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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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Recording COVID-19 consultations: review of symptoms, risk factors, and proposed SNOMED CT terms
Jani, B., Pell, J. P., McGagh, D., Liyanage, H., Kelly, D., de Lusignan, S., Weatherburn, C., Burns, R., Sullivan, F., & Mair, F. S. (2020) · BJGP Open · doi:10.3399/bjgpopen20x101125 · Cited by 5
Clinical Characteristics and Outcomes of Diabetic COVID-19 patients in Kuwait
Alshukry, A., Abbas, M., Ali, Y., et al. (2020) · medRxiv · doi:10.1101/2020.08.20.20178525 · Cited by 5
Vulnerabilities in kidney transplant recipients with COVID‐19: a single center experience
Meziyerh, S., van der Helm, D., & de Vries, A. D. (2020) · Transplant International · doi:10.1111/tri.13714 · Cited by 5
Ageing, Comorbidity and Frailty-Synergistic Risk Factors for Covid-19 Adverse Outcomes
Emmerton, D., Khan, S., Conway, J., et al. (2020) · OBM Geriatrics · doi:10.21926/obm.geriatr.2003127 · Cited by 5
“28) increased risk of death from COVID-19 [19].”
BackgroundModeling COVID19 mortality in the US: Community context and mobility matterPreprint
McGough, S. F., Gan, R. W., Tibshirani, R. J., & Meyer, A. (2020) · medRxiv · doi:10.1101/2020.06.18.20134122 · Cited by 6
Cardiovascular and cardiometabolic prevention: high-level priority in the era of COVID-19
Dhindsa, D., Wong, N., & Sperling, L. (2020) · Cardiovascular endocrinology & metabolism · doi:10.1097/xce.0000000000000215 · Cited by 5
Hull, S., Williams, C., Ashworth, M., et al. (2020) · medRxiv · doi:10.1101/2020.05.23.20101741 · Cited by 5
Bertocchi, G., & Dimico, A. (2021) · Social Science Research Network · doi:10.2139/ssrn.3818649 · Cited by 5
“COVID-19 and race Within the medical and epidemiological literature, the thus far largest study on the racial impact of COVID-19 has been performed in the UK based on the medical records of more than 17 million individuals (Williamson et al., 2020, working on behalf of NHS England).”
BackgroundMethodInfluentialScott, J., Family, H. E., Kesten, J. M., Hines, L. A., & Millar, J. F. A. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1240402 · Cited by 3
Peixoto, V. R., Vieira, A., Aguiar, P., et al. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1215833 · Cited by 4
Ow, N. L., Attalla, S. S., Davies, G. A., et al. (2022) · BJGP Open · doi:10.3399/bjgpo.2021.0222 · Cited by 5
“Indeed, patients with moderatetosevere asthma are at higher risk of suffering from complications of COVID19,(13) and inhospital death.(14) Research is needed to shed light on patients’ behaviour and factors that contributed to outofstock situations, to understand what led to asthma treatment shortages, how out- ofstoc…”
BackgroundBrakenridge, C. J., Salim, A., Healy, G. N., Grigg, R., Carver, A., Rickards, K., Owen, N. G., & Dunstan, D. W. (2022) · JMIR Diabetes · doi:10.2196/36181 · Cited by 3
“Poorer glycemic control can also be a predictor of COVID-19 mortality [7,8].”
BackgroundAsthma Management in the Era of the COVID-19 Pandemic
Klouda, T. M., Pillarisetti, A., Xie, A., Kabra, S. K., Saradhi, N., & Katwa, U. (2021) · The Indian Journal of Pediatrics · doi:10.1007/s12098-021-03979-z · Cited by 5
Werneke, U., Gaughran, F., & Taylor, D. M. (2021) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253211027699 · Cited by 8
Diabetes and COVID19: a bidirectional relationship
Ranjit Unnikrishnan, I., & Misra, A. (2021) · European Journal of Clinical Nutrition · doi:10.1038/s41430-021-00961-y · Cited by 22
“It has been shown that among individuals with known diabetes, poor glycemic control preceding COVID19 infection (as measured by glycated hemoglobin levels) independently predicts adverse outcomes [6].”
