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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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“income countries, and studies suggest worse outcomes among COVID-19 patients with other respiratory diseases in these countries, such as COPD (11, 12) and asthma (13).”
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Does Biological Therapy Protect against Severe COVID-19?
Mazzucchelli, R., Almodóvar-González, R., Crespí-Villarías, N., et al. (2020) · medRxiv · doi:10.1101/2020.06.21.20136788 · Cited by 1
“2 [4] Clinical Research Department at Hospital Universitario Fundacion Alcorcon (Madrid, Spain) [5] Dermatology Department at Hospital Universitario Fundación Alcorcon (Madrid, Spain) [6] Pharmacy Department at Hospital Universitario Fundación Alcorcon (Madrid, Spain) [7] Infectious Diseases.”
BackgroundSalmon, R., & Monaghan, S. (2020) · Epidemiology and Infection · doi:10.1017/s0950268821000054 · Cited by 1
“The proportion of men and women in the whole group did not differ significantly, unlike the other UK studies, restricted to deaths in hospital [4,5,7].”
Is the psychological well-being of a population associated with COVID-19 related survival?Preprint
Feys, F. (2020) · medRxiv · doi:10.1101/2020.06.05.20123018 · Cited by 1
Leighton, S., Leighton, D., Herron, J., Upthegrove, R., Cavanagh, J., Gkoutos, G. V., Cullen, B., & Mallikarjun, P. K. (2020) · medRxiv · doi:10.1101/2020.05.21.20108936 · Cited by 1
Abdulaal, A., Patel, A., Charani, E., et al. (2020) · doi:10.2196/preprints.20259 · Cited by 1
Understanding the Importance of a Gendered Analysis of COVID-19
Adeniyi-Ogunyankin, G., & Peake, L. (2021) · COVID-19 and Similar Futures · doi:10.1007/978-3-030-70179-6_45 · Cited by 1
Unraveling the Enigma of COVID-19 pneumonia and lung diameters: An HR-CT based study
Mushtaq, M., Usmani, A., Surti, A., et al. (2026) · Pakistan Journal of Medical Sciences · doi:10.12669/pjms.42.4.13318
“25 A cross-sectional study in Nepal, identified low levels of oxygen in smokers.”
Jhun, J.-Y., Lee, Y. J., Na, H., et al. (2026) · Journal of Ginseng Research · doi:10.1016/j.jgr.2026.101019
“Risk factors for death from COVID-19 involve comorbidities including RA along with diabetes, asthma, respiratory disease, chronic heart disease, liver disease, stroke/dementia, lupus, and psoriasis [22].”
False Discovery Estimation in Record Linkage
Robach, K., Hof, M. H., & van de Wiel, M. A. (2025) · Statistics in Medicine · doi:10.1002/sim.70292
Jin, J., Lai, D. W. L., Lee, V. W. P., Yan, E., Ou, A. Y. T., & Wang, J. J. (2025) · Primary Health Care Research & Development · doi:10.1017/s1463423624000641 · Cited by 1
The Societal Impact of the COVID-19 Pandemic from the Perspective of Omani Society
Ambusaidi, A. K., & Al-Zari, A. (2024) · Dirasat Human and Social Sciences · doi:10.35516/hum.v51i3.7791
Naji, A. S., Barwari, Z. A. M., AL-Kheroo, K. N., Yassin, A. K., Saleh, T. A., Tawfiq, S. A., Rashid, N. G., Hasan, K. M., Mohamed, A. S., Qayyim, M. K. A., et al. (2024) · Jordan Medical Journal · doi:10.35516/jmj.v58i1.2395
“…had negative results; these were mostly false-negative due to either improper sampling, degradation of the viral RNA during shipping/storage, low viral loads, incorrect nucleic acid extraction, or the presence of amplification inhibitors and mutation(s) in the RT-PCR target region [23, 24].”
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Mustafa, M., Attaallah, A. M., Amir, O., et al. (2022) · Health Science Reports · doi:10.1002/hsr2.889
“05), but, the poor outcomes are due to diabetes per se or associated comorbidities still not fully clarified.(11) Up to now, information concerning the clinical characteristics and the outcomes of diabetic COVID‐19 subjects was scarce particularly in Sudan.”
BackgroundInfluentialAamir, M. S., Liaqat, H., Ali, M., et al. (2022) · Pakistan journal of health sciences · doi:10.54393/pjhs.v3i05.225
Mikiewicz, M., Polok, K., Somionka, P., Krzywoń, J., Włudarczyk, A., Górka, J., & Szczeklik, W. (2022) · Anaesthesiology Intensive Therapy · doi:10.5114/ait.2022.118333 · Cited by 1
“thanks to the intense efforts of researchers, the risk factors for severe COVid-19 have been identified, including diabetes, obesity, cardiovascular diseases, and others [1].”
BackgroundStudy of care home referrals during three COVID‐19 national lockdowns
Badrakalimuthu, V. R. (2022) · Progress in Neurology and Psychiatry · doi:10.1002/pnp.760
Loughran, M., & Latham, R. (2022) · Medicine, Science and the Law · doi:10.1177/00258024221099691
Intersecting Epidemics of Many Unknowns: Human Immunodeficiency Virus and Covid-19
Tomy, A. D., & Chy, T. (2022) · Journal of Biomedicine and Biochemistry · doi:10.57238/jbb.2022.17450 · Cited by 1
“Residents in a few states are being randomly sampled for seroinspection (19); these serosurveys might provide estimates of prior SARS-CoV-2 contamination in PLWH if sampling processes include special interest groups like PLWH.”
BackgroundBrakenridge, C., Salim, A., Healy, G., et al. (2022) · doi:10.2196/preprints.36181
Impact of COVID-19 pandemic on physical activity of the Republic of Mordovia population
Usanova, A. A., Kunyaeva, T. A., Goncharova, L. N., et al. (2021) · Аcademy of Medicine and Sports · doi:10.15829/2712-7567-2021-37
The impact of environmental mycobiomes on geographic variation in COVID-19 mortalityPreprint
Ladau, J., Abuabara, K., Walker, A. M., Joachimiak, M. P., Bansal, I., Wu, Y., Hoffman, E. B., Kuo, C., Falco, N., Streich, J., et al. (2021) · medRxiv · doi:10.1101/2021.12.14.21267549
Self-citationTimothy, R., Chin-see, R. A., Martyniuk, J., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-1029118/v1
NHS: inequality and incorporation
Farah, W. (2021) · RACE & CLASS · doi:10.1177/03063968211045547
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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