Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jan 25;19(1):e1003871.
doi: 10.1371/journal.pmed.1003871. eCollection 2022 Jan.

Overall and cause-specific hospitalisation and death after COVID-19 hospitalisation in England: A cohort study using linked primary care, secondary care, and death registration data in the OpenSAFELY platform

Krishnan Bhaskaran  1 , Christopher T Rentsch  1 , George Hickman  2 , William J Hulme  2 , Anna Schultze  1 , Helen J Curtis  2 , Kevin Wing  1 , Charlotte Warren-Gash  1 , Laurie Tomlinson  1 , Chris J Bates  3 , Rohini Mathur  1 , Brian MacKenna  2 , Viyaasan Mahalingasivam  1 , Angel Wong  1 , Alex J Walker  2 , Caroline E Morton  2 , Daniel Grint  1 , Amir Mehrkar  2 , Rosalind M Eggo  1 , Peter Inglesby  2 , Ian J Douglas  1 , Helen I McDonald  1 , Jonathan Cockburn  3 , Elizabeth J Williamson  1 , David Evans  2 , John Parry  3 , Frank Hester  3 , Sam Harper  3 , Stephen Jw Evans  1 , Sebastian Bacon  2 , Liam Smeeth  1 , Ben Goldacre  2
Affiliations

Overall and cause-specific hospitalisation and death after COVID-19 hospitalisation in England: A cohort study using linked primary care, secondary care, and death registration data in the OpenSAFELY platform

Krishnan Bhaskaran et al. PLoS Med. .

Abstract

Background: There is concern about medium to long-term adverse outcomes following acute Coronavirus Disease 2019 (COVID-19), but little relevant evidence exists. We aimed to investigate whether risks of hospital admission and death, overall and by specific cause, are raised following discharge from a COVID-19 hospitalisation.

Methods and findings: With the approval of NHS-England, we conducted a cohort study, using linked primary care and hospital data in OpenSAFELY to compare risks of hospital admission and death, overall and by specific cause, between people discharged from COVID-19 hospitalisation (February to December 2020) and surviving at least 1 week, and (i) demographically matched controls from the 2019 general population; and (ii) people discharged from influenza hospitalisation in 2017 to 2019. We used Cox regression adjusted for age, sex, ethnicity, obesity, smoking status, deprivation, and comorbidities considered potential risk factors for severe COVID-19 outcomes. We included 24,673 postdischarge COVID-19 patients, 123,362 general population controls, and 16,058 influenza controls, followed for ≤315 days. COVID-19 patients had median age of 66 years, 13,733 (56%) were male, and 19,061 (77%) were of white ethnicity. Overall risk of hospitalisation or death (30,968 events) was higher in the COVID-19 group than general population controls (fully adjusted hazard ratio [aHR] 2.22, 2.14 to 2.30, p < 0.001) but slightly lower than the influenza group (aHR 0.95, 0.91 to 0.98, p = 0.004). All-cause mortality (7,439 events) was highest in the COVID-19 group (aHR 4.82, 4.48 to 5.19 versus general population controls [p < 0.001] and 1.74, 1.61 to 1.88 versus influenza controls [p < 0.001]). Risks for cause-specific outcomes were higher in COVID-19 survivors than in general population controls and largely similar or lower in COVID-19 compared with influenza patients. However, COVID-19 patients were more likely than influenza patients to be readmitted or die due to their initial infection or other lower respiratory tract infection (aHR 1.37, 1.22 to 1.54, p < 0.001) and to experience mental health or cognitive-related admission or death (aHR 1.37, 1.02 to 1.84, p = 0.039); in particular, COVID-19 survivors with preexisting dementia had higher risk of dementia hospitalisation or death (age- and sex-adjusted HR 2.47, 1.37 to 4.44, p = 0.002). Limitations of our study were that reasons for hospitalisation or death may have been misclassified in some cases due to inconsistent use of codes, and we did not have data to distinguish COVID-19 variants.

Conclusions: In this study, we observed that people discharged from a COVID-19 hospital admission had markedly higher risks for rehospitalisation and death than the general population, suggesting a substantial extra burden on healthcare. Most risks were similar to those observed after influenza hospitalisations, but COVID-19 patients had higher risks of all-cause mortality, readmission or death due to the initial infection, and dementia death, highlighting the importance of postdischarge monitoring.

