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OpenSAFELY: factors associated with COVID-19-related hospital death in the linked electronic health records of 17 million adult NHS patients
Open accessPreprint — published as 10.1038/s41586-020-2521-4 · Paper page
Abstract
Background: Establishing who is at risk from a novel rapidly arising cause of death, and why, requires a new approach to epidemiological research with very large datasets and timely data. Working on behalf of NHS England we therefore set out to deliver a secure and pseudonymised analytics platform inside the data centre of a major primary care electronic health records vendor establishing coverage across detailed primary care records for a substantial proportion of all patients in England. The following results are preliminary. Data sources: Primary care electronic health records managed by the electronic health record vendor TPP, pseudonymously linked to patient-level data from the COVID-19 Patient Notification System (CPNS) for death of hospital inpatients with confirmed COVID-19, using the new OpenSAFELY platform. Population: 17,425,445 adults. Time period: 1st Feb 2020 to 25th April 2020. Primary outcome: Death in hospital among people with confirmed COVID-19. Methods: Cohort study analysed by Cox-regression to generate hazard ratios: age and sex adjusted, and multiply adjusted for co-variates selected prospectively on the basis of clinical interest and prior findings. Results: There were 5683 deaths attributed to COVID-19. In summary after full adjustment, death from COVID-19 was strongly associated with: being male (hazard ratio 1.99, 95%CI 1.88-2.10); older age and deprivation (both with a strong gradient); uncontrolled diabetes (HR 2.36 95% CI 2.18-2.56); severe asthma (HR 1.25 CI 1.08-1.44); and various other prior medical conditions. Compared to people with ethnicity recorded as white, black people were at higher risk of death, with only partial attenuation in hazard ratios from the fully adjusted model (age-sex adjusted HR 2.17 95% CI 1.84-2.57; fully adjusted HR 1.71 95% CI 1.44-2.02); with similar findings for Asian people (age-sex adjusted HR 1.95 95% CI 1.73-2.18; fully adjusted HR 1.62 95% CI 1.431.82). Conclusions: We have quantified a range of clinical risk factors for death from COVID-19, some of which were not previously well characterised, in the largest cohort study conducted by any country to date. People from Asian and black groups are at markedly increased risk of in-hospital death from COVID-19, and contrary to some prior speculation this is only partially attributable to pre-existing clinical risk factors or deprivation; further research into the drivers of this association is therefore urgently required. Deprivation is also a major risk factor with, again, little of the excess risk explained by co-morbidity or other risk factors. The findings for clinical risk factors are concordant with policies in the UK for protecting those at highest risk. Our OpenSAFELY platform is rapidly adding further NHS patients’ records; we will update and extend these results regularly.
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“However, most associations observed between baseline characteristics and mortality or intubation are in line with prior epidemiological studies [17,19].”
From Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study (2021) · cites this paper as [17]
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“study found that HIV-positive individuals had more than double the risk of COVID-19–related mortality than HIV-uninfected individuals after controlling for known confounding factors.(39) Similarly, a retrospective analysis of > 20,000 South African adults with COVID-19 showed that HIV was associated with a doubling of…”
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“Recent mortality data strongly indicate that Black, Asian, and Minority Ethnic (BAME) groups are at increased risk of death from COVID-19 even after adjusting for multiple other covariates [9, 10, 46, 47].”
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Shastri, M. D., Shukla, S. D., Chong, W. C., Rajendra, K. C., Dua, K., Patel, R. P., Peterson, G. M., & O’Toole, R. (2020) · Respiratory Medicine · doi:10.1016/j.rmed.2020.106237 · Cited by 110
“One of the largest cohort studies conducted to date from the UK reported an increased risk for in-hospital COVID-19 death in ex-smokers compared to never-smokers (HR 1⋅8 [95% CI 1⋅7–1⋅9]) when adjusted for age and sex [64].”
