Adiposity and Mortality among Patients Severely Ill with COVID-19 and non-COVID-19 Respiratory Conditions: A Cross-Context Comparison Study in the UK (preprint)

Objective: To assess the causality of adiposity for mortality among patients severely ill with COVID-19 and non-COVID-19 respiratory conditions by examining the consistency of associations across temporal and geographical contexts where biases vary Design: Prospective cohort study Setting: 297 intensive care units (ICUs) in England, Wales, and Northern Ireland monitored by the Intensive Care National Audit and Research Centre Case Mix Programme Participants: Patients aged [≥]16 years admitted to ICU with COVID-19 (N=33,352; Feb 2020-Aug 2021) and non-COVID-19 respiratory conditions (N=24,739; Feb 2018-Aug 2019) Main outcome measure: 30-day mortality post ICU admission Results: Compared with non-COVID-19 respiratory patients, COVID-19 patients were younger, less often of a white ethnic group, and more often with extreme obesity (body mass index (BMI) [≥] 40kg/m2). COVID-19 patients had fewer comorbidities but higher mortality (35% vs. 23% mortality in non-COVID-19). Socio-demographic and comorbidity factors and their associations with BMI and mortality varied more by date than geographical region of ICU admission, particularly among COVID-19 patients. Among COVID-19 patients, higher BMI was associated with a small excess mortality (hazard ratio (HR) per standard deviation (SD)=1.05; 95% CI=1.03, 1.08), driven by extreme obesity (HR per SD=1.21; 95% CI=1.13, 1.31 vs. normal-weight). Extreme obesity was strongly associated with higher mortality only during Feb-April 2020 (HR=1.49, 95% CI=1.27, 1.73 vs. normal-weight); this association weakened thereafter (BMI-date interaction P=0.03). Among non-COVID-19 respiratory patients, higher BMI was associated with lower mortality (HR per SD=0.84; 95% CI=0.82, 0.87), seen across all overweight/obesity groups. These negative obesity-mortality associations were similar across most admission dates and regions. Conclusions: Obesity is associated with higher mortality among COVID-19 patients, but lower mortality among non-COVID respiratory patients. These associations appear vulnerable to confounding/selection bias in both patient groups, questioning the existence or stability of causal effects. Among COVID-19 patients, unfavourable obesity-mortality associations differ by admission date. Among non-COVID-19 respiratory patients, favourable obesity-mortality associations may reflect comorbidity-induced weight loss.

Impact of vaccination on COVID-19-associated admissions to critical care in England: a population cohort study of linked data (preprint)

Introduction This study aims to explore the impact of COVID-19 vaccination on critical care by examining associations between vaccination and admission to critical care with COVID-19 during England's Delta wave, by age group, dose, and over time. Methods We used linked routinely-collected data to conduct a population cohort study of patients admitted to adult critical care in England for management of COVID-19 between 1 May and 15 December 2021. Included participants were the whole population of England aged 18 years or over (44.7 million), including 10,141 patients admitted to critical care with COVID-19. The intervention was vaccination with one, two, or a booster/three doses of any COVID-19 vaccine. Results Compared with unvaccinated patients, vaccinated patients were older (median 64 years for patients receiving two or more doses versus 50 years for unvaccinated), with higher levels of severe comorbidity (20.3% versus 3.9%) and immunocompromise (15.0% versus 2.3%). Compared with patients who were unvaccinated, those vaccinated with two doses had a relative risk reduction (RRR) of between 90.1% (patients aged 18-29, 95% CI, 86.8% to 92.7%) and 95.9% (patients aged 60-69, 95% CI, 95.5% to 96.2%). Waning was only observed for those aged 70+, for whom the RRR reduced from 97.3% (91.0% to 99.2%) to 86.7% (85.3% to 90.1%) between May and December but increased again to 98.3% (97.6% to 98.8%) with a booster/third dose. Conclusion Important demographic and clinical differences exist between vaccinated and unvaccinated patients admitted to critical care with COVID-19. While not a causal analysis, our findings are consistent with a substantial and sustained impact of vaccination on reducing admissions to critical care during England's Delta wave, with evidence of waning predominantly restricted to those aged 70+.

Predicting COVID-19 related death using the OpenSAFELY platform (preprint)

Objectives To compare approaches for obtaining relative and absolute estimates of risk of 28-day COVID-19 mortality for adults in the general population of England in the context of changing levels of circulating infection. Design Three designs were compared. (A) case-cohort which does not explicitly account for the time-changing prevalence of COVID-19 infection, (B) 28-day landmarking, a series of sequential overlapping sub-studies incorporating time-updating proxy measures of the prevalence of infection, and (C) daily landmarking. Regression models were fitted to predict 28-day COVID-19 mortality. Setting Working on behalf of NHS England, we used clinical data from adult patients from all regions of England held in the TPP SystmOne electronic health record system, linked to Office for National Statistics (ONS) mortality data, using the OpenSAFELY platform. Participants Eligible participants were adults aged 18 or over, registered at a general practice using TPP software on 1st March 2020 with recorded sex, postcode and ethnicity. 11,972,947 individuals were included, and 7,999 participants experienced a COVID-19 related death. The study period lasted 100 days, ending 8th June 2020. Predictors A range of demographic characteristics and comorbidities were used as potential predictors. Local infection prevalence was estimated with three proxies: modelled based on local prevalence and other key factors; rate of A&E COVID-19 related attendances; and rate of suspected COVID-19 cases in primary care. Main outcome measures COVID-19 related death. Results All models discriminated well between patients who did and did not experience COVID-19 related death, with C-statistics ranging from 0.92-0.94. Accurate estimates of absolute risk required data on local infection prevalence, with modelled estimates providing the best performance. Conclusions Reliable estimates of absolute risk need to incorporate changing local prevalence of infection. Simple models can provide very good discrimination and may simplify implementation of risk prediction tools in practice.

Trends in Intensive Care for Patients with COVID-19 in England, Wales and Northern Ireland (preprint)

Rationale: Examining trends in patient characteristics, processes of care and outcomes, across an epidemic, provides important opportunities for learning. Objectives: To report and explore changes in admission rates, patient characteristics, processes of care and outcomes for all patients with COVID-19 admitted to intensive care units (ICUs) in England, Wales and Northern Ireland. Methods: Population cohort of 10,287 patients with COVID-19 in the Case Mix Programme national clinical audit from 1 February to 2 July, 2020. Analyses were stratified by time period (pre-peak, peak, post-peak) and geographical region. Multivariable logistic regression was used to estimate differences in 28-day mortality, adjusting for patient characteristics over time. Main results: Admissions to ICU peaked simultaneously across regions on 1 April, with ongoing admissions peaking ten days later. Compared with pre- and post-peak periods, patients admitted during the peak were slightly younger but had greater respiratory and renal dysfunction. Use of invasive ventilation and renal replacement reduced over time. Twenty-eight-day mortality reduced from 43.5% (95% CI 41.6% to 45.5%) pre-peak to 34.3% (95% CI 32.3% to 36.2%) post-peak; a difference of −8.8% (95% CI: −5.2%, −12.3%) after adjusting for patient characteristics. London experienced the highest admission rate and had higher mortality during the peak period but a greater reduction in post-peak mortality. Conclusion: This study highlights changes in patient characteristics, processes of care and outcomes, during the UK COVID-19 epidemic. After adjusting for the changes in patient characteristics and first 24-hour physiology, there was substantial improvement in 28-day mortality over the course of the epidemic.