefit disproportionately from green space. METHOD: Data were extracted from the Sax Institute's 45 and Up Study baseline (2006-2009, n = 267,153). The focus was on subsets of 13,196 people living in apartments and 66,453 people living in households within the cities of Sydney, Newcastle and Wollongong. Multilevel models adjusted for confounders tested associations between psychological distress (Kessler 10 scale) with percentage total green space, tree canopy and open grass within 1.6 km road network buffers. RESULTS: Psychological distress was higher in occupants of apartments (11.3%) compared with houses (7.9%). More green space was associated with less psychological distress for house-dwellers (OR = 0.94, 95% CI = 0.91-0.98), but there was no association for apartment-dwellers. More tree canopy was associated with lower psychological distress for house-dwellers (OR = 0.88, 95% CI = 0.85-0.92) and apartment-dwellers (OR = 0.87, 95% CI = 0.79-0.96). Open grass was associated with more psychological distress among house-dwellers (OR = 1.06, 95% CI = 1.00-1.13) and also for apartment-dwellers (OR = 1.20, 95% CI = 1.07-1.35). CONCLUSIONS: Overall, investments in tree canopy may benefit the mental health of house and apartment residents relatively equally. Urban tree canopy in densely populated areas where apartments are common needs to be protected. Further work is needed to understand factors constraining the prevention potential of open grass, to unlock its benefits for mental health.

Geographic variation in cardiometabolic risk factor prevalence explained by area-level disadvantage in the Illawarra-Shoalhaven region of the NSW, Australia.

Cardiometabolic risk factors (CMRFs) demonstrate significant geographic variation in their distribution. The study aims to quantify the general contextual effect of the areas on CMRFs; and the geographic variation explained by area-level socioeconomic disadvantage. A cross sectional design and multilevel logistic regression methods were adopted. Data included objectively measured routine pathology test data between years 2012 and 2017 on: fasting blood sugar level; glycated haemoglobin; total cholesterol; high density lipoprotein; urinary albumin creatinine ratio; estimated glomerular filtration rate; and body mass index. The 2011 Australian census based Index of Relative Socioeconomic Disadvantage (IRSD) were the area-level study variables, analysed at its smallest geographic unit of reporting. A total of 1,132,029 CMRF test results from 256,525 individuals were analysed. After adjusting for individual-level covariates, all CMRFs significantly associated with IRSD and the probability of higher risk CMRFs increases with greater area-level disadvantage. Though the specific contribution of IRSD in the geographic variation of CMRF ranged between 57.8 and 14.71%, the general contextual effect of areas were found minimal (ICCs 0.6-3.4%). The results support universal interventions proportional to the need and disadvantage level of populations for the prevention and control of CMRFs, rather than any area specific interventions as the contextual effects were found minimal in the study region.

Role of Area-Level Access to Primary Care on the Geographic Variation of Cardiometabolic Risk Factor Distribution: A Multilevel Analysis of the Adult Residents in the Illawarra-Shoalhaven Region of NSW, Australia.

BACKGROUND: Access to primary care is important for the identification, control and management of cardiometabolic risk factors (CMRFs). This study investigated whether differences in geographic access to primary care explained area-level variation in CMRFs. METHODS: Multilevel logistic regression models were used to derive the association between area-level access to primary care and seven discrete CMRFs after adjusting for individual and area-level co-variates. Two-step floating catchment area method was used to calculate the geographic access to primary care for the small areas within the study region. RESULTS: Geographic access to primary care was inversely associated with low high density lipoprotein (OR 0.94, CI 0.91-0.96) and obesity (OR 0.91, CI 0.88-0.93), after adjusting for age, sex and area-level disadvantage. The intra-cluster correlation coefficient (ICCs) of all the fully adjusted models ranged between 0.4-1.8%, indicating low general contextual effects of the areas on CMRF distribution. The area-level variation in CMRFs explained by primary care access was ≤10.5%. CONCLUSION: The findings of the study support proportionate universal interventions for the prevention and control of CMRFs, rather than any area specific interventions based on their primary care access, as the contextual influence of areas on all the analysed CMRFs were found to be minimal. The findings also call for future research that includes other aspects of primary care access, such as road-network access, financial affordability and individual-level acceptance of the services in order to gain an overall picture of the area-level contributing role of primary care on CMRFs in the study region.