Mikolai, J., Keenan, K. L., & Kulu, H. (2020) · SSM - Population Health · doi:10.1016/j.ssmph.2020.100628 · Cited by 137
“…of COVID-19 suggests that infections and deaths from the disease operate along existing axes of social inequalities, and that individuals from ethnic minorities, poorer socioeconomic backgrounds and deprived areas are more likely to suffer (Jordan & Adab, 2020; Williamson et al., 2020).”
Bektas, A., Schurman, S. H., Franceschi, C., & Ferrucci, L. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00196-8 · Cited by 102
“Interestingly, at least in studies conducted in adult and older COVID-19 patients, prognostic factors for mortality are the same as those found associated with a high likelihood and prospective risk of chronic inflammation, namely older age, male sex, obesity, smoking, cardiovascular diseases, asthma or other respirat…”
Cardiometabolic Traits, Sepsis, and Severe COVID-19
Ponsford, M., Gkatzionis, A., Walker, V. M., Grant, A. J., Wootton, R. E., Moore, L. S. P., Fatumo, S., Mason, A. M., Zuber, V., Willer, C. J., et al. (2020) · Circulation · doi:10.1161/circulationaha.120.050753 · Cited by 124
SARS-CoV-2 pandemic: An overview
Martellucci, C. A., Flacco, M. E., Cappadona, R., Bravi, F., Mantovani, L. G., & Manzoli, L. (2020) · Advances in Biological Regulation · doi:10.1016/j.jbior.2020.100736 · Cited by 116
Reilev, M., Kristensen, K. B., Pottegård, A., Lund, L. C., Hallas, J., Ernst, M., Christiansen, C. F., Sørensen, H. T., Johansen, N. B., Brun, N. C., et al. (2020) · International Journal of Epidemiology · doi:10.1093/ije/dyaa140 · Cited by 267
“In accordance with previous descriptive studies, older men with co-morbidities dominated the subgroup of cases with severe or fatal disease.(24,25) Additionally, we found that men had a 2.”
ResultThe Wider Impacts of the Coronavirus Pandemic on the NHS*
Propper, C., Stoye, G., & Zaranko, B. (2020) · Fiscal Studies · doi:10.1111/1475-5890.12227 · Cited by 108
Epidemiology of COVID-19 in the Kingdom of Saudi Arabia: An Ecological Study
Alyami, M. H., Naser, A. Y., Orabi, M. A. A., Alwafi, H. H., & Alyami, H. S. (2020) · Frontiers in Public Health · doi:10.3389/fpubh.2020.00506 · Cited by 109
Metabolic Syndrome and COVID 19: Endocrine-Immune-Vascular Interactions Shapes Clinical Course
Bansal, R., Gubbi, S., & Muniyappa, R. (2020) · Endocrinology · doi:10.1210/endocr/bqaa112 · Cited by 119
Mudanças alimentares na coorte NutriNet Brasil durante a pandemia de covid-19
Steele, E. M., Rauber, F., Costa, C. D. S., Leite, M. A., Gabe, K. T., Louzada, M. L. D. C., Levy, R. B., & Monteiro, C. A. (2020) · Revista de Saúde Pública · doi:10.11606/s1518-8787.2020054002950 · Cited by 171
COVID‐19 and Ethnic Inequalities in England and Wales*
Platt, L., & Warwick, R. (2020) · Fiscal Studies · doi:10.1111/1475-5890.12228 · Cited by 160
COVID‐19: we must not forget about Indigenous health and equity
McLeod, M., Gurney, J., Harris, R. B., Cormack, D. M., & King, P. T. (2020) · Australian and New Zealand Journal of Public Health · doi:10.1111/1753-6405.13015 · Cited by 139
Sattar, N., Ho, F. K., Gill, J. M., Ghouri, N., Gray, S. R., Celis-Morales, C. A., Katikireddi, S. V., Berry, C., Pell, J. P., McMurray, J. J., et al. (2020) · Diabetes & Metabolic Syndrome: Clinical Research & Reviews · doi:10.1016/j.dsx.2020.06.060 · Cited by 104
“When taken in context with other emerging data [2,3,5], our results support the need for public health campaigns to help and support individuals across different ethnic groups who are overweight or obese to lose weight to lessen their chances of severe COVID-19.”
