Risk of severe COVID-19 outcomes after autumn 2022 COVID-19 booster vaccinations: a pooled analysis of national prospective cohort studies involving 7.4 million adults in England, Northern Ireland, Scotland and Wales.

Background: UK COVID-19 vaccination policy has evolved to offering COVID-19 booster doses to individuals at increased risk of severe Illness from COVID-19. Building on our analyses of vaccine effectiveness of first, second and initial booster doses, we aimed to identify individuals at increased risk of severe outcomes (i.e., COVID-19 related hospitalisation or death) post the autumn 2022 booster dose. Methods: We undertook a national population-based cohort analysis across all four UK nations through linked primary care, vaccination, hospitalisation and mortality data. We included individuals who received autumn 2022 booster doses of BNT162b2 (Comirnaty) or mRNA-1273 (Spikevax) during the period September 1, 2022 to December 31, 2022 to investigate the risk of severe COVID-19 outcomes. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for the association between demographic and clinical factors and severe COVID-19 outcomes after the autumn booster dose. Analyses were adjusted for age, sex, body mass index (BMI), deprivation, urban/rural areas and comorbidities. Stratified analyses were conducted by vaccine type. We then conducted a fixed-effect meta-analysis to combine results across the four UK nations. Findings: Between September 1, 2022 and December 31, 2022, 7,451,890 individuals ≥18 years received an autumn booster dose. 3500 had severe COVID-19 outcomes (2.9 events per 1000 person-years). Being male (male vs female, aHR 1.41 (1.32-1.51)), older adults (≥80 years vs 18-49 years; 10.43 (8.06-13.50)), underweight (BMI <18.5 vs BMI 25.0-29.9; 2.94 (2.51-3.44)), those with comorbidities (≥5 comorbidities vs none; 9.45 (8.15-10.96)) had a higher risk of COVID-19 hospitalisation or death after the autumn booster dose. Those with a larger household size (≥11 people within household vs 2 people; 1.56 (1.23-1.98)) and from more deprived areas (most deprived vs least deprived quintile; 1.35 (1.21-1.51)) had modestly higher risks. We also observed at least a two-fold increase in risk for those with various chronic neurological conditions, including Down's syndrome, immunodeficiency, chronic kidney disease, cancer, chronic respiratory disease, or cardiovascular disease. Interpretation: Males, older individuals, underweight individuals, those with an increasing number of comorbidities, from a larger household or more deprived areas, and those with specific underlying health conditions remained at increased risk of COVID-19 hospitalisation and death after the autumn 2022 vaccine booster dose. There is now a need to focus on these risk groups for investigating immunogenicity and efficacy of further booster doses or therapeutics. Funding: National Core Studies-Immunity, UK Research and Innovation (Medical Research Council and Economic and Social Research Council), Health Data Research UK, the Scottish Government, and the University of Edinburgh.

Risk of COVID-19 death in adults who received booster COVID-19 vaccinations in England.

The emergence of the COVID-19 vaccination has been critical in changing the course of the COVID-19 pandemic. To ensure protection remains high in vulnerable groups booster vaccinations in the UK have been targeted based on age and clinical vulnerabilities. We undertook a national retrospective cohort study using data from the 2021 Census linked to electronic health records. We fitted cause-specific Cox models to examine the association between health conditions and the risk of COVID-19 death and all-other-cause death for adults aged 50-100-years in England vaccinated with a booster in autumn 2022. Here we show, having learning disabilities or Down Syndrome (hazard ratio=5.07;95% confidence interval=3.69-6.98), pulmonary hypertension or fibrosis (2.88;2.43-3.40), motor neuron disease, multiple sclerosis, myasthenia or Huntington's disease (2.94, 1.82-4.74), cancer of blood and bone marrow (3.11;2.72-3.56), Parkinson's disease (2.74;2.34-3.20), lung or oral cancer (2.57;2.04 to 3.24), dementia (2.64;2.46 to 2.83) or liver cirrhosis (2.65;1.95 to 3.59) was associated with an increased risk of COVID-19 death. Individuals with cancer of the blood or bone marrow, chronic kidney disease, cystic fibrosis, pulmonary hypotension or fibrosis, or rheumatoid arthritis or systemic lupus erythematosus had a significantly higher risk of COVID-19 death relative to other causes of death compared with individuals who did not have diagnoses. Policy makers should continue to priorities vulnerable groups for subsequent COVID-19 booster doses to minimise the risk of COVID-19 death.

Hepatitis of unknown aetiology in children - epidemiological overview of cases reported in Europe, 1 January to 16 June 2022.

Following the report of an excess in paediatric cases of severe acute hepatitis of unknown aetiology by the United Kingdom (UK) on 5 April 2022, 427 cases were reported from 20 countries in the World Health Organization European Region to the European Surveillance System TESSy from 1 January 2022 to 16 June 2022. Here, we analysed demographic, epidemiological, clinical and microbiological data available in TESSy. Of the reported cases, 77.3% were 5 years or younger and 53.5% had a positive test for adenovirus, 10.4% had a positive RT-PCR for SARS-CoV-2 and 10.3% were coinfected with both pathogens. Cases with adenovirus infections were significantly more likely to be admitted to intensive care or high-dependency units (OR = 2.11; 95% CI: 1.18-3.74) and transplanted (OR = 3.36; 95% CI: 1.19-9.55) than cases with a negative test result for adenovirus, but this was no longer observed when looking at this association separately between the UK and other countries. Aetiological studies are needed to ascertain if adenovirus plays a role in this possible emergence of hepatitis cases in children and, if confirmed, the mechanisms that could be involved.

