London School of Hygiene & Tropical Medicine

The findings of what is the largest and most detailed analysis of its kind are published in Nature.

The study gives detailed information on the size of the risk associated with various pre-existing medical conditions such as diabetes and obesity. Consistent with previous work, it also indicates higher risk of death from COVID-19 for men, older people, and people with greater deprivation. People of Asian and Black ethnic backgrounds were also found to be at a higher risk of death: however, crucially, and contrary to prior speculation, this increased risk was only partially attributable to pre-existing clinical risk factors and deprivation.

The study reports the first use of a new data analysis platform to support COVID-19 research, using patients’ health records in near-real-time on an unprecedented scale. The research team developed OpenSAFELY, a secure analytics environment running across detailed pseudonymized data for 40% of all National Health Service patients in England. Among the electronic health records of 17,278,392 adults, there were 10,926 deaths in and out of hospital that were linked to COVID-19.

This is a very substantial expansion of previous work that was urgently pre-printed in May, which reported on factors associated with 5,707 deaths in hospital.

Professor Liam Smeeth, Professor of Clinical Epidemiology at LSHTM, NHS doctor and co-lead on the study, says: “We need highly accurate data on which patients are most at risk in order to manage the pandemic and improve patient care. The answers provided by this OpenSAFELY analysis are of crucial importance to countries around the world. For example, it is very concerning to see that the higher risks faced by people from BME backgrounds are not attributable to identifiable underlying health conditions.”

In line with previous studies, men had a greater (1.59-fold-higher) risk of COVID-19-related death than women, and age was also found to be a risk factor — people aged 80 or above had a 20-fold-increased risk compared to 50–59-year-old people. Black and South Asian people, and those of mixed background, were 1.62–1.88 times more likely to die with COVID-19 than white people, after taking into account their prior medical conditions.

The most deprived people in the cohort were 1.8 times more likely than the least deprived to die with COVID-19; clinical factors made only a small contribution to this risk, suggesting that social factors have a role.

Pre-existing medical conditions — including obesity (especially a BMI of over 40), diabetes, severe asthma, and respiratory, chronic heart, liver, neurological and autoimmune diseases — were all found to be associated with an increased risk of COVID-19-related death. The authors note that their reported effects should not necessarily be interpreted as causal. Smoking and hypertension both had a slight negative association with risk, for example, but the authors suggest that this could be a result of interactions with other clinical factors, and they note that further studies are needed to better understand these relationships.

The authors caution that as clinically suspected but unconfirmed cases of COVID-19 were included, some patients might have been incorrectly identified as having COVID-19 and, conversely, some deaths — particularly at earlier stages — might have been misclassified as non-COVID-19. They also explain that the sample may not be fully representative (only 17% of general practices in London were included, for example) and that primary care records can sometimes be incomplete (ethnicity was missing for around 26% of individuals, for instance).

Publication

Elizabeth J. Williamson, Alex J. Walker, Krishnan Bhaskaran, Seb Bacon, Chris Bates, Caroline E. Morton, Helen J. Curtis, Amir Mehrkar, David Evans, Peter Inglesby, Jonathan Cockburn, Helen I. McDonald, Brian MacKenna, Laurie Tomlinson, Ian J. Douglas, Christopher T. Rentsch, Rohini Mathur, Angel Y. S. Wong, Richard Grieve, David Harrison, Harriet Forbes, Anna Schultze, Richard Croker, John Parry, Frank Hester, Sam Harper, Rafael Perera, Stephen J. W. Evans, Liam Smeeth & Ben Goldacre. OpenSAFELY: factors associated with COVID-19 death in 17 million patients. Nature. DOI:10.1038/s41586-020-2521-4 (2020).