Bravi, F., Flacco, M. E., Carradori, T., Volta, C. A., Cosenza, G., Togni, A. D., Martellucci, C. A., Parruti, G., Mantovani, L. G., & Manzoli, L. (2020) · PLoS ONE · doi:10.1371/journal.pone.0235248 · Cited by 86
“Thus, the present study confirms prior findings on the independent relationship of older age and male gender with death [44], and of COPD with progression towards severe disease [26].”
ResultHarrison, E. M., Docherty, A. B., Barr, B., Buchan, I. E., Carson, G., Drake, T. M., Dunning, J. W., Fairfield, C. J., Gamble, C. L., Green, C., et al. (2020) · SSRN Electronic Journal · doi:10.2139/ssrn.3618215 · Cited by 68
Selenium and RNA Virus Interactions: Potential Implications for SARS-CoV-2 Infection (COVID-19)
Hiffler, L., & Rakotoambinina, B. (2020) · Frontiers in Nutrition · doi:10.3389/fnut.2020.00164 · Cited by 115
Grint, D. J., Wing, K., Houlihan, C. F., Gibbs, H. P., Evans, S. J. W., Williamson, E., McDonald, H. I., Bhaskaran, K., Evans, D., Walker, A. J., et al. (2021) · Clinical Infectious Diseases · doi:10.1093/cid/ciab754 · Cited by 92
Self-citationSingh, A. K., & Khunti, K. (2020) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2020.108266 · Cited by 92
“[46] Williamson E, Walker AJ, Bhaskaran KJ, Bacon S, Bates C, Morton CE, et al.”
The global impact of SARS-CoV-2 in 181 people with cystic fibrosis
McClenaghan, E., Cosgriff, R., Brownlee, K. G., Ahern, S., Burgel, P., Byrnes, C. A., Colombo, C., Corvol, H., Cheng, S. Y., Daneau, G., et al. (2020) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2020.10.003 · Cited by 89
When Two Pandemics Meet: Why Is Obesity Associated with Increased COVID-19 Mortality?
Lockhart, S. M., & O’Rahilly, S. (2020) · Med · doi:10.1016/j.medj.2020.06.005 · Cited by 98
“Obesity is Associated with Severe 350 Forms of COVID-19.”
BackgroundInfluentialSex differences in immune responses to SARS-CoV-2 that underlie disease outcomes
Takahashi, T., Wong, P., Ellingson, M., et al. (2020) · medRxiv · doi:10.1101/2020.06.06.20123414 · Cited by 87
Ethnicity, household composition and COVID-19 mortality: a national linked data study
Nafilyan, V., Islam, N., Ayoubkhani, D., et al. (2020) · medRxiv · doi:10.1101/2020.11.27.20238147 · Cited by 85
Self-citationNon‐steroidal anti‐inflammatory drugs, prostaglandins, and COVID‐19
Robb, C. T., Goepp, M., Rossi, A. G., & Yao, C. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15206 · Cited by 104
“without underlying medical conditions can also develop severe disease (Huang et al., 2020; Oxley et al., 2020; Williamson et al., 2020).”
BackgroundIndseth, T., Grøsland, M., Arnesen, T. M., Skyrud, K. D., Kløvstad, H., Veneti, L., Telle, K. E., & Kjøllesdal, M. K. R. (2021) · Scandinavian Journal of Public Health · doi:10.1177/1403494820984026 · Cited by 83
“Social disadvantage, as experienced by many immigrants, has also been linked to increased risk of COVID-19 [5,6].”
BackgroundSaso, A., Skirrow, H., & Kampmann, B. (2020) · Vaccines · doi:10.3390/vaccines8030556 · Cited by 100
“Risk factors for adverse outcomes had already been established [2,3] with healthy women of childbearing age, newborn babies and infants generally considered to be less severely affected by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) than other age groups [4,5].”