BackgroundNo evidence of tocilizumab treatment efficacy for severe to critical SARS-CoV2 infected patients
Burlacu, R., London, J., Fleury, A., Sené, T., Diallo, A., Meyssonnier, V., Zeller, V., Galland, J., Huscenot, T., Rubenstein, E., et al. (2021) · Medicine · doi:10.1097/md.0000000000026023 · Cited by 5
Inflammatory bowel disease clinical service recovery during the COVID-19 pandemic
Din, S., Gaya, D., Kammermeier, J., et al. (2021) · Frontline Gastroenterology · doi:10.1136/flgastro-2021-101805 · Cited by 4
Ponsford, M. J., Burton, R. J., Smith, L., et al. (2021) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2020-207157 · Cited by 4
Clough, H. E., McIntyre, K. M., Patterson, G. E., Harris, J. P., & Rushton, J. (2021) · BMJ Open · doi:10.1136/bmjopen-2020-044707 · Cited by 4
Lipworth, S., Rigby, I., Cheng, V., et al. (2021) · medRxiv · doi:10.1101/2021.01.12.21249654 · Cited by 4
Recalde, M., Pistillo, A., Fernández‐Bertolín, S., Roel, E., Aragón, M., Freisling, H., Prieto‐Alhambra, D., Burn, E., & Duarte‐Salles, T. (2020) · medRxiv · doi:10.1101/2020.11.25.20237776 · Cited by 6
What GI Physicians Need to Know During COVID-19 Pandemic
Thuluvath, P., Alukal, J., Ravindran, N., et al. (2020) · Digestive Diseases and Sciences · doi:10.1007/s10620-020-06625-4 · Cited by 4
Wark, P., Pathinayake, P., Kaiko, G., et al. (2020) · medRxiv · doi:10.1101/2020.07.26.20162248 · Cited by 4
“mortality, only those with asthma that had required the recent use of oral corticosteroids had increased mortality (29).”
BackgroundCardiac and Pulmonary Transplant Considerations During COVID-19 Pandemic
Pasrija, C., Shah, A., Kaczorowski, D., et al. (2020) · Innovations · doi:10.1177/1556984520937007 · Cited by 4
Ranking the explanatory power of factors associated with worldwide new Covid-19 casesPreprint
Moustakas, A. (2021) · Research Square · doi:10.21203/rs.3.rs-702119/v1 · Cited by 2
“The availability of hospital beds per 100k inhabitants, hand washing facilities, the effect of Covid-19 in the older people as well as prevalence of other diseases and smokers have been highlighted [19, 41, 42] and this study confirms their importance.”
BackgroundAkhtar, S., Anis, I., Kumar, N. A., Ihsan, M. T., Raheem, A., & Bano, S. (2024) · BMC Pediatrics · doi:10.1186/s12887-024-04572-x · Cited by 6
“During the early phase of the COVID-19 pandemic, children were thought to be less affected, with mild respiratory symptoms and low morbidity and mortality [1, 2].”
BackgroundMutch, C., Ross, D., Bularga, A., et al. (2022) · The Journal of the Royal College of Physicians of Edinburgh · doi:10.1177/14782715221120137 · Cited by 3
“Duration hospital stay (days) 8 (3, 19) 9 (4, 20) 7 (2, 19) 0.”
Alothaid, H., Alshehri, M., Yusuf, A., Alzahrani, M. E., McDaniel, J. T., Alamri, S. M., Aldughaim, M. S., Alswaidi, F., & Al-Qahtani, A. A. (2022) · Journal of Infection and Public Health · doi:10.1016/j.jiph.2022.04.015 · Cited by 4
“This is in agreement with reports in several other studies across the globe that indicate males being more predisposed to a high risk of mortality post-COVID-19 infection [20,25,26].”
Corcillo, A., Saqib, A., Sithamparanathan, N., Khanam, A., Williams, J., Gulati, A., Kariyawasam, D., & Karalliedde, J. J. (2022) · International Journal of Endocrinology · doi:10.1155/2022/8030765 · Cited by 4
“Compared to people without diabetes, people with diabetes have been reported to have higher mortality [17].”
BackgroundA public health framework for the equitable global allocation of vaccines: COVID-NEEDS
Jain, V., & Lorgelly, P. (2022) · Journal of Public Health Policy · doi:10.1057/s41271-021-00325-7 · Cited by 3
COVID-19: A Catalyst for Transforming Randomized Trials
Lee, J., Price, J. C., Jackson, W. M., Whittington, R. A., & Ioannidis, J. P. A. (2021) · Journal of Neurosurgical Anesthesiology · doi:10.1097/ana.0000000000000804 · Cited by 3
Régis, S., Nuiro, S. P., Merat, W., et al. (2021) · Biology · doi:10.3390/biology10100991 · Cited by 3
Lipworth, S., Rigby, I., Cheng, V., Bannister, P. G., Harriss, E., Cook, K. A., Cai, E., Tattan, M., Epie, T., Manoharan, L., et al. (2021) · Wellcome Open Research · doi:10.12688/wellcomeopenres.16735.1 · Cited by 8
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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