PubMed Disclaimer

Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests. The authors declare that: AS is employed by LSHTM on a fellowship sponsored by GSK. CWG is supported by a Wellcome Intermediate Clinical Fellowship (201440/Z/16/Z), and also holds grants from the Alzheimer’s Society, the British Heart Foundation and the Rosetrees Trust for unrelated work. RM has received consulting fees from AMGEN unrelated to the submitted work. ID has received grants from and holds shares in GSK. HIM is funded by the National Institute for Health Research (NIHR) Health Protection Research Unit (HPRU) in Vaccines and Immunisation, a partnership between Public Health England and the London School of Hygiene & Tropical Medicine. JP is an employee of TPP (Leeds) Ltd who own SystmOne. BG has received research funding from the Laura and John Arnold Foundation, the NHS National Institute for Health Research (NIHR), the NIHR School of Primary Care Research, the NIHR Oxford Biomedical Research Centre, the Mohn-Westlake Foundation, NIHR Applied Research Collaboration Oxford and Thames Valley, the Wellcome Trust, the Good Thinking Foundation, Health Data Research UK (HDRUK), the Health Foundation, and the World Health Organisation; he also receives personal income from speaking and writing for lay audiences on the misuse of science.

Figures

Fig 1
Fig 1. Study flow chart.
COVID-19, Coronavirus Disease 2019; STP, Sustainability and Transformation Plans; SUS, Secondary Uses Service.
Fig 2
Fig 2
Cumulative incidence of (A) admission or death (composite outcome), and (B) all-cause mortality, in patients discharged from COVID-19 hospital admissions, influenza hospital admissions, and in matched general population controls. COVID-19, Coronavirus Disease 2019.
Fig 3
Fig 3. HRs comparing exposed (prior COVID-19 hospitalisation) and controls for risk of subsequent hospital admission or death (composite outcome) and all-cause mortality.
Footnotes: *All models restricted to individuals with complete data on BMI and smoking (n = 23,153/24,673 (94%) in the COVID-19 group, 113,757/123,362 (92%) in general population controls and 14,904/16,058 (93%) in influenza controls (see S1 Table). Median time at risk in the COVID-19 group was 61 days for the composite outcome and 167 days for death; total time at risk followed a bimodal distribution corresponding to the 2 main pandemic waves in England. BMI, body mass index; COVID-19, Coronavirus Disease 2019; HR, hazard ratio; IMD, index of multiple deprivation.
Fig 4
Fig 4. Cumulative incidence of cause-specific admission/death in patients discharged from COVID-19 hospital admissions, influenza hospital admissions, and in matched general population controls.
Footnotes: For each subpanel, the outcome was defined as the first hospitalisation or death record with an ICD-10 code in the given category listed as the primary reason for hospitalisation/underlying cause of death. Deaths from other causes were treated as competing risks. In the influenza group, only patients entering the study in 2019 were included in analysis of cause-specific outcomes, as linked cause of death data were only available from 2019 onwards. COVID-19, Coronavirus Disease 2019; ICD, International Classification of Diseases; LRTI, lower respiratory tract infection.
Fig 5
Fig 5. HRs comparing exposed (prior COVID-19 hospitalisation) and controls for cause-specific hospital admission/deaths.
Footnotes: In the influenza group, only patients entering the study in 2019 were included in analysis of cause-specific outcomes, as linked cause of death data were only available from 2019 onwards. All models restricted to individuals with complete data on BMI and smoking (n = 23,153/24,673 (94%) in the COVID-19 group, 113,757/123,362 (92%) in general population controls and 6,161/6,689 (92%) in influenza (2019 only) controls (see S1 Table). Median time at risk in the COVID-19 group ranged from 91 to 108 days across outcomes; total time at risk followed a bimodal distribution corresponding to the 2 main pandemic waves in England. BMI, body mass index; COVID-19, Coronavirus Disease 2019; HR, hazard ratio; LRTI, lower respiratory tract infection.
See this image and copyright information in PMC

References

    1. World Health Organization. WHO Coronavirus (COVID-19) Dashboard 2021 [cited 2021 May 12]. Available from: https://covid19.who.int.
    1. Oran DP, Topol EJ. Prevalence of Asymptomatic SARS-CoV-2 Infection. Ann Intern Med. 2020;173(5):362–7. doi: 10.7326/M20-3012 - DOI - PMC - PubMed
    1. Prieto-Alhambra D, Balló E, Coma E, Mora N, Aragón M, Prats-Uribe A, et al.. Filling the gaps in the characterization of the clinical management of COVID-19: 30-day hospital admission and fatality rates in a cohort of 118 150 cases diagnosed in outpatient settings in Spain. Int J Epidemiol. 2020;49(6):1930–9. doi: 10.1093/ije/dyaa190 - DOI - PMC - PubMed
    1. Clift AK, Coupland CAC, Keogh RH, Diaz-Ordaz K, Williamson E, Harrison EM, et al.. Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality from coronavirus 19 in adults: national derivation and validation cohort study. BMJ. 2020;371:m3731. doi: 10.1136/bmj.m3731 - DOI - PMC - PubMed
    1. Mathur R, Rentsch CT, Morton CE, Hulme WJ, Schultze A, MacKenna B, et al.. Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform. Lancet. 2021;397(10286):1711–24. doi: 10.1016/S0140-6736(21)00634-6 - DOI - PMC - PubMed

Publication types

MeSH terms