BackgroundPiscoya, A., Ng-Sueng, L. F., del Riego, A. P., Cerna-Viacava, R., Pasupuleti, V., Roman, Y. M., Thota, P., White, C. M., & Hernández, A. V. (2020) · PLoS ONE · doi:10.1371/journal.pone.0243705 · Cited by 81
Perez‐Guzman, P. N., Daunt, A., Mukherjee, S. K., Crook, P., Forlano, R., Kont, M. D., Løchen, A., Vollmer, M., Middleton, P. K., Judge, R., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa1091 · Cited by 81
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“This resembles the finding of a study of COVID-19 hospital deaths demonstrating that medical risk factors did little to explain the higher risks of the deprived and of immigrants in the UK [69].”
ResultAsthma and the Coronavirus Disease 2019 Pandemic: A Literature Review
Morais‐Almeida, M., Pité, H., Aguiar, R., Ansotegui, I. J., & Bousquet, J. (2020) · International Archives of Allergy and Immunology · doi:10.1159/000509057 · Cited by 98
Jacobs, M., Eeckhoutte, H. P. V., Wijnant, S. R. A., Janssens, W., Joos, G., Brusselle, G., & Bracke, K. R. (2020) · European Respiratory Journal · doi:10.1183/13993003.02378-2020 · Cited by 96
“6 SARS-CoV-2 infection [12, 13].”
BackgroundShaping more resilient and just food systems: Lessons from the COVID-19 Pandemic
Bellamy, A. S., Furness, E., Nicol, P., Pitt, H., & Taherzadeh, A. (2021) · AMBIO · doi:10.1007/s13280-021-01532-y · Cited by 88
Hegyi, P. J., Váncsa, S., Ocskay, K., Dembrovszky, F., Kiss, S., Farkas, N., Erőss, B. M., Szakács, Z., Hegyi, P. J., & Pár, G. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.626425 · Cited by 70
British Medical Journal Publishing Group (2021) · BMJ · doi:10.1136/bmj.n2997 · Cited by 106
HIV and COVID-19: Intersecting Epidemics With Many Unknowns
Lesko, C. R., & Bengtson, A. M. (2020) · American Journal of Epidemiology · doi:10.1093/aje/kwaa158 · Cited by 133
“Ambiguity about the meaning of the term ―independent risk factor‖ make it highly likely that results will be misinterpreted and misapplied (20, 21).”
BackgroundMeyerowitz, E. A., Kim, A. Y., Ard, K. L., Basgoz, N. O., Chu, J. T., Hurtado, R. M., Lee, C. K., He, W. W., Minukas, T., Nelson, S. B., et al. (2020) · AIDS · doi:10.1097/qad.0000000000002607 · Cited by 77
Smoking and the risk of COVID-19 in a large observational population studyPreprint
Israel, A., Feldhamer, E., Lahad, A., Levin‐Zamir, D., & Lavie, G. (2020) · medRxiv · doi:10.1101/2020.06.01.20118877 · Cited by 64
Rabaan, A. A., Al-Ahmed, S. H., Garout, M. A., Al‐Qaaneh, A. M., Sule, A. A., Tirupathi, R., Mutair, A. S. A., Alhumaid, S., Hasan, A., Dhawan, M. K., et al. (2021) · Pathogens · doi:10.3390/pathogens10050565 · Cited by 84
Abdulaal, A., Patel, A. M., Charani, E., Denny, S., Mughal, N., & Moore, L. S. P. (2020) · Journal of Medical Internet Research · doi:10.2196/20259 · Cited by 88
Societal Impacts of Pandemics: Comparing COVID-19 With History to Focus Our Response
Patterson, G. E., McIntyre, K. M., Clough, H. E., & Rushton, J. (2021) · Frontiers in Public Health · doi:10.3389/fpubh.2021.630449 · Cited by 114
Obesity and covid-19: the role of the food industry
Tan, M., He, F. J., & MacGregor, G. A. (2020) · BMJ · doi:10.1136/bmj.m2237 · Cited by 78
Andrews, C., Schultze, A., Curtis, H. J., et al. (2022) · medRxiv · doi:10.1101/2022.06.23.22276802 · Cited by 72
“The deployment of TPP SystmOne software is known to be geographically clustered (6), and factors such as sex, age, ethnicity and levels of deprivation, which are important clinical risk factors for death from COVID-19 (7), show regional variability across England (8).”