The effect of community-based interventions for cardiovascular disease secondary prevention on behavioural risk factors.

Cardiovascular disease (CVD) is the leading cause of death worldwide, and its prevalence is increasing; with limited healthcare resources, secondary prevention programmes outside traditional hospital settings are needed, but their effectiveness is unclear. We aimed to assess the effectiveness of secondary prevention cardiovascular risk reduction programmes delivered in venues situated within the community on modification of behavioural risk factors. We searched five databases (MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane library) to identify trials of health behaviour interventions for adults with CVD in community-based venues. Primary outcomes were changes in physical activity, diet, smoking and/or alcohol consumption. Two reviewers independently assessed articles for eligibility and risk of bias; statistical analysis used Revman v5.3. Of 5905 articles identified, 41 articles (38 studies) (n = 7970) were included. Interventions were mainly multifactorial, educational, psychological and physical activity-based. Meta-analyses identified increased steps/week (Mean Difference (MD): 7480; 95% CI 1,940, 13,020) and minutes of physical activity/week (MD: 59.96; 95% CI 15.67, 104.25) associated with interventions. There was some evidence for beneficial effects on peak VO2, blood pressure, total cholesterol and mental health. Variation in outcome measurements reported for other behavioural risk factors limited our ability to perform meta-analyses. Effective interventions were based in homes, general practices or outpatient settings, individually tailored and often multicomponent with a theoretical framework. Our review identified evidence that interventions for secondary CVD prevention, delivered in various community-based venues, have positive effects on physical activity; such opportunities should be promoted by health professionals.

Reasons for non-participation in the Northern Ireland Bowel Cancer Screening Programme: a qualitative study.

OBJECTIVES: To identify the reasons why some people do not participate in bowel cancer screening so that steps can be taken to improve informed decision-making. DESIGN: Qualitative study, using focus groups with thematic analysis of data to identify, analyse and report patterns. Transcripts were repeatedly read and inductively coded using a phenomenological perspective, and organised into key themes. SETTING: Belfast and Armagh, two areas of Northern Ireland with relatively low uptake of bowel cancer screening. PARTICIPANTS: Ten women and 18 men in three single-gender focus groups (two male and one female), each with 9-10 participants. Study participants were recruited by convenience sampling from the general public and were eligible for, but had not taken part in, the Northern Ireland Bowel Cancer Screening Programme. RESULTS: Key themes identified were fear of cancer; the test procedure; social norms; past experience of cancer and screening; lack of knowledge or understanding about bowel cancer screening; and resulting behaviour towards the test. Fear about receiving bad news and reluctance to conduct the test themselves were reactions that participants seemed willing to overcome after taking part in open discussion about the test. CONCLUSIONS: We identified barriers to participation in bowel cancer screening and used these insights to develop new materials to support delivery of the programme. Some of the issues raised have been identified in other UK settings, suggesting that knowledge about barriers, and strategies to improve uptake, may be generalisable.

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1.

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10(-5)) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10(-5)). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10(-10), odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression.

Complement factor B polymorphism 32W protects against age-related macular degeneration.

PURPOSE: The 32Q (rs641153; A) and 32W (rs12614; T) variants of complement factor B (CFB) cause less efficient complement activation in vitro than the common 32R variant. This is thought to be the reason that the 32Q variant is associated with decreased risk of age-related macular degeneration (AMD). We investigated whether the 32W variant was also associated with decreased risk of AMD. METHODS: We genotyped 367 cases with neovascular AMD and 251 disease-free controls. Association with the disease phenotype was assessed by logistic regression for polymorphisms of CFB alone and in combination with smoking status and genetic risk markers of complement factor H (CFH) and HtrA serine peptidase 1 (HTRA1). We performed meta-analysis of all previously published reports of 32W allele frequency in AMD cases and controls. RESULTS: The CFB variant 32W was associated with protection against neovascular AMD, compared to the common 32R variant (odds ratio 0.64, p<0.05, in logistic regression with CFB variants; odds ratio 0.53, p<0.05, in logistic regression with CFB variants, CFH haplotypes, HTRA1 rs10490924 genotype, and smoking status). Meta-analysis (n=1,795) including this study and two others of neovascular AMD showed a combined odds ratio of 0.75 (p<0.05) for 32W, compared to 32R. Meta-analysis (n=2,600) of all reported studies of all types of AMD showed a combined odds ratio of 0.79 (p<0.01). CONCLUSIONS: Our study shows that the 32W variant of CFB is associated with protection against AMD, in keeping with evidence of its functional effect on the complement system. The protective effect is less strong than that associated with 32Q.