Geographic variation in cardiometabolic risk distribution: A cross-sectional study of 256,525 adult residents in the Illawarra-Shoalhaven region of the NSW, Australia.

INTRODUCTION: Metabolic risk factors for cardiovascular disease (CVD) warrant significant public health concern globally. This study aims to utilise the regional database of a major laboratory network to describe the geographic distribution pattern of eight different cardiometabolic risk factors (CMRFs), which in turn can potentially generate hypotheses for future research into locality specific preventive approaches. METHOD: A cross-sectional design utilising de-identified laboratory data on eight CMRFs including fasting blood sugar level (FBSL); glycated haemoglobin (HbA1c); total cholesterol (TC); high density lipoprotein (HDL); albumin creatinine ratio (ACR); estimated glomerular filtration rate (eGFR); body mass index (BMI); and diabetes mellitus (DM) status was used to undertake descriptive and spatial analyses. CMRF test results were dichotomised into 'higher risk' and 'lower risk' values based on existing risk definitions. Australian Census Statistical Area Level 1 (SA1) were used as the geographic units of analysis, and an Empirical Bayes (EB) approach was used to smooth rates at SA1 level. Choropleth maps demonstrating the distribution of CMRFs rates at SA1 level were produced. Spatial clustering of CMRFs was assessed using Global Moran's I test and Local Indicators of Spatial Autocorrelation (LISA). RESULTS: A total of 1,132,016 test data derived from 256,525 individuals revealed significant geographic variation in the distribution of 'higher risk' CMRF findings. The populated eastern seaboard of the study region demonstrated the highest rates of CMRFs. Global Moran's I values were significant and positive at SA1 level for all CMRFs. The highest spatial autocorrelation strength was found among obesity rates (0.328), and the lowest for albuminuria (0.028). LISA tests identified significant High-High (HH) and Low-Low (LL) spatial clusters of CMRFs, with LL predominantly in the less populated northern, central and southern regions of the study area. CONCLUSION: The study describes a range of CMRFs with different distributions in the study region. The results allow generation of hypotheses to test in future research concerning location specific population health approaches.

Geographic and area-level socioeconomic variation in cardiometabolic risk factor distribution: a systematic review of the literature.

INTRODUCTION: A growing number of publications report variation in the distribution of cardiometabolic risk factors (CMRFs) at different geographic scales. A review of these variations may help inform policy and health service organisation. AIM: To review studies reporting variation in the geographic distribution of CMRFs and its association with various proxy measures of area-level socioeconomic disadvantage (ASED) among the adult ( ≥ 18 years) population across the world. METHODS: A systematic search for published articles was conducted in four databases (MEDLINE (Ovid), PubMed, Scopus and Web of Science) considering the interdisciplinary nature of the review question. Population-based cross-sectional and cohort studies on geographic variations of one or more biological proxies of CMRFs with/without an analysed contextual association with ASED were included. Two independent reviewers screened the studies and PRISMA guidelines were followed in the study selection and reporting. RESULT: A total of 265 studies were retrieved and screened, resulting in 24 eligible studies. The review revealed reports of variation in the distribution of CMRFs, at varying geographic scales, in multiple countries. In addition, consistent associations between ASED and higher prevalence of CMRFs were demonstrated. The reports were mainly from industrialised nations and small area geographic units were frequently used. CONCLUSION: Geographic variation in cardiometabolic risk exists across multiple spatial scales and is positively associated with ASED. This association is independent of individual-level factors and provides an imperative for area-based approaches to informing policy and health service organisation. The study protocol is registered in International prospective register of systematic reviews (Register No: CRD42018115294) PROSPERO 2018.

The role of pneumonia and secondary bacterial infection in fatal and serious outcomes of pandemic influenza a(H1N1)pdm09.