BackgroundSelf-citation
Metadata
- Authors
- Collaborative, T. O., Williamson, E., Walker, A. J., Bhaskaran, K., Bacon, S., Bates, C., Morton, C. E., Curtis, H. J., Mehrkar, A., Evans, D., Inglesby, P., Cockburn, J., McDonald, H. I., MacKenna, B., Tomlinson, L., Douglas, I. J., Rentsch, C. T., Mathur, R., Wong, A., Grieve, R., Harrison, D., Forbes, H., Schultze, A., Croker, R., Parry, J., Hester, F., Harper, S., Perera, R., Evans, S., Smeeth, L., & Goldacre, B.
- Affiliations
- London School of Hygiene & Tropical Medicine (GB)
- University of Oxford (GB)
- National Institute for Health and Care Research (GB)
- Corresponding author
- Goldacre, Ben
- ORCID
- Williamson, Elizabeth
- Walker, Alex J
- Bhaskaran, Krishnan
- Bacon, Seb
- Morton, Caroline E
- Curtis, Helen J
- Inglesby, Peter
- Cockburn, Jonathan
- McDonald, Helen I
- MacKenna, Brian
- Tomlinson, Laurie
- Douglas, Ian J
- Rentsch, Christopher T
- Mathur, Rohini
- Wong, Angel
- Grieve, Richard
- Harrison, David
- Schultze, Anna
- Croker, Richard
- Hester, Frank
- Perera, Raf
- Evans, Stephen
- Smeeth, Liam
- Goldacre, Ben
- Venue
- Nature
- Publisher
- openRxiv
- Published
- 2020-05-07
- Volume
- 584
- Issue
- 7821
- Pages
- 430-436
- ISSN
- 0028-0836 (ISSN-L)
- PMC
- PMC7611074
- OpenAlex
- W3047144258
- Cited by
- 6,674
- References
- 32
- Citations by year
- 2026: 176 · 2025: 303 · 2024: 698 · 2023: 904 · 2022: 1505 · 2021: 2173 · 2020: 908
- FWCI
- 179.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- medRxiv (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- PubMed Central (acceptedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- Funders
- London School of Hygiene and Tropical Medicine
- Wellcome Trust (107731/Z/15/Z, 201375/Z/16/Z, 201375, 107731)
- UK Research and Innovation
- National Institute for Health Research Health Protection Research Unit
- National Institute for Health and Care Research
- British Heart Foundation (FS/19/19/34175)
- Department of Health and Social Care
- Royal Society
- Diabetes UK
- Public Health England
- Medical Research Council (MR/S003940/1)
- NIHR Oxford Biomedical Research Centre
- National Institute for Health and Care Research Applied Research Collaboration Oxford and Thames Valley
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Oncology › COVID-19 and healthcare impacts
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Keywords
- COVID-19 pandemic, COVID-19 mortality, risk factors, OpenSAFELY, primary care electronic health records, sex differences, age, socioeconomic deprivation, diabetes mellitus, severe asthma, ethnicity, NHS England, cohort studies
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Aging, Asthma, Diabetes Mellitus, Female, Humans, Hypertension, Male, Middle Aged, Pneumonia, Viral, Sex Characteristics, Smoking, State Medicine, Cohort Studies, Proportional Hazards Models, Age Distribution, Coronavirus Infections, Risk Assessment, Black People, Asian People, Young Adult, Pandemics
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