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.

Identifying pre-existing conditions and multimorbidity patterns associated with in-hospital mortality in patients with COVID-19.

We investigated the association between a wide range of comorbidities and COVID-19 in-hospital mortality and assessed the influence of multi morbidity on the risk of COVID-19-related death using a large, regional cohort of 6036 hospitalized patients. This retrospective cohort study was conducted using Patient Administration System Admissions and Discharges data. The International Classification of Diseases 10th edition (ICD-10) diagnosis codes were used to identify common comorbidities and the outcome measure. Individuals with lymphoma (odds ratio [OR], 2.78;95% CI,1.64-4.74), metastatic cancer (OR, 2.17; 95% CI,1.25-3.77), solid tumour without metastasis (OR, 1.67; 95% CI,1.16-2.41), liver disease (OR: 2.50, 95% CI,1.53-4.07), congestive heart failure (OR, 1.69; 95% CI,1.32-2.15), chronic obstructive pulmonary disease (OR, 1.43; 95% CI,1.18-1.72), obesity (OR, 5.28; 95% CI,2.92-9.52), renal disease (OR, 1.81; 95% CI,1.51-2.19), and dementia (OR, 1.44; 95% CI,1.17-1.76) were at increased risk of COVID-19 mortality. Asthma was associated with a lower risk of death compared to non-asthma controls (OR, 0.60; 95% CI,0.42-0.86). Individuals with two (OR, 1.79; 95% CI, 1.47-2.20; P < 0.001), and three or more comorbidities (OR, 1.80; 95% CI, 1.43-2.27; P < 0.001) were at increasingly higher risk of death when compared to those with no underlying conditions. Furthermore, multi morbidity patterns were analysed by identifying clusters of conditions in hospitalised COVID-19 patients using k-mode clustering, an unsupervised machine learning technique. Six patient clusters were identified, with recognisable co-occurrences of COVID-19 with different combinations of diseases, namely, cardiovascular (100%) and renal (15.6%) diseases in patient Cluster 1; mental and neurological disorders (100%) with metabolic and endocrine diseases (19.3%) in patient Cluster 2; respiratory (100%) and cardiovascular (15.0%) diseases in patient Cluster 3, cancer (5.9%) with genitourinary (9.0%) as well as metabolic and endocrine diseases (9.6%) in patient Cluster 4; metabolic and endocrine diseases (100%) and cardiovascular diseases (69.1%) in patient Cluster 5; mental and neurological disorders (100%) with cardiovascular diseases (100%) in patient Cluster 6. The highest mortality of 29.4% was reported in Cluster 6.

Individual risk factors and critical care unit effects on Invasive Candida Infection occurring in critical care units in the UK: A multilevel model.

Geographical variation is observed in invasive candida infection (ICI) and differences between critical care units (CCUs) may contribute. To examine rates, risk factors and individual and unit-level variation of ICI in UK CCUs. Data from the Fungal Infection Risk Evaluation Study was used to examine individuals admitted to 96 CCUs in the UK; July 2009-March 2011. Cases were non-neutropenic individuals aged 18 years and over with ICI identified after admission. Mixed-effects Poisson regression models adjusted for the CCU. There were 225 cases of ICI, a rate of 6.84/10 000 bed days and a threefold variation between the lowest and highest UK regions. Independent risk factors included abdominal surgery (adjusted incidence rate ratio (AIRR) 2.03 95% CI 1.49, 2.76), parenteral nutrition (AIRR 1.89 95% CI 1.33, 2.70), fungal colonisation at two or more sites (AIRR 2.30 95% CI 1.34, 3.95) and indwelling devices. Approximately 4% of the variation in ICI rates could be attributed to the CCU. We identified independent risk factors for ICI and showed, for the first time, that the critical care unit effect was small. Despite this, future studies should consider the hierarchical structure of the data to ensure robust estimates.

Changing epidemiology of Pneumocystis pneumonia, Northern Ireland, UK and implications for prevention, 1 July 2011-31 July 2012.

PURPOSE: There is a lack of consensus about which non-human immunodeficiency virus (HIV) patient groups would benefit from prophylaxis. Here, we analysed an enhanced Pneumocystis jirovecii database to describe the epidemiology of Pneumocystis pneumonia (PCP) and P. jirovecii colonizations in Northern Ireland (NI) with a view to identifying risk groups who may benefit from prophylaxis. METHODOLOGY: We prospectively collected information on demographics, clinical severity and clinical features for all hospital inpatients in NI aged ≥18 years with P. jirovecii confirmed in any respiratory tract sample. We defined P. jirovecii colonization or PCP according to clinical symptoms and radiological findings. We compared P. jirovecii colonization to PCP using exact logistic regression and presented the odds ratios (OR), 95 % confidence intervals (CI) and likelihood ratio test P-values.Results/Key findings. Overall, 36/49 (73 %) of P. jirovecii detections were categorized as PCP. A total of 28/36 (78 %) were in non-HIV patients, of which 18 (64 %) had cancer. The odds of PCP compared to P. jirovecii colonization were eight times higher in those with current exposure to chemotherapy (OR 8.73; 95 % CI 0.84, ∞), 16 times higher for those diagnosed with HIV (OR 16.2; 95 % CI 1.71, ∞) and 12 times higher for those ever exposed to another immunosuppressive drug (OR 12.1; 95 % CI 1.94, ∞). CONCLUSION: The greatest burden of PCP is now in the non-HIV group, particularly cancer patients. We recommend increasing clinician awareness of PCP risk and strengthening prevention guidelines in non-HIV patients, and promoting the consideration of prophylaxis on a case-by-case basis.