BACKGROUND: The aim of this study was to estimate the prevalence of pneumonia and secondary bacterial infections during the pandemic of influenza A(H1N1)pdm09. METHODS: A systematic review was conducted to identify relevant literature in which clinical outcomes of pandemic influenza A(H1N1)pdm09 infection were described. Published studies (between 01/01/2009 and 05/07/2012) describing cases of fatal or hospitalised A(H1N1)pdm09 and including data on bacterial testing or co-infection. RESULTS: Seventy five studies met the inclusion criteria. Fatal cases with autopsy specimen testing were reported in 11 studies, in which any co-infection was identified in 23% of cases (Streptococcus pneumoniae 29%). Eleven studies reported bacterial co-infection among hospitalised cases of A(H1N1)2009pdm with confirmed pneumonia, with a mean of 19% positive for bacteria (Streptococcus pneumoniae 54%). Of 16 studies of intensive care unit (ICU) patients, bacterial co-infection identified in a mean of 19% of cases (Streptococcus pneumoniae 26%). The mean prevalence of bacterial co-infection was 12% in studies of hospitalised patients not requiring ICU (Streptococcus pneumoniae 33%) and 16% in studies of paediatric patients hospitalised in general or pediatric intensive care unit (PICU) wards (Streptococcus pneumoniae 16%). CONCLUSION: We found that few studies of the 2009 influenza pandemic reported on bacterial complications and testing. Of studies which did report on this, secondary bacterial infection was identified in almost one in four patients, with Streptococcus pneumoniae the most common bacteria identified. Bacterial complications were associated with serious outcomes such as death and admission to intensive care. Prevention and treatment of bacterial secondary infection should be an integral part of pandemic planning, and improved uptake of routine pneumococcal vaccination in adults with an indication may reduce the impact of a pandemic.

Serious Mental Illness, Neighborhood Disadvantage, and Type 2 Diabetes Risk: A Systematic Review of the Literature.

AIM OF THE STUDY: This review aims to systematically synthesize the body of literature examining the association between neighborhood socioeconomic disadvantage and serious mental illness (SMI)-type 2 diabetes (T2D) co-occurrence. METHODS: We conducted an electronic search of four databases: PubMed, Scopus, Medline, and Web of Science. Studies were considered eligible if they were published in English, peer reviewed, quantitative, and focused on the association between neighborhood disadvantage and SMI-T2D comorbidity. Study conduct and reporting complied with PRISMA guidelines, and the protocol is made available at PROSPERO (CRD42017083483). RESULTS: The one eligible study identified reported a higher burden of T2D in persons with SMI but provided only a tentative support for the association between neighborhood disadvantage and SMI-T2D co-occurrence. CONCLUSION: Research into neighborhood effects on SMI-T2D comorbidity is still in its infancy and the available evidence inconclusive. This points to an urgent need for attention to the knowledge gap in this important area of public health. Further research is needed to understand the health resource implications of the association between neighborhood deprivation and SMI-T2D comorbidity and the casual pathways linking them.

A scenario-based evaluation of the Middle East respiratory syndrome coronavirus and the Hajj.

Between April 2012 and June 2014, 820 laboratory-confirmed cases of the Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported in the Arabian Peninsula, Europe, North Africa, Southeast Asia, the Middle East, and the United States. The observed epidemiology is different to SARS, which showed a classic epidemic curve and was over in eight months. The much longer persistence of MERS-CoV in the population, with a lower reproductive number, some evidence of human-to-human transmission but an otherwise sporadic pattern, is difficult to explain. Using available epidemiological data, we implemented mathematical models to explore the transmission dynamics of MERS-CoV in the context of mass gatherings such as the Hajj pilgrimage, and found a discrepancy between the observed and expected epidemiology. The fact that no epidemic occurred in returning Hajj pilgrims in either 2012 or 2013 contradicts the long persistence of the virus in human populations. The explanations for this discrepancy include an ongoing, repeated nonhuman/sporadic source, a large proportion of undetected or unreported human-to-human cases, or a combination of the two. Furthermore, MERS-CoV is occurring in a region that is a major global transport hub and hosts significant mass gatherings, making it imperative to understand the source and means of the yet unexplained and puzzling ongoing persistence of the virus in the human population.