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OpenSAFELY: factors associated with COVID-19 death in 17 million patients

Our take —

This study, covering over 17 million adults in England, confirms previously observed associations with mortality: higher risks were seen with older age, male sex, chronic comorbidities, socioeconomic deprivation, and nonwhite ethnicity. Although causality cannot be inferred for any given risk factor owing to the study design, the size of the analysis provides a striking replication of results observed elsewhere in smaller studies.

Study design

Retrospective Cohort

Study population and setting

This study analyzed electronic medical records from 17,278,392 adults aged 18 years and over from the National Health Service in England, representing approximately 40% of the adult population in England, to estimate risk factors for COVID-19 mortality. Registered active adult patients with >1 year of prior follow-up and with recorded age, sex, and “deprivation” (a measure related to poverty, derived from area of residence) were eligible for inclusion; the study period was from February 1 to May 6, 2020. Risk factors for COVID-19 mortality were assessed with Cox proportional hazards models 1) adjusted for age and sex; and 2) adjusted simultaneously for all included risk factors.

Summary of Main Findings

There were 10,926 deaths (0.06%) attributed to COVID-19 in the study population. In the fully adjusted model, the risk of mortality increased with every decade of age: relative to the reference category aged 50-59 years, the hazard ratio (HR) for death was 20.61 (95% CI: 18.72-22.70) for those aged 80 years and older. Men had a higher hazard of mortality relative to women (HR: 1.59, 95% CI: 1.53-1.65). Mortality risks for Black (HR: 1.48, 1.30 to 1.69), South Asian (HR: 1.44, 1.32-1.58), and mixed ethnicities (HR: 1.43, 1.11-1.85) were higher relative to white ethnicity. The most deprived quintile (from a geographically-defined index of socioeconomic status) had 1.80 times (1.69-1.91) the mortality hazard of the least deprived quintile. Multiple comorbidities were associated with increased mortality risk, including obesity, diabetes, chronic heart disease, chronic liver disease, kidney dysfunction, recently diagnosed cancer, and severe asthma. Although smoking and hypertension were associated with higher mortality in the age- and sex-adjusted model, they were not in the fully adjusted model. Post-hoc analyses of smoking and hypertension indicated that controlling for chronic respiratory disease (for smoking) and for diabetes and obesity (for hypertension) explained much of the changes in hazard ratios.

Study Strengths

The primary strength of this study is its size; it was able to cover a significant proportion of the adult population of England.

Limitations

Estimated hazard ratios for covariates were derived from a model that adjusted simultaneously for all covariates; results for a given risk factor cannot be interpreted causally due to possible mediation, unmeasured confounding, and collider stratification bias. There were high proportions of missing data for ethnicity (26%), obesity (22%), and hypertension (10%). Some deaths may have been missed due to misclassification. Although the dataset was very large, it may not have been representative of the population of England (e.g., only 17% of health care practices in London were included). The study does not address risk factors for non-fatal but nonetheless severe manifestations of COVID-19.

Value added

This extremely large study confirms associations seen in other studies and provides further evidence for the role of structural inequalities in COVID-19 impacts.

This review was posted on: 21 July 2020