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

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.